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Sample records for cellular tissue properties

  1. [Cellular subcutaneous tissue. Anatomic observations].

    Marquart-Elbaz, C; Varnaison, E; Sick, H; Grosshans, E; Cribier, B

    2001-11-01

    We showed in a companion paper that the definition of the French "subcutaneous cellular tissue" considerably varied from the 18th to the end of the 20th centuries and has not yet reached a consensus. To address the anatomic reality of this "subcutaneous cellular tissue", we investigated the anatomic structures underlying the fat tissue in normal human skin. Sixty specimens were excised from the surface to the deep structures (bone, muscle, cartilage) on different body sites of 3 cadavers from the Institut d'Anatomie Normale de Strasbourg. Samples were paraffin-embedded, stained and analysed with a binocular microscope taking x 1 photographs. Specimens were also excised and fixed after subcutaneous injection of Indian ink, after mechanic tissue splitting and after performing artificial skin folds. The aspects of the deep parts of the skin greatly varied according to their anatomic localisation. Below the adipose tissue, we often found a lamellar fibrous layer which extended from the interlobular septa and contained horizontally distributed fat cells. No specific tissue below the hypodermis was observed. Artificial skin folds concerned either exclusively the dermis, when they were superficial or included the hypodermis, but no specific structure was apparent in the center of the fold. India ink diffused to the adipose tissue, mainly along the septa, but did not localise in a specific subcutaneous compartment. This study shows that the histologic aspects of the deep part of the skin depend mainly on the anatomic localisation. Skin is composed of epidermis, dermis and hypodermis and thus the hypodermis can not be considered as being "subcutaneous". A difficult to individualise, fibrous lamellar structure in continuity with the interlobular septa is often found under the fat lobules. This structure is a cleavage line, as is always the case with loose connective tissues, but belongs to the hypodermis (i.e. fat tissue). No specific tissue nor any virtual space was

  2. Molecular, cellular, and tissue engineering

    Bronzino, Joseph D

    2015-01-01

    Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering. Molecular, Cellular, and Tissue Engineering, the fourth volume of the handbook, presents material from respected scientists with diverse backgrounds in molecular biology, transport phenomena, physiological modeling, tissue engineering, stem cells, drug delivery systems, artificial organs, and personalized medicine. More than three dozen specific topics are examined, including DNA vaccines, biomimetic systems, cardiovascular dynamics, biomaterial scaffolds, cell mechanobiology, synthetic biomaterials, pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, nanobiomaterials for tissue engineering, biomedical imaging of engineered tissues, gene therapy, noninvasive targeted protein and peptide drug deliver...

  3. A human pericardium biopolymeric scaffold for autologous heart valve tissue engineering: cellular and extracellular matrix structure and biomechanical properties in comparison with a normal aortic heart valve.

    Straka, Frantisek; Schornik, David; Masin, Jaroslav; Filova, Elena; Mirejovsky, Tomas; Burdikova, Zuzana; Svindrych, Zdenek; Chlup, Hynek; Horny, Lukas; Daniel, Matej; Machac, Jiri; Skibová, Jelena; Pirk, Jan; Bacakova, Lucie

    2018-04-01

    The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p structures of the two tissues, the dense part of fibrous HP (49 ± 2%) and the lamina fibrosa of NAV (47 ± 4%), was similar. In both tissues, the secant elastic modulus (Es) was significantly lower in the transversal direction (p structure and has the biomechanical properties required for a tissue from which an autologous heart valve replacement may be constructed.

  4. Mechanical properties and cellular response of novel electrospun nanofibers for ligament tissue engineering: Effects of orientation and geometry.

    Pauly, Hannah M; Kelly, Daniel J; Popat, Ketul C; Trujillo, Nathan A; Dunne, Nicholas J; McCarthy, Helen O; Haut Donahue, Tammy L

    2016-08-01

    Electrospun nanofibers are a promising material for ligamentous tissue engineering, however weak mechanical properties of fibers to date have limited their clinical usage. The goal of this work was to modify electrospun nanofibers to create a robust structure that mimics the complex hierarchy of native tendons and ligaments. The scaffolds that were fabricated in this study consisted of either random or aligned nanofibers in flat sheets or rolled nanofiber bundles that mimic the size scale of fascicle units in primarily tensile load bearing soft musculoskeletal tissues. Altering nanofiber orientation and geometry significantly affected mechanical properties; most notably aligned nanofiber sheets had the greatest modulus; 125% higher than that of random nanofiber sheets; and 45% higher than aligned nanofiber bundles. Modifying aligned nanofiber sheets to form aligned nanofiber bundles also resulted in approximately 107% higher yield stresses and 140% higher yield strains. The mechanical properties of aligned nanofiber bundles were in the range of the mechanical properties of the native ACL: modulus=158±32MPa, yield stress=57±23MPa and yield strain=0.38±0.08. Adipose derived stem cells cultured on all surfaces remained viable and proliferated extensively over a 7 day culture period and cells elongated on nanofiber bundles. The results of the study suggest that aligned nanofiber bundles may be useful for ligament and tendon tissue engineering based on their mechanical properties and ability to support cell adhesion, proliferation, and elongation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Imaging in cellular and tissue engineering

    Yu, Hanry

    2013-01-01

    Details on specific imaging modalities for different cellular and tissue engineering applications are scattered throughout articles and chapters in the literature. Gathering this information into a single reference, Imaging in Cellular and Tissue Engineering presents both the fundamentals and state of the art in imaging methods, approaches, and applications in regenerative medicine. The book underscores the broadening scope of imaging applications in cellular and tissue engineering. It covers a wide range of optical and biological applications, including the repair or replacement of whole tiss

  6. Global properties of cellular automata

    Jen, E.

    1986-01-01

    Cellular automata are discrete mathematical systems that generate diverse, often complicated, behavior using simple deterministic rules. Analysis of the local structure of these rules makes possible a description of the global properties of the associated automata. A class of cellular automata that generate infinitely many aperoidic temporal sequences is defined,a s is the set of rules for which inverses exist. Necessary and sufficient conditions are derived characterizing the classes of ''nearest-neighbor'' rules for which arbitrary finite initial conditions (i) evolve to a homogeneous state; (ii) generate at least one constant temporal sequence

  7. Cellular signalling properties in microcircuits

    Toledo-Rodriguez, Maria; El Manira, Abdeljabbar; Wallén, Peter

    2005-01-01

    Molecules and cells are the signalling elements in microcircuits. Recent studies have uncovered bewildering diversity in postsynaptic signalling properties in all areas of the vertebrate nervous system. Major effort is now being invested in establishing the specialized signalling properties...

  8. CELLULAR CONTROL OF CONNECTIVE TISSUE MATRIX TENSION†

    Langevin, Helene M.; Nedergaard, Maiken; Howe, Alan

    2013-01-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occur...

  9. CELLULAR CONTROL OF CONNECTIVE TISSUE MATRIX TENSION†

    Langevin, Helene M.; Nedergaard, Maiken; Howe, Alan

    2013-01-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function and cancer. PMID:23444198

  10. Cellular control of connective tissue matrix tension.

    Langevin, Helene M; Nedergaard, Maiken; Howe, Alan K

    2013-08-01

    The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function, and cancer. Copyright © 2013 Wiley Periodicals, Inc.

  11. Biodegradable polycaprolactone-chitosan three-dimensional scaffolds fabricated by melt stretching and multilayer deposition for bone tissue engineering: assessment of the physical properties and cellular response

    Thuaksuban, Nuttawut; Nuntanaranont, Thongchai; Suttapreyasri, Srisurang; Pattanachot, Wachirapan; Cheung, Lim Kwong

    2011-01-01

    Fabrication of polycaprolactone (PCL)-chitosan (CS) three-dimensional (3D) scaffolds using the novel technique of melt stretching and multilayer deposition was introduced. In brief, firstly, the PCL-CS monofilaments containing 0% (pure PCL), 10%, 20% and 30% CS by weight were fabricated by melting and stretching processes. Secondly, the desired multilayer (3D) scaffolds were fabricated by arranging and depositing the filaments. Physical properties of the filaments and the scaffolds were evaluated. MC3T3-E1 cell lines were seeded on the scaffolds to assess their proliferation. A typical micro-groove pattern was found on the surfaces of pure PCL filaments due to stretching. The filaments of PCL-30%CS had the highest tendency of fracture during stretching and could not be used to form the scaffold. Increasing CS proportions tended to reduce the micro-groove pattern, surface roughness, tensile strength and elasticity of the filaments, whilst compressive strength of the PCL-CS scaffolds was not affected. The average pore size and porosity of the scaffolds were 536.90 ± 17.91 μm and 45.99 ± 2.8% respectively. Over 60 days, degradation of the scaffolds gradually increased (p > 0.05). The more CS containing scaffolds were found to increase in water uptake, but decrease in degradation rate. During the culture period, the growth of the cells in PCL-CS groups was significantly higher than in the pure PCL group (p < 0.05). On culture-day 21, the growth in the PCL-20%CS group was significantly higher than the other groups (p < 0.05). In conclusion, the PCL-20%CS scaffolds obtained the optimum results in terms of physical properties and cellular response.

  12. Biodegradable polycaprolactone-chitosan three-dimensional scaffolds fabricated by melt stretching and multilayer deposition for bone tissue engineering: assessment of the physical properties and cellular response

    Thuaksuban, Nuttawut; Nuntanaranont, Thongchai; Suttapreyasri, Srisurang [Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Prince of Songkla University, Kanjanavanij Road, Hatyai, Songkhla, 90112 (Thailand); Pattanachot, Wachirapan [Polymer Science Program, Faculty of Science, Prince of Songkla University, Kanjanavanij Road, Hatyai, Songkhla, 90112 (Thailand); Cheung, Lim Kwong, E-mail: nuttawut.t@psu.ac.t [Discipline of Oral and Maxillofacial Surgery, Faculty of Dentistry, the University of Hong Kong, Hong Kong (China)

    2011-02-15

    Fabrication of polycaprolactone (PCL)-chitosan (CS) three-dimensional (3D) scaffolds using the novel technique of melt stretching and multilayer deposition was introduced. In brief, firstly, the PCL-CS monofilaments containing 0% (pure PCL), 10%, 20% and 30% CS by weight were fabricated by melting and stretching processes. Secondly, the desired multilayer (3D) scaffolds were fabricated by arranging and depositing the filaments. Physical properties of the filaments and the scaffolds were evaluated. MC3T3-E1 cell lines were seeded on the scaffolds to assess their proliferation. A typical micro-groove pattern was found on the surfaces of pure PCL filaments due to stretching. The filaments of PCL-30%CS had the highest tendency of fracture during stretching and could not be used to form the scaffold. Increasing CS proportions tended to reduce the micro-groove pattern, surface roughness, tensile strength and elasticity of the filaments, whilst compressive strength of the PCL-CS scaffolds was not affected. The average pore size and porosity of the scaffolds were 536.90 {+-} 17.91 {mu}m and 45.99 {+-} 2.8% respectively. Over 60 days, degradation of the scaffolds gradually increased (p > 0.05). The more CS containing scaffolds were found to increase in water uptake, but decrease in degradation rate. During the culture period, the growth of the cells in PCL-CS groups was significantly higher than in the pure PCL group (p < 0.05). On culture-day 21, the growth in the PCL-20%CS group was significantly higher than the other groups (p < 0.05). In conclusion, the PCL-20%CS scaffolds obtained the optimum results in terms of physical properties and cellular response.

  13. Cellular immunotherapy for soft tissue sarcomas

    Finkelstein, Steven Eric; Fishman, Mayer; Conley, Anthony P.; Gabrilovich, Dmitry; Antonia, Scott; Chiappori, Alberto

    2015-01-01

    SUMMARY Soft tissue sarcomas are rare neoplasms, with approximately 9,000 new cases in the United States every year. Unfortunately, there is little progress in the treatment of metastatic soft tissue sarcomas in the past two decades beyond the standard approaches of surgery, chemotherapy, and radiation. Immunotherapy is a modality complementary to conventional therapy,. It is appealing because functional anti-tumor activity could affect both local-regional and systemic disease and act over a prolonged period of time. In this report, we review immunotherapeutic investigative strategies being developed, including several tumor vaccine, antigen vaccine, and dendritic cell vaccine strategies. PMID:22401634

  14. Tissue Engineering Strategies for Myocardial Regeneration: Acellular Versus Cellular Scaffolds?

    Domenech, Maribella; Polo-Corrales, Lilliana; Ramirez-Vick, Jaime E; Freytes, Donald O

    2016-12-01

    Heart disease remains one of the leading causes of death in industrialized nations with myocardial infarction (MI) contributing to at least one fifth of the reported deaths. The hypoxic environment eventually leads to cellular death and scar tissue formation. The scar tissue that forms is not mechanically functional and often leads to myocardial remodeling and eventual heart failure. Tissue engineering and regenerative medicine principles provide an alternative approach to restoring myocardial function by designing constructs that will restore the mechanical function of the heart. In this review, we will describe the cellular events that take place after an MI and describe current treatments. We will also describe how biomaterials, alone or in combination with a cellular component, have been used to engineer suitable myocardium replacement constructs and how new advanced culture systems will be required to achieve clinical success.

  15. Role of cellular adhesions in tissue dynamics spectroscopy

    Merrill, Daniel A.; An, Ran; Turek, John; Nolte, David

    2014-02-01

    Cellular adhesions play a critical role in cell behavior, and modified expression of cellular adhesion compounds has been linked to various cancers. We tested the role of cellular adhesions in drug response by studying three cellular culture models: three-dimensional tumor spheroids with well-developed cellular adhesions and extracellular matrix (ECM), dense three-dimensional cell pellets with moderate numbers of adhesions, and dilute three-dimensional cell suspensions in agarose having few adhesions. Our technique for measuring the drug response for the spheroids and cell pellets was biodynamic imaging (BDI), and for the suspensions was quasi-elastic light scattering (QELS). We tested several cytoskeletal chemotherapeutic drugs (nocodazole, cytochalasin-D, paclitaxel, and colchicine) on three cancer cell lines chosen from human colorectal adenocarcinoma (HT-29), human pancreatic carcinoma (MIA PaCa-2), and rat osteosarcoma (UMR-106) to exhibit differences in adhesion strength. Comparing tumor spheroid behavior to that of cell suspensions showed shifts in the spectral motion of the cancer tissues that match predictions based on different degrees of cell-cell contacts. The HT-29 cell line, which has the strongest adhesions in the spheroid model, exhibits anomalous behavior in some cases. These results highlight the importance of using three-dimensional tissue models in drug screening with cellular adhesions being a contributory factor in phenotypic differences between the drug responses of tissue and cells.

  16. Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue

    Schafer, M.J.; White, T.A.; Evans, G.; Tonne, J.M.; Verzosa, G.C.; Stout, M.B.; Mazula, D.L.; Palmer, A.K.; Baker, D.J.; Jensen, M.D.; Torbenson, M.S.; Miller, J.D.; Ikeda, Y.; Tchkonia, T.; Deursen, J.M.A. van; Kirkland, J.L.; LeBrasseur, N.K.

    2016-01-01

    Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the

  17. Spatial differences of cellular origins and in vivo hypoxia modify contractile properties of pulmonary artery smooth muscle cells: lessons for arterial tissue engineering.

    Hall, S M; Soueid, A; Smith, T; Brown, R A; Haworth, S G; Mudera, V

    2007-01-01

    Tissue engineering of functional arteries is challenging. Within the pulmonary artery wall, smooth muscle cells (PASMCs) have site-specific developmental and functional phenotypes, reflecting differing contractile roles. The force generated by PASMCs isolated from the inner 25% and outer 50% of the media of intrapulmonary elastic arteries from five normal and eight chronically hypoxic (hypertensive) 14 day-old piglets was quantified in a three-dimensional (3D) collagen construct, using a culture force monitor. Outer medial PASMCs from normal piglets exerted more force (528 +/- 50 dynes) than those of hypoxic piglets (177 +/- 42 dynes; p engineering of major blood vessels.

  18. A dynamic cellular vertex model of growing epithelial tissues

    Lin, Shao-Zhen; Li, Bo; Feng, Xi-Qiao

    2017-04-01

    Intercellular interactions play a significant role in a wide range of biological functions and processes at both the cellular and tissue scales, for example, embryogenesis, organogenesis, and cancer invasion. In this paper, a dynamic cellular vertex model is presented to study the morphomechanics of a growing epithelial monolayer. The regulating role of stresses in soft tissue growth is revealed. It is found that the cells originating from the same parent cell in the monolayer can orchestrate into clustering patterns as the tissue grows. Collective cell migration exhibits a feature of spatial correlation across multiple cells. Dynamic intercellular interactions can engender a variety of distinct tissue behaviors in a social context. Uniform cell proliferation may render high and heterogeneous residual compressive stresses, while stress-regulated proliferation can effectively release the stresses, reducing the stress heterogeneity in the tissue. The results highlight the critical role of mechanical factors in the growth and morphogenesis of epithelial tissues and help understand the development and invasion of epithelial tumors.

  19. Controlled cellular energy conversion in brown adipose tissue thermogenesis

    Horowitz, J. M.; Plant, R. E.

    1978-01-01

    Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

  20. Cellular and tissue expression of DAPIT, a phylogenetically conserved peptide

    H. Kontro

    2012-05-01

    Full Text Available DAPIT (Diabetes Associated Protein in Insulin-sensitive Tissues is a small, phylogenetically conserved, 58 amino acid peptide that was previously shown to be down-regulated at mRNA level in insulin-sensitive tissues of type 1 diabetes rats. In this study we characterize a custom made antibody against DAPIT and confirm the mitochondrial presence of DAPIT on cellular level. We also show that DAPIT is localized in lysosomes of HUVEC and HEK 293T cells. In addition, we describe the histological expression of DAPIT in several tissues of rat and man and show that it is highly expressed especially in cells with high aerobic metabolism and epithelial cells related to active transport of nutrients and ions. We propose that DAPIT, in addition to indicated subunit of mitochondrial F-ATPase, is also a subunit of lysosomal V-ATPase suggesting that it is a common component in different proton pumps.

  1. Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink

    Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D.; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

    2016-01-01

    Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types. PMID:27166839

  2. Bioprinting Cellularized Constructs Using a Tissue-specific Hydrogel Bioink.

    Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun-Wook; Seol, Young-Joon; Forsythe, Steven D; Bishop, Colin; Shupe, Thomas; Soker, Shay; Atala, Anthony

    2016-04-21

    Bioprinting has emerged as a versatile biofabrication approach for creating tissue engineered organ constructs. These constructs have potential use as organ replacements for implantation in patients, and also, when created on a smaller size scale as model "organoids" that can be used in in vitro systems for drug and toxicology screening. Despite development of a wide variety of bioprinting devices, application of bioprinting technology can be limited by the availability of materials that both expedite bioprinting procedures and support cell viability and function by providing tissue-specific cues. Here we describe a versatile hyaluronic acid (HA) and gelatin-based hydrogel system comprised of a multi-crosslinker, 2-stage crosslinking protocol, which can provide tissue specific biochemical signals and mimic the mechanical properties of in vivo tissues. Biochemical factors are provided by incorporating tissue-derived extracellular matrix materials, which include potent growth factors. Tissue mechanical properties are controlled combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear or multi-arm), and functional groups to yield extrudable bioinks and final construct shear stiffness values over a wide range (100 Pa to 20 kPa). Using these parameters, hydrogel bioinks were used to bioprint primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This methodology provides a general framework that can be adapted for future customization of hydrogels for biofabrication of a wide range of tissue construct types.

  3. 78 FR 44133 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    2013-07-23

    ...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide... documents issued from the Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and...

  4. 77 FR 65693 - Cellular, Tissue and Gene Therapies Advisory Committee; Amendment of Notice

    2012-10-30

    ...] Cellular, Tissue and Gene Therapies Advisory Committee; Amendment of Notice AGENCY: Food and Drug... notice of a meeting of the Cellular, Tissue and Gene Therapies Advisory Committee. This meeting was... announced that a meeting of the Cellular, Tissue and Gene Therapies Advisory Committee would be held on...

  5. 78 FR 79699 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    2013-12-31

    ...] Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue, and Gene Therapies Advisory Committee. General Function of the Committee: To provide... updates on guidance documents issued from the Office of Cellular, Tissue, and Gene Therapies, Center for...

  6. Systematic profiling of spatiotemporal tissue and cellular stiffness in the developing brain.

    Iwashita, Misato; Kataoka, Noriyuki; Toida, Kazunori; Kosodo, Yoichi

    2014-10-01

    Accumulating evidence implicates the significance of the physical properties of the niche in influencing the behavior, growth and differentiation of stem cells. Among the physical properties, extracellular stiffness has been shown to have direct effects on fate determination in several cell types in vitro. However, little evidence exists concerning whether shifts in stiffness occur in vivo during tissue development. To address this question, we present a systematic strategy to evaluate the shift in stiffness in a developing tissue using the mouse embryonic cerebral cortex as an experimental model. We combined atomic force microscopy measurements of tissue and cellular stiffness with immunostaining of specific markers of neural differentiation to correlate the value of stiffness with the characteristic features of tissues and cells in the developing brain. We found that the stiffness of the ventricular and subventricular zones increases gradually during development. Furthermore, a peak in tissue stiffness appeared in the intermediate zone at E16.5. The stiffness of the cortical plate showed an initial increase but decreased at E18.5, although the cellular stiffness of neurons monotonically increased in association with the maturation of the microtubule cytoskeleton. These results indicate that tissue stiffness cannot be solely determined by the stiffness of the cells that constitute the tissue. Taken together, our method profiles the stiffness of living tissue and cells with defined characteristics and can therefore be utilized to further understand the role of stiffness as a physical factor that determines cell fate during the formation of the cerebral cortex and other tissues. © 2014. Published by The Company of Biologists Ltd.

  7. 76 FR 22405 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    2011-04-21

    ...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide... June 29, 2011, the committee will discuss cellular and gene therapy products for the treatment of...

  8. Tissue and cellular biomechanics during corneal wound injury and repair.

    Raghunathan, Vijay Krishna; Thomasy, Sara M; Strøm, Peter; Yañez-Soto, Bernardo; Garland, Shaun P; Sermeno, Jasmyne; Reilly, Christopher M; Murphy, Christopher J

    2017-08-01

    Corneal wound healing is an enormously complex process that requires the simultaneous cellular integration of multiple soluble biochemical cues, as well as cellular responses to the intrinsic chemistry and biophysical attributes associated with the matrix of the wound space. Here, we document how the biomechanics of the corneal stroma are altered through the course of wound repair following keratoablative procedures in rabbits. Further we documented the influence that substrate stiffness has on stromal cell mechanics. Following corneal epithelial debridement, New Zealand white rabbits underwent phototherapeutic keratectomy (PTK) on the right eye (OD). Wound healing was monitored using advanced imaging modalities. Rabbits were euthanized and corneas were harvested at various time points following PTK. Tissues were characterized for biomechanics with atomic force microscopy and with histology to assess inflammation and fibrosis. Factor analysis was performed to determine any discernable patterns in wound healing parameters. The matrix associated with the wound space was stiffest at 7days post PTK. The greatest number of inflammatory cells were observed 3days after wounding. The highest number of myofibroblasts and the greatest degree of fibrosis occurred 21days after wounding. While all clinical parameters returned to normal values 400days after wounding, the elastic modulus remained greater than pre-surgical values. Factor analysis demonstrated dynamic remodeling of stroma occurs between days 10 and 42 during corneal stromal wound repair. Elastic modulus of the anterior corneal stroma is dramatically altered following PTK and its changes coincide initially with the development of edema and inflammation, and later with formation of stromal haze and population of the wound space with myofibroblasts. Factor analysis demonstrates strongest correlation between elastic modulus, myofibroblasts, fibrosis and stromal haze thickness, and between edema and central corneal

  9. Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.

    Schafer, Marissa J; White, Thomas A; Evans, Glenda; Tonne, Jason M; Verzosa, Grace C; Stout, Michael B; Mazula, Daniel L; Palmer, Allyson K; Baker, Darren J; Jensen, Michael D; Torbenson, Michael S; Miller, Jordan D; Ikeda, Yasuhiro; Tchkonia, Tamara; van Deursen, Jan M; Kirkland, James L; LeBrasseur, Nathan K

    2016-06-01

    Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16(INK4a) promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  10. Modeling the mechanics of cancer: effect of changes in cellular and extra-cellular mechanical properties.

    Katira, Parag; Bonnecaze, Roger T; Zaman, Muhammad H

    2013-01-01

    Malignant transformation, though primarily driven by genetic mutations in cells, is also accompanied by specific changes in cellular and extra-cellular mechanical properties such as stiffness and adhesivity. As the transformed cells grow into tumors, they interact with their surroundings via physical contacts and the application of forces. These forces can lead to changes in the mechanical regulation of cell fate based on the mechanical properties of the cells and their surrounding environment. A comprehensive understanding of cancer progression requires the study of how specific changes in mechanical properties influences collective cell behavior during tumor growth and metastasis. Here we review some key results from computational models describing the effect of changes in cellular and extra-cellular mechanical properties and identify mechanistic pathways for cancer progression that can be targeted for the prediction, treatment, and prevention of cancer.

  11. Cellularized cylindrical fiber/hydrogel composites for ligament tissue engineering.

    Thayer, Patrick S; Dimling, Anna F; Plessl, Daniel S; Hahn, Mariah R; Guelcher, Scott A; Dahlgren, Linda A; Goldstein, Aaron S

    2014-01-13

    Electrospun meshes suffer from poor cell infiltration and limited thickness, which restrict their use to thin tissue applications. Herein, we demonstrate two complementary processes to overcome these limitations and achieve elastomeric composites that may be suitable for ligament repair. First, C3H10T1/2 mesenchymal stem cells were incorporated into electrospun meshes using a hybrid electrospinning/electrospraying process. Second, electrospun meshes were rolled and formed into composites with an interpenetrating polyethylene glycol (PEG) hydrogel network. Stiffer composites were formed from poly(lactic-co-glycolic acid) (PLGA) meshes, while softer and more elastic composites were formed from poly(ester-urethane urea) (PEUUR) meshes. As-spun PLGA and PEUUR rolled meshes had tensile moduli of 19.2 ± 1.9 and 0.86 ± 0.34 MPa, respectively, which changed to 11.6 ± 4.8 and 1.05 ± 0.39 MPa with the incorporation of a PEG hydrogel phase. In addition, cyclic tensile testing indicated that PEUUR-based composites deformed elastically to at least 10%. Finally, C3H10T1/2 cells incorporated into electrospun meshes survived the addition of the PEG phase and remained viable for up to 5 days. These results indicate that the fabricated cellularized composites are support cyclic mechanical conditioning, and have potential application in ligament repair.

  12. Cellular and molecular screening of connective tissue dysplasia in adolescent athletes (pilot study

    M. V. Dvornichenko

    2017-01-01

    Full Text Available The purpose of the study is to evaluate the cellular and molecular parameters of bone remodeling in the blood as potential markers of undifferentiated forms of connective tissue dysplasiaMaterials and methods. The structural and functional status of cellular elements of in vitro culturing of mononuclear leukocytes of peripheral blood in adolescent athletes connected with phenotypic manifestations of undifferentiated connective tissue dysplasia (UCTD were investigated. 25 pupils of sport schools from 10–14 years old (main disciplines: figure skating, gymnastics, athletics were examined with the help of express analysis. The average age of the examined adolescents was (12,0 ± 1,7 years. Clinical examination of adolescents allowed ranking the UCTD signs on a scale of 4–11,5 points.Results. A comparison of questionnaire survey results and an evaluation of bone remodeling distant markers allowed the revelation of 2 groups in the distribution of adolescent athletes: those with minimal signs of UCTD (scores lesser than 7 points – 10 pupils, and those with expressed UCTD phenotype (scores are equal or more than 7 points –15 pupils. Significant statistical decrease in the content of collagen type I degradation products (CrossLaps (by 80% and ionized calcium (by 5% has been determined in the peripheral blood of adolescent athletes with expressed UCTD phenotype. In conditions of short-term 72-h cultivation of mononuclear leukocytes in the presence of a 3D matrix imitating the properties of the mineral substance of the regenerating bone tissue, morphofunctional features of cellular reaction in adolescent athletes with clinical manifestations of UCTD, as well the heterogeneity of the cell population associated with the appearance of cells with an osteoblast-like phenotype in the blood have been revealed. The results of investigation propose the use of distant cellular and molecular parameters of bone remodeling to screen the mechanisms and dynamics

  13. Stochastic properties of disturbed Elementary Cellular Automata

    Posiewnik, M.

    2005-01-01

    Cellular automata are class of simple mathematical systems that generate diverse, often complicated behaviour. Evolution of such a system is given by set of local and deterministic rules. However, in spite of simplicity of 'interactions' it's global behaviour can't be, in general, simply predicted or even can not be predicted in time shorter that time of it's strict evolution. We get as, a systems well known 1-dimensional, Wolfram class automata, and connect it into the reservoir consists of some random source (noise). In our experiment we are interested in: a) numeric verification of ergodicity for such a coupled system. b) finding it's probability distribution and evolution. c) finding some analogous for 'real' quantities and behaviour. d) using the dynamical systems and Markov chains theory to describe the system, and to make any predictions of it's behaviour. (author)

  14. 75 FR 66381 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    2010-10-28

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide...

  15. 76 FR 49774 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    2011-08-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide...

  16. 76 FR 64951 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    2011-10-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide...

  17. 78 FR 15726 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    2013-03-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of...

  18. Viscoelastic properties of cellular polypropylene ferroelectrets

    Gaal, M.; Bovtun, Viktor; Stark, W.; Erhard, A.; Yakymenko, Y.; Kreutzbruck, M.

    2016-01-01

    Roč. 119, č. 12 (2016), s. 1-12, č. článku 125101. ISSN 0021-8979 R&D Projects: GA ČR GA15-08389S Institutional support: RVO:68378271 Keywords : ferroelectrets * viscoelastic properties * ultrasonic Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.068, year: 2016

  19. Computing aggregate properties of preimages for 2D cellular automata.

    Beer, Randall D

    2017-11-01

    Computing properties of the set of precursors of a given configuration is a common problem underlying many important questions about cellular automata. Unfortunately, such computations quickly become intractable in dimension greater than one. This paper presents an algorithm-incremental aggregation-that can compute aggregate properties of the set of precursors exponentially faster than naïve approaches. The incremental aggregation algorithm is demonstrated on two problems from the two-dimensional binary Game of Life cellular automaton: precursor count distributions and higher-order mean field theory coefficients. In both cases, incremental aggregation allows us to obtain new results that were previously beyond reach.

  20. Cellular proliferation and regeneration following tissue damage. Progress report. [Eyes

    Harding, C.V.

    1976-10-01

    Results are reported from a study of wound healing in tissues of the eye, particularly lens, cornea, and surrounding tissues. The reactions of these tissues to mechanical injuries, as well as injuries induced by chemotoxic agents were studied. It is postulated that a better understanding of the basic reactions of the eye to injurious agents may be of importance in the evaluation of potential environmental hazards.

  1. The cellular environment of cancerous human tissue. Interfacial and dangling water as a "hydration fingerprint".

    Abramczyk, Halina; Brozek-Pluska, Beata; Krzesniak, Marta; Kopec, Monika; Morawiec-Sztandera, Alina

    2014-08-14

    Despite a large number of publications, the role of water in the cellular environment of biological tissue has not been clarified. Characterizing the biological interface is a key challenge in understanding the interactions of water in the tissue. Although we often assume that the properties of the bulk water can be translated to the crowded biological environment, this approach must be considerably revised when considering the biological interface. To our knowledge, few studies have directly monitored the interactions and accumulation of water in the restricted environments of the biological tissue upon realistic crowding conditions. The present study focuses on a molecular picture of water molecules at the biological interface, or specifically, water molecules adjacent to the hydrophobic and hydrophilic surfaces of normal and cancerous tissues. We recorded and analyzed the IR and Raman spectra of the νs(OH) stretching modes of water at the biological interfaces of the human breast and neck tissues. The results revealed dramatic changes in the water content in the tissue and are potentially relevant to both the fundamental problems of interfacial water modeling and the molecular diagnostics of cancer as a 'hydration fingerprint'. Herein, we will discuss the origin of the vibrational substructures observed for the νs(OH) stretching modes of water, showing that the interfacial water interacting via H-bond with other water molecules and biomolecules at the biological surface and free OH vibration of the dangling water are sensitive indicators of the pathology between the normal (noncancerous) and cancerous tissue and cancer types. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. The role of focal adhesion kinase in the regulation of cellular mechanical properties

    Mierke, Claudia Tanja

    2013-01-01

    The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation. (paper)

  3. The role of focal adhesion kinase in the regulation of cellular mechanical properties

    Mierke, Claudia Tanja

    2013-12-01

    The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation.

  4. Cellular Force Microscopy for in Vivo Measurements of Plant Tissue Mechanics1[W][OA

    Routier-Kierzkowska, Anne-Lise; Weber, Alain; Kochova, Petra; Felekis, Dimitris; Nelson, Bradley J.; Kuhlemeier, Cris; Smith, Richard S.

    2012-01-01

    Although growth and morphogenesis are controlled by genetics, physical shape change in plant tissue results from a balance between cell wall loosening and intracellular pressure. Despite recent work demonstrating a role for mechanical signals in morphogenesis, precise measurement of mechanical properties at the individual cell level remains a technical challenge. To address this challenge, we have developed cellular force microscopy (CFM), which combines the versatility of classical microindentation techniques with the high automation and resolution approaching that of atomic force microscopy. CFM’s large range of forces provides the possibility to map the apparent stiffness of both plasmolyzed and turgid tissue as well as to perform micropuncture of cells using very high stresses. CFM experiments reveal that, within a tissue, local stiffness measurements can vary with the level of turgor pressure in an unexpected way. Altogether, our results highlight the importance of detailed physically based simulations for the interpretation of microindentation results. CFM’s ability to be used both to assess and manipulate tissue mechanics makes it a method of choice to unravel the feedbacks between mechanics, genetics, and morphogenesis. PMID:22353572

  5. Cellular and Porous Materials Thermal Properties Simulation and Prediction

    Öchsner, Andreas; de Lemos, Marcelo J S

    2008-01-01

    Providing the reader with a solid understanding of the fundamentals as well as an awareness of recent advances in properties and applications of cellular and porous materials, this handbook and ready reference covers all important analytical and numerical methods for characterizing and predicting thermal properties. In so doing it directly addresses the special characteristics of foam-like and hole-riddled materials, combining theoretical and experimental aspects for characterization purposes.

  6. Simulation of electrochemical processes in cardiac tissue based on cellular automaton

    Avdeev, S A; Bogatov, N M

    2014-01-01

    A new class of cellular automata using special accumulative function for nonuniformity distribution is presented. Usage of this automata type for simulation of excitable media applied to electrochemical processes in human cardiac tissue is shown

  7. Bioinspired Cellular Structures: Additive Manufacturing and Mechanical Properties

    Stampfl, J.; Pettermann, H. E.; Liska, R.

    Biological materials (e.g., wood, trabecular bone, marine skeletons) rely heavily on the use of cellular architecture, which provides several advantages. (1) The resulting structures can bear the variety of "real life" load spectra using a minimum of a given bulk material, featuring engineering lightweight design principles. (2) The inside of the structures is accessible to body fluids which deliver the required nutrients. (3) Furthermore, cellular architectures can grow organically by adding or removing individual struts or by changing the shape of the constituting elements. All these facts make the use of cellular architectures a reasonable choice for nature. Using additive manufacturing technologies (AMT), it is now possible to fabricate such structures for applications in engineering and biomedicine. In this chapter, we present methods that allow the 3D computational analysis of the mechanical properties of cellular structures with open porosity. Various different cellular architectures including disorder are studied. In order to quantify the influence of architecture, the apparent density is always kept constant. Furthermore, it is shown that how new advanced photopolymers can be used to tailor the mechanical and functional properties of the fabricated structures.

  8. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation

    Niessen, Carien M.; Leckband, Deborah; Yap, Alpha S.

    2013-01-01

    This review addresses the cellular and molecular mechanisms of cadherin-based tissue morphogenesis. Tissue physiology is profoundly influenced by the distinctive organizations of cells in organs and tissues. In metazoa, adhesion receptors of the classical cadherin family play important roles in establishing and maintaining such tissue organization. Indeed, it is apparent that cadherins participate in a range of morphogenetic events that range from support of tissue integrity to dynamic cellular rearrangements. A comprehensive understanding of cadherin-based morphogenesis must then define the molecular and cellular mechanisms that support these distinct cadherin biologies. Here we focus on four key mechanistic elements: the molecular basis for adhesion through cadherin ectodomains; the regulation of cadherin expression at the cell surface; cooperation between cadherins and the actin cytoskeleton; and regulation by cell signaling. We discuss current progress and outline issues for further research in these fields. PMID:21527735

  9. Cellular dosimetry for radon progeny alpha particles in bronchial tissue

    Mohamed, A.; Hofmann, W.; Balashazy, I.

    1996-01-01

    Inhaled radon progeny are deposited in different regions of the human bronchial tree as functions of particle size and flow rate. Following deposition and mucociliary clearance, the sensitive bronchial basal and secretory cells are irradiated by two different alpha particle sources: (i) radon progeny in the sol and/or gel phase of the mucous layer, and (ii) radon progeny within the bronchial epithelium. In the case of internally deposited radionuclides, direct measurement of the energy absorbed from the ionizing radiation emitted by the decaying radionuclides is rarely, if ever, possible. Therefore, one must rely on dosimetric models to obtain estimates of the spatial and temporal patterns of energy deposition in tissues and organs of the body. When the radionuclide is uniformly distributed throughout the volume of a tissue of homogeneous composition and when the size of the tissue is large compared to the range of the particulate emissions of the radionuclide, then the dose rate within the tissue is also uniform and the calculation of absorbed dose can proceed without complication. However, if non-uniformities in the spatial and temporal distributions of the radionuclide are coupled with heterogeneous tissue composition, then the calculation of absorbed dose becomes complex and uncertain. Such is the case with the dosimetry of inhaled radon and radon progeny in the respiratory tract. There are increasing demands to obtain a definitive explanation of the role of alpha particles emitted from radon daughters in the induction of lung cancer. Various authors have attempted to evaluate the dose to the bronchial region of the respiratory tract due to the inhalation of radon daughters

  10. Automated and Adaptable Quantification of Cellular Alignment from Microscopic Images for Tissue Engineering Applications

    Xu, Feng; Beyazoglu, Turker; Hefner, Evan; Gurkan, Umut Atakan

    2011-01-01

    Cellular alignment plays a critical role in functional, physical, and biological characteristics of many tissue types, such as muscle, tendon, nerve, and cornea. Current efforts toward regeneration of these tissues include replicating the cellular microenvironment by developing biomaterials that facilitate cellular alignment. To assess the functional effectiveness of the engineered microenvironments, one essential criterion is quantification of cellular alignment. Therefore, there is a need for rapid, accurate, and adaptable methodologies to quantify cellular alignment for tissue engineering applications. To address this need, we developed an automated method, binarization-based extraction of alignment score (BEAS), to determine cell orientation distribution in a wide variety of microscopic images. This method combines a sequenced application of median and band-pass filters, locally adaptive thresholding approaches and image processing techniques. Cellular alignment score is obtained by applying a robust scoring algorithm to the orientation distribution. We validated the BEAS method by comparing the results with the existing approaches reported in literature (i.e., manual, radial fast Fourier transform-radial sum, and gradient based approaches). Validation results indicated that the BEAS method resulted in statistically comparable alignment scores with the manual method (coefficient of determination R2=0.92). Therefore, the BEAS method introduced in this study could enable accurate, convenient, and adaptable evaluation of engineered tissue constructs and biomaterials in terms of cellular alignment and organization. PMID:21370940

  11. Cell patch seeding and functional analysis of cellularized scaffolds for tissue engineering

    Kumar, P R Anil [Division of Implant Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012 (India); Varma, H K [Bioceramics Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012 (India); Kumary, T V [Division of Implant Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012 (India)

    2007-03-01

    Cell seeding has a direct impact on the final structure and function of tissue constructs, especially for applications like tissue engineering and regeneration. In this study seeding cell patches retrieved from the thermoresponsive poly(N-isopropylacrylamide) surface were used to generate in vitro tissue constructs. Porous and dense bone substitute materials were cellularized using osteoblast cells by a patch transfer and a trypsin method. The function and proliferation of cells was analyzed after 7 days of culture. The relative cell growth rate was found to be higher in cellularized porous hydroxyapatite (PHA) than in dense hydroxyapatite. Live-dead staining confirmed viable cells inside the pores of PHA. Increased alkaline phosphatase activity of cells transferred by the cell patch over the trypsin method revealed the significance of cell patch seeding. This novel method of generating tissue constructs by cell patch seeding was successful in cellularizing scaffolds with intact cell function.

  12. Cell patch seeding and functional analysis of cellularized scaffolds for tissue engineering

    Kumar, P R Anil; Varma, H K; Kumary, T V

    2007-01-01

    Cell seeding has a direct impact on the final structure and function of tissue constructs, especially for applications like tissue engineering and regeneration. In this study seeding cell patches retrieved from the thermoresponsive poly(N-isopropylacrylamide) surface were used to generate in vitro tissue constructs. Porous and dense bone substitute materials were cellularized using osteoblast cells by a patch transfer and a trypsin method. The function and proliferation of cells was analyzed after 7 days of culture. The relative cell growth rate was found to be higher in cellularized porous hydroxyapatite (PHA) than in dense hydroxyapatite. Live-dead staining confirmed viable cells inside the pores of PHA. Increased alkaline phosphatase activity of cells transferred by the cell patch over the trypsin method revealed the significance of cell patch seeding. This novel method of generating tissue constructs by cell patch seeding was successful in cellularizing scaffolds with intact cell function

  13. Numerical calculations of effective elastic properties of two cellular structures

    Tuncer, Enis

    2005-01-01

    Young's moduli of regular two-dimensional truss-like and eye-shaped structures are simulated using the finite element method. The structures are idealizations of soft polymeric materials used in ferro-electret applications. In the simulations, the length scales of the smallest representative units are varied, which changes the dimensions of the cell walls in the structures. A power-law expression with a quadratic as the exponent term is proposed for the effective Young's moduli of the systems as a function of the solid volume fraction. The data are divided into three regions with respect to the volume fraction: low, intermediate and high. The parameters of the proposed power-law expression in each region are later represented as a function of the structural parameters, the unit-cell dimensions. The expression presented can be used to predict a structure/property relationship in materials with similar cellular structures. The contribution of the cell-wall thickness to the elastic properties becomes significant at concentrations >0.15. The cell-wall thickness is the most significant factor in predicting the effective Young's modulus of regular cellular structures at high volume fractions of solid. At lower concentrations of solid, the eye-shaped structure yields a lower Young's modulus than a truss-like structure with similar anisotropy. Comparison of the numerical results with those of experimental data for poly(propylene) show good agreement regarding the influence of cell-wall thickness on elastic properties of thin cellular films

  14. Model of adipose tissue cellularity dynamics during food restriction.

    Soula, H A; Géloën, A; Soulage, C O

    2015-01-07

    Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases related to obesity. Size of fat cells depends on the balance of synthesis and mobilization of lipids and can undergo important variations throughout the life of the organism. These variations usually occur when storing and releasing lipids according to energy demand. In particular when confronted to severe food restriction, adipocyte releases its lipid content via a process called lipolysis. We propose a mathematical model that combines cell diameter distribution and lipolytic response to show that lipid release is a surface (radius squared) limited mechanism. Since this size-dependent rate affects the cell׳s shrinkage speed, we are able to predict the cell size distribution evolution when lipolysis is the only factor at work: such as during an important food restriction. Performing recurrent surgical biopsies on rats, we measured the evolution of adipose cell size distribution for the same individual throughout the duration of the food restriction protocol. We show that our microscopic model of size dependent lipid release can predict macroscopic size distribution evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization.

    Wang, Sheng; Huang, Peng; Chen, Xiaoyuan

    2016-09-01

    Targeted delivery of therapeutic agents is an important way to improve the therapeutic index and reduce side effects. To design nanoparticles for targeted delivery, both enhanced tumor tissue accumulation/retention and enhanced cellular internalization should be considered simultaneously. So far, there have been very few nanoparticles with immutable structures that can achieve this goal efficiently. Hierarchical targeting, a novel targeting strategy based on stimuli responsiveness, shows good potential to enhance both tumor tissue accumulation/retention and cellular internalization. Here, the recent design and development of hierarchical targeting nanoplatforms, based on changeable particle sizes, switchable surface charges and activatable surface ligands, will be introduced. In general, the targeting moieties in these nanoplatforms are not activated during blood circulation for efficient tumor tissue accumulation, but re-activated by certain internal or external stimuli in the tumor microenvironment for enhanced cellular internalization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Overcoming cellular and tissue barriers to improve liposomal drug delivery

    Kohli, Aditya G.

    Forty years of liposome research have demonstrated that the anti-tumor efficacy of liposomal therapies is, in part, driven by three parameters: 1) liposome formulation and lipid biophysics, 2) accumulation and distribution in the tumor, and 3) release of the payload at the site of interest. This thesis outlines three studies that improve on each of these delivery steps. In the first study, we engineer a novel class of zwitterlipids with an inverted headgroup architecture that have remarkable biophysical properties and may be useful for drug delivery applications. After intravenous administration, liposomes accumulate in the tumor by the enhanced permeability and retention effect. However, the tumor stroma often limits liposome efficacy by preventing distribution into the tumor. In the second study, we demonstrate that depletion of hyaluronan in the tumor stroma improves the distribution and efficacy of DoxilRTM in murine 4T1 tumors. Once a liposome has distributed to the therapeutic site, it must release its payload over the correct timescale. Few facile methods exist to quantify the release of liposome therapeutics in vivo. In the third study, we outline and validate a simple, robust, and quantitative method for tracking the rate and extent of release of liposome contents in vivo. This tool should facilitate a better understanding of the pharmacodynamics of liposome-encapsulated drugs in animals. This work highlights aspects of liposome behavior that have prevented successful clinical translation and proposes alternative approaches to improve liposome drug delivery.

  17. Emergent material properties of developing epithelial tissues.

    Machado, Pedro F; Duque, Julia; Étienne, Jocelyn; Martinez-Arias, Alfonso; Blanchard, Guy B; Gorfinkiel, Nicole

    2015-11-23

    Force generation and the material properties of cells and tissues are central to morphogenesis but remain difficult to measure in vivo. Insight is often limited to the ratios of mechanical properties obtained through disruptive manipulation, and the appropriate models relating stress and strain are unknown. The Drosophila amnioserosa epithelium progressively contracts over 3 hours of dorsal closure, during which cell apices exhibit area fluctuations driven by medial myosin pulses with periods of 1.5-6 min. Linking these two timescales and understanding how pulsatile contractions drive morphogenetic movements is an urgent challenge. We present a novel framework to measure in a continuous manner the mechanical properties of epithelial cells in the natural context of a tissue undergoing morphogenesis. We show that the relationship between apicomedial myosin fluorescence intensity and strain during fluctuations is consistent with a linear behaviour, although with a lag. We thus used myosin fluorescence intensity as a proxy for active force generation and treated cells as natural experiments of mechanical response under cyclic loading, revealing unambiguous mechanical properties from the hysteresis loop relating stress to strain. Amnioserosa cells can be described as a contractile viscoelastic fluid. We show that their emergent mechanical behaviour can be described by a linear viscoelastic rheology at timescales relevant for tissue morphogenesis. For the first time, we establish relative changes in separate effective mechanical properties in vivo. Over the course of dorsal closure, the tissue solidifies and effective stiffness doubles as net contraction of the tissue commences. Combining our findings with those from previous laser ablation experiments, we show that both apicomedial and junctional stress also increase over time, with the relative increase in apicomedial stress approximately twice that of other obtained measures. Our results show that in an epithelial

  18. Viscoelastic Properties of Human Tracheal Tissues.

    Safshekan, Farzaneh; Tafazzoli-Shadpour, Mohammad; Abdouss, Majid; Shadmehr, Mohammad B

    2017-01-01

    The physiological performance of trachea is highly dependent on its mechanical behavior, and therefore, the mechanical properties of its components. Mechanical characterization of trachea is key to succeed in new treatments such as tissue engineering, which requires the utilization of scaffolds which are mechanically compatible with the native human trachea. In this study, after isolating human trachea samples from brain-dead cases and proper storage, we assessed the viscoelastic properties of tracheal cartilage, smooth muscle, and connective tissue based on stress relaxation tests (at 5% and 10% strains for cartilage and 20%, 30%, and 40% for smooth muscle and connective tissue). After investigation of viscoelastic linearity, constitutive models including Prony series for linear viscoelasticity and quasi-linear viscoelastic, modified superposition, and Schapery models for nonlinear viscoelasticity were fitted to the experimental data to find the best model for each tissue. We also investigated the effect of age on the viscoelastic behavior of tracheal tissues. Based on the results, all three tissues exhibited a (nonsignificant) decrease in relaxation rate with increasing the strain, indicating viscoelastic nonlinearity which was most evident for cartilage and with the least effect for connective tissue. The three-term Prony model was selected for describing the linear viscoelasticity. Among different models, the modified superposition model was best able to capture the relaxation behavior of the three tracheal components. We observed a general (but not significant) stiffening of tracheal cartilage and connective tissue with aging. No change in the stress relaxation percentage with aging was observed. The results of this study may be useful in the design and fabrication of tracheal tissue engineering scaffolds.

  19. Investigation of tissue cellularity at the tip of the core biopsy needle with optical coherence tomography.

    Iftimia, Nicusor; Park, Jesung; Maguluri, Gopi; Krishnamurthy, Savitri; McWatters, Amanda; Sabir, Sharjeel H

    2018-02-01

    We report the development and the pre-clinical testing of a new technology based on optical coherence tomography (OCT) for investigating tissue composition at the tip of the core biopsy needle. While ultrasound, computed tomography, and magnetic resonance imaging are routinely used to guide needle placement within a tumor, they still do not provide the resolution needed to investigate tissue cellularity (ratio between viable tumor and benign stroma) at the needle tip prior to taking a biopsy core. High resolution OCT imaging, however, can be used to investigate tissue morphology at the micron scale, and thus to determine if the biopsy core would likely have the expected composition. Therefore, we implemented this capability within a custom-made biopsy gun and evaluated its capability for a correct estimation of tumor tissue cellularity. A pilot study on a rabbit model of soft tissue cancer has shown the capability of this technique to provide correct evaluation of tumor tissue cellularity in over 85% of the cases. These initial results indicate the potential benefit of the OCT-based approach for improving the success of the core biopsy procedures.

  20. Study of Stevia rebaudiana Bertoni antioxidant activities and cellular properties.

    Bender, Cecilia; Graziano, Sara; Zimmermann, Benno F

    2015-01-01

    The aim of our study was to determine the antioxidant activities, cytotoxicity and proliferative properties in Stevia rebaudiana leaves and stems. Leaves extracts exhibited a higher antioxidant activity than stems extract, through oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays. Stevioside and rebaudioside A, the main sweetening metabolites in stevia leaves, exhibited a low ORAC value in comparison with plant extracts, while did not elicit any CAA. Stevia rebaudiana did not exhibit toxicity against HepG2 (hepatocellular carcinoma) human cells. No proliferative nor catalase modulations were observed in cells treated with such extracts. Our findings support the promising role of stevia that, apart from its sweetness, can act as a source of antioxidants, even at the intracellular level. This activity makes S. rebaudiana crude extract an interesting resource of natural sweetness with antioxidant properties which may find numerous applications in foods and nutritional supplements industries.

  1. Cellular automata and integrodifferential equation models for cell renewal in mosaic tissues

    Bloomfield, J. M.; Sherratt, J. A.; Painter, K. J.; Landini, G.

    2010-01-01

    Mosaic tissues are composed of two or more genetically distinct cell types. They occur naturally, and are also a useful experimental method for exploring tissue growth and maintenance. By marking the different cell types, one can study the patterns formed by proliferation, renewal and migration. Here, we present mathematical modelling suggesting that small changes in the type of interaction that cells have with their local cellular environment can lead to very different outcomes for the composition of mosaics. In cell renewal, proliferation of each cell type may depend linearly or nonlinearly on the local proportion of cells of that type, and these two possibilities produce very different patterns. We study two variations of a cellular automaton model based on simple rules for renewal. We then propose an integrodifferential equation model, and again consider two different forms of cellular interaction. The results of the continuous and cellular automata models are qualitatively the same, and we observe that changes in local environment interaction affect the dynamics for both. Furthermore, we demonstrate that the models reproduce some of the patterns seen in actual mosaic tissues. In particular, our results suggest that the differing patterns seen in organ parenchymas may be driven purely by the process of cell replacement under different interaction scenarios. PMID:20375040

  2. Mechanical properties of human atherosclerotic intima tissue.

    Akyildiz, Ali C; Speelman, Lambert; Gijsen, Frank J H

    2014-03-03

    Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components. In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared. Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies. Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme. This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Simulation of a plane wavefront propagating in cardiac tissue using a cellular automata model

    Barbosa, Carlos R Hall

    2003-01-01

    We present a detailed description of a cellular automata model for the propagation of action potential in a planar cardiac tissue, which is very fast and easy to use. The model incorporates anisotropy in the electrical conductivity and a spatial variation of the refractory time. The transmembrane potential distribution is directly derived from the cell states, and the intracellular and extracellular potential distributions are calculated for the particular case of a plane wavefront. Once the potential distributions are known, the associated current densities are calculated by Ohm's law, and the magnetic field is determined at a plane parallel to the cardiac tissue by applying the law of Biot and Savart. The results obtained for propagation speed and for magnetic field amplitude with the cellular automata model are compared with values predicted by the bidomain formulation, for various angles between wavefront propagation and fibre direction, characterizing excellent agreement between the models

  4. The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration.

    Albawardi, Alia; Almarzooqi, Saeeda; Saraswathiamma, Dhanya; Abdul-Kader, Hidaya Mohammed; Souid, Abdul-Kader; Alfazari, Ali S

    2015-01-01

    The purpose of this in vitro study was to develop a useful biomarker (e.g., cellular respiration, or mitochondrial O2 consumption) for measuring activities of mTOR inhibitors. It measured the effects of commonly used immunosuppressants (sirolimus-rapamycin, tacrolimus, and cyclosporine) on cellular respiration in target tissues (kidney, liver, and heart) from C57BL/6 mice. The mammalian target of rapamycin (mTOR), a serine/ threonine kinase that supports nutrient-dependent cell growth and survival, is known to control energy conversion processes within the mitochondria. Consistently, inhibitors of mTOR (e.g., rapamycin, also known as sirolimus or Rapamune®) have been shown to impair mitochondrial function. Inhibitors of the calcium-dependent serine/threonine phosphatase calcineurin (e.g., tacrolimus and cyclosporine), on the other hand, strictly prevent lymphokine production leading to a reduced T-cell function. Sirolimus (10 μM) inhibited renal (22%, P=0.002), hepatic (39%, Prespiration. Tacrolimus and cyclosporine had no or minimum effects on cellular respiration in these tissues. Thus, these results clearly demonstrate that impaired cellular respiration (bioenergetics) is a sensitive biomarker of the immunosuppressants that target mTOR.

  5. X-ray micro-tomography for investigations of brain tissues on cellular level

    Khimchenko, Anna; Schulz, Georg; Deyhle, Hans; Thalmann, Peter; Zanette, Irene; Zdora, Marie-Christine; Bikis, Christos; Hipp, Alexander; Hieber, Simone E.; Schweighauser, Gabriel; Hench, Jürgen; Müller, Bert

    2016-10-01

    X-ray imaging in absorption contrast mode is well established for hard tissue visualization. However, performance for lower density materials is limited due to a reduced contrast. Our aim is three-dimensional (3D) characterization of micro-morphology of human brain tissues down to (sub-)cellular resolution within a laboratory environment. Using the laboratory-based microtomography (μCT) system nanotom m (GE Sensing and Inspection Technologies GmbH, Wunstorf, Germany) and synchrotron radiation at the Diamond-Manchester Imaging Branchline I13-2 (Diamond Light Source, Didcot, UK), we have acquired 3D data with a resolution down to 0.45 μm for visualization of a human cerebellum specimen down to cellular level. We have shown that all selected modalities, namely laboratory-based absorption contrast micro-tomography (LBμCT), synchrotron radiation based in-line single distance phase contrast tomography (SDPR) and synchrotron radiation based single-grating interferometry (GI), can reach cellular resolution for tissue samples with a size in the mm-range. The results are discussed qualitatively in comparison to optical microscopy of haematoxylin and eosin (HE) stained sections. As phase contrast yields to a better data quality for soft tissues and in order to overcome restrictions of limited beamline access for phase contrast measurements, we have equipped the μCT system nanotom m with a double-grating phase contrast set-up. Preliminary experimental results of a knee sample consisting of a bony part and a cartilage demonstrate that phase contrast data exhibits better quality compared to absorption contrast. Currently, the set-up is under adjustment. It is expected that cellular resolution would also be achieved. The questions arise (1) what would be the quality gain of laboratory-based phase contrast in comparison to laboratory-based absorption contrast tomography and (2) could laboratory-based phase contrast data provide comparable results to synchrotron radiation based

  6. Diffusion-weighted imaging for the cellularity assessment and matrix characterization of soft tissue tumour.

    Robba, Tiziana; Chianca, Vito; Albano, Domenico; Clementi, Valeria; Piana, Raimondo; Linari, Alessandra; Comandone, Alessandro; Regis, Guido; Stratta, Maurizio; Faletti, Carlo; Borrè, Alda

    2017-11-01

    To evaluate whether apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) is able to investigate the histological features of soft tissue tumours. We reviewed MRIs of soft tissue tumours performed from 2012 to 2015 to calculate the average ADCs. We included 46 patients (27 male; mean age: 57 years, range 12-85 years) with histologically proven soft tissue tumours (10 benign, 2 intermediate 34 malignant) grouped into eight tumour type classes. An experienced pathologist assigned a semi-quantitative cellularity score (very high, high, medium and low) and tumour grading. The t test, ANOVA and linear regression were used to correlate ADC with clinicopathological data. Approximate receiver operating characteristic curves were created to predict possible uses of ADC to differentiate benign from malignant tumours. There was a significant difference (p < 0.01) in ADCs between these three groups excluding myxoid sarcomas. A significant difference was also evident between the tumour type classes (p < 0.001), grade II and III myxoid lesions (p < 0.05), tumour grading classes (p < 0.001) and cellularity scores classes (p < 0.001), with the lowest ADCs in the very high cellularity. While the linear regression analysis showed a significant relationship between ADC and tumour cellularity (r = 0.590, p ≤ 0.05) and grading (r = 0.437, p ≤ 0.05), no significant relationship was found with age, gender, tumour size and histological subtype. An optimal cut-off ADC value of 1.45 × 10 -3 mm 2 /s with 76.8% accuracy was found to differentiate benign from malignant tumours. DWI may offer adjunctive information about soft tissue tumours, but its clinical role is still to be defined.

  7. The connection between cellular mechanoregulation and tissue patterns during bone healing.

    Repp, Felix; Vetter, Andreas; Duda, Georg N; Weinkamer, Richard

    2015-09-01

    The formation of different tissues in the callus during secondary bone healing is at least partly influenced by mechanical stimuli. We use computer simulations to test the consequences of different hypotheses of the mechanoregulation at the cellular level on the patterns of tissues formed during healing. The computational study is based on an experiment on sheep, where after a tibial osteotomy, histological sections were harvested at different time points. In the simulations, we used a recently proposed basic phenomenological model, which allows ossification to occur either via endochondral or intramembranous ossification, but tries otherwise to employ a minimal number of simulation parameters. The model was extended to consider also the possibility of bone resorption and consequently allowing a description of the full healing progression till the restoration of the cortex. Specifically, we investigated how three changes in the mechanoregulation influence the resulting tissue patterns: (1) a time delay between stimulation of the cell and the formation of the tissue, (2) a variable mechanosensitivity of the cells, and (3) an independence of long time intervals of the soft tissue maturation from the mechanical stimulus. For all three scenarios, our simulations do not show qualitative differences in the time development of the tissue patterns. Largest differences were observed in the intermediate phases of healing in the amount and location of the cartilage. Interestingly, the course of healing was virtually unaltered in case of scenario (3) where tissue maturation proceeded independent of mechanical stimulation.

  8. Origami-based cellular metamaterial with auxetic, bistable, and self-locking properties

    Kamrava, Soroush; Mousanezhad, Davood; Ebrahimi, Hamid; Ghosh, Ranajay; Vaziri, Ashkan

    2017-04-01

    We present a novel cellular metamaterial constructed from Origami building blocks based on Miura-ori fold. The proposed cellular metamaterial exhibits unusual properties some of which stemming from the inherent properties of its Origami building blocks, and others manifesting due to its unique geometrical construction and architecture. These properties include foldability with two fully-folded configurations, auxeticity (i.e., negative Poisson’s ratio), bistability, and self-locking of Origami building blocks to construct load-bearing cellular metamaterials. The kinematics and force response of the cellular metamaterial during folding were studied to investigate the underlying mechanisms resulting in its unique properties using analytical modeling and experiments.

  9. Micro-/nano-engineered cellular responses for soft tissue engineering and biomedical applications.

    Tay, Chor Yong; Irvine, Scott Alexander; Boey, Freddy Y C; Tan, Lay Poh; Venkatraman, Subbu

    2011-05-23

    The development of biomedical devices and reconstruction of functional ex vivo tissues often requires the need to fabricate biomimetic surfaces with features of sub-micrometer precision. This can be achieved with the advancements in micro-/nano-engineering techniques, allowing researchers to manipulate a plethora of cellular behaviors at the cell-biomaterial interface. Systematic studies conducted on these 2D engineered surfaces have unraveled numerous novel findings that can potentially be integrated as part of the design consideration for future 2D and 3D biomaterials and will no doubt greatly benefit tissue engineering. In this review, recent developments detailing the use of micro-/nano-engineering techniques to direct cellular orientation and function pertinent to soft tissue engineering will be highlighted. Particularly, this article aims to provide valuable insights into distinctive cell interactions and reactions to controlled surfaces, which can be exploited to understand the mechanisms of cell growth on micro-/nano-engineered interfaces, and to harness this knowledge to optimize the performance of 3D artificial soft tissue grafts and biomedical applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Some Properties of topological pressure on cellular automata

    Chih-Hung Chang

    2014-09-01

    Full Text Available This paper investigates the ergodicity and the power rule of the topological pressure of a cellular automaton. If a cellular automaton is either leftmost or rightmost premutive (due to the terminology given by Hedlund [Math.~Syst.~Theor.~3, 320-375, 1969], then it is ergodic with respect to the uniform Bernoulli measure. More than that, the relation of topological pressure between the original cellular automaton and its power rule is expressed in a closed form. As an application, the topological pressure of a linear cellular automaton can be computed explicitly.

  11. Optical scatter imaging of cellular and mitochondrial swelling in brain tissue models of stroke

    Johnson, Lee James

    2001-08-01

    The severity of brain edema resulting from a stroke can determine a patient's survival and the extent of their recovery. Cellular swelling is the microscopic source of a significant part of brain edema. Mitochondrial swelling also appears to be a determining event in the death or survival of the cells that are injured during a stroke. Therapies for reducing brain edema are not effective in many cases and current treatments of stroke do not address mitochondrial swelling at all. This dissertation is motivated by the lack of a complete understanding of cellular swelling resulting from stroke and the lack of a good method to begin to study mitochondrial swelling resulting from stroke in living brain tissue. In this dissertation, a novel method of detecting mitochondrial and cellular swelling in living hippocampal slices is developed and validated. The system is used to obtain spatial and temporal information about cellular and mitochondrial swelling resulting from various models of stroke. The effect of changes in water content on light scatter and absorption are examined in two models of brain edema. The results of this study demonstrate that optical techniques can be used to detect changes in water content. Mie scatter theory, the theoretical basis of the dual- angle scatter ratio imaging system, is presented. Computer simulations based on Mie scatter theory are used to determine the optimal angles for imaging. A detailed account of the early systems is presented to explain the motivations for the system design, especially polarization, wavelength and light path. Mitochondrial sized latex particles are used to determine the system response to changes in scattering particle size and concentration. The dual-angle scatter ratio imaging system is used to distinguish between osmotic and excitotoxic models of stroke injury. Such distinction cannot be achieved using the current techniques to study cellular swelling in hippocampal slices. The change in the scatter ratio is

  12. A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity.

    Cerchiari, Alec E; Garbe, James C; Jee, Noel Y; Todhunter, Michael E; Broaders, Kyle E; Peehl, Donna M; Desai, Tejal A; LaBarge, Mark A; Thomson, Matthew; Gartner, Zev J

    2015-02-17

    Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue-ECM boundary, rather than by differential homo- and heterotypic energies of cell-cell interaction. Surprisingly, interactions with the tissue-ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell-cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell-cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell-ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer.

  13. Modulation of the mechanical properties of ventricular extracellular matrix hydrogels with a carbodiimide crosslinker and investigation of their cellular compatibility

    Kyohei Fujita

    2018-01-01

    Full Text Available Hydrogels made from the cardiac extracellular matrix (ECM as two-dimensional (2D or 3D cell-culture substrates have beneficial biochemical effects on the differentiation of stem cells into cardiomyocytes. The mechanical properties of the substrates that match those of the host tissues have been identified as critical biophysical cues for coaxing the tissue-specific differentiation of stem cells. The objectives of the present study are (1 to fabricate hydrogels comprising pure ventricular ECM (vECM, (2 to make the gels possess mechanical properties similar to those of the decellularized ventricular tissue, and (3 to evaluate the cellular compatibility of the hydrogels. In order to achieve these aims, (1 a simplified protocol was developed to produce vECM solution easily and rapidly, (2 N-(3-Dimethylaminopropyl-N’-ethylcarbodiimide hydrochloride (EDAC was chosen to crosslink the hydrogels made from the vECM solution to enhance their mechanical properties and stabilize the microstructure of the gels, (3 rat embryonic fibroblasts or cardiomyocytes were cultured on these gels to determine the cellular compatibility of the gels. In particular, the nonlinearity and viscoelasticity of the gels were characterized quantitatively using a newly proposed nonlinear Kelvin model. The results showed that EDAC treatment allowed modulation of the mechanical properties of the gels to the same level as those of decellularized ventricular tissue in terms of the equilibrium elasticity and relaxation coefficient. Cell culture confirmed the cellular compatibility of the gels. Furthermore, an empirical relationship between the equilibrium elastic modulus of the gels and the vECM and EDAC concentrations was derived, which is important to tailor the mechanical properties of the gels. Finally, the influence of the mechanical properties of the gels on the behavior of cultured fibroblasts and cardiomyocytes was discussed.

  14. Mechanical properties of brain tissue by indentation : interregional variation

    Dommelen, van J.A.W.; Sande, van der T.P.J.; Hrapko, M.; Peters, G.W.M.

    2010-01-01

    Although many studies on the mechanical properties of brain tissue exist, some controversy concerning the possible differences in mechanical properties of white and gray matter tissue remains. Indentation experiments are conducted on white and gray matter tissue of various regions of the cerebrum

  15. Acoustic and thermal properties of tissue

    Retat, L.; Rivens, I.; ter Haar, G. R.

    2012-10-01

    Differences in ultrasound (US) and thermal properties of abdominal soft tissues may affect the delivery of thermal therapies such as high intensity focused ultrasound and may provide a basis for US monitoring of such therapies. 21 rat livers were obtained, within one hour of surgical removal. For a single liver, 3 lobes were selected and each treated in one of 3 ways: maintained at room temperature, water bath heated to 50°C ± 1°C for 10 ± 0.5 minutes, or water bath heated to 60°C ± 1°C for 10 ± 0.6 minutes. The attenuation coefficient, speed of sound and thermal conductivity of fresh rat liver was measured. The attenuation coefficients and speed of sound were measured using the finite-amplitude insertion-substitution (FAIS) method. For each rat liver, the control and treated lobes were scanned using a pair of weakly focused 2.5 MHz Imasonic transducers over the range 1.8 to 3 MHz. The conductivity measurement apparatus was designed to provide one-dimensional heat flow through each specimen using a combination of insulation, heat source and heat sink. Using 35 MHz US images to determine the volume of air trapped in the system, the thermal conductivity was corrected using a simulation based on the Helmhotz bio-heat equation. The process of correlating these results with biological properties is discussed.

  16. The cellular distribution of histone H5 in embryonic and adult tissues of Xenopus laevis and chicken

    Moorman, A. F.; de Boer, P. A.; Lamers, W. H.; Charles, R.

    1986-01-01

    The cellular distribution of histone H5 in embryonic and adult tissues of Xenopus laevis and chicken has been established with monoclonal antibodies to histone H5. Both in Xenopus and in chicken, the protein has presumably a more widespread cellular distribution than hitherto expected but is absent

  17. Production, properties, and applications of hydrocolloid cellular solids.

    Nussinovitch, Amos

    2005-02-01

    Many common synthetic and edible materials are, in fact, cellular solids. When classifying the structure of cellular solids, a few variables, such as open vs. closed cells, flexible vs. brittle cell walls, cell-size distribution, cell-wall thickness, cell shape, the uniformity of the structure of the cellular solid and the different scales of length are taken into account. Compressive stress-strain relationships of most cellular solids can be easily identified according to their characteristic sigmoid shape, reflecting three deformation mechanisms: (i) elastic distortion under small strains, (ii) collapse and/or fracture of the cell walls, and (iii) densification. Various techniques are used to produce hydrocolloid (gum) cellular solids. The products of these include (i) sponges, obtained when the drying gel contains the occasionally produced gas bubbles; (ii) sponges produced by the immobilization of microorganisms; (iii) solid foams produced by drying foamed solutions or gels containing oils, and (iv) hydrocolloid sponges produced by enzymatic reactions. The porosity of the manufactured cellular solid is subject to change and depends on its composition and the processing technique. The porosity is controlled by a range of methods and the resulting surface structures can be investigated by microscopy and analyzed using fractal methods. Models used to describe stress-strain behaviors of hydrocolloid cellular solids as well as multilayered products and composites are discussed in detail in this manuscript. Hydrocolloid cellular solids have numerous purposes, simple and complex, ranging from dried texturized fruits to carriers of vitamins and other essential micronutrients. They can also be used to control the acoustic response of specific dry food products, and have a great potential for future use in countless different fields, from novel foods and packaging to medicine and medical care, daily commodities, farming and agriculture, and the environmental, chemical

  18. Intermittent straining accelerates the development of tissue properties in engineered heart valve tissue

    Rubbens, M.P.; Mol, A.; Boerboom, R.A.; Bank, R.A.; Baaijens, F.P.T.; Bouten, C.V.C.

    2009-01-01

    Tissue-engineered heart valves lack sufficient amounts of functionally organized structures and consequently do not meet in vivo mechanical demands. To optimize tissue architecture and hence improve mechanical properties, various in vitro mechanical conditioning protocols have been proposed, of

  19. Tissue properties and collagen remodeling in heart valve tissue engineering

    Geemen, van D.

    2012-01-01

    Valvular heart disease is a major health problem worldwide causing morbidity and mortality. Heart valve replacement is frequently applied to avoid serious cardiac, pulmonary, or systemic problems. However, the current replacements do not consist of living tissue and, consequently, cannot grow,

  20. Is central dogma a global property of cellular information flow?

    Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar

    2012-01-01

    The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcripts to proteins show nullity. These data suggest that the organizing structure guiding cellular processes is observed at omics-wide scale, and not at single molecule level. The central dogma, thus, globally emerges as an average integrated flow of cellular information.

  1. Is central dogma a global property of cellular information flow?

    Vincent ePiras

    2012-11-01

    Full Text Available The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcript to protein show nullity. These data suggest that the organizing structure guiding cellular processes is observed at omics-wide scale and not at single molecule level. The central dogma, thus, globally emerges as an average integrated flow of cellular information.

  2. Imaging cellular and subcellular structure of human brain tissue using micro computed tomography

    Khimchenko, Anna; Bikis, Christos; Schweighauser, Gabriel; Hench, Jürgen; Joita-Pacureanu, Alexandra-Teodora; Thalmann, Peter; Deyhle, Hans; Osmani, Bekim; Chicherova, Natalia; Hieber, Simone E.; Cloetens, Peter; Müller-Gerbl, Magdalena; Schulz, Georg; Müller, Bert

    2017-09-01

    Brain tissues have been an attractive subject for investigations in neuropathology, neuroscience, and neurobiol- ogy. Nevertheless, existing imaging methodologies have intrinsic limitations in three-dimensional (3D) label-free visualisation of extended tissue samples down to (sub)cellular level. For a long time, these morphological features were visualised by electron or light microscopies. In addition to being time-consuming, microscopic investigation includes specimen fixation, embedding, sectioning, staining, and imaging with the associated artefacts. More- over, optical microscopy remains hampered by a fundamental limit in the spatial resolution that is imposed by the diffraction of visible light wavefront. In contrast, various tomography approaches do not require a complex specimen preparation and can now reach a true (sub)cellular resolution. Even laboratory-based micro computed tomography in the absorption-contrast mode of formalin-fixed paraffin-embedded (FFPE) human cerebellum yields an image contrast comparable to conventional histological sections. Data of a superior image quality was obtained by means of synchrotron radiation-based single-distance X-ray phase-contrast tomography enabling the visualisation of non-stained Purkinje cells down to the subcellular level and automated cell counting. The question arises, whether the data quality of the hard X-ray tomography can be superior to optical microscopy. Herein, we discuss the label-free investigation of the human brain ultramorphology be means of synchrotron radiation-based hard X-ray magnified phase-contrast in-line tomography at the nano-imaging beamline ID16A (ESRF, Grenoble, France). As an example, we present images of FFPE human cerebellum block. Hard X-ray tomography can provide detailed information on human tissues in health and disease with a spatial resolution below the optical limit, improving understanding of the neuro-degenerative diseases.

  3. Hybrid cellular automaton modeling of nutrient modulated cell growth in tissue engineering constructs.

    Chung, C A; Lin, Tze-Hung; Chen, Shih-Di; Huang, Hsing-I

    2010-01-21

    Mathematic models help interpret experimental results and accelerate tissue engineering developments. We develop in this paper a hybrid cellular automata model that combines the differential nutrient transport equation to investigate the nutrient limited cell construct development for cartilage tissue engineering. Individual cell behaviors of migration, contact inhibition and cell collision, coupled with the cell proliferation regulated by oxygen concentration were carefully studied. Simplified two-dimensional simulations were performed. Using this model, we investigated the influence of cell migration speed on the overall cell growth within in vitro cell scaffolds. It was found that intense cell motility can enhance initial cell growth rates. However, since cell growth is also significantly modulated by the nutrient contents, intense cell motility with conventional uniform cell seeding method may lead to declined cell growth in the final time because concentrated cell population has been growing around the scaffold periphery to block the nutrient transport from outside culture media. Therefore, homogeneous cell seeding may not be a good way of gaining large and uniform cell densities for the final results. We then compared cell growth in scaffolds with various seeding modes, and proposed a seeding mode with cells initially residing in the middle area of the scaffold that may efficiently reduce the nutrient blockage and result in a better cell amount and uniform cell distribution for tissue engineering construct developments.

  4. Radiation risk of tissue late effects, a net consequence of probabilities of various cellular responses

    Feinendegen, L.E.

    1991-01-01

    Late effects from the exposure to low doses of ionizing radiation are hardly or not at all observed in man mainly due to the low values of risk coefficients that preclude statistical analyses of data from populations that are exposed to doses less than 0.2 Gy. In order to arrive at an assessment of potential risk from radiation exposure in the low dose range, the microdosimetry approach is essential. In the low dose range, ionizing radiation generates particle tracks, mainly electrons, which are distributed rather heterogeneously within the exposed tissue. Taking the individual cell as the elemental unit of life, observations and calculations of cellular responses to being hit by energy depositions events from low LET type are analysed. It emerges that besides the probability of a hit cell to sustain a detrimental effect with the consequense of malignant transformation there are probabilities of various adaptive responses that equipp the hit cell with a benefit. On the one hand, an improvement of cellular radical detoxification was observed in mouse bone marrow cells; another adaptive response pertaining to improved DNA repair, was reported for human lymphocytes. The improved radical detoxification in mouse bone marrow cells lasts for a period of 5-10 hours and improved DNA repair in human lymphocytes was seen for some 60 hours following acute irradiation. It is speculated that improved radical detoxification and improved DNA repair may reduce the probability of spontaneous carcinogenesis. Thus it is proposed to weigh the probability of detriment for a hit cell within a multicellular system against the probability of benefit through adaptive responses in other hit cells in the same system per radiation exposure. In doing this, the net effect of low doses of low LET radiation in tissue with individual cells being hit by energy deposition events could be zero or even beneficial. (orig./MG)

  5. Gelatin Scaffolds with Controlled Pore Structure and Mechanical Property for Cartilage Tissue Engineering.

    Chen, Shangwu; Zhang, Qin; Nakamoto, Tomoko; Kawazoe, Naoki; Chen, Guoping

    2016-03-01

    Engineering of cartilage tissue in vitro using porous scaffolds and chondrocytes provides a promising approach for cartilage repair. However, nonuniform cell distribution and heterogeneous tissue formation together with weak mechanical property of in vitro engineered cartilage limit their clinical application. In this study, gelatin porous scaffolds with homogeneous and open pores were prepared using ice particulates and freeze-drying. The scaffolds were used to culture bovine articular chondrocytes to engineer cartilage tissue in vitro. The pore structure and mechanical property of gelatin scaffolds could be well controlled by using different ratios of ice particulates to gelatin solution and different concentrations of gelatin. Gelatin scaffolds prepared from ≥70% ice particulates enabled homogeneous seeding of bovine articular chondrocytes throughout the scaffolds and formation of homogeneous cartilage extracellular matrix. While soft scaffolds underwent cellular contraction, stiff scaffolds resisted cellular contraction and had significantly higher cell proliferation and synthesis of sulfated glycosaminoglycan. Compared with the gelatin scaffolds prepared without ice particulates, the gelatin scaffolds prepared with ice particulates facilitated formation of homogeneous cartilage tissue with significantly higher compressive modulus. The gelatin scaffolds with highly open pore structure and good mechanical property can be used to improve in vitro tissue-engineered cartilage.

  6. New multifunctional lightweight materials based on cellular metals - manufacturing, properties and applications

    Stephani, Guenter; Quadbeck, Peter; Andersen, Olaf

    2009-01-01

    Cellular metallic materials are a new class of materials which have been the focus of numerous scientific studies over the past few years. The increasing interest in cellular metals is due to the fact that the introduction of pores into the materials significantly lowers the density. These highly porous materials also possess combinations of properties which are not possible to achieve with other materials. Besides the drastic weight and material savings that arise from the cell structure, there are also other application-specific benefits such as noise and energy absorption, heat insulation, mechanical damping, filtration effects and also catalytic properties. Cellular metallic materials are hence multi-functional lightweight materials.

  7. New insights into the cellular makeup and progenitor potential of palatal connective tissues.

    Pall, Emoke; Cenariu, Mihai; Kasaj, Adrian; Florea, Adrian; Soancă, Andrada; Roman, Alexandra; Georgiu, Carmen

    2017-12-01

    The present study investigated the regenerative potential of connective tissues harvested from two palatal areas widely used as donor sites for muco-gingival surgical approaches. Connective tissue grafts (CTGs) were obtained by de-epithelialisation of a free gingival graft (deCTG) and by a split flap approach from a previous donor site (reCTG). Two types of mesenchymal stem cell (MSCs) were isolated and were named de-epithelialised MSCs (deMSCs) and re-entry MSCs (reMSCs). The cells were characterised and cellular functionality was investigated. CTGs were evaluated using immunohistochemical and ultrastructural approaches. No significant differences were observed regarding the frequency of colony-forming unit- fibroblasts, migration potential, and population doubling time between the two cell lines (p > 0.05). Both cell lines showed positivity for CD105, CD73, CD90, and CD44 and negative expression for CD34/45, CD14, CD79a, and HLA-DR. MSCs from both cell lines successfully differentiated into osteogenic, adipogenic, and chondrogenic lineages. Cells expressing antigens characteristic of CD34+ stromal cells (CD34+, αSMA-, CD31-) were traced in both CTGs. Ultrastructural analysis highlighted the presence of putative progenitors, namely fibroblasts,-in the pericapillary regions and in remote regions of the lamina propria- and pericytes-surrounding the capillaries. This study provides supplementary arguments for the use of CTG grafts in clinical practice due to the presence of putative progenitor cell. However, results were inconclusive regarding clinical decision-making to determine optimal harvesting area. Prior harvesting in the donor area did not appear to alter the regenerative capabilities of the connective tissue. © 2017 Wiley Periodicals, Inc.

  8. Production and properties of bronze based cellular materials

    Strobl, S.; Danninger, H.

    2001-01-01

    For production of lightweight components, cellular materials offer attractive potential. Here, manufacturing of sintered bodies from bronze hollow spheres is described. The process starts with fabrication of hollow copper particles by cementation of Cu on iron particles. The still fragile Cu shells are consolidated by coating with Sn and subsequent gravity sintering. The resulting specimens exhibit a closed cell bronze structure with rather consistent morphology and cell wall thickness. The apparent density may range between 1.5 and 3.0 gcm -3 and can be controlled by variation of particle size and wall thickness. The mechanical behavior of the structures esp. during compressive loading is described and related to the microstructural parameters. (author)

  9. AFM studies of environmental effects on nanomechanical properties and cellular structure of human hair

    Bhushan, Bharat; Chen, Nianhuan

    2006-01-01

    Characterization of cellular structure and physical and mechanical properties of hair are essential to develop better cosmetic products and advance biological and cosmetic science. Although the morphology of the cellular structure of human hair has been traditionally investigated using scanning electron microscopy and transmission electron microscopy, these techniques provide limited capability to in situ study of the physical and mechanical properties of human hair in various environments. Atomic force microscopy (AFM) overcomes these problems and can be used for characterization in ambient conditions without requiring specific sample preparations and surface treatment. In this study, film thickness, adhesive forces and effective Young's modulus of various hair surfaces were measured at different environments (humidity and temperature) using force calibration plot technique with an AFM. Torsional resonance mode phase contrast images were also taken in order to characterize the morphology and cellular structure changes of human hair at different humidity. The correlation between the nanomechanical properties and the cellular structure of hair is discussed

  10. Investigating the effects of ABC transporter-based acquired drug resistance mechanisms at the cellular and tissue scale.

    Liu, Cong; Krishnan, J; Xu, Xiao Yun

    2013-03-01

    In this paper we systematically investigate the effects of acquired drug resistance at the cellular and tissue scale, with a specific focus on ATP-binding cassette (ABC) transporter-based mechanisms and contrast this with other representative intracellular resistance mechanisms. This is done by developing in silico models wherein the drug resistance mechanism is overlaid on a coarse-grained description of apoptosis; these cellular models are coupled with interstitial drug transport, allowing for a transparent examination of the effect of acquired drug resistances at the tissue level. While ABC transporter-mediated resistance mechanisms counteract drug effect at the cellular level, its tissue-level effect is more complicated, revealing unexpected trends in tissue response as drug stimuli are systematically varied. Qualitatively different behaviour is observed in other drug resistance mechanisms. Overall the paper (i) provides insight into the tissue level functioning of a particular resistance mechanism, (ii) shows that this is very different from other resistance mechanisms of an apparently similar type, and (iii) demonstrates a concrete instance of how the functioning of a negative feedback based cellular adaptive mechanism can have unexpected higher scale effects.

  11. Free Radical Scavenging and Cellular Antioxidant Properties of Astaxanthin.

    Dose, Janina; Matsugo, Seiichi; Yokokawa, Haruka; Koshida, Yutaro; Okazaki, Shigetoshi; Seidel, Ulrike; Eggersdorfer, Manfred; Rimbach, Gerald; Esatbeyoglu, Tuba

    2016-01-14

    Astaxanthin is a coloring agent which is used as a feed additive in aquaculture nutrition. Recently, potential health benefits of astaxanthin have been discussed which may be partly related to its free radical scavenging and antioxidant properties. Our electron spin resonance (ESR) and spin trapping data suggest that synthetic astaxanthin is a potent free radical scavenger in terms of diphenylpicryl-hydrazyl (DPPH) and galvinoxyl free radicals. Furthermore, astaxanthin dose-dependently quenched singlet oxygen as determined by photon counting. In addition to free radical scavenging and singlet oxygen quenching properties, astaxanthin induced the antioxidant enzyme paroxoanase-1, enhanced glutathione concentrations and prevented lipid peroxidation in cultured hepatocytes. Present results suggest that, beyond its coloring properties, synthetic astaxanthin exhibits free radical scavenging, singlet oxygen quenching, and antioxidant activities which could probably positively affect animal and human health.

  12. Do Surface Porosity and Pore Size Influence Mechanical Properties and Cellular Response to PEEK?

    Torstrick, F Brennan; Evans, Nathan T; Stevens, Hazel Y; Gall, Ken; Guldberg, Robert E

    2016-11-01

    Despite its widespread use in orthopaedic implants such as soft tissue fasteners and spinal intervertebral implants, polyetheretherketone (PEEK) often suffers from poor osseointegration. Introducing porosity can overcome this limitation by encouraging bone ingrowth; however, the corresponding decrease in implant strength can potentially reduce the implant's ability to bear physiologic loads. We have previously shown, using a single pore size, that limiting porosity to the surface of PEEK implants preserves strength while supporting in vivo osseointegration. However, additional work is needed to investigate the effect of pore size on both the mechanical properties and cellular response to PEEK. (1) Can surface porous PEEK (PEEK-SP) microstructure be reliably controlled? (2) What is the effect of pore size on the mechanical properties of PEEK-SP? (3) Do surface porosity and pore size influence the cellular response to PEEK? PEEK-SP was created by extruding PEEK through NaCl crystals of three controlled ranges: 200 to 312, 312 to 425, and 425 to 508 µm. Micro-CT was used to characterize the microstructure of PEEK-SP. Tensile, fatigue, and interfacial shear tests were performed to compare the mechanical properties of PEEK-SP with injection-molded PEEK (PEEK-IM). The cellular response to PEEK-SP, assessed by proliferation, alkaline phosphatase activity, vascular endothelial growth factor production, and calcium content of osteoblast, mesenchymal stem cell, and preosteoblast (MC3T3-E1) cultures, was compared with that of machined smooth PEEK and Ti6Al4V. Micro-CT analysis showed that PEEK-SP layers possessed pores that were 284 ± 35 µm, 341 ± 49 µm, and 416 ± 54 µm for each pore size group. Porosity and pore layer depth ranged from 61% to 69% and 303 to 391 µm, respectively. Mechanical testing revealed tensile strengths > 67 MPa and interfacial shear strengths > 20 MPa for all three pore size groups. All PEEK-SP groups exhibited > 50% decrease

  13. β-Amyloid pathogenesis: Chemical properties versus cellular levels

    Tiwari, Manish Kumar; Kepp, Kasper Planeta

    2016-01-01

    Although genetic Aβ variants cause early-onset Alzheimer's disease, literature reports on Aβ properties are heterogeneous, obscuring molecular mechanisms, as illustrated by recent failures of Aβ-level targeting trials. Thus, we combined available data on Aβ levels and ratios, aggregation propensi...

  14. High-resolution cellular MRI: gadolinium and iron oxide nanoparticles for in-depth dual-cell imaging of engineered tissue constructs.

    Di Corato, Riccardo; Gazeau, Florence; Le Visage, Catherine; Fayol, Delphine; Levitz, Pierre; Lux, François; Letourneur, Didier; Luciani, Nathalie; Tillement, Olivier; Wilhelm, Claire

    2013-09-24

    Recent advances in cell therapy and tissue engineering opened new windows for regenerative medicine, but still necessitate innovative noninvasive imaging technologies. We demonstrate that high-resolution magnetic resonance imaging (MRI) allows combining cellular-scale resolution with the ability to detect two cell types simultaneously at any tissue depth. Two contrast agents, based on iron oxide and gadolinium oxide rigid nanoplatforms, were used to "tattoo" endothelial cells and stem cells, respectively, with no impact on cell functions, including their capacity for differentiation. The labeled cells' contrast properties were optimized for simultaneous MRI detection: endothelial cells and stem cells seeded together in a polysaccharide-based scaffold material for tissue engineering appeared respectively in black and white and could be tracked, at the cellular level, both in vitro and in vivo. In addition, endothelial cells labeled with iron oxide nanoparticles could be remotely manipulated by applying a magnetic field, allowing the creation of vessel substitutes with in-depth detection of individual cellular components.

  15. Modular design of artificial tissue homeostasis: robust control through synthetic cellular heterogeneity.

    Miles Miller

    Full Text Available Synthetic biology efforts have largely focused on small engineered gene networks, yet understanding how to integrate multiple synthetic modules and interface them with endogenous pathways remains a challenge. Here we present the design, system integration, and analysis of several large scale synthetic gene circuits for artificial tissue homeostasis. Diabetes therapy represents a possible application for engineered homeostasis, where genetically programmed stem cells maintain a steady population of β-cells despite continuous turnover. We develop a new iterative process that incorporates modular design principles with hierarchical performance optimization targeted for environments with uncertainty and incomplete information. We employ theoretical analysis and computational simulations of multicellular reaction/diffusion models to design and understand system behavior, and find that certain features often associated with robustness (e.g., multicellular synchronization and noise attenuation are actually detrimental for tissue homeostasis. We overcome these problems by engineering a new class of genetic modules for 'synthetic cellular heterogeneity' that function to generate beneficial population diversity. We design two such modules (an asynchronous genetic oscillator and a signaling throttle mechanism, demonstrate their capacity for enhancing robust control, and provide guidance for experimental implementation with various computational techniques. We found that designing modules for synthetic heterogeneity can be complex, and in general requires a framework for non-linear and multifactorial analysis. Consequently, we adapt a 'phenotypic sensitivity analysis' method to determine how functional module behaviors combine to achieve optimal system performance. We ultimately combine this analysis with Bayesian network inference to extract critical, causal relationships between a module's biochemical rate-constants, its high level functional behavior in

  16. Modular design of artificial tissue homeostasis: robust control through synthetic cellular heterogeneity.

    Miller, Miles; Hafner, Marc; Sontag, Eduardo; Davidsohn, Noah; Subramanian, Sairam; Purnick, Priscilla E M; Lauffenburger, Douglas; Weiss, Ron

    2012-01-01

    Synthetic biology efforts have largely focused on small engineered gene networks, yet understanding how to integrate multiple synthetic modules and interface them with endogenous pathways remains a challenge. Here we present the design, system integration, and analysis of several large scale synthetic gene circuits for artificial tissue homeostasis. Diabetes therapy represents a possible application for engineered homeostasis, where genetically programmed stem cells maintain a steady population of β-cells despite continuous turnover. We develop a new iterative process that incorporates modular design principles with hierarchical performance optimization targeted for environments with uncertainty and incomplete information. We employ theoretical analysis and computational simulations of multicellular reaction/diffusion models to design and understand system behavior, and find that certain features often associated with robustness (e.g., multicellular synchronization and noise attenuation) are actually detrimental for tissue homeostasis. We overcome these problems by engineering a new class of genetic modules for 'synthetic cellular heterogeneity' that function to generate beneficial population diversity. We design two such modules (an asynchronous genetic oscillator and a signaling throttle mechanism), demonstrate their capacity for enhancing robust control, and provide guidance for experimental implementation with various computational techniques. We found that designing modules for synthetic heterogeneity can be complex, and in general requires a framework for non-linear and multifactorial analysis. Consequently, we adapt a 'phenotypic sensitivity analysis' method to determine how functional module behaviors combine to achieve optimal system performance. We ultimately combine this analysis with Bayesian network inference to extract critical, causal relationships between a module's biochemical rate-constants, its high level functional behavior in isolation, and

  17. Analysis of terahertz dielectric properties of pork tissue

    Huang, Yuqing; Xie, Qiaoling; Sun, Ping

    2017-10-01

    Seeing that about 70% component of fresh biological tissues is water, many scientists try to use water models to describe the dielectric properties of biological tissues. The classical water dielectric models are Debye model, Double Debye model and Cole-Cole model. This work aims to determine a suitable model by comparing three models above with experimental data. These models are applied to fresh pork tissue. By means of least square method, the parameters of different models are fitted with the experimental data. Comparing different models on both dielectric function, the Cole-Cole model is verified the best to describe the experiments of pork tissue. The correction factor α of the Cole-Cole model is an important modification for biological tissues. So Cole-Cole model is supposed to be a priority selection to describe the dielectric properties for biological tissues in the terahertz range.

  18. Human tissue optical properties measurements and light propagation modelling

    Dam, JS

    2006-07-01

    Full Text Available Biomedical Optics is the study of the optical properties of living biological material, especially its scattering and absorption characteristics, and their significance to light propagation within the material. Determination of tissue optical...

  19. Ergodic properties and thermodynamic behavior of elementary reversible cellular automata. I. Basic properties

    Takesue, Shinji

    1989-01-01

    This is the first part of a series devoted to the study of thermodynamic behavior of large dynamical systems with the use of a family of full-discrete and conservative models named elementary reversible cellular automata (ERCAs). In this paper, basic properties such as conservation laws and phase space structure are investigated in preparation for the later studies. ERCAs are a family of one-dimensional reversible cellular automata having two Boolean variables on each site. Reflection and Boolean conjugation symmetries divide them into 88 equivalence classes. For each rule, additive conserved quantities written in a certain form are regarded as a kind of energy, if they exist. By the aid of the discreteness of the variables, every ERCA satisfies the Liouville theorem or the preservation of phase space volume. Thus, if an energy exists in the above sense, statistical mechanics of the model can formally be constructed. If a locally defined quantity is conserved, however, it prevents the realization of statistical mechanics. The existence of such a quantity is examined for each class and a number of rules which have at least one energy but no local conservation laws are selected as hopeful candidates for the realization of thermodynamic behavior. In addition, the phase space structure of ERCAs is analyzed by enumerating cycles exactly in the phase space for systems of comparatively small sizes. As a result, it is revealed that a finite ERCA is not ergodic, that is, a large number of orbits coexist on an energy surface. It is argued that this fact does not necessarily mean the failure of thermodynamic behavior on the basis of an analogy with the ergodic nature of infinite systems

  20. Effects of tissue mechanical properties on susceptibility to histotripsy-induced tissue damage

    Vlaisavljevich, Eli; Kim, Yohan; Owens, Gabe; Roberts, William; Cain, Charles; Xu, Zhen

    2014-01-01

    Histotripsy is a non-invasive tissue ablation method capable of fractionating tissue by controlling acoustic cavitation. To determine the fractionation susceptibility of various tissues, we investigated histotripsy-induced damage on tissue phantoms and ex vivo tissues with different mechanical strengths. A histotripsy bubble cloud was formed at tissue phantom surfaces using 5-cycle long ultrasound pulses with peak negative pressure of 18 MPa and PRFs of 10, 100, and 1000 Hz. Results showed significantly smaller lesions were generated in tissue phantoms of higher mechanical strength. Histotripsy was also applied to 43 different ex vivo porcine tissues with a wide range of mechanical properties. Gross morphology demonstrated stronger tissues with higher ultimate stress, higher density, and lower water content were more resistant to histotripsy damage in comparison to weaker tissues. Based on these results, a self-limiting vessel-sparing treatment strategy was developed in an attempt to preserve major vessels while fractionating the surrounding target tissue. This strategy was tested in porcine liver in vivo. After treatment, major hepatic blood vessels and bile ducts remained intact within a completely fractionated liver volume. These results identify varying susceptibilities of tissues to histotripsy therapy and provide a rational basis to optimize histotripsy parameters for treatment of specific tissues.

  1. Modelling the electrical properties of tissue as a porous medium

    Smye, S W; Evans, C J; Robinson, M P; Sleeman, B D

    2007-01-01

    Models of the electrical properties of biological tissue have been the subject of many studies. These models have sought to explain aspects of the dielectric dispersion of tissue. This paper develops a mathematical model of the complex permittivity of tissue as a function of frequency f, in the range 10 4 7 Hz, which is derived from a formulation used to describe the complex permittivity of porous media. The model introduces two parameters, porosity and percolation probability, to the description of the electrical properties of any tissue which comprises a random arrangement of cells. The complex permittivity for a plausible porosity and percolation probability distribution is calculated and compared with the published measured electrical properties of liver tissue. Broad agreement with the experimental data is noted. It is suggested that future detailed experimental measurements should be undertaken to validate the model. The model may be a more convenient method of parameterizing the electrical properties of biological tissue and subsequent measurement of these parameters in a range of tissues may yield information of biological and clinical significance

  2. The influence of freezing and tissue porosity on the material properties of vegetable tissues

    Ralfs, Julie D

    2002-07-01

    Tissue porosity and fluid flow have been shown to be important parameters affecting the mechanical and sensorial behaviour of edible plant tissues. The quantity of fluid and the manner with which it was released on compression of the plant tissue were also important regarding the sensory perception and a good indication of any structural damage resulting from freezing, for example. Potato, carrot and Chinese water chestnut were used to study the effects freezing has on model plant tissues. Mechanical and structural measurements of the plant tissue were correlated with sensory analysis. Conventional freezing was shown to cause severe structural damage predominantly in the form of cavities between or through cells, resulting in decreases in mechanical strength and stiffness, and samples that were perceived in the mouth as 'soft' and 'wet'. The location and size of the cavities formed from ice crystals, depended on the particular plant tissue being frozen, the processing it was subjected to prior to freezing, the size of the sample and the cooling regime employed to freeze the tissue. Cavitation in the tissue resulted in an increase in tissue porosity, which enabled fluid to flow more easily from the tissue on compression, thus affecting the mechanical properties and sensory perception. Freezing damage to plant tissues was shown to be reduced, and sometimes prevented, when active antifreeze proteins (AFPs) were introduced into the tissues by vacuum infiltration or transformation and the tissue was frozen at a suitable cooling rate. Theoretical modelling was applied to the fluid flow and porosity data to test the validity of the models and to subsequently predict the mechanical behaviour of potato from the structural properties of the tissue. (author)

  3. The influence of freezing and tissue porosity on the material properties of vegetable tissues

    Ralfs, Julie D.

    2002-01-01

    Tissue porosity and fluid flow have been shown to be important parameters affecting the mechanical and sensorial behaviour of edible plant tissues. The quantity of fluid and the manner with which it was released on compression of the plant tissue were also important regarding the sensory perception and a good indication of any structural damage resulting from freezing, for example. Potato, carrot and Chinese water chestnut were used to study the effects freezing has on model plant tissues. Mechanical and structural measurements of the plant tissue were correlated with sensory analysis. Conventional freezing was shown to cause severe structural damage predominantly in the form of cavities between or through cells, resulting in decreases in mechanical strength and stiffness, and samples that were perceived in the mouth as 'soft' and 'wet'. The location and size of the cavities formed from ice crystals, depended on the particular plant tissue being frozen, the processing it was subjected to prior to freezing, the size of the sample and the cooling regime employed to freeze the tissue. Cavitation in the tissue resulted in an increase in tissue porosity, which enabled fluid to flow more easily from the tissue on compression, thus affecting the mechanical properties and sensory perception. Freezing damage to plant tissues was shown to be reduced, and sometimes prevented, when active antifreeze proteins (AFPs) were introduced into the tissues by vacuum infiltration or transformation and the tissue was frozen at a suitable cooling rate. Theoretical modelling was applied to the fluid flow and porosity data to test the validity of the models and to subsequently predict the mechanical behaviour of potato from the structural properties of the tissue. (author)

  4. Characterization of printable cellular micro-fluidic channels for tissue engineering

    Zhang, Yahui; Chen, Howard; Ozbolat, Ibrahim T; Yu, Yin

    2013-01-01

    Tissue engineering has been a promising field of research, offering hope of bridging the gap between organ shortage and transplantation needs. However, building three-dimensional (3D) vascularized organs remains the main technological barrier to be overcome. One of the major challenges is the inclusion of a vascular network to support cell viability in terms of nutrients and oxygen perfusion. This paper introduces a new approach to the fabrication of vessel-like microfluidic channels that has the potential to be used in thick tissue or organ fabrication in the future. In this research, we investigate the manufacturability of printable micro-fluidic channels, where micro-fluidic channels support mechanical integrity as well as enable fluid transport in 3D. A pressure-assisted solid freeform fabrication platform is developed with a coaxial needle dispenser unit to print hollow hydrogel filaments. The dispensing rheology is studied, and effects of material properties on structural formation of hollow filaments are analyzed. Sample structures are printed through the developed computer-controlled system. In addition, cell viability and gene expression studies are presented in this paper. Cell viability shows that cartilage progenitor cells (CPCs) maintained their viability right after bioprinting and during prolonged in vitro culture. Real-time PCR analysis yielded a relatively higher expression of cartilage-specific genes in alginate hollow filament encapsulating CPCs, compared with monolayer cultured CPCs, which revealed that printable semi-permeable micro-fluidic channels provided an ideal environment for cell growth and function. (paper)

  5. Effects of Inflammation on Multiscale Biomechanical Properties of Cartilaginous Cells and Tissues.

    Nguyen, Q T; Jacobsen, T D; Chahine, N O

    2017-11-13

    Cells within cartilaginous tissues are mechanosensitive and thus require mechanical loading for regulation of tissue homeostasis and metabolism. Mechanical loading plays critical roles in cell differentiation, proliferation, biosynthesis, and homeostasis. Inflammation is an important event occurring during multiple processes, such as aging, injury, and disease. Inflammation has significant effects on biological processes as well as mechanical function of cells and tissues. These effects are highly dependent on cell/tissue type, timing, and magnitude. In this review, we summarize key findings pertaining to effects of inflammation on multiscale mechanical properties at subcellular, cellular, and tissue level in cartilaginous tissues, including alterations in mechanotransduction and mechanosensitivity. The emphasis is on articular cartilage and the intervertebral disc, which are impacted by inflammatory insults during degenerative conditions such as osteoarthritis, joint pain, and back pain. To recapitulate the pro-inflammatory cascades that occur in vivo, different inflammatory stimuli have been used for in vitro and in situ studies, including tumor necrosis factor (TNF), various interleukins (IL), and lipopolysaccharide (LPS). Therefore, this review will focus on the effects of these stimuli because they are the best studied pro-inflammatory cytokines in cartilaginous tissues. Understanding the current state of the field of inflammation and cell/tissue biomechanics may potentially identify future directions for novel and translational therapeutics with multiscale biomechanical considerations.

  6. The effects of matrix inhomogeneities on the cellular mechanical environment in tissue-engineered cartilage: an in silico investigation

    Khoshgoftar, M.; Wilson, W.; Ito, K.; Donkelaar, C.C. van

    2014-01-01

    Mechanical stimulation during cartilage tissue-engineering enhances extracellular matrix (ECM) synthesis and thereby improves the mechanical properties of tissue engineered (TE) cartilage. Generally, these mechanical stimuli are of a fixed magnitude. However, as a result of ECM synthesis and spatial

  7. Structure and properties of porous films based on aliphatic copolyamide developed for cellular technologies

    Dobrovol`skaya, I.P.; Popryadukhin, P.V.; Yudin, V. E.; Ivankova, E.M.; Elokhovskiy, V.Y.; Weishauptová, Zuzana; Balík, Karel

    2015-01-01

    Roč. 26, č. 1 (2015), article number 46 ISSN 0957-4530 Institutional support: RVO:67985891 Keywords : porous film * aliphatic copolyamide * structure * properties Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.272, year: 2015 http://www.stem-art.com/Library/Science/Structure%20and%20properties%20of%20porous%20films%20based%20on%20aliphatic%20copolyamide%20developed%20for%20cellular%20technologies.pdf

  8. Spatial distribution patterns of energy deposition and cellular radiation effects in lung tissue following simulated exposure to alpha particles

    Hofmann, W.; Crawford-Brown, D.J.

    1990-01-01

    Randomly oriented sections of rat tissue have been digitised to provide the contours of tissue-air interfaces and the locations of individual cell nuclei in the alveolated region of the lung. Sources of alpha particles with varying irradiation geometries and densities are simulated to compute the resulting random pattern of cellular irradiation, i.e. spatial coordinates, frequency, track length, and energy of traversals by the emitted alpha particles. Probabilities per unit track lengths, derived from experimental data on in vitro cellular inactivation and transformation, are then applied to the results of the alpha exposure simulations to yield an estimate of the number of both dead and viable transformed cells and their spatial distributions. If lung cancer risk is linearly related to the number of transformed cells, the carcinogenic risk for hot particles is always smaller than that for a uniform nuclide distribution of the same activity. (author)

  9. The influence of Cellular Interactions in Tissue Engineering for Cartilage Repair

    Hendriks, J.A.A.

    2006-01-01

    Tissues are complex 3-dimensional structures with a highly organized architecture made up of cells and matrix. The cells and matrix in a tissue are continuously interacting with each other and (cells from) their surrounding tissues to maintain their form and function. Interactions of cells with

  10. WE-DE-202-02: Are Track Structure Simulations Truly Needed for Radiobiology at the Cellular and Tissue Levels?

    Stewart, R. [University of Washington (United States)

    2016-06-15

    Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological

  11. WE-DE-202-02: Are Track Structure Simulations Truly Needed for Radiobiology at the Cellular and Tissue Levels?

    Stewart, R.

    2016-01-01

    Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are the most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological

  12. The Study Of Properties Of The Word Of Mouth Marketing Using Cellular Automata

    Kowalska-Styczeń Agnieszka

    2014-02-01

    Full Text Available This article presents the possibility of using cellular automata, to study the properties of word of mouth (w-o-m marketing. Cellular automata allow to analyze the dynamics of changes in views and attitudes in social groups based on local interactions between people in small groups of friends, family members etc. The proposed paper shows the possibility of modelling the dynamics of word of mouth mechanism, if the basic assumptions of this process are: different size groups where this phenomenon occurs, and varied access to information. On the competing firms market, the dependence of the w-o-m mechanism dynamics on the model parameters is shown

  13. Chemical linkage to injected tissues is a distinctive property of oxidized avidin.

    Rita De Santis

    Full Text Available We recently reported that the oxidized avidin, named AvidinOX®, resides for weeks within injected tissues as a consequence of the formation of Schiff's bases between its aldehyde groups and tissue protein amino groups. We also showed, in a mouse pre-clinical model, the usefulness of AvidinOX for the delivery of radiolabeled biotin to inoperable tumors. Taking into account that AvidinOX is the first oxidized glycoprotein known to chemically link to injected tissues, we tested in the mouse a panel of additional oxidized glycoproteins, with the aim of investigating the phenomenon. We produced oxidized ovalbumin and mannosylated streptavidin which share with avidin glycosylation pattern and tetrameric structure, respectively and found that neither of them linked significantly to cells in vitro nor to injected tissues in vivo, despite the presence of functional aldehyde groups. The study, extended to additional oxidized glycoproteins, showed that the in vivo chemical conjugation is a distinctive property of the oxidized avidin. Relevance of the high cationic charge of avidin into the stable linkage of AvidinOX to tissues is demonstrated as the oxidized acetylated avidin lost the property. Plasmon resonance on matrix proteins and cellular impedance analyses showed in vitro that avidin exhibits a peculiar interaction with proteins and cells that allows the formation of highly stable Schiff's bases, after oxidation.

  14. Novel technique for online characterization of cartilaginous tissue properties.

    Yuan, Tai-Yi; Huang, Chun-Yuh; Yong Gu, Wei

    2011-09-01

    The goal of tissue engineering is to use substitutes to repair and restore organ function. Bioreactors are an indispensable tool for monitoring and controlling the unique environment for engineered constructs to grow. However, in order to determine the biochemical properties of engineered constructs, samples need to be destroyed. In this study, we developed a novel technique to nondestructively online-characterize the water content and fixed charge density of cartilaginous tissues. A new technique was developed to determine the tissue mechano-electrochemical properties nondestructively. Bovine knee articular cartilage and lumbar annulus fibrosus were used in this study to demonstrate that this technique could be used on different types of tissue. The results show that our newly developed method is capable of precisely predicting the water volume fraction (less than 3% disparity) and fixed charge density (less than 16.7% disparity) within cartilaginous tissues. This novel technique will help to design a new generation of bioreactors which are able to actively determine the essential properties of the engineered constructs, as well as regulate the local environment to achieve the optimal conditions for cultivating constructs.

  15. ultrasound reflecting the morphological properties in soft tissue

    Lorentzen, Torben; Larsen, Torben; Court-Payen, Michel

    2014-01-01

    Ultrasound (US) is an image modality providing the examiner with real-time images which reflect the morphological properties in soft tissue. Different types of transducers are used for different kind of exams. US is cheap, fast, and safe. US is widely used in abdominal imaging including obstetrics...

  16. In-Vivo Techniques for Measuring Electrical Properties of Tissues.

    1980-09-01

    probe Electromagnetic energy Dielectric properties Monopole antenna In-situ tissues , Antemortem/Pos tmortem studies Renal blood flow 10 ABSTRACT... mice or rats, which were positioned beneath a fixed measurement probe. Several alternative methods involving the use of semi-rigid or flexible coaxial

  17. Multiscale mechanics of hierarchical structure/property relationships in calcified tissues and tissue/material interfaces

    Katz, J. Lawrence; Misra, Anil; Spencer, Paulette; Wang, Yong; Bumrerraj, Sauwanan; Nomura, Tsutomu; Eppell, Steven J.; Tabib-Azar, Massood

    2007-01-01

    This paper presents a review plus new data that describes the role hierarchical nanostructural properties play in developing an understanding of the effect of scale on the material properties (chemical, elastic and electrical) of calcified tissues as well as the interfaces that form between such tissues and biomaterials. Both nanostructural and microstructural properties will be considered starting with the size and shape of the apatitic mineralites in both young and mature bovine bone. Microstructural properties for human dentin and cortical and trabecular bone will be considered. These separate sets of data will be combined mathematically to advance the effects of scale on the modeling of these tissues and the tissue/biomaterial interfaces as hierarchical material/structural composites. Interfacial structure and properties to be considered in greatest detail will be that of the dentin/adhesive (d/a) interface, which presents a clear example of examining all three material properties, (chemical, elastic and electrical). In this case, finite element modeling (FEA) was based on the actual measured values of the structure and elastic properties of the materials comprising the d/a interface; this combination provides insight into factors and mechanisms that contribute to premature failure of dental composite fillings. At present, there are more elastic property data obtained by microstructural measurements, especially high frequency ultrasonic wave propagation (UWP) and scanning acoustic microscopy (SAM) techniques. However, atomic force microscopy (AFM) and nanoindentation (NI) of cortical and trabecular bone and the dentin-enamel junction (DEJ) among others have become available allowing correlation of the nanostructural level measurements with those made on the microstructural level

  18. Cellular Automata on Graphs: Topological Properties of ER Graphs Evolved towards Low-Entropy Dynamics

    Marc-Thorsten Hütt

    2012-06-01

    Full Text Available Cellular automata (CA are a remarkably  efficient tool for exploring general properties of complex systems and spatiotemporal patterns arising from local rules. Totalistic cellular automata,  where the update  rules depend  only on the density of neighboring states, are at the same time a versatile  tool for exploring  dynamical  processes on graphs. Here we briefly review our previous results on cellular automata on graphs, emphasizing some systematic relationships between network architecture and dynamics identified in this way. We then extend the investigation  towards graphs obtained in a simulated-evolution procedure, starting from Erdő s–Rényi (ER graphs and selecting for low entropies of the CA dynamics. Our key result is a strong association of low Shannon entropies with a broadening of the graph’s degree distribution.

  19. Antimicrobial properties of nudibranchs tissues extracts from South Andaman, India

    Kota Veeraswamy Reddy

    2015-07-01

    Full Text Available Objective: To evaluate the antimicrobial properties of tissues extracts of different nudibranchs such as Phyllidia varicosa, Plakobranchus ocellatus, Phyllidiella rosans and Halgerda stricklandi against bacterial and fungal pathogens. Methods: Nudibranchs tissue samples were subjected to organic solvent extraction for antimicrobial activity by well diffusion method. Results: The crude extract 50 μL (0.2 mg of Phyllidia varicosa showed the maximum inhibitory zone (22 mm against Shigella flexneri. Plakobranchus ocellatus extract of 50 μL (0.2 mg showed the maximum inhibitory zone against Shigella flexneri (22 mm and Staphylococcus aureus (19 mm and no significant activity was found against the fungal pathogens. Conclusions: This work reveals that nudibranch tissues contain the antimicrobial secondary metabolites, which leads the significant activity against bacterial pathogens and further emphasizes detailed study on novel drug discovery from nudibranch tissues against certain human bacterial infections.

  20. Structures of non-cellular tissues of the body and their importance in otorhinolaryngology

    S. N. Shatokhina

    2016-01-01

    Full Text Available We present  the  results of our studies  in various pathological   conditions   in  otorhinolaryngology performed  with  a diagnostic  technology  of functional morphology  of non-cellular tissue structures  (mouth  fluid, surgical wound  exudation, blood  serum, and  others. With the  use of methods of cuniform and  marginal dehydration of biological fluids, the possibility of developing essentially novel criteria was shown, such as:• prediction  of complicated  course of post-operative wound  healing in subjects with a lamellar morphotype in the  wound  exudation  resulting from cholesterol residues due to massive cell death;• prediction  of a polypous  rhinosinusitis  relapse in subjects with an increase in the proliferation marker, anisotropic  parallels lines in the  dehydrated  serum  obtained from the  blood  taken from the inferior nasal turbinate;• diagnostics   of  the  middle  ear  cholesteatoma in children by combination of cuniform and marginal  dehydration of the  mouth  fluid. The singularity of the  technique  is based  on triple sampling  of the  fluid:  first sample  was  taken immediately  after awakening, the  second  one, after a few minutes  of active swallowing movements  and  the  third one,  after trans-tympanicair pumping.  Detection  of the  structural  signs of congestive effusion and the lamellar morphotype as a destruction marker in the third sample suggested the presence  of cholesteatoma;• assessment  of  treatment  efficacy  in  patients with chronic tonsillitis and of the indications to tonsillectomy in patients  with persisting pathological  characteristics   of  the  exudation   from the palatal tonsil lacunes throughout the whole course of conservative treatment;• determination of the grade of activity / absence of activity of laryngeal cancer by identification of a basic spherolith with various degrees  of anisotropy

  1. Synchrony of plant cellular circadian clocks with heterogeneous properties under light/dark cycles.

    Okada, Masaaki; Muranaka, Tomoaki; Ito, Shogo; Oyama, Tokitaka

    2017-03-22

    Individual cells in a plant can work independently as circadian clocks, and their properties are the basis of various circadian phenomena. The behaviour of individual cellular clocks in Lemna gibba was orderly under 24-h light/dark cycles despite their heterogeneous free-running periods (FRPs). Here, we reveal the entrainment habits of heterogeneous cellular clocks using non-24-h light/dark cycles (T-cycles). The cellular rhythms of AtCCA1::LUC under T = 16 h cycles showed heterogeneous entrainment that was associated with their heterogeneous FRPs. Under T = 12 h cycles, most cells showed rhythms having ~24-h periods. This suggested that the lower limit of entrainment to the light/dark cycles of heterogeneous cellular circadian clocks is set to a period longer than 12 h, which enables them to be synchronous under ~24-h daily cycles without being perturbed by short light/dark cycles. The entrainment habits of individual cellular clocks are likely to be the basis of the circadian behaviour of plant under the natural day-night cycle with noisy environmental fluctuations. We further suggest that modifications of EARLY FLOWERING3 (ELF3) in individual cells deviate the entrainability to shorter T-cycles possibly by altering both the FRPs and light responsiveness.

  2. Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

    Blaesi, Aron H; Saka, Nannaji

    2016-07-25

    At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. Copyright © 2016. Published by Elsevier B.V.

  3. Gradual conversion of cellular stress patterns into pre-stressed matrix architecture during in vitro tissue growth.

    Bidan, Cécile M; Kollmannsberger, Philip; Gering, Vanessa; Ehrig, Sebastian; Joly, Pascal; Petersen, Ansgar; Vogel, Viola; Fratzl, Peter; Dunlop, John W C

    2016-05-01

    The complex arrangement of the extracellular matrix (ECM) produced by cells during tissue growth, healing and remodelling is fundamental to tissue function. In connective tissues, it is still unclear how both cells and the ECM become and remain organized over length scales much larger than the distance between neighbouring cells. While cytoskeletal forces are essential for assembly and organization of the early ECM, how these processes lead to a highly organized ECM in tissues such as osteoid is not clear. To clarify the role of cellular tension for the development of these ordered fibril architectures, we used an in vitro model system, where pre-osteoblastic cells produced ECM-rich tissue inside channels with millimetre-sized triangular cross sections in ceramic scaffolds. Our results suggest a mechanical handshake between actively contracting cells and ECM fibrils: the build-up of a long-range organization of cells and the ECM enables a gradual conversion of cell-generated tension to pre-straining the ECM fibrils, which reduces the work cells have to generate to keep mature tissue under tension. © 2016 The Author(s).

  4. Structure and Electromagnetic Properties of Cellular Glassy Carbon Monoliths with Controlled Cell Size

    Andrzej Szczurek

    2018-05-01

    Full Text Available Electromagnetic shielding is a topic of high importance for which lightweight materials are highly sought. Porous carbon materials can meet this goal, but their structure needs to be controlled as much as possible. In this work, cellular carbon monoliths of well-defined porosity and cell size were prepared by a template method, using sacrificial paraffin spheres as the porogen and resorcinol-formaldehyde (RF resin as the carbon precursor. Physicochemical studies were carried out for investigating the conversion of RF resin into carbon, and the final cellular monoliths were investigated in terms of elemental composition, total porosity, surface area, micropore volumes, and micro/macropore size distributions. Electrical and electromagnetic (EM properties were investigated in the static regime and in the Ka-band, respectively. Due to the phenolic nature of the resin, the resultant carbon was glasslike, and the special preparation protocol that was used led to cellular materials whose cell size increased with density. The materials were shown to be relevant for EM shielding, and the relationships between those properties and the density/cell size of those cellular monoliths were elucidated.

  5. A Cellular Automata-based Model for Simulating Restitution Property in a Single Heart Cell.

    Sabzpoushan, Seyed Hojjat; Pourhasanzade, Fateme

    2011-01-01

    Ventricular fibrillation is the cause of the most sudden mortalities. Restitution is one of the specific properties of ventricular cell. The recent findings have clearly proved the correlation between the slope of restitution curve with ventricular fibrillation. This; therefore, mandates the modeling of cellular restitution to gain high importance. A cellular automaton is a powerful tool for simulating complex phenomena in a simple language. A cellular automaton is a lattice of cells where the behavior of each cell is determined by the behavior of its neighboring cells as well as the automata rule. In this paper, a simple model is depicted for the simulation of the property of restitution in a single cardiac cell using cellular automata. At first, two state variables; action potential and recovery are introduced in the automata model. In second, automata rule is determined and then recovery variable is defined in such a way so that the restitution is developed. In order to evaluate the proposed model, the generated restitution curve in our study is compared with the restitution curves from the experimental findings of valid sources. Our findings indicate that the presented model is not only capable of simulating restitution in cardiac cell, but also possesses the capability of regulating the restitution curve.

  6. Receptor-mediated endocytosis generates nanomechanical force reflective of ligand identity and cellular property.

    Zhang, Xiao; Ren, Juan; Wang, Jingren; Li, Shixie; Zou, Qingze; Gao, Nan

    2018-08-01

    Whether environmental (thermal, chemical, and nutrient) signals generate quantifiable, nanoscale, mechanophysical changes in the cellular plasma membrane has not been well elucidated. Assessment of such mechanophysical properties of plasma membrane may shed lights on fundamental cellular process. Atomic force microscopic (AFM) measurement of the mechanical properties of live cells was hampered by the difficulty in accounting for the effects of the cantilever motion and the associated hydrodynamic force on the mechanical measurement. These challenges have been addressed in our recently developed control-based AFM nanomechanical measurement protocol, which enables a fast, noninvasive, broadband measurement of the real-time changes in plasma membrane elasticity in live cells. Here we show using this newly developed AFM platform that the plasma membrane of live mammalian cells exhibits a constant and quantifiable nanomechanical property, the membrane elasticity. This mechanical property sensitively changes in response to environmental factors, such as the thermal, chemical, and growth factor stimuli. We demonstrate that different chemical inhibitors of endocytosis elicit distinct changes in plasma membrane elastic modulus reflecting their specific molecular actions on the lipid configuration or the endocytic machinery. Interestingly, two different growth factors, EGF and Wnt3a, elicited distinct elastic force profiles revealed by AFM at the plasma membrane during receptor-mediated endocytosis. By applying this platform to genetically modified cells, we uncovered a previously unknown contribution of Cdc42, a key component of the cellular trafficking network, to EGF-stimulated endocytosis at plasma membrane. Together, this nanomechanical AFM study establishes an important foundation that is expandable and adaptable for investigation of cellular membrane evolution in response to various key extracellular signals. © 2017 Wiley Periodicals, Inc.

  7. Scanning probe recognition microscopy investigation of tissue scaffold properties

    Fan, Yuan; Chen, Qian; Ayres, Virginia M; Baczewski, Andrew D; Udpa, Lalita; Kumar, Shiva

    2007-01-01

    Scanning probe recognition microscopy is a new scanning probe microscopy technique which enables selective scanning along individual nanofibers within a tissue scaffold. Statistically significant data for multiple properties can be collected by repetitively fine-scanning an identical region of interest. The results of a scanning probe recognition microscopy investigation of the surface roughness and elasticity of a series of tissue scaffolds are presented. Deconvolution and statistical methods were developed and used for data accuracy along curved nanofiber surfaces. Nanofiber features were also independently analyzed using transmission electron microscopy, with results that supported the scanning probe recognition microscopy-based analysis. PMID:18203431

  8. Monitoring of tissue optical properties during thermal coagulation of ex vivo tissues.

    Nagarajan, Vivek Krishna; Yu, Bing

    2016-09-01

    Real-time monitoring of tissue status during thermal ablation of tumors is critical to ensure complete destruction of tumor mass, while avoiding tissue charring and excessive damage to normal tissues. Currently, magnetic resonance thermometry (MRT), along with magnetic resonance imaging (MRI), is the most commonly used technique for monitoring and assessing thermal ablation process in soft tissues. MRT/MRI is very expensive, bulky, and often subject to motion artifacts. On the other hand, light propagation within tissue is sensitive to changes in tissue microstructure and physiology which could be used to directly quantify the extent of tissue damage. Furthermore, optical monitoring can be a portable, and cost-effective alternative for monitoring a thermal ablation process. The main objective of this study, is to establish a correlation between changes in tissue optical properties and the status of tissue coagulation/damage during heating of ex vivo tissues. A portable diffuse reflectance spectroscopy system and a side-firing fiber-optic probe were developed to study the absorption (μa (λ)), and reduced scattering coefficients (μ's (λ)) of native and coagulated ex vivo porcine, and chicken breast tissues. In the first experiment, both porcine and chicken breast tissues were heated at discrete temperature points between 24 and 140°C for 2 minutes. Diffuse reflectance spectra (430-630 nm) of native and coagulated tissues were recorded prior to, and post heating. In a second experiment, porcine tissue samples were heated at 70°C and diffuse reflectance spectra were recorded continuously during heating. The μa (λ) and μ's (λ) of the tissues were extracted from the measured diffuse reflectance spectra using an inverse Monte-Carlo model of diffuse reflectance. Tissue heating was stopped when the wavelength-averaged scattering plateaued. The wavelength-averaged optical properties, and , for native porcine tissues (n = 66) at room temperature, were 5.4

  9. The dielectric properties of biological tissues: III. Parametric models for the dielectric spectrum of tissues

    Gabriel, S.; Lau, R.W.; Gabriel, C.

    1996-01-01

    A parametric model was developed to describe the variation of dielectric properties of tissues as a function of frequency. The experimental spectrum from 10 Hz to 100 GHz was modelled with four dispersion regions. The development of the model was based on recently acquired data, complemented by data surveyed from the literature. The purpose is to enable the prediction of dielectric data that are in line with those contained in the vast body of literature on the subject. The analysis was carried out on a Microsoft Excel spreadsheet. Parameters are given for 17 tissue types. (author)

  10. Design properties of hydrogel tissue-engineering scaffolds

    Zhu, Junmin; Marchant, Roger E

    2011-01-01

    This article summarizes the recent progress in the design and synthesis of hydrogels as tissue-engineering scaffolds. Hydrogels are attractive scaffolding materials owing to their highly swollen network structure, ability to encapsulate cells and bioactive molecules, and efficient mass transfer. Various polymers, including natural, synthetic and natural/synthetic hybrid polymers, have been used to make hydrogels via chemical or physical crosslinking. Recently, bioactive synthetic hydrogels have emerged as promising scaffolds because they can provide molecularly tailored biofunctions and adjustable mechanical properties, as well as an extracellular matrix-like microenvironment for cell growth and tissue formation. This article addresses various strategies that have been explored to design synthetic hydrogels with extracellular matrix-mimetic bioactive properties, such as cell adhesion, proteolytic degradation and growth factor-binding. PMID:22026626

  11. Topographic modelling of haptic properties of tissue products

    Rosen, B-G; Fall, A; Farbrot, A; Bergström, P; Rosen, S

    2014-01-01

    The way a product or material feels when touched, haptics, has been shown to be a property that plays an important role when consumers determine the quality of products For tissue products in constant touch with the skin, ''softness'' becomes a primary quality parameter. In the present work, the relationship between topography and the feeling of the surface has been investigated for commercial tissues with varying degree of texture from the low textured crepe tissue to the highly textured embossed- and air-dried tissue products. A trained sensory panel at was used to grade perceived haptic ''roughness''. The technique used to characterize the topography was Digital light projection (DLP) technique, By the use of multivariate statistics, strong correlations between perceived roughness and topography were found with predictability of above 90 percent even though highly textured products were included. Characterization was made using areal ISO 25178-2 topography parameters in combination with non-contacting topography measurement. The best prediction ability was obtained when combining haptic properties with the topography parameters auto-correlation length (Sal), peak material volume (Vmp), core roughness depth (Sk) and the maximum height of the surface (Sz)

  12. The regeneration of epidermal cells of Saintpaulia leaves as a new plant-tissue system for cellular radiation biology

    Engels, F.M.; Laan, F.M. van der; Leenhouts, H.P.; Chadwick, K.H.

    1980-01-01

    investigation of the nucleus of epidermal cells of the petioles of Saintpaulia leaves by cytofluorimetry revealed that all cells are in a non-cycling pre DNA synthesis phase. Cultivation of dissected leaves results in a synchronous regeneration process of a defined number of cells. Five days after onset of cultivation the cells reach the first mitosis. The nuclear development during the regeneration process is described. Irradiation of the leaves results in a directly visible inhibition of this regenerating capability which is used to quantify cell survival in a tissue. The data show that the radiation response has a similar shape to that of the survival of single cells in culture. This response can be observed before the first mitosis of the cells and its application as a new plant tissue system for cellular radiation research is discussed. (author)

  13. The mechanical properties of human adipose tissues and their relationships to the structure and composition of the extracellular matrix.

    Alkhouli, Nadia; Mansfield, Jessica; Green, Ellen; Bell, James; Knight, Beatrice; Liversedge, Neil; Tham, Ji Chung; Welbourn, Richard; Shore, Angela C; Kos, Katarina; Winlove, C Peter

    2013-12-01

    Adipose tissue (AT) expansion in obesity is characterized by cellular growth and continuous extracellular matrix (ECM) remodeling with increased fibrillar collagen deposition. It is hypothesized that the matrix can inhibit cellular expansion and lipid storage. Therefore, it is important to fully characterize the ECM's biomechanical properties and its interactions with cells. In this study, we characterize and compare the mechanical properties of human subcutaneous and omental tissues, which have different physiological functions. AT was obtained from 44 subjects undergoing surgery. Force/extension and stress/relaxation data were obtained. The effects of osmotic challenge were measured to investigate the cellular contribution to tissue mechanics. Tissue structure and its response to tensile strain were determined using nonlinear microscopy. AT showed nonlinear stress/strain characteristics of up to a 30% strain. Comparing paired subcutaneous and omental samples (n = 19), the moduli were lower in subcutaneous: initial 1.6 ± 0.8 (means ± SD) and 2.9 ± 1.5 kPa (P = 0.001), final 11.7 ± 6.4 and 32 ± 15.6 kPa (P matrix fibers. These results suggest that subcutaneous AT has greater capacity for expansion and recovery from mechanical deformation than omental AT.

  14. Bioprinting of hybrid tissue constructs with tailorable mechanical properties

    Schuurman, W; Khristov, V; Pot, M W; Dhert, W J A; Malda, J; Van Weeren, P R

    2011-01-01

    Tissue/organ printing aims to recapitulate the intrinsic complexity of native tissues. For a number of tissues, in particular those of musculoskeletal origin, adequate mechanical characteristics are an important prerequisite for their initial handling and stability, as well as long-lasting functioning. Hence, organized implants, possessing mechanical characteristics similar to the native tissue, may result in improved clinical outcomes of regenerative approaches. Using a bioprinter, grafts were constructed by alternate deposition of thermoplastic fibers and (cell-laden) hydrogels. Constructs of different shapes and sizes were manufactured and mechanical properties, as well as cell viability, were assessed. This approach yields novel organized viable hybrid constructs, which possess favorable mechanical characteristics, within the same range as those of native tissues. Moreover, the approach allows the use of multiple hydrogels and can thus produce constructs containing multiple cell types or bioactive factors. Furthermore, since the hydrogel is supported by the thermoplastic material, a broader range of hydrogel types can be used compared to bioprinting of hydrogels alone. In conclusion, we present an innovative and versatile approach for bioprinting, yielding constructs of which the mechanical stiffness provided by thermoplastic polymers can potentially be tailored, and combined specific cell placement patterns of multiple cell types embedded in a wide range of hydrogels. (communication)

  15. Bioprinting of hybrid tissue constructs with tailorable mechanical properties

    Schuurman, W; Khristov, V; Pot, M W; Dhert, W J A; Malda, J [Department of Orthopaedics, University Medical Center Utrecht (Netherlands); Van Weeren, P R, E-mail: j.malda@umcutrecht.nl [Faculty of Veterinary Sciences, Department of Equine Sciences, Utrecht University (Netherlands)

    2011-06-15

    Tissue/organ printing aims to recapitulate the intrinsic complexity of native tissues. For a number of tissues, in particular those of musculoskeletal origin, adequate mechanical characteristics are an important prerequisite for their initial handling and stability, as well as long-lasting functioning. Hence, organized implants, possessing mechanical characteristics similar to the native tissue, may result in improved clinical outcomes of regenerative approaches. Using a bioprinter, grafts were constructed by alternate deposition of thermoplastic fibers and (cell-laden) hydrogels. Constructs of different shapes and sizes were manufactured and mechanical properties, as well as cell viability, were assessed. This approach yields novel organized viable hybrid constructs, which possess favorable mechanical characteristics, within the same range as those of native tissues. Moreover, the approach allows the use of multiple hydrogels and can thus produce constructs containing multiple cell types or bioactive factors. Furthermore, since the hydrogel is supported by the thermoplastic material, a broader range of hydrogel types can be used compared to bioprinting of hydrogels alone. In conclusion, we present an innovative and versatile approach for bioprinting, yielding constructs of which the mechanical stiffness provided by thermoplastic polymers can potentially be tailored, and combined specific cell placement patterns of multiple cell types embedded in a wide range of hydrogels. (communication)

  16. Macro-architectured cellular materials: Properties, characteristic modes, and prediction methods

    Ma, Zheng-Dong

    2017-12-01

    Macro-architectured cellular (MAC) material is defined as a class of engineered materials having configurable cells of relatively large (i.e., visible) size that can be architecturally designed to achieve various desired material properties. Two types of novel MAC materials, negative Poisson's ratio material and biomimetic tendon reinforced material, were introduced in this study. To estimate the effective material properties for structural analyses and to optimally design such materials, a set of suitable homogenization methods was developed that provided an effective means for the multiscale modeling of MAC materials. First, a strain-based homogenization method was developed using an approach that separated the strain field into a homogenized strain field and a strain variation field in the local cellular domain superposed on the homogenized strain field. The principle of virtual displacements for the relationship between the strain variation field and the homogenized strain field was then used to condense the strain variation field onto the homogenized strain field. The new method was then extended to a stress-based homogenization process based on the principle of virtual forces and further applied to address the discrete systems represented by the beam or frame structures of the aforementioned MAC materials. The characteristic modes and the stress recovery process used to predict the stress distribution inside the cellular domain and thus determine the material strengths and failures at the local level are also discussed.

  17. Release Properties and Cellular Uptake in Caco-2 Cells of Size-Controlled Chitosan Nanoparticles.

    Je, Hyun Jeong; Kim, Eun Suh; Lee, Ji-Soo; Lee, Hyeon Gyu

    2017-12-20

    The influences of particle size on the physicochemical, release, and cellular uptake properties of chitosan nanoparticles (CSNPs) were investigated. Ionotropic CSNPs of different sizes (200-1000 nm) loaded with two model core materials (resveratrol or coumarin-6) were prepared using tripolyphosphate and carrageenan as cross-linkers. With an increase of particle size, zeta potential (34.6 ± 0.5 to 51.1 ± 0.9) and entrapment efficiency (14.9 ± 1.4 to 40.9 ± 1.9) of the CSNPs were significantly (p cellular uptake of CSNPs were significantly increased from 3.70 ± 0.03 to 5.24 ± 0.20 with an increase of particle size from 200 to 600 nm, whereas those significantly decreased from 5.24 ± 0.20 to 4.55 ± 0.2 for particles larger than 600 nm in transwell assay. Moreover, much the same uptake patterns were also observed in confocal microscopy and flow cytometry. Investigation of cellular uptake of CSNPs revealed positive correlations between ZP and EE and indicated the effects of complex factors of nanoparticles other than size. These results provide a better understanding of CSNPs absorption and raises the possibility of controlling alternative nanoparticle properties to enhance bioavailability.

  18. Three-dimensional immersive virtual reality for studying cellular compartments in 3D models from EM preparations of neural tissues

    Cali, Corrado

    2015-07-14

    Advances for application of electron microscopy to serial imaging are opening doors to new ways of analyzing cellular structure. New and improved algorithms and workflows for manual and semiautomated segmentation allow to observe the spatial arrangement of the smallest cellular features with unprecedented detail in full three-dimensions (3D). From larger samples, higher complexity models can be generated; however, they pose new challenges to data management and analysis. Here, we review some currently available solutions and present our approach in detail. We use the fully immersive virtual reality (VR) environment CAVE (cave automatic virtual environment), a room where we are able to project a cellular reconstruction and visualize in 3D, to step into a world created with Blender, a free, fully customizable 3D modeling software with NeuroMorph plug-ins for visualization and analysis of electron microscopy (EM) preparations of brain tissue. Our workflow allows for full and fast reconstructions of volumes of brain neuropil using ilastik, a software tool for semiautomated segmentation of EM stacks. With this visualization environment, we can walk into the model containing neuronal and astrocytic processes to study the spatial distribution of glycogen granules, a major energy source that is selectively stored in astrocytes. The use of CAVE was key to observe a nonrandom distribution of glycogen, and led us to develop tools to quantitatively analyze glycogen clustering and proximity to other subcellular features. This article is protected by copyright. All rights reserved.

  19. Ultrastructural and cellular damage to rat lung with x-rays: a search for target cell in lung tissue

    Furuta, I

    1975-03-01

    Radiation effects on the peripheral alveoli of conventional rats were examined by means of electron microscopy. The right hemithorax alone was exposed to various single doses of x rays. The initial cellular lesions selectively involved the cytoplasms of alveolar capillary endothelial (Ed) and type 1 epithelial (Ep 1) cells in a dose-dependent fashion, where the major alterations were multifocal vacuolations and swellings. These lesions became visible as early as 1 hr after 1000 R (the assumed mean lethal dose for Ed cells) and more. However, progenitor Ep 2 cells exhibited no obvious cytoplasmic lesions by the doses below 2000 R, indicating that Ep 2 cells are more resistant to x rays. With time following 1000 R, the capillary Ed blebbing abruptly developed in various forms from the sites presumably other than the Ed junctions. The Ed blebs and interstitial edema progressed until about 2 weeks without recovery, while some signs of cellular recovery were recognized in Ep 1 cells during this period. The observations after a long period of 6 months following 1000 R showed that the typical pulmonary fibrotic changes were initiated in the interstitium perhaps around unrepaired capillaries. Further, inflammatory reaction characterized by massive cellular infiltations was superimposed on developing pulmonary fibrosis. Considering the current knowledge about the cell sensitivity and renewal in stable tissues, the present results imply that capillary Ed cell is the primary target for the radiation lesion leading to the secondary pulmonary alterations.

  20. The effects of matrix inhomogeneities on the cellular mechanical environment in tissue-engineered cartilage : an in silico investigation

    Khoshgoftar, M.; Wilson, W.; Ito, K.; Donkelaar, van C.C.

    2014-01-01

    Mechanical stimulation during cartilage tissue-engineering (TE) enhances extracellular matrix (ECM) synthesis and thereby improves the mechanical properties of TE cartilage. Generally, these mechanical stimuli are of a fixed magnitude. However, as a result of ECM synthesis and spatial variations

  1. Biosynthetic hydrogels--studies on chemical and physical characteristics on long-term cellular response for tissue engineering.

    Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

    2014-07-01

    Biosynthetic hydrogels can meet the drawbacks caused by natural and synthetic ones for biomedical applications. In the current article we present a novel biosynthetic alginate-poly(propylene fumarate) copolymer based chemically crosslinked hydrogel scaffolds for cardiac tissue engineering applications. Partially crosslinked PA hydrogel and fully cross linked PA-A hydrogel scaffolds were prepared. The influence of chemical and physical (morphology and architecture of hydrogel) characteristics on the long term cellular response was studied. Both these hydrogels were cytocompatible and showed no genotoxicity upon contact with fibroblast cells. Both PA and PA-A were able to resist deleterious effects of reactive oxygen species and sustain the viability of L929 cells. The hydrogel incubated oxidative stress induced cells were capable of maintaining the intra cellular reduced glutathione (GSH) expression to the normal level confirmed their protective effect. Relatively the PA hydrogel was found to be unstable in the cell culture medium. The PA-A hydrogel was able to withstand appreciable cyclic stretching. The cyclic stretching introduced complex macro and microarchitectural features with interconnected pores and more structured bound water which would provide long-term viability of around 250% after the 24th day of culture. All these qualities make PA-A hydrogel form a potent candidate for cardiac tissue engineering. © 2013 Wiley Periodicals, Inc.

  2. Tissue architecture and function: dynamic reciprocity via extra- and intra-cellular matrices

    Xu, Ren; Boudreau, Aaron; Bissell, Mina J

    2008-12-23

    Mammary gland development, functional differentiation, and homeostasis are orchestrated and sustained by a balance of biochemical and biophysical cues from the organ's microenvironment. The three-dimensional microenvironment of the mammary gland, predominantly 'encoded' by a collaboration between the extracellular matrix (ECM), hormones, and growth factors, sends signals from ECM receptors through the cytoskeletal intracellular matrix to nuclear and chromatin structures resulting in gene expression; the ECM in turn is regulated and remodeled by signals from the nucleus. In this chapter, we discuss how coordinated ECM deposition and remodeling is necessary for mammary gland development, how the ECM provides structural and biochemical cues necessary for tissue-specific function, and the role of the cytoskeleton in mediating the extra - to intracellular dialogue occurring between the nucleus and the microenvironment. When operating normally, the cytoskeletal-mediated dynamic and reciprocal integration of tissue architecture and function directs mammary gland development, tissue polarity, and ultimately, tissue-specific gene expression. Cancer occurs when these dynamic interactions go awry for an extended time.

  3. Layer-by-layer bioassembly of cellularized polylactic acid porous membranes for bone tissue engineering

    Guduric, Vera; Metz, Carole; Siadous, Robin; Bareille, Reine; Levato, Riccardo; Engel, Elisabeth; Fricain, Jean-Christophe; Devillard, Raphaël; Luzanin, Ognjan; Catros, Sylvain

    2017-01-01

    The conventional tissue engineering is based on seeding of macroporous scaffold on its surface ("top-down" approach). The main limitation is poor cell viability in the middle of the scaffold due to poor diffusion of oxygen and nutrients and insufficient vascularization. Layer-by-Layer (LBL)

  4. Growth hormone receptor antagonist (GHA) transgenic mice have increased subcutaneous adipose tissue mass, altered glucose homeostasis, and no change in white adipose tissue cellular senescence

    Comisford, Ross; Lubbers, Ellen R.; Householder, Lara; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L.; List, Edward O.; Kopchick, John J.; Berryman, Darlene E.

    2015-01-01

    Background Growth hormone (GH) resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests long-lived GH resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. OBJECTIVE The objective of this study was to examine white adipose tissue (WAT) senescence, WAT distribution, and glucose homeostasis in dwarf growth hormone receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. METHODS 18mo old female GHA mice and wild type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose, and glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase (SA-β-gal) staining to quantify the senescent cell burden and real time qPCR to quantify gene expression of senescence markers p16 and IL-6. RESULTS GHA mice had a 22% reduction in total body weight, 33% reduction in lean mass, and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p<.05) and a 1.7 fold increase in extra-/intraperitoneal WAT ratio compared to controls (p<.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. CONCLUSIONS Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin

  5. A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties.

    Salinas, Evelia Y; Hu, Jerry C; Athanasiou, Kyriacos

    2018-04-26

    The use of tissue-engineered articular cartilage (TEAC) constructs has the potential to become a powerful treatment option for cartilage lesions resulting from trauma or early stages of pathology. Although fundamental tissue-engineering strategies based on the use of scaffolds, cells, and signals have been developed, techniques that lead to biomimetic AC constructs that can be translated to in vivo use are yet to be fully confirmed. Mechanical stimulation during tissue culture can be an effective strategy to enhance the mechanical, structural, and cellular properties of tissue-engineered constructs toward mimicking those of native AC. This review focuses on the use of mechanical stimulation to attain and enhance the properties of AC constructs needed to translate these implants to the clinic. In vivo, mechanical loading at maximal and supramaximal physiological levels has been shown to be detrimental to AC through the development of degenerative changes. In contrast, multiple studies have revealed that during culture, mechanical stimulation within narrow ranges of magnitude and duration can produce anisotropic, mechanically robust AC constructs with high cellular viability. Significant progress has been made in evaluating a variety of mechanical stimulation techniques on TEAC, either alone or in combination with other stimuli. These advancements include determining and optimizing efficacious loading parameters (e.g., duration and frequency) to yield improvements in construct design criteria, such as collagen II content, compressive stiffness, cell viability, and fiber organization. With the advancement of mechanical stimulation as a potent strategy in AC tissue engineering, a compendium detailing the results achievable by various stimulus regimens would be of great use for researchers in academia and industry. The objective is to list the qualitative and quantitative effects that can be attained when direct compression, hydrostatic pressure, shear, and tensile

  6. Fluorinated cellular polypropylene films with time-invariant excellent surface electret properties by post-treatments

    An Zhenlian; Mao Mingjun; Yao Junlan; Zhang Yewen; Xia Zhongfu

    2010-01-01

    In this work, to improve the electret properties of cellular polypropylene films, they were fluorinated and post-treated with nitrous oxide and by isothermal crystallization. Surface electret properties of the samples were investigated by thermally stimulated discharge current measurements, and their compositions and structures were analysed by attenuated total reflection infrared spectroscopy and wide angle x-ray diffraction, respectively. Time-dependent deterioration of surface electret properties was observed for the fluorinated samples without the nitrous oxide post-treatment. However, deterioration did not occur for the fluorinated samples post-treated with nitrous oxide, and time-invariant excellent surface electret properties or deep surface charge traps were obtained by the combined post-treatments of the fluorinated samples with nitrous oxide and by isothermal crystallization. Based on the analyses of composition and structure of the treated samples, the deterioration was clarified to be due to a trace of oxygen in the reactive mixture, which led to the formation of peroxy RO 2 . radicals in the fluorinated surface layer. The time invariability of surface electret properties was owing to the rapid termination of the peroxy RO 2 . radicals by nitrous oxide. And the deep surface charge traps resulted from the isothermal crystallization treatment which led to an increase in the efficient charging interface between the crystallite and amorphous region and its property change.

  7. Actin—Towards a Deeper Understanding of the Relationship Between Tissue Context, Cellular Function and Tumorigenesis

    Spencer, Virginia A.

    2011-01-01

    It is well-established that the actin cytoskeleton plays an important role in tumor development yet the contribution made by nuclear actin is ill-defined. In a recent study, nuclear actin was identified as a key mediator through which laminin type III (LN1) acts to control epithelial cell growth. In the breast, epithelial tumors are surrounded by an environment which lacks LN1. These findings point to actin as a potential mediator of tumor development. Here our current understanding of the roles of cytoplasmic and nuclear actin in normal and tumor cell growth is reviewed, relating these functions to cell phenotype in a tissue context

  8. Correlation between the mechanical and histological properties of liver tissue.

    Yarpuzlu, Berkay; Ayyildiz, Mehmet; Tok, Olgu Enis; Aktas, Ranan Gulhan; Basdogan, Cagatay

    2014-01-01

    In order to gain further insight into the mechanisms of tissue damage during the progression of liver diseases as well as the liver preservation for transplantation, an improved understanding of the relation between the mechanical and histological properties of liver is necessary. We suggest that this relation can only be established truly if the changes in the states of those properties are investigated dynamically as a function of post mortem time. In this regard, we first perform mechanical characterization experiments on three bovine livers to investigate the changes in gross mechanical properties (stiffness, viscosity, and fracture toughness) for the preservation periods of 5, 11, 17, 29, 41 and 53h after harvesting. Then, the histological examination is performed on the samples taken from the same livers to investigate the changes in apoptotic cell count, collagen accumulation, sinusoidal dilatation, and glycogen deposition as a function of the same preservation periods. Finally, the correlation between the mechanical and histological properties is investigated via the Spearman's Rank-Order Correlation method. The results of our study show that stiffness, viscosity, and fracture toughness of bovine liver increase as the preservation period is increased. These macroscopic changes are very strongly correlated with the increase in collagen accumulation and decrease in deposited glycogen level at the microscopic level. Also, we observe that the largest changes in mechanical and histological properties occur after the first 11-17h of preservation. © 2013 Elsevier Ltd. All rights reserved.

  9. Two key temporally distinguishable molecular and cellular components of white adipose tissue browning during cold acclimation.

    Jankovic, Aleksandra; Golic, Igor; Markelic, Milica; Stancic, Ana; Otasevic, Vesna; Buzadzic, Biljana; Korac, Aleksandra; Korac, Bato

    2015-08-01

    White to brown adipose tissue conversion and thermogenesis can be ignited by different conditions or agents and its sustainability over the long term is still unclear. Browning of rat retroperitoneal white adipose tissue (rpWAT) during cold acclimation involves two temporally apparent components: (1) a predominant non-selective browning of most adipocytes and an initial sharp but transient induction of uncoupling protein 1, peroxisome proliferator-activated receptor (PPAR) coactivator-1α, PPARγ and PPARα expression, and (2) the subsistence of relatively few thermogenically competent adipocytes after 45 days of cold acclimation. The different behaviours of two rpWAT beige/brown adipocyte subsets control temporal aspects of the browning process, and thus regulation of both components may influence body weight and the potential successfulness of anti-obesity therapies. Conversion of white into brown adipose tissue may have important implications in obesity resistance and treatment. Several browning agents or conditions ignite thermogenesis in white adipose tissue (WAT). To reveal the capacity of WAT to function in a brownish/burning mode over the long term, we investigated the progression of the rat retroperitoneal WAT (rpWAT) browning during 45 days of cold acclimation. During the early stages of cold acclimation, the majority of rpWAT adipocytes underwent multilocularization and thermogenic-profile induction, as demonstrated by the presence of a multitude of uncoupling protein 1 (UCP1)-immunopositive paucilocular adipocytes containing peroxisome proliferator-activated receptor (PPAR) coactivator-1α (PGC-1α) and PR domain-containing 16 (PRDM16) in their nuclei. After 45 days, all adipocytes remained PRDM16 immunopositive, but only a few multilocular adipocytes rich in mitochondria remained UCP1/PGC-1α immunopositive. Molecular evidence showed that thermogenic recruitment of rpWAT occurred following cold exposure, but returned to starting levels after cold

  10. Physicochemical properties and membrane biofouling of extra-cellular polysaccharide produced by a Micrococcus luteus strain.

    Feng, Lei; Li, Xiufen; Song, Ping; Du, Guocheng; Chen, Jian

    2014-07-01

    The physicochemical properties of the extra-cellular polysaccharide (EPS) produced by a Micrococcus luteus strain, a dominating strain isolated from membrane biofouling layer, were determined in this study. The EPS isolated from this strain was measured to have an average molecular weight of 63,540 Da and some typical polysaccharide absorption peaks in Fourier transform infrared spectrum. Monosaccharide components of the EPS contained rhamnose, fucose, arabinose, xylose, mannose, galactose and glucose in a molar ratio of 0.2074:0.0454:0.0262:0.0446:1.7942:1.2086:0.4578. Pseudo plastic properties were also observed for the EPS through the rheological measurement. The EPS was further characterized for its behavior to cause membrane flux decline. The results showed that both flux declines for polyvinylidenefluoride (PVDF) and polypropylene membranes became more severe as EPS feed concentration increased. A higher irreversible fouling for the PVDF membrane suggested that the EPS had the larger fouling potential to this microfiltration membrane.

  11. Targeting dendritic cells through gold nanoparticles: A review on the cellular uptake and subsequent immunological properties.

    Ahmad, Suhana; Zamry, Anes Ateqah; Tan, Hern-Tze Tina; Wong, Kah Keng; Lim, JitKang; Mohamud, Rohimah

    2017-11-01

    Gold nanoparticles (NPs) have been proposed as a highly potential tool in immunotherapies due to its advantageous properties including customizable size and shapes, surface functionality and biocompatibility. Dendritic cells (DCs), the sentinels of immune response, have been of interest to be manipulated by using gold NPs for targeted delivery of immunotherapeutic agent. Researches done especially in human DCs showed a variation of gold NPs effects on cellular uptake and internalization, DC maturation and subsequent T cells priming as well as cytotoxicity. In this review, we describe the synthesis and physiochemical properties of gold NPs as well as the importance of gold NPs in immunotherapies through their actions on human DCs. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Biochemical and cellular properties of Gluconacetobacter xylinus cultures exposed to different modes of rotating magnetic field

    Fijałkowski Karol

    2017-06-01

    Full Text Available The aim of the present study was to evaluate the impact of a rotating magnetic field (RMF on cellular and biochemical properties of Gluconacetobacter xylinus during the process of cellulose synthesis by these bacteria. The application of the RMF during bacterial cellulose (BC production intensified the biochemical processes in G. xylinus as compared to the RMF-unexposed cultures. Moreover, the RMF had a positive impact on the growth of cellulose-producing bacteria. Furthermore, the application of RMF did not increase the number of mutants unable to produce cellulose. In terms of BC production efficacy, the most favorable properties were found in the setting where RMF generator was switched off for the first 72 h of cultivation and switched on for the further 72 h. The results obtained can be used in subsequent studies concerning the optimization of BC production using different types of magnetic fields including RMF, especially.

  13. Modeling the properties of closed-cell cellular materials from tomography images using finite shell elements

    Caty, O.; Maire, E.; Youssef, S.; Bouchet, R.

    2008-01-01

    Closed-cell cellular materials exhibit several interesting properties. These properties are, however, very difficult to simulate and understand from the knowledge of the cellular microstructure. This problem is mostly due to the highly complex organization of the cells and to their very fine walls. X-ray tomography can produce three-dimensional (3-D) images of the structure, enabling one to visualize locally the damage of the cell walls that would result in the structure collapsing. These data could be used for meshing with continuum elements of the structure for finite element (FE) calculations. But when the density is very low, the walls are fine and the meshes based on continuum elements are not suitable to represent accurately the structure while preserving the representativeness of the model in terms of cell size. This paper presents a shell FE model obtained from tomographic 3-D images that allows bigger volumes of low-density closed-cell cellular materials to be calculated. The model is enriched by direct thickness measurement on the tomographic images. The values measured are ascribed to the shell elements. To validate and use the model, a structure composed of stainless steel hollow spheres is firstly compressed and scanned to observe local deformations. The tomographic data are also meshed with shells for a FE calculation. The convergence of the model is checked and its performance is compared with a continuum model. The global behavior is compared with the measures of the compression test. At the local scale, the model allows the local stress and strain field to be calculated. The calculated deformed shape is compared with the deformed tomographic images

  14. Tissue repair in myxobacteria: A cooperative strategy to heal cellular damage.

    Vassallo, Christopher N; Wall, Daniel

    2016-04-01

    Damage repair is a fundamental requirement of all life as organisms find themselves in challenging and fluctuating environments. In particular, damage to the barrier between an organism and its environment (e.g. skin, plasma membrane, bacterial cell envelope) is frequent because these organs/organelles directly interact with the external world. Here, we discuss the general strategies that bacteria use to cope with damage to their cell envelope and their repair limits. We then describe a novel damage-coping mechanism used by multicellular myxobacteria. We propose that cell-cell transfer of membrane material within a population serves as a wound-healing strategy and provide evidence for its utility. We suggest that--similar to how tissues in eukaryotes have evolved cooperative methods of damage repair--so too have some bacteria that live a multicellular lifestyle. © 2016 WILEY Periodicals, Inc.

  15. The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

    Lawton, P.A.

    1995-01-01

    Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author)

  16. The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

    Lawton, P.A.

    1995-12-31

    Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author).

  17. Growth Hormone Receptor Antagonist Transgenic Mice Have Increased Subcutaneous Adipose Tissue Mass, Altered Glucose Homeostasis and No Change in White Adipose Tissue Cellular Senescence.

    Comisford, Ross; Lubbers, Ellen R; Householder, Lara A; Suer, Ozan; Tchkonia, Tamara; Kirkland, James L; List, Edward O; Kopchick, John J; Berryman, Darlene E

    2016-01-01

    Growth hormone (GH)-resistant/deficient mice experience improved glucose homeostasis and substantially increased lifespan. Recent evidence suggests that long-lived GH-resistant/deficient mice are protected from white adipose tissue (WAT) dysfunction, including WAT cellular senescence, impaired adipogenesis and loss of subcutaneous WAT in old age. This preservation of WAT function has been suggested to be a potential mechanism for the extended lifespan of these mice. The objective of this study was to examine WAT senescence, WAT distribution and glucose homeostasis in dwarf GH receptor antagonist (GHA) transgenic mice, a unique mouse strain having decreased GH action but normal longevity. 18-month-old female GHA mice and wild-type (WT) littermate controls were used. Prior to dissection, body composition, fasting blood glucose as well as glucose and insulin tolerance tests were performed. WAT distribution was determined by weighing four distinct WAT depots at the time of dissection. Cellular senescence in four WAT depots was assessed using senescence-associated β-galactosidase staining to quantify the senescent cell burden, and real-time qPCR to quantify gene expression of senescence markers p16 and IL-6. GHA mice had a 22% reduction in total body weight, a 33% reduction in lean mass and a 10% increase in body fat percentage compared to WT controls. GHA mice had normal fasting blood glucose and improved insulin sensitivity; however, they exhibited impaired glucose tolerance. Moreover, GHA mice displayed enhanced lipid storage in the inguinal subcutaneous WAT depot (p < 0.05) and a 1.7-fold increase in extra-/intraperitoneal WAT ratio compared to controls (p < 0.05). Measurements of WAT cellular senescence showed no difference between GHA mice and WT controls. Similar to other mice with decreased GH action, female GHA mice display reduced age-related lipid redistribution and improved insulin sensitivity, but no change in cellular senescence. The similar abundance of

  18. Nutrition and tissue regeneration from irradiated places: a study of cellular nutrition for the place submitted to radiotherapy

    Furtunato, Clayton R.V.; Romano, Déborah R.A.

    2017-01-01

    This paper presents a physico-chemical study of the interaction of radiation with skin by ionizing radiation, presenting the hazards caused by the process. Throughout the work it is shown the importance of cellular nutrition during the period of radiotherapeutic treatment, besides having updated data on the application of natural substances for the regeneration of the place submitted to the treatment. Cancer is a problem of public health and according to data provided by the National Cancer Institute José Alencar Gomes da Silva (INCA), 420,310 new cases were registered in Brazil in 2016, of which 214,350 are among women (primary location 'breast') and 205,960 among male (primary location 'prostate'). Despite advances in technology, the hazards caused by ionizing radiation in contact with the skin are high degree of aggressiveness. Therefore, there is great importance in developing scientific studies in order to evaluate and minimize its damages during its application for radiotherapeutic purposes. The use of Aloe Vera (extracted from the slug) on the irradiated site is easily found among people undergoing radiation therapy. How is it about a stimulator of cellular and healing multiplication favors the tissue regeneration, becoming important its application, due to the radiodermatitis that appear during the treatment. Thus, the objective of this work is to present a bibliographic study of the mechanisms related to the interaction of radiation with matter, as well as the beneficial effects of the substance on irradiated living tissue and to expose such data in graph and tables to quantify its use

  19. Validity of the Cauchy-Born rule applied to discrete cellular-scale models of biological tissues

    Davit, Y.

    2013-04-30

    The development of new models of biological tissues that consider cells in a discrete manner is becoming increasingly popular as an alternative to continuum methods based on partial differential equations, although formal relationships between the discrete and continuum frameworks remain to be established. For crystal mechanics, the discrete-to-continuum bridge is often made by assuming that local atom displacements can be mapped homogeneously from the mesoscale deformation gradient, an assumption known as the Cauchy-Born rule (CBR). Although the CBR does not hold exactly for noncrystalline materials, it may still be used as a first-order approximation for analytic calculations of effective stresses or strain energies. In this work, our goal is to investigate numerically the applicability of the CBR to two-dimensional cellular-scale models by assessing the mechanical behavior of model biological tissues, including crystalline (honeycomb) and noncrystalline reference states. The numerical procedure involves applying an affine deformation to the boundary cells and computing the quasistatic position of internal cells. The position of internal cells is then compared with the prediction of the CBR and an average deviation is calculated in the strain domain. For center-based cell models, we show that the CBR holds exactly when the deformation gradient is relatively small and the reference stress-free configuration is defined by a honeycomb lattice. We show further that the CBR may be used approximately when the reference state is perturbed from the honeycomb configuration. By contrast, for vertex-based cell models, a similar analysis reveals that the CBR does not provide a good representation of the tissue mechanics, even when the reference configuration is defined by a honeycomb lattice. The paper concludes with a discussion of the implications of these results for concurrent discrete and continuous modeling, adaptation of atom-to-continuum techniques to biological

  20. Real-time in vivo imaging of butterfly wing development: revealing the cellular dynamics of the pupal wing tissue.

    Masaki Iwata

    cellular dynamics of living wing tissues in butterflies.

  1. Real-time in vivo imaging of butterfly wing development: revealing the cellular dynamics of the pupal wing tissue.

    Iwata, Masaki; Ohno, Yoshikazu; Otaki, Joji M

    2014-01-01

    Butterfly wings are covered with regularly arranged single-colored scales that are formed at the pupal stage. Understanding pupal wing development is therefore crucial to understand wing color pattern formation. Here, we successfully employed real-time in vivo imaging techniques to observe pupal hindwing development over time in the blue pansy butterfly, Junonia orithya. A transparent sheet of epithelial cells that were not yet regularly arranged was observed immediately after pupation. Bright-field imaging and autofluorescent imaging revealed free-moving hemocytes and tracheal branches of a crinoid-like structure underneath the epithelium. The wing tissue gradually became gray-white, epithelial cells were arranged regularly, and hemocytes disappeared, except in the bordering lacuna, after which scales grew. The dynamics of the epithelial cells and scale growth were also confirmed by fluorescent imaging. Fluorescent in vivo staining further revealed that these cells harbored many mitochondria at the surface of the epithelium. Organizing centers for the border symmetry system were apparent immediately after pupation, exhibiting a relatively dark optical character following treatment with fluorescent dyes, as well as in autofluorescent images. The wing tissue exhibited slow and low-frequency contraction pulses with a cycle of approximately 10 to 20 minutes, mainly occurring at 2 to 3 days postpupation. The pulses gradually became slower and weaker and eventually stopped. The wing tissue area became larger after contraction, which also coincided with an increase in the autofluorescence intensity that might have been caused by scale growth. Examination of the pattern of color development revealed that the black pigment was first deposited in patches in the central areas of an eyespot black ring and a parafocal element. These results of live in vivo imaging that covered wide wing area for a long time can serve as a foundation for studying the cellular dynamics of living

  2. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low

    Kadhim, Munira A

    2012-08-22

    The above studies will provide fundamental mechanistic information relating genetic predisposition to important low dose phenomena, and will aid in the development of Department of Energy policy, as well as radiation risk policy for the public and the workplace. We believe the proposed studies accurately reflect the goals of the DOE low dose program. To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e. less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these "non-targeted responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate non-targeted effects of ionizing radiation with a focus on the induction of genomic instability (GI) in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/CaH and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition in these models on genomic instability. We will specifically focus on the effects of low doses of low LET radiation, down to the dose of 10mGy (0.01Gy) X-rays. Using conventional X-ray and we will be able to assess the role of genetic variation under various conditions at a range of doses down to the very low dose of 0.01Gy. Irradiations will be carried out using facilities in routine operation for such studies. Mechanistic studies of instability in different cell

  3. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  4. MAPU: Max-Planck Unified database of organellar, cellular, tissue and body fluid proteomes.

    Zhang, Yanling; Zhang, Yong; Adachi, Jun; Olsen, Jesper V; Shi, Rong; de Souza, Gustavo; Pasini, Erica; Foster, Leonard J; Macek, Boris; Zougman, Alexandre; Kumar, Chanchal; Wisniewski, Jacek R; Jun, Wang; Mann, Matthias

    2007-01-01

    Mass spectrometry (MS)-based proteomics has become a powerful technology to map the protein composition of organelles, cell types and tissues. In our department, a large-scale effort to map these proteomes is complemented by the Max-Planck Unified (MAPU) proteome database. MAPU contains several body fluid proteomes; including plasma, urine, and cerebrospinal fluid. Cell lines have been mapped to a depth of several thousand proteins and the red blood cell proteome has also been analyzed in depth. The liver proteome is represented with 3200 proteins. By employing high resolution MS and stringent validation criteria, false positive identification rates in MAPU are lower than 1:1000. Thus MAPU datasets can serve as reference proteomes in biomarker discovery. MAPU contains the peptides identifying each protein, measured masses, scores and intensities and is freely available at http://www.mapuproteome.com using a clickable interface of cell or body parts. Proteome data can be queried across proteomes by protein name, accession number, sequence similarity, peptide sequence and annotation information. More than 4500 mouse and 2500 human proteins have already been identified in at least one proteome. Basic annotation information and links to other public databases are provided in MAPU and we plan to add further analysis tools.

  5. Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses.

    Martines, Roosecelis Brasil; Ng, Dianna L; Greer, Patricia W; Rollin, Pierre E; Zaki, Sherif R

    2015-01-01

    Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. Novel vanillin derivatives: Synthesis, anti-oxidant, DNA and cellular protection properties.

    Scipioni, Matteo; Kay, Graeme; Megson, Ian; Kong Thoo Lin, Paul

    2018-01-01

    Antioxidants have been the subject of intense research interest mainly due to their beneficial properties associated with human health and wellbeing. Phenolic molecules, such as naturally occurring Resveratrol and Vanillin, are well known for their anti-oxidant properties, providing a starting point for the development of new antioxidants. Here we report, for the first time, the synthesis of a number of new vanillin through the reductive amination reaction between vanillin and a selection of amines. All the compounds synthesised, exhibited strong antioxidant properties in DPPH, FRAP and ORAC assays, with compounds 1b and 2c being the most active. The latter also demonstrated the ability to protect plasmid DNA from oxidative damage in the presence of the radical initiator AAPH. At cellular level, neuroblastoma SH-SY5Y cells were protected from oxidative damage (H 2 O 2 , 400 μM) with both 1b and 2c. The presence of a tertiary amino group, along with the number of vanillin moieties in the molecule contribute for the antioxidant activity. Furthermore, the delocalization of the electron pair of the nitrogen and the presence of an electron donating substituent to enhance the antioxidant properties of this new class of compounds. In our opinion, vanillin derivatives 1b and 2c described in this work can provide a viable platform for the development of antioxidant based therapeutics. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Finite element analysis of the mechanical properties of cellular aluminium based on micro-computed tomography

    Veyhl, C.; Belova, I.V.; Murch, G.E.; Fiedler, T.

    2011-01-01

    Research highlights: → Elastic and plastic anisotropy is observed for both materials → Both show qualitatively similar characteristics with quantitative differences → Distinctly higher mechanical properties for closed-cell foam → The 'big' and 'small' models show good agreement for the closed-cell foam. - Abstract: In the present paper, the macroscopic mechanical properties of open-cell M-Pore sponge (porosity of 91-93%) and closed-cell Alporas foam (porosity of 80-86%) are investigated. The complex geometry of these cellular materials is scanned by micro-computed tomography and used in finite element (FE) analysis. The mechanical properties are determined by uni-axial compression simulations in three perpendicular directions (x-, y- and z-direction). M-Pore and Alporas exhibit the same qualitative mechanical characteristics but with quantitative differences. In both cases, strong anisotropy is observed for Young's modulus and the 0.002 offset yield stress. Furthermore, for the investigated relative density range a linear dependence between relative density and mechanical properties is found. Finally, a distinctly higher Young's modulus and 0.002 offset yield stress is observed for Alporas.

  8. WATER VAPOUR PERMEABILITY PROPERTIES OF CELLULAR WOOD MATERIAL AND CONDENSATION RISK OF COMPOSITE PANEL WALLS

    Janis IEJAVS

    2016-09-01

    Full Text Available Invention of light weight cellular wood material (CWM with a trade mark of Dendrolight is one of innovations in wood industry of the last decade. The aim of the research was to define the water vapour permeability properties of CWM and to analyse the condensation risk of various wall envelopes where solid wood cellular material is used. To determine the water vapour permeability of CWM, test samples were produced in the factory using routine production technology and tested according to the standard EN 12086:2014. Water vapour permeability factor (μ and other properties of six different configurations of CWM samples were determined. Using the experimental data the indicative influence of geometrical parameters such as lamella thickness, number of lamellas and material direction were investigated and evaluated. To study the condensation risk within the wall envelope containing CWM calculation method given in LVS EN ISO 13788:2012 was used. To ease the calculation process previously developed JavaScript calculation software that had only capability to calculate thermal transmittance was extended so that condensation risk in multi-layer composite walls can be analysed. Water vapour permeability factor in CWM is highly direction dependant. If parallel and perpendicular direction of CWM is compared the value of water vapour permeability factor can differentiate more than two times. Another significant factor for condensation risk analysis is overall thickness of CWM since it directly influences the equivalent air layer thickness. The influence of other factors such as lamella thickness, or groove depth is minor when water vapour permeability properties are compared. From the analysis of CWM performance in building envelope it can be concluded that uninsulated CWM panels used during winter months will pose the risk of condensation damage to structure, but the risk can be reduced or prevented if insulation layer is applied to the CWM panel wall

  9. Elastic properties of synthetic materials for soft tissue modeling

    Mansy, H A; Grahe, J R; Sandler, R H

    2008-01-01

    Mechanical models of soft tissue are useful for studying vibro-acoustic phenomena. They may be used for validating mathematical models and for testing new equipment and techniques. The objective of this study was to measure density and visco-elastic properties of synthetic materials that can be used to build such models. Samples of nine different materials were tested under dynamic (0.5 Hz) compressive loading conditions. The modulus of elasticity of the materials was varied, whenever possible, by adding a softener during manufacturing. The modulus was measured over a nine month period to quantify the effect of ageing and softener loss on material properties. Results showed that a wide range of the compression elasticity modulus (10 to 1400 kPa) and phase (3.5 0 -16.7 0 ) between stress and strain were possible. Some materials tended to exude softener over time, resulting in a weight loss and elastic properties change. While the weight loss under normal conditions was minimal in all materials (<3% over nine months), loss under accelerated weight-loss conditions can reach 59%. In the latter case an elasticity modulus increase of up to 500% was measured. Key advantages and limitations of candidate materials were identified and discussed

  10. Effects of hypoxia on the immunomodulatory properties of adipose tissue-derived mesenchymal stem cells

    M. Roemeling-Van Rhijn (Marieke); F.K.F. Mensah (Fane ); S.S. Korevaar (Sander); M.J.C. Leijs (Maarten J.C.); G.J.V.M. van Osch (Gerjo); J.N.M. IJzermans (Jan); M.G.H. Betjes (Michiel); C.C. Baan (Carla); W. Weimar (Willem); M.J. Hoogduijn (Martin)

    2013-01-01

    textabstractAdipose tissue-derived mesenchymal stem cells (ASC) are of great interest as a cellular therapeutic agent for regenerative and immunomodulatory purposes. The function of ASC adapts to environmental conditions, such as oxygen tension. Oxygen levels within tissues are typically much lower

  11. Cellular and circuit properties supporting different sensory coding strategies in electric fish and other systems.

    Marsat, Gary; Longtin, André; Maler, Leonard

    2012-08-01

    Neural codes often seem tailored to the type of information they must carry. Here we contrast the encoding strategies for two different communication signals in electric fish and describe the underlying cellular and network properties that implement them. We compare an aggressive signal that needs to be quickly detected, to a courtship signal whose quality needs to be evaluated. The aggressive signal is encoded by synchronized bursts and a predictive feedback input is crucial in separating background noise from the communication signal. The courtship signal is accurately encoded through a heterogenous population response allowing the discrimination of signal differences. Most importantly we show that the same strategies are used in other systems arguing that they evolved similar solutions because they faced similar tasks. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Realisation and qualification of a tissue equivalent proportional counter with a multi-cellular geometry for the individual neutron dosimetry

    Hoflack, Ch.

    1999-01-01

    The present day dosimetry means for radiations with a strong ionization density cannot fulfill the future radioprotection regulations which will require an individual dosimetry with active dosemeters. The aim of this work is the study and development of an individual dosemeter based on a tissue equivalent proportional counter and with a multi-cellular geometry allowing to reach a sensibility equivalent to environmental dosemeters. A pressure regulation bench has been added to the detector in order to reduce the degassing of the detector parts and to reach a sufficient service life for the implementation of the characterization tests. The hole counter system has been adopted for the first prototypes in order to reduce the sensibility of the wires multiplication system with respect to mechanical vibrations. Tests performed with an internal alpha source have shown that a better electrical efficiency can be reached when more severe mechanical limits are adopted during the construction. The dose equivalent response of the prototype for mono-energy neutrons of 144 keV to 2.5 MeV is analyzed experimentally and by simulation. During experiments with normal incidence neutrons, the prototype fulfills the requirements of the CEI N O 1323 standard for energies comprised between 400 keV and 2.5 MeV, while the simulation indicates a satisfactory response up to 200 keV. A preliminary study of the behaviour of the detector with respect to the neutrons incidence indicates that the multi-cellular geometry is efficient for large angles (the sensibility of the prototype is increased by a factor 3). Finally, simulation studies have to be made to optimize the electrical operation and the geometry of the next prototype. (J.S.)

  13. Stochastic multi-scale analysis of homogenised properties considering uncertainties in cellular solid microstructures using a first-order perturbation

    Khairul Salleh Basaruddin

    Full Text Available Randomness in the microstructure due to variations in microscopic properties and geometrical information is used to predict the stochastically homogenised properties of cellular media. Two stochastic problems at the micro-scale level that commonly occur due to fabrication inaccuracies, degradation mechanisms or natural heterogeneity were analysed using a stochastic homogenisation method based on a first-order perturbation. First, the influence of Young's modulus variation in an adhesive on the macroscopic properties of an aluminium-adhesive honeycomb structure was investigated. The fluctuations in the microscopic properties were then combined by varying the microstructure periodicity in a corrugated-core sandwich plate to obtain the variation of the homogenised property. The numerical results show that the uncertainties in the microstructure affect the dispersion of the homogenised property. These results indicate the importance of the presented stochastic multi-scale analysis for the design and fabrication of cellular solids when considering microscopic random variation.

  14. Book review of “Imaging in Cellular and Tissue Engineering” edited by Y Hanry Yu and Nur Aida Abdul Rahim

    Brey, Eric Michael

    2014-01-01

    This article is a review of the book “Imaging in Cellular and Tissue Engineering” (ISBN-13: 978-1439848036, $149.95, 298 Pages, 114 Illustrations) edited by Y Hanry Yu and Nur Aida Abdul Rahim published by the CRC Press (Taylor&Francis) in 2013. The contents of the book and its relevance to tissue engineering and regenerative medicine are discussed in this invited review.

  15. Improvement of the in vivo cellular repopulation of decellularized cardiovascular tissues by a detergent-free, non-proteolytic, actin-disassembling regimen.

    Assmann, Alexander; Struß, Marc; Schiffer, Franziska; Heidelberg, Friederike; Munakata, Hiroshi; Timchenko, Elena V; Timchenko, Pavel E; Kaufmann, Tim; Huynh, Khon; Sugimura, Yukiharu; Leidl, Quentin; Pinto, Antonio; Stoldt, Volker R; Lichtenberg, Artur; Akhyari, Payam

    2017-12-01

    Low immunogenicity and high repopulation capacity are crucial determinants for the functional and structural performance of acellular cardiovascular implants. The present study evaluates a detergent-free, non-proteolytic, actin-disassembling regimen (BIO) for decellularization of heart valve and vessel grafts, particularly focusing on their bio-functionality. Rat aortic conduits (rAoC; n = 89) and porcine aortic valve samples (n = 106) are decellularized using detergents (group DET) or the BIO regimen. BIO decellularization results in effective elimination of cellular proteins and significantly improves removal of DNA as compared with group DET, while the extracellular matrix (ECM) structure as well as mechanical properties are preserved. The architecture of rAoC in group BIO allows for improved bio-functionalization with fibronectin (FN) in a standardized rat implantation model: BIO treatment significantly increases speed and amount of autologous medial cellular repopulation in vivo (p < 0.001) and decreases the formation of hyperplastic intima (p < 0.001) as compared with FN-coated DET-decellularized grafts. Moreover, there are no signs of infiltration with inflammatory cells. The present biological, detergent-free, non-proteolytic regimen balances effective decellularization and ECM preservation in cardiovascular grafts, and provides optimized bio-functionality. Additionally, this study implies that the actin-disassembling regimen may be a promising approach for bioengineering of acellular scaffolds from other muscular tissues, as for example myocardium or intestine. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Traffic Accident Propagation Properties and Control Measures for Urban Links Based on Cellular Automata

    Xian-sheng Li

    2013-01-01

    Full Text Available With the rapid development of urban transport and the sharp increase in vehicle population, traffic accidents form one of the most important causes of urban traffic congestion other than the imbalance between traffic supply and demand. Traffic congestion causes severe problems, such as environment contamination and energy dissipation. Therefore, it would be useful to analyze the congestion propagation characteristics after traffic accidents. Numerical analysis and computer simulation were two of the typical methods used at present to study the traffic congestion propagation properties. The latter was more widespread as it is more consistent with the actual traffic flow and more visual than the former. In this paper, an improved cellular automata (CA model was presented to analyze traffic congestion propagation properties and to evaluate control strategies. In order to apply them to urban traffic flow simulation, the CA models have been improved and expanded on. Computer simulations were built for congestion not only extending to the upstream intersection, but also the upstream intersection and the entire road network, respectively. Congestion propagation characteristics after road traffic accidents were obtained, and controls of different severities and durations were analyzed. The results provide the theoretical foundation and practical means for the control of congestion.

  17. Effects of storage methods on time-related changes of titanium surface properties and cellular response

    Lu Haibin; Zhou Lei; Wan Lei; Li Shaobing; Rong Mingdeng; Guo Zehong

    2012-01-01

    Titanium implants are sold in the market as storable medical devices. All the implants have a certain shelf life during which they maintain their sterility, but variations of the surface properties through this duration have not been subject to a comprehensive assessment. The aim of this study was to investigate the effects of storage methods on time-related changes of titanium surface properties. Acid-etched titanium discs (Sa = 0.82 µm) were placed in a sealed container (tradition method) or submerged in the ddH 2 O/NaCl solution (0.15 mol L −1 )/CaCl 2 solution (0.15 mol L −1 ), and new titanium discs were used as a control group. SEM and optical profiler showed that surface morphology and roughness did not change within different groups, but the XPS analysis confirmed that the surface chemistry altered by different storage protocols as the storage duration increased, and the contact angle also varied with storage methods. The storage method also affected the protein adsorption capacity and cellular response on the titanium surface. All titanium discs stored in the solution maintained their excellent bioactivity even after four weeks storage time, but titanium discs stored in a traditional manner decreased substantially in an age-dependent manner. Much effort is needed to improve the storage methods in order to maintain the bioactivity of a titanium dental implant. (paper)

  18. Effects of Mechanical Properties on Tumor Invasion: Insights from a Cellular Model

    Li, YZ

    2014-08-01

    Understanding the regulating mechanism of tumor invasion is of crucial importance for both fundamental cancer research and clinical applications. Previous in vivo experiments have shown that invasive cancer cells dissociate from the primary tumor and invade into the stroma, forming an irregular invasive morphology. Although cell movements involved in tumor invasion are ultimately driven by mechanical forces of cell-cell interactions and tumor-host interactions, how these mechanical properties affect tumor invasion is still poorly understood. In this study, we use a recently developed two-dimensional cellular model to study the effects of mechanical properties on tumor invasion. We study the effects of cell-cell adhesions as well as the degree of degradation and stiffness of extracellular matrix (ECM). Our simulation results show that cell-cell adhesion relationship must be satisfied for tumor invasion. Increased adhesion to ECM and decreased adhesion among tumor cells result in invasive tumor behaviors. When this invasive behavior occurs, ECM plays an important role for both tumor morphology and the shape of invasive cancer cells. Increased stiffness and stronger degree of degradation of ECM promote tumor invasion, generating more aggressive tumor invasive morphologies. It can also generate irregular shape of invasive cancer cells, protruding towards ECM. The capability of our model suggests it a useful tool to study tumor invasion and might be used to propose optimal treatment in clinical applications.

  19. Whole Body Hyperthermia in Mice Confers Delayed Radioprotection at Cellular and Tissue Levels: Inducible Heat Shock Proteins as Endogenous Radioprotectors

    Malytina, Y. V.; Sements, T. N.; Semina, O. V.; Mosin, A. F.; Kabakov, A.

    2004-01-01

    It was previously shown on heat shock protein (Hsp)-over expressing cell lines that the increased intracellular content of Hsp 70 or Hsp27 is associated with the elevated radioresistance. However, it was so far unknown whether the in vivo Fsp induction by stressful preconditioning can confer radioprotection at the tissue and cellular levels. In the present study, we examined how the in vivo up-regulation of the Hsp expression in response to mild whole body hyperthermia (42 degrees C, 10 min) in mice changes susceptibility of their bone marrow stem cells and thymocytes to subsequent gamma-irradiation. to assess the expectable contribution of stress-inducible Hsp we used injections with Quercetin, a flavonoid inhibiting the stress-responsive Hsp induction. The results demonstrate that the bone marrow stem cells and thymocytes from heat-preconditioned mice were more radioresistant than those from the non-preconditioned animals. the radioprotection was well manifested if mice or their isolated thymocytes were irradiated 18-25 h after the in vivo hyperthermia. This delayed radioprotection resulting from the heat preconditioning was suppressed in Quercetin-injected mice. The revealed correlation between the intracellular Hsp accumulation and the acquired Quercetin-sensitive radioprotection suggests a beneficial role of Hsps as of endogenous radioprotectors. Our finding discovers new ways for artificial modulation of effects of irradiation on target cells via manipulating the Hsp expression. (Author) 17 refs

  20. Probiotic Properties and Cellular Antioxidant Activity of Lactobacillus plantarum MA2 Isolated from Tibetan Kefir Grains.

    Tang, Wei; Li, Chao; He, Zengguo; Pan, Fen; Pan, Shuo; Wang, Yanping

    2017-11-20

    Lactobacillus plantarum MA2 was isolated from traditional Chinese Tibetan kefir grains. Its antioxidant properties had been demonstrated in vitro and in vivo previously. In the present study, the probiotic characteristics of this strain were further evaluated by investigating its acid and bile salt tolerances, cell surface hydrophobicity, and autoaggregation, respectively. In addition, the cellular antioxidant activity (CAA) assay was applied to test the antioxidant capacity of the isolate in different growth phases. Same method was also used to evaluate the antioxidant capacity of its fermentation supernatant, cell-free extract, and intact cell quantitatively. The results of probiotic characteristic tests showed that MA2 could survive at pH 2.5 and 0.3% bile salt. Meanwhile, the measurements of cell surface hydrophobicity and autoaggregation were 45.29 ± 2.15 and 6.30 ± 0.34%, respectively. The results of cellular antioxidant activity tests indicated that MA2 had high antioxidant potential. The CAA value of logarithmic phase cell-free extract of MA2 (39,450.00 ± 424.05 μmol quercetin equivalents/100 g sample) was significantly higher than that in stationary phase cell-free extract (3395.98 ± 126.06 μmol quercetin equivalents/100 g sample) and that of fermentation supernatant in logarithmic phase (2174.41 ± 224.47 μmol quercetin equivalents/100 g sample) (p < 0.05). The CAA method was successively applied to evaluate the antioxidant capacity of MA2 in this study, which suggests that it could be used as a useful method for lactic acid bacteria antioxidant potential evaluation.

  1. Multiscale Modeling of Antibody Drug Conjugates: Connecting tissue and cellular distribution to whole animal pharmacokinetics and potential implications for efficacy

    Cilliers, Cornelius; Guo, Hans; Liao, Jianshan; Christodolu, Nikolas; Thurber, Greg M.

    2016-01-01

    Antibody drug conjugates exhibit complex pharmacokinetics due to their combination of macromolecular and small molecule properties. These issues range from systemic concerns, such as deconjugation of the small molecule drug during the long antibody circulation time or rapid clearance from non-specific interactions, to local tumor tissue heterogeneity, cell bystander effects, and endosomal escape. Mathematical models can be used to study the impact of these processes on overall distribution in an efficient manner, and several types of models have been used to analyze varying aspects of antibody distribution including physiologically based pharmacokinetic (PBPK) models and tissue-level simulations. However, these processes are quantitative in nature and cannot be handled qualitatively in isolation. For example, free antibody from deconjugation of the small molecule will impact the distribution of conjugated antibodies within the tumor. To incorporate these effects into a unified framework, we have coupled the systemic and organ-level distribution of a PBPK model with the tissue-level detail of a distributed parameter tumor model. We used this mathematical model to analyze new experimental results on the distribution of the clinical antibody drug conjugate Kadcyla in HER2 positive mouse xenografts. This model is able to capture the impact of the drug antibody ratio (DAR) on tumor penetration, the net result of drug deconjugation, and the effect of using unconjugated antibody to drive ADC penetration deeper into the tumor tissue. This modeling approach will provide quantitative and mechanistic support to experimental studies trying to parse the impact of multiple mechanisms of action for these complex drugs. PMID:27287046

  2. Histological properties of intramuscular connective tissues in native ...

    The conventional histological study revealed that except the endomysium which was similar in both muscles, the other intramuscular connective tissues' layers varied between leg and breast muscles and were affected by sex. All the connective tissue fibers were observed in all the intramuscular connective tissues of both ...

  3. Awakened by cellular stress: isolation and characterization of a novel population of pluripotent stem cells derived from human adipose tissue.

    Saleh Heneidi

    Full Text Available Advances in stem cell therapy face major clinical limitations, particularly challenged by low rates of post-transplant cell survival. Hostile host factors of the engraftment microenvironment such as hypoxia, nutrition deprivation, pro-inflammatory cytokines, and reactive oxygen species can each contribute to unwanted differentiation or apoptosis. In this report, we describe the isolation and characterization of a new population of adipose tissue (AT derived pluripotent stem cells, termed Multilineage Differentiating Stress-Enduring (Muse Cells, which are isolated using severe cellular stress conditions, including long-term exposure to the proteolytic enzyme collagenase, serum deprivation, low temperatures and hypoxia. Under these conditions, a highly purified population of Muse-AT cells is isolated without the utilization of cell sorting methods. Muse-AT cells grow in suspension as cell spheres reminiscent of embryonic stem cell clusters. Muse-AT cells are positive for the pluripotency markers SSEA3, TR-1-60, Oct3/4, Nanog and Sox2, and can spontaneously differentiate into mesenchymal, endodermal and ectodermal cell lineages with an efficiency of 23%, 20% and 22%, respectively. When using specific differentiation media, differentiation efficiency is greatly enhanced in Muse-AT cells (82% for mesenchymal, 75% for endodermal and 78% for ectodermal. When compared to adipose stem cells (ASCs, microarray data indicate a substantial up-regulation of Sox2, Oct3/4, and Rex1. Muse-ATs also exhibit gene expression patterns associated with the down-regulation of genes involved in cell death and survival, embryonic development, DNA replication and repair, cell cycle and potential factors related to oncogenecity. Gene expression analysis indicates that Muse-ATs and ASCs are mesenchymal in origin; however, Muse-ATs also express numerous lymphocytic and hematopoietic genes, such as CCR1 and CXCL2, encoding chemokine receptors and ligands involved in stem cell

  4. Paramyxovirus Infection Mimics In Vivo Cellular Dynamics in Three-Demensional Human Bronchio-Epithelial Tissue-Like Assemblies

    Deatly, Anne M.; Lin, Yen-Huei; McCarthy, Maureen; Chen, Wei; Miller, Lynn Z.; Quiroz, Jorge; Nowak, Becky M.; Lerch, Robert A.; Udem, Stephen A.; Goodwin, Thomas J.

    2012-01-01

    , cotton rat, guinea pig, ferret, and hamster) fail to accurately imitate viral replication and human disease states (8). Lacking an authentic model has impeded the development and evaluation of live, attenuated vaccine candidates. Development of a physiologically relevant in vitro tissue culture model that reproduces characteristics of the HRE, the primary target of RSV and PIV3, would aid in predicting clinical attenuation and safety of vaccine candidates. Successful tissue engineering of a 3D human intestinal model using novel NASA technology inspired the development of a tri-culture 3D model for the HRE. Sequential layering of primary mesenchymal cells (comprised of normal human fibroblasts and endothelial cells) followed by BEAS-2B epithelial cells derived from human bronchi and tracheae were recapitulated on Cultisphere and/or cytodex3 microcarriers in cylindrical vessels that rotate horizontally creating an organized epithelial structure. Horizontal rotation randomizes the gravity vector modeling aspects of microgravity. Mesenchymal and epithelial cells grown under these conditions reproduce the structural organization, multi-cellular complexity, and differentiation state of the HRE. The opportunity to study respiratory viruses in a nasal epithelium model is invaluable because the most promising respiratory virus vaccine candidates are live attenuated viruses for intranasal administration. Here we characterize the interactions of respiratory viruses and epithelial cells grown under modeled microgravity in comparison to gravity-ladened monolayers. 3D HBE TLAs and traditional monolayers (2D) are infected at 35 C, the upper temperature of the upper HRE, to simulate in vivo infection conditions. Growth kinetics of wild type (wt) RSV and PIV3 viruses were compared in 2D and 3D cells to that of strains attenuated in humans or rhesus macaques. This novel 3D HBE model also offers an opportunity to study whether the epithelial cell function, especially in host defenses

  5. Physical Property Control on the Cellular Uptake Pathway and Spatial Distribution of Nanoparticles in Cells.

    Ahn, Sungsook; Seo, Eunseok; Kim, Ki Hean; Lee, Sang Joon

    2015-06-01

    Nanoparticles have been developed in broad biomedical research in terms of effective cellular interactions to treat and visualize diseased cells. Considering the charge and polar functional groups of proteins that are embedded in cellular membranes, charged nanoparticles have been strategically developed to enhance electrostatic cellular interactions. In this study, we show that cellular uptake efficiency, pathway, and spatial distribution of gold nanoparticles in a cell are significantly modulated based on the surface condition of gold nanoparticles and human cancer cells that were tuned by controlling the pH of the medium and by introducing an electron beam. Cellular uptake efficiency is increased when electrostatic attraction is induced between the cells and the gold nanoparticles. Cell surface modification changes the cellular uptake pathways of the gold nanoparticles and concentrates the gold nanoparticles at the membrane region. Surface modification of the gold nanoparticles also contributes to deep penetration and homogeneous spatial distributions in a cell.

  6. A Nanoflare-Based Cellular Automaton Model and the Observed Properties of the Coronal Plasma

    Lopez-Fuentes, Marcelo; Klimchuk, James Andrew

    2016-01-01

    We use the cellular automaton model described in Lopez Fuentes and Klimchuk to study the evolution of coronal loop plasmas. The model, based on the idea of a critical misalignment angle in tangled magnetic fields, produces nanoflares of varying frequency with respect to the plasma cooling time. We compare the results of the model with active region (AR) observations obtained with the Hinode/XRT and SDOAIA instruments. The comparison is based on the statistical properties of synthetic and observed loop light curves. Our results show that the model reproduces the main observational characteristics of the evolution of the plasma in AR coronal loops. The typical intensity fluctuations have amplitudes of 10 percent - 15 percent both for the model and the observations. The sign of the skewness of the intensity distributions indicates the presence of cooling plasma in the loops. We also study the emission measure (EM) distribution predicted by the model and obtain slopes in log(EM) versus log(T) between 2.7 and 4.3, in agreement with published observational values.

  7. A NANOFLARE-BASED CELLULAR AUTOMATON MODEL AND THE OBSERVED PROPERTIES OF THE CORONAL PLASMA

    Fuentes, Marcelo López [Instituto de Astronomía y Física del Espacio, CONICET-UBA, CC. 67, Suc. 28, 1428 Buenos Aires (Argentina); Klimchuk, James A., E-mail: lopezf@iafe.uba.ar [NASA Goddard Space Flight Center, Code 671, Greenbelt, MD 20771 (United States)

    2016-09-10

    We use the cellular automaton model described in López Fuentes and Klimchuk to study the evolution of coronal loop plasmas. The model, based on the idea of a critical misalignment angle in tangled magnetic fields, produces nanoflares of varying frequency with respect to the plasma cooling time. We compare the results of the model with active region (AR) observations obtained with the Hinode /XRT and SDO /AIA instruments. The comparison is based on the statistical properties of synthetic and observed loop light curves. Our results show that the model reproduces the main observational characteristics of the evolution of the plasma in AR coronal loops. The typical intensity fluctuations have amplitudes of 10%–15% both for the model and the observations. The sign of the skewness of the intensity distributions indicates the presence of cooling plasma in the loops. We also study the emission measure (EM) distribution predicted by the model and obtain slopes in log(EM) versus log(T) between 2.7 and 4.3, in agreement with published observational values.

  8. Biological Properties of Iron Oxide Nanoparticles for Cellular and Molecular Magnetic Resonance Imaging

    Claus-Christian Glüer

    2010-12-01

    Full Text Available Superparamagnetic iron-oxide particles (SPIO are used in different ways as contrast agents for magnetic resonance imaging (MRI: Particles with high nonspecific uptake are required for unspecific labeling of phagocytic cells whereas those that target specific molecules need to have very low unspecific cellular uptake. We compared iron-oxide particles with different core materials (magnetite, maghemite, different coatings (none, dextran, carboxydextran, polystyrene and different hydrodynamic diameters (20–850 nm for internalization kinetics, release of internalized particles, toxicity, localization of particles and ability to generate contrast in MRI. Particle uptake was investigated with U118 glioma cells und human umbilical vein endothelial cells (HUVEC, which exhibit different phagocytic properties. In both cell types, the contrast agents Resovist, B102, non-coated Fe3O4 particles and microspheres were better internalized than dextran-coated Nanomag particles. SPIO uptake into the cells increased with particle/iron concentrations. Maximum intracellular accumulation of iron particles was observed between 24 h to 36 h of exposure. Most particles were retained in the cells for at least two weeks, were deeply internalized, and only few remained adsorbed at the cell surface. Internalized particles clustered in the cytosol of the cells. Furthermore, all particles showed a low toxicity. By MRI, monolayers consisting of 5000 Resovist-labeled cells could easily be visualized. Thus, for unspecific cell labeling, Resovist and microspheres show the highest potential, whereas Nanomag particles are promising contrast agents for target-specific labeling.

  9. Fibroblast-Derived Extracellular Matrices: An Alternative Cell Culture System That Increases Metastatic Cellular Properties.

    Michael T Scherzer

    Full Text Available Poor survival rates from lung cancer can largely be attributed to metastatic cells that invade and spread throughout the body. The tumor microenvironment (TME is composed of multiple cell types, as well as non-cellular components. The TME plays a critical role in the development of metastatic cancers by providing migratory cues and changing the properties of the tumor cells. The Extracellular Matrix (ECM, a main component of the TME, has been shown to change composition during tumor progression, contributing to cancer cell invasion and survival away from the primary cancer site. Although the ECM is well-known to influence the fate of tumor progression, little is known about the molecular mechanisms that are affected by the cancer cell-ECM interactions. It is imperative that these mechanisms are elucidated in order to properly understand and prevent lung cancer dissemination. However, common in vitro studies do not incorporate these interactions into everyday cell culture assays. We have adopted a model that examines decellularized human fibroblast-derived ECM as a 3-dimensional substrate for growth of lung adenocarcinoma cell lines. Here, we have characterized the effect of fibroblast-derived matrices on the properties of various lung-derived epithelial cell lines, including cancerous and non-transformed cells. This work highlights the significance of the cell-ECM interaction and its requirement for incorporation into in vitro experiments. Implementation of a fibroblast-derived ECM as an in vitro technique will provide researchers with an important factor to manipulate to better recreate and study the TME.

  10. Microstructure and in vitro cellular response to novel soy protein-based porous structures for tissue regeneration applications.

    Olami, Hilla; Zilberman, Meital

    2016-02-01

    Interest in the development of new bioresorbable structures for various tissue engineering applications is on the rise. In the current study, we developed and studied novel soy protein-based porous blends as potential new scaffolds for such applications. Soy protein has several advantages over the various types of natural proteins employed for biomedical applications due to its low price, non-animal origin and relatively long storage time and stability. In the present study, blends of soy protein with other polymers (gelatin, pectin and alginate) were added and chemically cross-linked using the cross-linking agents carbodiimide or glyoxal, and the porous structure was obtained through lyophilization. The resulting blend porous structures were characterized using environmental scanning microscopy, and the cytotoxicity of these scaffolds was examined in vitro. The biocompatibility of the scaffolds was also evaluated in vitro by seeding and culturing human fibroblasts on these scaffolds. Cell growth morphology and adhesion were examined histologically. The results show that these blends can be assembled into porous three-dimensional structures by combining chemical cross-linking with freeze-drying. The achieved blend structures combine suitable porosity with a large pore size (100-300 µm). The pore structure in the soy-alginate scaffolds possesses adequate interconnectivity compared to that of the soy-gelatin scaffolds. However, porous structure was not observed for the soy-pectin blend, which presented a different structure with significantly lower porosities than all other groups. The in vitro evaluation of these porous soy blends demonstrated that soy-alginate blends are advantageous over soy-gelatin blends and exhibited adequate cytocompatibility along with better cell infiltration and stability. These soy protein scaffolds may be potentially useful as a cellular/acellular platform for skin regeneration applications. © The Author(s) 2015.

  11. Experimental study and constitutive modeling of the viscoelastic mechanical properties of the human prolapsed vaginal tissue.

    Peña, Estefania; Calvo, B; Martínez, M A; Martins, P; Mascarenhas, T; Jorge, R M N; Ferreira, A; Doblaré, M

    2010-02-01

    In this paper, the viscoelastic mechanical properties of vaginal tissue are investigated. Using previous results of the authors on the mechanical properties of biological soft tissues and newly experimental data from uniaxial tension tests, a new model for the viscoelastic mechanical properties of the human vaginal tissue is proposed. The structural model seems to be sufficiently accurate to guarantee its application to prediction of reliable stress distributions, and is suitable for finite element computations. The obtained results may be helpful in the design of surgical procedures with autologous tissue or prostheses.

  12. Analysis of bone architecture sensitivity for changes in mechanical loading, cellular activity, mechanotransduction, and tissue properties

    Cox, L.G.E.; Rietbergen, van B.; Donkelaar, van C.C.; Ito, K.

    2011-01-01

    Bone has an architecture which is optimized for its mechanical environment. In various conditions, this architecture is altered, and the underlying cause for this change is not always known. In the present paper, we investigated the sensitivity of the bone microarchitecture for four factors: changes

  13. Lunar Dust and Lunar Simulant Activation, Monitoring, Solution and Cellular Toxicity Properties

    Wallace, William; Jeevarajan, A. S.

    2009-01-01

    During the Apollo missions, many undesirable situations were encountered that must be mitigated prior to returning humans to the moon. Lunar dust (that part of the lunar regolith less than 20 microns in diameter) was found to produce several problems with mechanical equipment and could have conceivably produced harmful physiological effects for the astronauts. For instance, the abrasive nature of the dust was found to cause malfunctions of various joints and seals of the spacecraft and suits. Additionally, though efforts were made to exclude lunar dust from the cabin of the lunar module, a significant amount of material nonetheless found its way inside. With the loss of gravity correlated with ascent from the lunar surface, much of the finer fraction of this dust began to float and was inhaled by the astronauts. The short visits tothe Moon during Apollo lessened exposure to the dust, but the plan for future lunar stays of up to six months demands that methods be developed to minimize the risk of dust inhalation. The guidelines for what constitutes "safe" exposure will guide the development of engineering controls aimed at preventing the presence of dust in the lunar habitat. This work has shown the effects of grinding on the activation level of lunar dust, the changes in dissolution properties of lunar simulant, and the production of cytokines by cellular systems. Grinding of lunar dust leads to the production of radicals in solution and increased dissolution of lunar simulant in buffers of different pH. Additionally, ground lunar simulant has been shown to promote the production of IL-6 and IL-8, pro-inflammatory cytokines, by alveolar epithelial cells. These results provide evidence of the need for further studies on these materials prior to returning to the lunar surface.

  14. Histological characterization and quantification of cellular events following neural and fibroblast(-like) stem cell grafting in healty and demyelinated CNS tissue

    Praet, J.; SANTERMANS, Eva; Reekmans, K.; de Vocht, N.; Le Blon, D.; Hoornaert, C.; Daans, J.; Goossens, H.; Berneman, Z.; HENS, Niel; Van der Linden, A.; Ponsaerts, P.

    2014-01-01

    Preclinical animal studies involving intracerebral (stem) cell grafting are gaining popularity in many laboratories due to the reported beneficial effects of cell grafting on various diseases or traumata of the central nervous system (CNS). In this chapter, we describe a histological workflow to characterize and quantify cellular events following neural and fibroblast(-like) stem cell grafting in healthy and demyelinated CNS tissue. First, we provide standardized protocols to isolate and cult...

  15. The cellular prion protein interacts with the tissue non-specific alkaline phosphatase in membrane microdomains of bioaminergic neuronal cells.

    Myriam Ermonval

    Full Text Available BACKGROUND: The cellular prion protein, PrP(C, is GPI anchored and abundant in lipid rafts. The absolute requirement of PrP(C in neurodegeneration associated to prion diseases is well established. However, the function of this ubiquitous protein is still puzzling. Our previous work using the 1C11 neuronal model, provided evidence that PrP(C acts as a cell surface receptor. Besides a ubiquitous signaling function of PrP(C, we have described a neuronal specificity pointing to a role of PrP(C in neuronal homeostasis. 1C11 cells, upon appropriate induction, engage into neuronal differentiation programs, giving rise either to serotonergic (1C11(5-HT or noradrenergic (1C11(NE derivatives. METHODOLOGY/PRINCIPAL FINDINGS: The neuronal specificity of PrP(C signaling prompted us to search for PrP(C partners in 1C11-derived bioaminergic neuronal cells. We show here by immunoprecipitation an association of PrP(C with an 80 kDa protein identified by mass spectrometry as the tissue non-specific alkaline phosphatase (TNAP. This interaction occurs in lipid rafts and is restricted to 1C11-derived neuronal progenies. Our data indicate that TNAP is implemented during the differentiation programs of 1C11(5-HT and 1C11(NE cells and is active at their cell surface. Noteworthy, TNAP may contribute to the regulation of serotonin or catecholamine synthesis in 1C11(5-HT and 1C11(NE bioaminergic cells by controlling pyridoxal phosphate levels. Finally, TNAP activity is shown to modulate the phosphorylation status of laminin and thereby its interaction with PrP. CONCLUSION/SIGNIFICANCE: The identification of a novel PrP(C partner in lipid rafts of neuronal cells favors the idea of a role of PrP in multiple functions. Because PrP(C and laminin functionally interact to support neuronal differentiation and memory consolidation, our findings introduce TNAP as a functional protagonist in the PrP(C-laminin interplay. The partnership between TNAP and PrP(C in neuronal cells may

  16. The chemical composition of synthetic bone substitutes influences tissue reactions in vivo: histological and histomorphometrical analysis of the cellular inflammatory response to hydroxyapatite, beta-tricalcium phosphate and biphasic calcium phosphate ceramics

    Ghanaati, Shahram; Barbeck, Mike; Hilbig, Ulrike; Rausch, Vera; Unger, Ronald E; Kirkpatrick, Charles James; Detsch, Rainer; Ziegler, Guenter; Deisinger, Ulrike; Sader, Robert

    2012-01-01

    Bone substitute material properties such as granule size, macroporosity, microporosity and shape have been shown to influence the cellular inflammatory response to a bone substitute material. Keeping these parameters constant, the present study analyzed the in vivo tissue reaction to three bone substitute materials (granules) with different chemical compositions (hydroxyapatite (HA), beta-tricalcium phosphate (TCP) and a mixture of both with a HA/TCP ratio of 60/40 wt%). Using a subcutaneous implantation model in Wistar rats for up to 30 days, tissue reactions, including the induction of multinucleated giant cells and the extent of implantation bed vascularization, were assessed using histological and histomorphometrical analyses. The results showed that the chemical composition of the bone substitute material significantly influenced the cellular response. When compared to HA, TCP attracted significantly greater multinucleated giant cell formations within the implantation bed. Furthermore, the vascularization of the implantation bed of TCP was significantly higher than that of HA implantation beds. The biphasic bone substitute group combined the properties of both groups. Within the first 15 days, high giant cell formation and vascularization rates were observed, which were comparable to the TCP-group. However, after 15 days, the tissue reaction, i.e. the extent of multinucleated giant cell formation and vascularization, was comparable to the HA-group. In conclusion, the combination of both compounds HA and TCP may be a useful combination for generating a scaffold for rapid vascularization and integration during the early time points after implantation and for setting up a relatively slow degradation. Both of these factors are necessary for successful bone tissue regeneration.

  17. Three-dimensional immersive virtual reality for studying cellular compartments in 3D models from EM preparations of neural tissues

    Cali, Corrado; Baghabrah, Jumana; Boges, Daniya; Holst, Glendon; Kreshuk, Anna; Hamprecht, Fred A.; Srinivasan, Madhusudhanan; Lehvä slaiho, Heikki; Magistretti, Pierre J.

    2015-01-01

    Advances for application of electron microscopy to serial imaging are opening doors to new ways of analyzing cellular structure. New and improved algorithms and workflows for manual and semiautomated segmentation allow to observe the spatial

  18. Laser-induced damage in biological tissue: Role of complex and dynamic optical properties of the medium

    Ahmed, Elharith M.

    Since its invention in the early 1960's, the laser has been used as a tool for surgical, therapeutic, and diagnostic purposes. To achieve maximum effectiveness with the greatest margin of safety it is important to understand the mechanisms of light propagation through tissue and how that light affects living cells. Lasers with novel output characteristics for medical and military applications are too often implemented prior to proper evaluation with respect to tissue optical properties and human safety. Therefore, advances in computational models that describe light propagation and the cellular responses to laser exposure, without the use of animal models, are of considerable interest. Here, a physics-based laser-tissue interaction model was developed to predict the spatial and temporal temperature and pressure rise during laser exposure to biological tissues. Our new model also takes into account the dynamic nature of tissue optical properties and their impact on the induced temperature and pressure profiles. The laser-induced retinal damage is attributed to the formation of microbubbles formed around melanosomes in the retinal pigment epithelium (RPE) and the damage mechanism is assumed to be photo-thermal. Selective absorption by melanin creates these bubbles that expand and collapse around melanosomes, destroying cell membranes and killing cells. The Finite Element (FE) approach taken provides suitable ground for modeling localized pigment absorption which leads to a non-uniform temperature distribution within pigmented cells following laser pulse exposure. These hot-spots are sources for localized thermo-elastic stresses which lead to rapid localized expansions that manifest themselves as microbubbles and lead to microcavitations. Model predictions for the interaction of lasers at wavelengths of 193, 694, 532, 590, 1314, 1540, 2000, and 2940 nm with biological tissues were generated and comparisons were made with available experimental data for the retina

  19. Influence of tissue- and cell-scale extracellular matrix distribution on the mechanical properties of tissue-engineered cartilage

    Khoshgoftar, M.; Wilson, W.; Ito, K.; Donkelaar, C.C. van

    2013-01-01

    The insufficient load-bearing capacity of today's tissue- engineered (TE) cartilage limits its clinical application. Generally, cartilage TE studies aim to increase the extracellular matrix (ECM) content, as this is thought to determine the load-bearing properties of the cartilage. However, there

  20. Influence of tissue- and cell-scale extracellular matrix distribution on the mechanical properties of tissue engineered cartilage

    Khoshgoftar, M.; Wilson, W.; Ito, K.; Donkelaar, van C.C.

    2013-01-01

    The insufficient load-bearing capacity of today’s tissue- engineered (TE) cartilage limits its clinical application. Generally, cartilage TE studies aim to increase the extracellular matrix (ECM) content, as this is thought to determine the load-bearing properties of the cartilage. However, there

  1. Viscoelastic properties of bovine orbital connective tissue and fat: constitutive models.

    Yoo, Lawrence; Gupta, Vijay; Lee, Choongyeop; Kavehpore, Pirouz; Demer, Joseph L

    2011-12-01

    Reported mechanical properties of orbital connective tissue and fat have been too sparse to model strain-stress relationships underlying biomechanical interactions in strabismus. We performed rheological tests to develop a multi-mode upper convected Maxwell (UCM) model of these tissues under shear loading. From 20 fresh bovine orbits, 30 samples of connective tissue were taken from rectus pulley regions and 30 samples of fatty tissues from the posterior orbit. Additional samples were defatted to determine connective tissue weight proportion, which was verified histologically. Mechanical testing in shear employed a triborheometer to perform: strain sweeps at 0.5-2.0 Hz; shear stress relaxation with 1% strain; viscometry at 0.01-0.5 s(-1) strain rate; and shear oscillation at 1% strain. Average connective tissue weight proportion was 98% for predominantly connective tissue and 76% for fatty tissue. Connective tissue specimens reached a long-term relaxation modulus of 668 Pa after 1,500 s, while corresponding values for fatty tissue specimens were 290 Pa and 1,100 s. Shear stress magnitude for connective tissue exceeded that of fatty tissue by five-fold. Based on these data, we developed a multi-mode UCM model with variable viscosities and time constants, and a damped hyperelastic response that accurately described measured properties of both connective and fatty tissues. Model parameters differed significantly between the two tissues. Viscoelastic properties of predominantly connective orbital tissues under shear loading differ markedly from properties of orbital fat, but both are accurately reflected using UCM models. These viscoelastic models will facilitate realistic global modeling of EOM behavior in binocular alignment and strabismus.

  2. Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS hybrid composite for bone tissue engineering applications

    Ain, Qurat Ul [Department of Materials Engineering, School of Chemical and Materials Engineering, National University of Sciences and Technology, H-12, Islamabad (Pakistan); Khan, Ahmad Nawaz, E-mail: ahmad.nawaz@scme.nust.edu.pk [Department of Materials Engineering, School of Chemical and Materials Engineering, National University of Sciences and Technology, H-12, Islamabad (Pakistan); Nabavinia, Mahboubeh [Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA (United States); Mujahid, Mohammad [Department of Materials Engineering, School of Chemical and Materials Engineering, National University of Sciences and Technology, H-12, Islamabad (Pakistan)

    2017-06-01

    The bioactivity and mechanical properties of hybrid composites of hydroxyapatite (HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are investigated, first time, for regeneration and repair of the bone tissues. HA is synthesized to obtain the spherically shaped nanoparticles in the size range of 60 ± 20 nm. Various concentrations of HA ranging from 1 to 30 wt% are dispersed in TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron microscope shows the uniform dispersion of HA ≤ 10 wt% in TOPAS and at higher concentrations > 10 wt%, agglomeration occurs in the hybrid composites. Tunable mechanical properties are achieved as the compressive modulus and strength are increased around 140% from 6.4 to 15.3 MPa and 185% from 0.26 to 0.74 MPa, respectively. Such increase in the mechanical properties of TOPAS is attributed to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing to better dispersion and interfacial interactions. In comparison to neat TOPAS, hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation significantly. The cell density and proliferation of TOPAS/HA hybrid composites is enhanced 9 and 3 folds, respectively, after 1 day culturing in preosteoblasts cells. Moreover, the morphology of cells changed from spherical to flattened spread morphology demonstrating clearly the migration of the cells for the formation of interconnected cellular network. Additionally, very few dead cells are found in hybrid composites showing their cytocompatibility. Overall, the hybrid composites of TOPAS/HA exhibited superior strength and stiffness along with enhanced cytocompatibility for bone tissue engineering applications. - Highlights: • TOPAS/HA hybrid composites exhibited enhanced mechanical properties owing to better dispersion and interaction of HA. • Without affecting the degradation rate, the

  3. Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS hybrid composite for bone tissue engineering applications

    Ain, Qurat Ul; Khan, Ahmad Nawaz; Nabavinia, Mahboubeh; Mujahid, Mohammad

    2017-01-01

    The bioactivity and mechanical properties of hybrid composites of hydroxyapatite (HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are investigated, first time, for regeneration and repair of the bone tissues. HA is synthesized to obtain the spherically shaped nanoparticles in the size range of 60 ± 20 nm. Various concentrations of HA ranging from 1 to 30 wt% are dispersed in TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron microscope shows the uniform dispersion of HA ≤ 10 wt% in TOPAS and at higher concentrations > 10 wt%, agglomeration occurs in the hybrid composites. Tunable mechanical properties are achieved as the compressive modulus and strength are increased around 140% from 6.4 to 15.3 MPa and 185% from 0.26 to 0.74 MPa, respectively. Such increase in the mechanical properties of TOPAS is attributed to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing to better dispersion and interfacial interactions. In comparison to neat TOPAS, hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation significantly. The cell density and proliferation of TOPAS/HA hybrid composites is enhanced 9 and 3 folds, respectively, after 1 day culturing in preosteoblasts cells. Moreover, the morphology of cells changed from spherical to flattened spread morphology demonstrating clearly the migration of the cells for the formation of interconnected cellular network. Additionally, very few dead cells are found in hybrid composites showing their cytocompatibility. Overall, the hybrid composites of TOPAS/HA exhibited superior strength and stiffness along with enhanced cytocompatibility for bone tissue engineering applications. - Highlights: • TOPAS/HA hybrid composites exhibited enhanced mechanical properties owing to better dispersion and interaction of HA. • Without affecting the degradation rate, the

  4. Tissue-Level Mechanical Properties of Bone Contributing to Fracture Risk.

    Nyman, Jeffry S; Granke, Mathilde; Singleton, Robert C; Pharr, George M

    2016-08-01

    Tissue-level mechanical properties characterize mechanical behavior independently of microscopic porosity. Specifically, quasi-static nanoindentation provides measurements of modulus (stiffness) and hardness (resistance to yielding) of tissue at the length scale of the lamella, while dynamic nanoindentation assesses time-dependent behavior in the form of storage modulus (stiffness), loss modulus (dampening), and loss factor (ratio of the two). While these properties are useful in establishing how a gene, signaling pathway, or disease of interest affects bone tissue, they generally do not vary with aging after skeletal maturation or with osteoporosis. Heterogeneity in tissue-level mechanical properties or in compositional properties may contribute to fracture risk, but a consensus on whether the contribution is negative or positive has not emerged. In vivo indentation of bone tissue is now possible, and the mechanical resistance to microindentation has the potential for improving fracture risk assessment, though determinants are currently unknown.

  5. Electromagnetic Properties of Tissue in the Optical Region

    Yaws, K. M; Mixon, D. G; Roach, W. P

    2007-01-01

    .... Currently, voids exist in frequency specific electromagnetic properties such as the complex dielectric permittivity and conductivity necessary to define refractive index and attenuation values...

  6. Isolation and cellular properties of mesenchymal cells derived from the decidua of human term placenta.

    Kanematsu, Daisuke; Shofuda, Tomoko; Yamamoto, Atsuyo; Ban, Chiaki; Ueda, Takafumi; Yamasaki, Mami; Kanemura, Yonehiro

    2011-09-01

    The clinical promise of cell-based therapies is generally recognized, and has driven an intense search for good cell sources. In this study, we isolated plastic-adherent cells from human term decidua vera, called decidua-derived-mesenchymal cells (DMCs), and compared their properties with those of bone marrow-derived-mesenchymal stem cells (BM-MSCs). The DMCs strongly expressed the mesenchymal cell marker vimentin, but not cytokeratin 19 or HLA-G, and had a high proliferative potential. That is, they exhibited a typical fibroblast-like morphology for over 30 population doublings. Cells phenotypically identical to the DMCs were identified in the decidua vera, and genotyping confirmed that the DMCs were derived from the maternal components of the fetal adnexa. Flow cytometry analysis showed that the expression pattern of CD antigens on the DMCs was almost identical to that on BM-MSCs, but some DMCs expressed the CD45 antigen, and over 50% of them also expressed anti-fibroblast antigen. In vitro, the DMCs showed good differentiation into chondrocytes and moderate differentiation into adipocytes, but scant evidence of osteogenesis, compared with the BM-MSCs. Gene expression analysis showed that, compared with BM-MSCs, the DMCs expressed higher levels of TWIST2 and RUNX2 (which are associated with early mesenchymal development and/or proliferative capacity), several matrix metalloproteinases (MMP1, 3, 10, and 12), and cytokines (BMP2 and TGFB2), and lower levels of MSX2, interleukin 26, and HGF. Although DMCs did not show the full multipotency of BM-MSCs, their higher proliferative ability indicates that their cultivation would require less maintenance. Furthermore, the use of DMCs avoids the ethical concerns associated with the use of embryonic tissues, because they are derived from the maternal portion of the placenta, which is otherwise discarded. Thus, the unique properties of DMCs give them several advantages for clinical use, making them an interesting and

  7. Cellular localization of peptide hydrolases in chicken embryo tissues and influence of gamma irradiation on their activity

    Khristov, D; Marinopolski, G

    1975-01-01

    Studied was the influence of chicken embryo irradiation at 600 R and 1000 R gamma rays on the activity of tissue peptide hydrolases in mitochondrial-lysosomal, microsomal and supernatant (cell hyaloplasm) cell fractions. The investigation was performed 50 to 168 hours post irradiation. The wole tissue (of the whole embryo) was examined following irradiation of 4-day-old embryos whose liver, muscle and brain tissues were post irradiation examined on day 12 and 16 of incubation. Prior to treatment, the tissues were threfold rinsed with sucrose solution to eliminate proeinase inhibitors. Lysosome membranes were destroyed by adding 0.5 % desoxycholate. It was found that: Peptide hydrolase activity of mitochondrial-lysosomal cell fractions of tissues of whole 6-day chicken embryos is 4-5 times as high as that of cell hyaloplasm. Peptide hydrolase activity of mitochondrial-lysosomal fractions of liver tissues decreases on day 18 and 19 post incubation, while the same fraction of muscle and brain tissues shows high activity. Peptide hydrolase activity of microsomal fraction and of cell hyaloplasm rises during embryonal development and exceeds the activity of liver tissue mitochondrial fraction. Peptide hydrolase activity of mitochondrial-lysosomal fraction of tissue of whole 6-day-old embryos 50 hours post irradiation is higher than the activity of non-irradiated embryos. Later the activity of this fraction diminishes and on the 168 hr post irradiation it drops below the normal. Microsomal fraction and cell hyaloplasm activity likewise show deviation from the norm. Peptide hydrolase activity of mitochondrial-lysosomal fraction of liver, muscle and brain tissue of 14 and 18-day-old embryos is higher than the control 50 hours post irradiation and then declines. The activity of mitochondrial-lysosomal fraction of embryo brain tissue changes most strikingly on irradiation, while other brain cell fractions change less compared with liver and muscle fractions.

  8. Cellular localization of peptide hydrolases in chicken embryo tissues and influence of gamma irradiation on their activity

    Khristov, D.; Marinopolski, G.

    1975-01-01

    Studied was the influence of chicken embryo irradiation at 600 R and 1000 R gamma rays on the activity of tissue peptide hydrolases in mitochondrial-lysosomal, microsomal and supernatant (cell hyaloplasm) cell fractions. The investigation was performed 50 to 168 hours post irradiation. The wole tissue (of the whole embryo) was examined following irradiation of 4-day-old embryos whose liver, muscle and brain tissues were post irradiation examined on day 12 and 16 of incubation. Prior to treatment, the tissues were threfold rinsed with sucrose solution to eliminate proeinase inhibitors. Lysosome membranes were destroyed by adding 0.5 % desoxycholate. It was found that: Peptide hydrolase activity of mitochondrial-lysosomal cell fractions of tissues of whole 6-day chicken embryos is 4-5 times as high as that of cell hyaloplasm. Peptide hydrolase activity of mitochondrial-lysosomal fractions of liver tissues decreases on day 18 and 19 post incubation, while the same fraction of muscle and brain tissues shows high activity. Peptide hydrolase activity of microsomal fraction and of cell hyaloplasm rises during embryonal development and exceeds the activity of liver tissue mitochondrial fraction. Peptide hydrolase activity of mitochondrial-lysosomal fraction of tissue of whole 6-day-old embryos 50 hours post irradiation is higher than the activity of non-irradiated embryos. Later the activity of this fraction diminishes and on the 168 hr post irradiation it drops below the normal. Microsomal fraction and cell hyaloplasm activity likewise show deviation from the norm. Peptide hydrolase activity of mitochondrial-lysosomal fraction of liver, muscle and brain tissue of 14 and 18-day-old embryos is higher than the control 50 hours post irradiation and then declines. The activity of mitochondrial-lysosomal fraction of embryo brain tissue changes most strikingly on irradiation, while other brain cell fractions change less compared with liver and muscle fractions

  9. Sensitivity of tissue differentiation and bone healing predictions to tissue properties

    Isaksson, H.E.; Donkelaar, van C.C.; Ito, K.

    2009-01-01

    Computational models are employed as tools to investigate possible mechano-regulation pathways for tissue differentiation and bone healing. However, current models do not account for the uncertainty in input parameters, and often include assumptions about parameter values that are not yet

  10. Light scattering properties of bovine muscle tissue in vitro, a comparison of methods

    Zijp, J.R.; ten Bosch, JJ; Benaron, DA; Chance, B; Ferrari, M; Kohl, M

    1998-01-01

    We measured the light scattering properties of muscular tissue using several methods, and compared the obtained results. Calculation of the extinction coefficient by using collimated transmission measurements and applying Beer's law is not appropriate. Probably surface roughness of the sample

  11. Study of the optical properties of solid tissue phantoms using single and double integrating sphere systems

    Monem, S

    2015-12-01

    Full Text Available light propagation mechanisms inside the tissues. In this work, two calibration models based on measurements adopting integrating sphere systems have been used to determine the optical properties of the studied solid phantoms. Integrating sphere...

  12. The role of an effective isotropic tissue modulus in the elastic properties of cancellous bone

    Kabel, J.; Rietbergen, van B.; Dalstra, M.; Odgaard, A.; Huiskes, H.W.J.

    1999-01-01

    Conceptually, the elastic characteristics of cancellous bone could be predicted directly from the trabecular morphology-or architecture-and by the elastic properties of the tissue itself. Although hardly any experimental evidence exists, it is often implicitly assumed that tissue anisotropy has a

  13. Polymer structure-property requirements for stereolithographic 3D printing of soft tissue engineering scaffolds.

    Mondschein, Ryan J; Kanitkar, Akanksha; Williams, Christopher B; Verbridge, Scott S; Long, Timothy E

    2017-09-01

    This review highlights the synthesis, properties, and advanced applications of synthetic and natural polymers 3D printed using stereolithography for soft tissue engineering applications. Soft tissue scaffolds are of great interest due to the number of musculoskeletal, cardiovascular, and connective tissue injuries and replacements humans face each year. Accurately replacing or repairing these tissues is challenging due to the variation in size, shape, and strength of different types of soft tissue. With advancing processing techniques such as stereolithography, control of scaffold resolution down to the μm scale is achievable along with the ability to customize each fabricated scaffold to match the targeted replacement tissue. Matching the advanced manufacturing technique to polymer properties as well as maintaining the proper chemical, biological, and mechanical properties for tissue replacement is extremely challenging. This review discusses the design of polymers with tailored structure, architecture, and functionality for stereolithography, while maintaining chemical, biological, and mechanical properties to mimic a broad range of soft tissue types. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Reliability of in vivo measurements of the dielectric properties of anisotropic tissue: a simulative study

    Huo Xuyang; Shi Xuetao; You Fusheng; Fu Feng; Liu Ruigang; Tang Chi; Dong Xiuzhen; Lu Qiang

    2013-01-01

    A simulative study was performed to measure the dielectric properties of anisotropic tissue using several in vivo and in vitro probes. COMSOL Multiphysics was selected to carry out the simulation. Five traditional probes and a newly designed probe were used in this study. One of these probes was an in vitro measurement probe and the other five were in vivo. The simulations were performed in terms of the minimal tissue volume for in vivo measurements, the calibration of a probe constant, the measurement performed on isotropic tissue and the measurement performed on anisotropic tissue. Results showed that the in vitro probe can be used to measure the in-cell dielectric properties of isotropic and anisotropic tissues. When measured with the five in vivo probes, the dielectric properties of isotropic tissue were all measured accurately. For the measurements performed on anisotropic tissue, large errors were observed when the four traditional in vivo probes were used, but only a small error was observed when the new in vivo probe was used. This newly designed five-electrode in vivo probe may indicate the dielectric properties of anisotropic tissue more accurately than these four traditional in vivo probes. (paper)

  15. How preconditioning affects the measurement of poro-viscoelastic mechanical properties in biological tissues

    Hosseini, S.M.; Wilson, W.; Ito, K.; Donkelaar, van C.C.

    2014-01-01

    It is known that initial loading curves of soft biological tissues are substantially different from subsequent loadings. The later loading curves are generally used for assessing the mechanical properties of a tissue, and the first loading cycles, referred to as preconditioning, are omitted.

  16. Role of differential physical properties in the collective mechanics and dynamics of tissues

    Das, Moumita

    Living cells and tissues are highly mechanically sensitive and active. Mechanical stimuli influence the shape, motility, and functions of cells, modulate the behavior of tissues, and play a key role in several diseases. In this talk I will discuss how collective biophysical properties of tissues emerge from the interplay between differential mechanical properties and statistical physics of underlying components, focusing on two complementary tissue types whose properties are primarily determined by (1) the extracellular matrix (ECM), and (2) individual and collective cell properties. I will start with the structure-mechanics-function relationships in articular cartilage (AC), a soft tissue that has very few cells, and its mechanical response is primarily due to its ECM. AC is a remarkable tissue: it can support loads exceeding ten times our body weight and bear 60+ years of daily mechanical loading despite having minimal regenerative capacity. I will discuss the biophysical principles underlying this exceptional mechanical response using the framework of rigidity percolation theory, and compare our predictions with experiments done by our collaborators. Next I will discuss ongoing theoretical work on how the differences in cell mechanics, motility, adhesion, and proliferation in a co-culture of breast cancer cells and healthy breast epithelial cells may modulate experimentally observed differential migration and segregation. Our results may provide insights into the mechanobiology of tissues with cell populations with different physical properties present together such as during the formation of embryos or the initiation of tumors. This work was partially supported by a Cottrell College Science Award.

  17. Variation in tissue outcome of ovine and human engineered heart valve constructs : relevance for tissue engineering

    Geemen, van D.; Driessen - Mol, A.; Grootzwagers, L.G.M.; Soekhradj - Soechit, R.S.; Riem Vis, P.W.; Baaijens, F.P.T.; Bouten, C.V.C.

    AIM: Clinical application of tissue engineered heart valves requires precise control of the tissue culture process to predict tissue composition and mechanical properties prior to implantation, and to understand the variation in tissue outcome. To this end we investigated cellular phenotype and

  18. Osteochondral Biopsy Analysis Demonstrates That BST-CarGel Treatment Improves Structural and Cellular Characteristics of Cartilage Repair Tissue Compared With Microfracture

    Méthot, Stéphane; Changoor, Adele; Tran-Khanh, Nicolas; Hoemann, Caroline D.; Stanish, William D.; Restrepo, Alberto; Shive, Matthew S.; Buschmann, Michael D.

    2016-01-01

    Objective The efficacy and safety of BST-CarGel, a chitosan-based medical device for cartilage repair, was compared with microfracture alone at 1 year during a multicenter randomized controlled trial (RCT) in the knee. The quality of repair tissue of osteochondral biopsies collected from a subset of patients was compared using blinded histological assessments. Methods The international RCT evaluated repair tissue quantity and quality by 3-dimensional quantitative magnetic resonance imaging as co-primary endpoints at 12 months. At an average of 13 months posttreatment, 21/41 BST-CarGel and 17/39 microfracture patients underwent elective second look arthroscopies as a tertiary endpoint, during which ICRS (International Cartilage Repair Society) macroscopic scoring was carried out, and osteochondral biopsies were collected. Stained histological sections were evaluated by blinded readers using ICRS I and II histological scoring systems. Collagen organization was evaluated using a polarized light microscopy score. Results BST-CarGel treatment resulted in significantly better ICRS macroscopic scores (P = 0.0002) compared with microfracture alone, indicating better filling, integration, and tissue appearance. Histologically, BST-CarGel resulted in a significant improvement of structural parameters—Surface Architecture (P = 0.007) and Surface/Superficial Assessment (P = 0.042)—as well as cellular parameters—Cell Viability (P = 0.006) and Cell Distribution (P = 0.032). No histological parameters were significantly better for the microfracture group. BST-CarGel treatment also resulted in a more organized repair tissue with collagen stratification more similar to native hyaline cartilage, as measured by polarized light microscopy scoring (P = 0.0003). Conclusion Multiple and independent analyses in this biopsy substudy demonstrated that BST-CarGel treatment results in improved structural and cellular characteristics of repair tissue at 1 year posttreatment compared with

  19. Correlation between the dielectric properties and biological activities of human ex vivo hepatic tissue

    Wang, Hang; You, Fusheng; Fu, Feng; Dong, Xiuzhen; Shi, Xuetao; He, Yong; Yang, Min; Yan, Qingguo

    2015-01-01

    Dielectric properties are vital biophysical features of biological tissues, and biological activity is an index to ascertain the active state of tissues. This study investigated the potential correlation between the dielectric properties and biological activities of human hepatic tissue with prolonged ex vivo time through correlation and regression analyses. The dielectric properties of 26 cases of normal human hepatic tissue at 10 Hz to 100 MHz were measured from 15 min after isolation to 24 h at 37 °C with 90% humidity. Cell morphologies, including nucleus area (NA) and alteration rate of intercellular area (ICAR), were analyzed as indicators of biological activities. Conductivity, complex resistivity, and NA exhibited opposing changes 1 h after isolation. Relative permittivity and ex vivo time were not closely correlated (p > 0.05). The dielectric properties measured at low frequencies (i.e. <1 MHz) were more sensitive than those measured at high frequencies in reflecting the biological activity of ex vivo tissue. Highly significant correlations were found between conductivity, resistivity and the ex vivo time (p < 0.05) as well as conductivity and the cell morphology (p < 0.05). The findings indicated that establishing the correlation between the dielectric properties and biological activities of human hepatic tissue is of great significance for promoting the role of dielectric properties in biological science, particularly in human biology. (paper)

  20. Validity of the Cauchy-Born rule applied to discrete cellular-scale models of biological tissues

    Davit, Y.; Osborne, J. M.; Byrne, H. M.; Gavaghan, D.; Pitt-Francis, J.

    2013-01-01

    The development of new models of biological tissues that consider cells in a discrete manner is becoming increasingly popular as an alternative to continuum methods based on partial differential equations, although formal relationships between

  1. Viscoelastic Properties of Dental Pulp Tissue and Ramifications on Biomaterial Development for Pulp Regeneration.

    Erisken, Cevat; Kalyon, Dilhan M; Zhou, Jian; Kim, Sahng G; Mao, Jeremy J

    2015-10-01

    A critical step in biomaterial selection effort is the determination of material as well as the biological properties of the target tissue. Previously, the selection of biomaterials and carriers for dental pulp regeneration has been solely based on empirical experience. In this study, first, the linear viscoelastic material functions and compressive properties of miniature pig dental pulp were characterized using small-amplitude oscillatory shear and uniaxial compression at a constant rate. They were then compared with the properties of hydrogels (ie, agarose, alginate, and collagen) that are widely used in tissue regeneration. The comparisons of the linear viscoelastic material functions of the native pulp tissue with those of the 3 hydrogels revealed the gel-like behavior of the pulp tissue over a relatively large range of time scales (ie, over the frequency range of 0.1-100 rps). At the constant gelation agent concentration of 2%, the dynamic properties (ie, storage and loss moduli and the tanδ) of the collagen-based gel approached those of the native tissue. Under uniaxial compression, the peak normal stresses and compressive moduli of the agarose gel were similar to those of the native tissue, whereas alginate and collagen exhibited significantly lower compressive properties. The linear viscoelastic and uniaxial compressive properties of the dental pulp tissue reported here should enable the more appropriate selection of biogels for dental pulp regeneration via the better tailoring of gelation agents and their concentrations to better mimic the dynamic and compressive properties of native pulp tissue. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  2. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.

    Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor; Wood, Tammara A; Christmann, Romy B; Farber, Harrison W; Lafyatis, Robert A; Denton, Christopher P; Hinchcliff, Monique E; Pioli, Patricia A; Mahoney, J Matthew; Whitfield, Michael L

    2017-03-23

    Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune

  3. Fluorescence spectral properties of stomach tissues with pathology

    Giraev, K. M.; Ashurbekov, N. A.; Lahina, M. A.

    2012-05-01

    Steady-state fluorescence and diffuse reflection spectra are measured for in vivo normal and pathological (chronic atrophic and ulcerating defects, malignant neoplasms) stomach mucous lining tissues. The degree of distortion of the fluorescence spectra is estimated taking light scattering and absorption into account. A combination of Gauss and Lorentz functions is used to decompose the fluorescence spectra. Potential groups of fluorophores are determined and indices are introduced to characterize the dynamics of their contributions to the resultant spectra as pathologies develop. Reabsorption is found to quench the fluorescence of structural proteins by as much as a factor of 3, while scattering of the light can increase the fluorescence intensity of flavin and prophyrin groups by as much as a factor of 2.

  4. Phenolsulphotransferase in human tissue: radiochemical enzymatic assay and biochemical properties

    Anderson, R.J.; Weinshilboum, R.M.

    1980-01-01

    Phenolsulphotransferase (EC 2.8.2.1) (PST) is an important catecholamine and drug metabolizing enzyme. Optimal conditions have been determined for the accurate measurement of PST activity in the human platelet, human renal cortex, and human jejunum with a radiochemical microassay. 3-Methoxy-4-hydroxyphenylglycol (MHPG) and 35 S-3'-phosphoadenosine-5'-phosphosulfate ( 35 S-PAPS) were the substrates for the reaction. The apparent Michaelis-Menten (Ksub(m)) values for MHPG with platelet, renal cortex, and jejunum were 1.09, 0.46 and 1.16 mmol/l, respectively. Apparent Ksub(m) values for PAPS in the same tissues were 0.14, 0.13 and 0.21 μmol/l. The pH optimum of the reacton in all three tissues was approximately 6.2-6.8 with three different buffer systems. The coefficients of variation for the assay of platelet, renal cortex, and jejunal activities were 6.2%, 3.4% and 4.4%, respectively. Mean platelet PST activity in blood samples from 75 randomly selected adult subjects was 5.0 +- 1.72 mmol of MHPG sulfate formed per hour per mg of platelet protein (8.3 X 10 -5 +- 2.9 X 10 -5 μmol min -1 mg -1 , mean +- S.D.). There was a 5-fold intersubject variation in platelet PST activity within two standard deviations of the mean value. Experiments in which partially purified human erythrocyte PST was added to platelet, kidney and gut homogenates under these assay conditions provided evidence that endogenous PST inhibitors did not affect the observed enzyme activity. (Auth.)

  5. Physical properties of hydrated tissue determined by surface interferometry of laser-induced thermoelastic deformation

    Dark, Marta L.; Perelman, Lev T.; Itzkan, Irving; Schaffer, Jonathan L.; Feld, Michael S.

    2000-02-01

    Knee meniscus is a hydrated tissue; it is a fibrocartilage of the knee joint composed primarily of water. We present results of interferometric surface monitoring by which we measure physical properties of human knee meniscal cartilage. The physical response of biological tissue to a short laser pulse is primarily thermomechanical. When the pulse is shorter than characteristic times (thermal diffusion time and acoustic relaxation time) stresses build and propagate as acoustic waves in the tissue. The tissue responds to the laser-induced stress by thermoelastic expansion. Solving the thermoelastic wave equation numerically predicts the correct laser-induced expansion. By comparing theory with experimental data, we can obtain the longitudinal speed of sound, the effective optical penetration depth and the Grüneisen coefficient. This study yields information about the laser-tissue interaction and determines properties of the meniscus samples that could be used as diagnostic parameters.

  6. Research on terahertz properties of rat brain tissue sections during dehydration

    Cui, Gangqiang; Liang, Jianfeng; Zhao, Hongwei; Zhao, Xianghui; Chang, Chao

    2018-01-01

    Biological tissue sections are always kept in a system purged with dry nitrogen for the measurement of terahertz spectrum. However, the injected nitrogen will cause dehydration of tissue sections, which will affect the accuracy of spectrum measurement. In this paper, terahertz time-domain spectrometer is used to measure the terahertz spectra of rat brain tissue sections during dehydration. The changes of terahertz properties, including terahertz transmittance, refractive index and extinction coefficient during dehydration are also analyzed. The amplitudes of terahertz time-domain spectra increase gradually during the dehydration process. Besides, the terahertz properties show obvious changes during the dehydration process. All the results indicate that the injected dry nitrogen has a significant effect on the terahertz spectra and properties of tissue sections. This study contributes to further research and application of terahertz technology in biomedical field.

  7. Cellular internalisation kinetics and cytotoxic properties of statistically designed and optimised neo-geometric copper nanocrystals.

    Murugan, Karmani; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2017-09-01

    This study aimed to highlight a statistic design to precisely engineer homogenous geometric copper nanoparticles (CuNPs) for enhanced intracellular drug delivery as a function of geometrical structure. CuNPs with a dual functionality comprising geometric attributes for enhanced cell uptake and exerting cytotoxic activity on proliferating cells were synthesized as a novel drug delivery system. This paper investigated the defined concentrations of two key surfactants used in the reaction to mutually control and manipulate nano-shape and optimisation of the geometric nanosystems. A statistical experimental design comprising a full factorial model served as a refining factor to achieve homogenous geometric nanoparticles using a one-pot method for the systematic optimisation of the geometric CuNPs. Shapes of the nanoparticles were investigated to determine the result of the surfactant variation as the aim of the study and zeta potential was studied to ensure the stability of the system and establish a nanosystem of low aggregation potential. After optimisation of the nano-shapes, extensive cellular internalisation studies were conducted to elucidate the effect of geometric CuNPs on uptake rates, in addition to the vital toxicity assays to further understand the cellular effect of geometric CuNPs as a drug delivery system. In addition to geometry; volume, surface area, orientation to the cell membrane and colloidal stability is also addressed. The outcomes of the study demonstrated the success of homogenous geometric NP formation, in addition to a stable surface charge. The findings of the study can be utilized for the development of a drug delivery system for promoted cellular internalisation and effective drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

    Guertler, Charlotte A; Okamoto, Ruth J; Schmidt, John L; Badachhape, Andrew A; Johnson, Curtis L; Bayly, Philip V

    2018-03-01

    The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Chronic alcohol abuse in men alters bone mechanical properties by affecting both tissue mechanical properties and microarchitectural parameters.

    Cruel, M; Granke, M; Bosser, C; Audran, M; Hoc, T

    2017-06-01

    Alcohol-induced secondary osteoporosis in men has been characterized by higher fracture prevalence and a modification of bone microarchitecture. Chronic alcohol consumption impairs bone cell activity and results in an increased fragility. A few studies highlighted effects of heavy alcohol consumption on some microarchitectural parameters of trabecular bone. But to date and to our knowledge, micro- and macro-mechanical properties of bone of alcoholic subjects have not been investigated. In the present study, mechanical properties and microarchitecture of trabecular bone samples from the iliac crest of alcoholic male patients (n=15) were analyzed and compared to a control group (n=8). Nanoindentation tests were performed to determine the tissue's micromechanical properties, micro-computed tomography was used to measure microarchitectural parameters, and numerical simulations provided the apparent mechanical properties of the samples. Compared to controls, bone tissue from alcoholic patients exhibited an increase of micromechanical properties at tissue scale, a significant decrease of apparent mechanical properties at sample scale, and significant changes in several microarchitectural parameters. In particular, a crucial role of structure model index (SMI) on mechanical properties was identified. 3D microarchitectural parameters are at least as important as bone volume fraction to predict bone fracture risk in the case of alcoholic patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Cellular composition of granulomatous lesions in gut-associated lymphoid tissues of goats during the first year after experimental infection with Mycobacterium avium subsp. paratuberculosis.

    Krüger, C; Köhler, H; Liebler-Tenorio, E M

    2015-01-15

    Mycobacterium avium subsp. paratuberculosis (MAP) causes lesions in naturally and experimentally infected ruminants which greatly differ in severity, cellular composition and number of mycobacteria. Morphologically distinct lesions are already found during the clinically inapparent phase of infection. The complex local host response and number of MAP were characterized at the initial sites of lesions, organized gut-associated lymphoid tissue, in experimentally infected goats. Tissues were collected at 3, 6, 9 and 12 month post-inoculation (mpi) from goat kids that had orally received 10 times 10mg of bacterial wet mass of MAP (JII-1961). The cellular composition of lesions in Peyer's patches in the jejunum and next to the ileocecal valve was evaluated in 21 MAP-inoculated goats, where lesions were compared with unaltered tissue of six control goats. CD68+, CD4+, CD8+, γδ T lymphocytes, B lymphocytes and plasma cells, MHC class II+ and CD25+ cells were demonstrated by immunohistochemistry in serial cryostat sections. At 3 mpi, extensive granulomatous infiltrates predominated, consisting of numerous epitheloid cells admixed with many CD4 and γδ T lymphocytes. Only single MAP were detected. This indicates a strong cellular immune reaction able to control MAP infection. γδ T lymphocytes were markedly increased in this type of lesion which may reflect their important role early in the pathogenesis of paratuberculosis. At 9 and 12 mpi, divergent lesions were observed which may reflect different outcomes of host-pathogen interactions. In five goats, minimal granulomatous lesions were surrounded by extensive lymphoplasmacytic infiltrates and no MAP were detected by immunohistochemistry. This was interpreted as effective host response that was able to eliminate MAP locally. In three goats, decreased numbers of lymphocytes, but extensive granulomatous infiltrates with numerous epitheloid cells containing increased numbers of mycobacteria were seen. This shift of the

  11. A descriptive study to provide evidence of the teratogenic and cellular effects of sibutramine and ephedrine on cardiac- and liver-tissue of chick embryos.

    Oberholzer, Hester Magdalena; Van Der Schoor, Ciska; Taute, Helena; Bester, Megan Jean

    2015-08-01

    Exposure to drugs during pregnancy is a major concern, as some teratogenic compounds can influence normal foetal development. Although the use of drugs during pregnancy should generally be avoided, exposure of the developing foetus to teratogens may occur unknowingly since these compounds may be hidden in products that are being marketed as "all natural." The aim of the current study was to investigate the possible teratogenic and cellular effects of sibutramine-a serotonin-norepinephrine reuptake inhibitor used in the treatment of obesity-on the heart and liver tissue of chick embryos. Ephedrine was used as a positive control. The chick embryo model was chosen because it has been used in studying developmental and experimental biology and teratology with great success. The embryos were exposed to three different concentrations of sibutramine and ephedrine respectively. The results obtained revealed that both compounds exhibited embryotoxicity when compared to the control groups. Liver and heart tissue of the exposed embryos was severely affected by these compounds in a dose-related manner. Morphology similar to that of muscle dystrophy was observed in the heart, where the muscle tissue was infiltrated by adipose and connective tissue. Severe liver steatosis was also noted. A more in-depth investigation into the molecular pathways involved might provide more information on the exact mechanism of toxicity of these products influencing embryonic development. © 2015 Wiley Periodicals, Inc.

  12. Nasal-Associated Lymphoid Tissue Is a Mucosal Inductive Site for Virus-Specific Humoral and Cellular Immune Responses

    Zuercher, A. W.; Coffin, S. E.; Thurnheer, M. CH.; Fundová, Petra; Cebra, J. J.

    2002-01-01

    Roč. 168, - (2002), s. 1796-1803 ISSN 0022-1767 Institutional research plan: CEZ:AV0Z5020903 Keywords : lymphoid tissue * virus-specific * humoral Subject RIV: EE - Microbiology, Virology Impact factor: 7.014, year: 2002

  13. Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications.

    Vedadghavami, Armin; Minooei, Farnaz; Mohammadi, Mohammad Hossein; Khetani, Sultan; Rezaei Kolahchi, Ahmad; Mashayekhan, Shohreh; Sanati-Nezhad, Amir

    2017-10-15

    Hydrogels have been recognized as crucial biomaterials in the field of tissue engineering, regenerative medicine, and drug delivery applications due to their specific characteristics. These biomaterials benefit from retaining a large amount of water, effective mass transfer, similarity to natural tissues and the ability to form different shapes. However, having relatively poor mechanical properties is a limiting factor associated with hydrogel biomaterials. Controlling the biomechanical properties of hydrogels is of paramount importance. In this work, firstly, mechanical characteristics of hydrogels and methods employed for characterizing these properties are explored. Subsequently, the most common approaches used for tuning mechanical properties of hydrogels including but are not limited to, interpenetrating polymer networks, nanocomposites, self-assembly techniques, and co-polymerization are discussed. The performance of different techniques used for tuning biomechanical properties of hydrogels is further compared. Such techniques involve lithography techniques for replication of tissues with complex mechanical profiles; microfluidic techniques applicable for generating gradients of mechanical properties in hydrogel biomaterials for engineering complex human tissues like intervertebral discs, osteochondral tissues, blood vessels and skin layers; and electrospinning techniques for synthesis of hybrid hydrogels and highly ordered fibers with tunable mechanical and biological properties. We finally discuss future perspectives and challenges for controlling biomimetic hydrogel materials possessing proper biomechanical properties. Hydrogels biomaterials are essential constituting components of engineered tissues with the applications in regenerative medicine and drug delivery. The mechanical properties of hydrogels play crucial roles in regulating the interactions between cells and extracellular matrix and directing the cells phenotype and genotype. Despite

  14. A systems biology approach reveals that tissue tropism to West Nile virus is regulated by antiviral genes and innate immune cellular processes.

    Mehul S Suthar

    2013-02-01

    -specific antiviral effector gene expression and innate immune cellular processes that control tissue tropism to WNV infection.

  15. Development of an ex vivo cellular model of rheumatoid arthritis: critical role of CD14-positive monocyte/macrophages in the development of pannus tissue.

    Nozaki, Toshiko; Takahashi, Kyoko; Ishii, Osamu; Endo, Sachio; Hioki, Kyoji; Mori, Toshihito; Kikukawa, Tadahiro; Boumpas, Dimitrios T; Ozaki, Shoichi; Yamada, Hidehiro

    2007-09-01

    To establish an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue (ST). Inflammatory cells that infiltrated pannus tissue from patients with rheumatoid arthritis (RA) were collected without enzyme digestion, and designated as ST-derived inflammatory cells. Single-cell suspensions of ST-derived inflammatory cells were cultured in medium alone. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. ST-derived inflammatory cells were transferred into the joints of immunodeficient mice to explore whether these cells could develop pannus. CD14 and CD2 cells were depleted by negative selection. Culture of ST-derived inflammatory cells from 92 of 111 patients with RA resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks. Ex vivo tissue contained fibroblasts, macrophages, T cells, and tartrate-resistant acid phosphatase-positive multinucleated cells. On calcium phosphate-coated slides, ST-derived inflammatory cell cultures showed numerous resorption pits. ST-derived inflammatory cell cultures continuously produced matrix metalloproteinase 9 and proinflammatory cytokines associated with osteoclastogenesis, such as tumor necrosis factor alpha, interleukin-8, and macrophage colony-stimulating factor. More importantly, transferring ST-derived inflammatory cells into the joints of immunodeficient mice resulted in the development of pannus tissue and erosive joint lesions. Both in vitro development and in vivo development of pannus tissue by ST-derived inflammatory cells were inhibited by depleting CD14-positive, but not CD2-positive, cells from ST-derived inflammatory cells. These findings suggest that overgrowth of inflammatory cells from human rheumatoid synovium simulates the development of pannus. This may prove informative in the screening of potential antirheumatic drugs.

  16. Estimating patient-specific soft-tissue properties in a TKA knee.

    Ewing, Joseph A; Kaufman, Michelle K; Hutter, Erin E; Granger, Jeffrey F; Beal, Matthew D; Piazza, Stephen J; Siston, Robert A

    2016-03-01

    Surgical technique is one factor that has been identified as critical to success of total knee arthroplasty. Researchers have shown that computer simulations can aid in determining how decisions in the operating room generally affect post-operative outcomes. However, to use simulations to make clinically relevant predictions about knee forces and motions for a specific total knee patient, patient-specific models are needed. This study introduces a methodology for estimating knee soft-tissue properties of an individual total knee patient. A custom surgical navigation system and stability device were used to measure the force-displacement relationship of the knee. Soft-tissue properties were estimated using a parameter optimization that matched simulated tibiofemoral kinematics with experimental tibiofemoral kinematics. Simulations using optimized ligament properties had an average root mean square error of 3.5° across all tests while simulations using generic ligament properties taken from literature had an average root mean square error of 8.4°. Specimens showed large variability among ligament properties regardless of similarities in prosthetic component alignment and measured knee laxity. These results demonstrate the importance of soft-tissue properties in determining knee stability, and suggest that to make clinically relevant predictions of post-operative knee motions and forces using computer simulations, patient-specific soft-tissue properties are needed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. Properties and cellular effects of particulate matter from direct emissions and ambient sources.

    Jin, Wenjie; Su, Shu; Wang, Bin; Zhu, Xi; Chen, Yilin; Shen, Guofeng; Liu, Junfeng; Cheng, Hefa; Wang, Xilong; Wu, Shuiping; Zeng, Eddy; Xing, Baoshan; Tao, Shu

    2016-10-14

    The pollution of particulate matter (PM) is of great concern in China and many other developing countries. It is generally recognized that the toxicity of PM is source and property dependent. However, the relationship between PM properties and toxicity is still not well understood. In this study, PM samples from direct emissions of wood, straw, coal, diesel combustion, cigarette smoking and ambient air were collected and characterized for their physicochemical properties. Their expression of intracellular reactive oxygen species (ROS) and levels of inflammatory cytokines (i.e., tumor necrosis factor-α (TNF-α)) was measured using a RAW264.7 cell model. Our results demonstrated that the properties of the samples from different origins exhibited remarkable differences. Significant increases in ROS were observed when the cells were exposed to PMs from biomass origins, including wood, straw and cigarettes, while increases in TNF-α were found for all the samples, particularly those from ambient air. The most important factor associated with ROS generation was the presence of water-soluble organic carbon, which was extremely abundant in the samples that directly resulted from biomass combustion. Metals, endotoxins and PM size were the most important properties associated with increases in TNF-α expression levels. The association of the origins of PM particles and physicochemical properties with cytotoxic properties is illustrated using a cluster analysis.

  18. A method for quantifying mechanical properties of tissue following viral infection.

    Vy Lam

    Full Text Available Viral infection and replication involves the reorganization of the actin network within the host cell. Actin plays a central role in the mechanical properties of cells. We have demonstrated a method to quantify changes in mechanical properties of fabricated model three-dimensional (3D connective tissue following viral infection. Using this method, we have characterized the impact of infection by the human herpesvirus, cytomegalovirus (HCMV. HCMV is a member of the herpesvirus family and infects a variety of cell types including fibroblasts. In the body, fibroblasts are necessary for maintaining connective tissue and function by creating mechanical force. Using this 3D connective tissue model, we observed that infection disrupted the cell's ability to generate force and reduced the cumulative contractile force of the tissue. The addition of HCMV viral particles in the absence of both viral gene expression and DNA replication was sufficient to disrupt tissue function. We observed that alterations of the mechanical properties are, in part, due to a disruption of the underlying complex actin microfilament network established by the embedded fibroblasts. Finally, we were able to prevent HCMV-mediated disruption of tissue function by the addition of human immune globulin against HCMV. This study demonstrates a method to quantify the impact of viral infection on mechanical properties which are not evident using conventional cell culture systems.

  19. Mesoporous cellular-structured carbons derived from glucose-fructose syrup and their adsorption properties towards acetaminophen

    Tzvetkov, George; Spassov, Tony; Kaneva, Nina; Tsyntsarski, Boyko

    Here, a series of cellular-structured and predominantly mesoporous carbons were prepared via carbonization of glucose-fructose syrup (GFS) with sulfuric acid and subsequent calcination between 400∘C and 700∘C. Comparative results on the microstructure, chemical and textural properties of the newly produced carbons are presented. Furthermore, their adsorption performance for removal of acetaminophen from water was tested and it was found that the carbon calcined at 700∘C has a maximum adsorption capacity (98.7mgṡg-1) among all samples due to its suitable textural properties (BET surface area of 418m2ṡg-1 and total pore volume of 0.2cm3ṡg-1). This study demonstrates the potential use of GFS as a precursor in the preparation of carbonaceous materials for removal of biologically-active micropollutants from water.

  20. Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties.

    Wheeler, Jason B; Mukherjee, Rupak; Stroud, Robert E; Jones, Jeffrey A; Ikonomidis, John S

    2015-02-25

    Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age. These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  1. Characterization of Mechanical Properties of Tissue Scaffolds by Phase Contrast Imaging and Finite Element Modeling.

    Bawolin, Nahshon K; Dolovich, Allan T; Chen, Daniel X B; Zhang, Chris W J

    2015-08-01

    In tissue engineering, the cell and scaffold approach has shown promise as a treatment to regenerate diseased and/or damaged tissue. In this treatment, an artificial construct (scaffold) is seeded with cells, which organize and proliferate into new tissue. The scaffold itself biodegrades with time, leaving behind only newly formed tissue. The degradation qualities of the scaffold are critical during the treatment period, since the change in the mechanical properties of the scaffold with time can influence cell behavior. To observe in time the scaffold's mechanical properties, a straightforward method is to deform the scaffold and then characterize scaffold deflection accordingly. However, experimentally observing the scaffold deflection is challenging. This paper presents a novel study on characterization of mechanical properties of scaffolds by phase contrast imaging and finite element modeling, which specifically includes scaffold fabrication, scaffold imaging, image analysis, and finite elements (FEs) modeling of the scaffold mechanical properties. The innovation of the work rests on the use of in-line phase contrast X-ray imaging at 20 KeV to characterize tissue scaffold deformation caused by ultrasound radiation forces and the use of the Fourier transform to identify movement. Once deformation has been determined experimentally, it is then compared with the predictions given by the forward solution of a finite element model. A consideration of the number of separate loading conditions necessary to uniquely identify the material properties of transversely isotropic and fully orthotropic scaffolds is also presented, along with the use of an FE as a form of regularization.

  2. Characterizing emergent properties of immunological systems with multi-cellular rule-based computational modeling.

    Chavali, Arvind K; Gianchandani, Erwin P; Tung, Kenneth S; Lawrence, Michael B; Peirce, Shayn M; Papin, Jason A

    2008-12-01

    The immune system is comprised of numerous components that interact with one another to give rise to phenotypic behaviors that are sometimes unexpected. Agent-based modeling (ABM) and cellular automata (CA) belong to a class of discrete mathematical approaches in which autonomous entities detect local information and act over time according to logical rules. The power of this approach lies in the emergence of behavior that arises from interactions between agents, which would otherwise be impossible to know a priori. Recent work exploring the immune system with ABM and CA has revealed novel insights into immunological processes. Here, we summarize these applications to immunology and, particularly, how ABM can help formulate hypotheses that might drive further experimental investigations of disease mechanisms.

  3. Invariant strings and pattern-recognizing properties of one-dimensional cellular automata

    Jen, E.

    1986-01-01

    A cellular automaton is a discrete dynamical system whose evolution is governed by a deterministic rule involving local interactions. It is shown that given an arbitrary string of values and an arbitry neighborhood size (representing the range of interaction), a simple procedure can be used to find the fules of that neighborhood size under which the string is unvarian. The set of nearestneighbor rules for which invariant strings exist is completely specified, as is the set of strings invariant under each such rule. For any automaton rule, an associated ''filtering'' rule is defined for which the only attractors are spatial sequences consisting of concatenations of invariant strings. A result is provided defining the rule of minimum neighborhood size for which an arbitrrily chosen string is the unique invariant string. The applications of filtering rules to pttern recognition problems are discussed

  4. A novel optical microscope for imaging large embryos and tissue volumes with sub-cellular resolution throughout.

    McConnell, Gail; Trägårdh, Johanna; Amor, Rumelo; Dempster, John; Reid, Es; Amos, William Bradshaw

    2016-09-23

    Current optical microscope objectives of low magnification have low numerical aperture and therefore have too little depth resolution and discrimination to perform well in confocal and nonlinear microscopy. This is a serious limitation in important areas, including the phenotypic screening of human genes in transgenic mice by study of embryos undergoing advanced organogenesis. We have built an optical lens system for 3D imaging of objects up to 6 mm wide and 3 mm thick with depth resolution of only a few microns instead of the tens of microns currently attained, allowing sub-cellular detail to be resolved throughout the volume. We present this lens, called the Mesolens, with performance data and images from biological specimens including confocal images of whole fixed and intact fluorescently-stained 12.5-day old mouse embryos.

  5. Cellular uptake of nanoparticles as determined by particle properties, experimental conditions, and cell type.

    Kettler, Katja; Veltman, Karin; van de Meent, Dik; van Wezel, Annemarie; Hendriks, A Jan

    2014-03-01

    The increased application of nanoparticles (NPs) is increasing the risk of their release into the environment. Although many toxicity studies have been conducted, the environmental risk is difficult to estimate, because uptake mechanisms are often not determined in toxicity studies. In the present study, the authors review dominant uptake mechanisms of NPs in cells, as well as the effect of NP properties, experimental conditions, and cell type on NP uptake. Knowledge of NP uptake is crucial for risk assessment and is essential to predict the behavior of NPs based on their physical-chemical properties. Important uptake mechanisms for eukaryotic cells are macropinocytosis, receptor-mediated endocytosis, and phagocytosis in specialized mammalian cells. The studies reviewed demonstrate that uptake into nonphagocytic cells depends strongly on NP size, with an uptake optimum at an NP diameter of approximately 50 nm. Increasing surface charges, either positive or negative, have been shown to increase particle uptake in comparison with uncharged NPs. Another important factor is the degree of (homo-) aggregation. Results regarding shape have been ambiguous. Difficulties in the production of NPs, with 1 property changed at a time, call for a full characterization of NP properties. Only then will it be possible to draw conclusions as to which property affected the uptake. © 2013 SETAC.

  6. Microstructure, Mechanical Properties and Corrosion Behavior of Porous Mg-6 wt.% Zn Scaffolds for Bone Tissue Engineering

    Yan, Yang; Kang, Yijun; Li, Ding; Yu, Kun; Xiao, Tao; Wang, Qiyuan; Deng, Youwen; Fang, Hongjie; Jiang, Dayue; Zhang, Yu

    2018-03-01

    Porous Mg-based scaffolds have been extensively researched as biodegradable implants due to their attractive biological and excellent mechanical properties. In this study, porous Mg-6 wt.% Zn scaffolds were prepared by powder metallurgy using ammonium bicarbonate particles as space-holder particles. The effects of space-holder particle content on the microstructure, mechanical properties and corrosion resistance of the Mg-6 wt.% Zn scaffolds were studied. The mean porosity and pore size of the open-cellular scaffolds were within the range 6.7-52.2% and 32.3-384.2 µm, respectively. Slight oxidation was observed at the grain boundaries and on the pore walls. The Mg-6 wt.% Zn scaffolds were shown to possess mechanical properties comparable with those of natural bone and had variable in vitro degradation rates. Increased content of space-holder particles negatively affected the mechanical behavior and corrosion resistance of the Mg-6 wt.% Zn scaffolds, especially when higher than 20%. These results suggest that porous Mg-6 wt.% Zn scaffolds are promising materials for application in bone tissue engineering.

  7. Tailoring the ligand shell for the control of cellular uptake and optical properties of nanocrystals

    Johannes Ostermann

    2015-01-01

    Full Text Available In this short review, the main challenges in the use of hydrophobic nanoparticles in biomedical application are addressed. It is shown how to overcome the different issues by the use of a polymeric encapsulation system, based on an amphiphilic polyisoprene-block-poly(ethylene glycol diblock copolymer. On the basis of this simple molecule, the development of a versatile and powerful phase transfer strategy is summarized, focusing on the main advantages like the adjustable size, the retained properties, the excellent shielding and the diverse functionalization properties of the encapsulated nanoparticles. Finally, the extraordinary properties of these encapsulated nanoparticles in terms of toxicity and specificity in a broad in vitro test is demonstrated.

  8. Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum.

    Chen, Mao Xiang; Gorman, Shelby A; Benson, Bill; Singh, Kuljit; Hieble, J Paul; Michel, Martin C; Tate, Simon N; Trezise, Derek J

    2004-06-01

    The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in human tissues and their cellular localisation in samples of colon and corpus cavernosum. SK1 mRNA was detected almost exclusively in neuronal tissues. SK2 mRNA distribution was restricted but more widespread than SK1, and was detected in adrenal gland, brain, prostate, bladder, liver and heart. SK3 mRNA was detected in almost every tissue examined. It was highly expressed in brain and in smooth muscle-rich tissues including the clitoris and the corpus cavernosum, and expression in the corpus cavernosum was upregulated up to 5-fold in patients undergoing sex-change operations. IK1 mRNA was present in surface-rich, secretory and inflammatory cell-rich tissues, highest in the trachea, prostate, placenta and salivary glands. In detailed immunohistochemical studies of the colon and the corpus cavernosum, SK1-like immunoreactivity was observed in the enteric neurons. SK3-like immunoreactivity was observed strongly in smooth muscle and vascular endothelium. IK1-like immunoreactivity was mainly observed in inflammatory cells and enteric neurons of the colon, but absent in corpus cavernosum. These distinctive patterns of distribution suggest that these channels are likely to have different biological functions and could be specifically targeted for a number of human diseases, such as irritable bowel syndrome, hypertension and erectile dysfunction.

  9. Physicochemical Properties and Cellular Responses of Strontium-Doped Gypsum Biomaterials

    Pouria, Amir; Bandegani, Hadis; Pourbaghi-Masouleh, Milad; Hesaraki, Saeed; Alizadeh, Masoud

    2012-01-01

    This paper describes some physical, structural, and biological properties of gypsum bioceramics doped with various amounts of strontium ions (0.19–2.23 wt%) and compares these properties with those of a pure gypsum as control. Strontium-doped gypsum (gypsum:Sr) was obtained by mixing calcium sulfate hemihydrate powder and solutions of strontium nitrate followed by washing the specimens with distilled water to remove residual salts. Gypsum was the only phase found in the composition of both pu...

  10. Characterizing the lung tissue mechanical properties using a micromechanical model of alveolar sac

    Karami, Elham; Seify, Behzad; Moghadas, Hadi; Sabsalinejad, Masoomeh; Lee, Ting-Yim; Samani, Abbas

    2017-03-01

    According to statistics, lung disease is among the leading causes of death worldwide. As such, many research groups are developing powerful tools for understanding, diagnosis and treatment of various lung diseases. Recently, biomechanical modeling has emerged as an effective tool for better understanding of human physiology, disease diagnosis and computer assisted medical intervention. Mechanical properties of lung tissue are important requirements for methods developed for lung disease diagnosis and medical intervention. As such, the main objective of this study is to develop an effective tool for estimating the mechanical properties of normal and pathological lung parenchyma tissue based on its microstructure. For this purpose, a micromechanical model of the lung tissue was developed using finite element (FE) method, and the model was demonstrated to have application in estimating the mechanical properties of lung alveolar wall. The proposed model was developed by assembling truncated octahedron tissue units resembling the alveoli. A compression test was simulated using finite element method on the created geometry and the hyper-elastic parameters of the alveoli wall were calculated using reported alveolar wall stress-strain data and an inverse optimization framework. Preliminary results indicate that the proposed model can be potentially used to reconstruct microstructural images of lung tissue using macro-scale tissue response for normal and different pathological conditions. Such images can be used for effective diagnosis of lung diseases such as Chronic Obstructive Pulmonary Disease (COPD).

  11. Studying the distribution of deep Raman spectroscopy signals using liquid tissue phantoms with varying optical properties.

    Vardaki, Martha Z; Gardner, Benjamin; Stone, Nicholas; Matousek, Pavel

    2015-08-07

    In this study we employed large volume liquid tissue phantoms, consisting of a scattering agent (Intralipid), an absorption agent (Indian ink) and a synthesized calcification powder (calcium hydroxyapatite (HAP)) similar to that found in cancerous tissues (e.g. breast and prostate), to simulate human tissues. We studied experimentally the magnitude and origin of Raman signals in a transmission Raman geometry as a function of optical properties of the medium and the location of calcifications within the phantom. The goal was to inform the development of future noninvasive cancer screening applications in vivo. The results provide insight into light propagation and Raman scattering distribution in deep Raman measurements, exploring also the effect of the variation of relative absorbance of laser and Raman photons within the phantoms. Most notably when modeling breast and prostate tissues it follows that maximum signals is obtained from the front and back faces of the tissue with the central region contributing less to the measured spectrum.

  12. From Cell to Tissue Properties-Modeling Skin Electroporation With Pore and Local Transport Region Formation.

    Dermol-Cerne, Janja; Miklavcic, Damijan

    2018-02-01

    Current models of tissue electroporation either describe tissue with its bulk properties or include cell level properties, but model only a few cells of simple shapes in low-volume fractions or are in two dimensions. We constructed a three-dimensional model of realistically shaped cells in realistic volume fractions. By using a 'unit cell' model, the equivalent dielectric properties of whole tissue could be calculated. We calculated the dielectric properties of electroporated skin. We modeled electroporation of single cells by pore formation on keratinocytes and on the papillary dermis which gave dielectric properties of the electroporated epidermis and papillary dermis. During skin electroporation, local transport regions are formed in the stratum corneum. We modeled local transport regions and increase in their radii or density which affected the dielectric properties of the stratum corneum. The final model of skin electroporation accurately describes measured electric current and voltage drop on the skin during electroporation with long low-voltage pulses. The model also accurately describes voltage drop on the skin during electroporation with short high-voltage pulses. However, our results indicate that during application of short high-voltage pulses additional processes may occur which increase the electric current. Our model connects the processes occurring at the level of cell membranes (pore formation), at the level of a skin layer (formation of local transport region in the stratum corneum) with the tissue (skin layers) and even level of organs (skin). Using a similar approach, electroporation of any tissue can be modeled, if the morphology of the tissue is known.

  13. Cellular interaction of a layer-by-layer based drug delivery system depending on material properties and cell types.

    Brueckner, Mandy; Jankuhn, Steffen; Jülke, Eva-Maria; Reibetanz, Uta

    2018-01-01

    Drug delivery systems (DDS) and their interaction with cells are a controversial topic in the development of therapeutic concepts and approaches. On one hand, DDS are very useful for protected and targeted transport of defined dosages of active agents. On the other hand, their physicochemical properties such as material, size, shape, charge, or stiffness have a huge impact on cellular uptake and intracellular processing. Additionally, even identical DDS can undergo a completely diverse interaction with different cell types. However, quite often in in vitro DDS/cell interaction experiments, those aspects are not considered and DDS and cells are randomly chosen. Hence, our investigations provide an insight into layer-by-layer designed microcarriers with modifications of only some of the most important parameters (surface charge, stiffness, and applied microcarrier/cell ratio) and their influence on cellular uptake and viability. We also considered the interaction of these differently equipped DDS with several cell types and investigated professional phagocytes (neutrophil granulocytes; macrophages) as well as non-professional phagocytes (epithelial cells) under comparable conditions. We found that even small modifications such as layer-by-layer (LbL)-microcarriers with positive or negative surface charge, or LbL-microcarriers with solid core or as hollow capsules but equipped with the same surface properties, show significant differences in interaction and viability, and several cell types react very differently to the offered DDS. As a consequence, the properties of the DDS have to be carefully chosen with respect to the addressed cell type with the aim to efficiently transport a desired agent.

  14. Characterization of the mechanical properties of resected porcine organ tissue using optical fiber photoelastic polarimetry.

    Hudnut, Alexa W; Babaei, Behzad; Liu, Sonya; Larson, Brent K; Mumenthaler, Shannon M; Armani, Andrea M

    2017-10-01

    Characterizing the mechanical behavior of living tissue presents an interesting challenge because the elasticity varies by eight orders of magnitude, from 50Pa to 5GPa. In the present work, a non-destructive optical fiber photoelastic polarimetry system is used to analyze the mechanical properties of resected samples from porcine liver, kidney, and pancreas. Using a quasi-linear viscoelastic fit, the elastic modulus values of the different organ systems are determined. They are in agreement with previous work. In addition, a histological assessment of compressed and uncompressed tissues confirms that the tissue is not damaged during testing.

  15. The group A streptococcal collagen-like protein 1, Scl1, mediates biofilm formation by targeting the EDA-containing variant of cellular fibronectin expressed in wounded tissue

    Oliver-Kozup, Heaven; Martin, Karen H.; Schwegler-Berry, Diane; Green, Brett J.; Betts, Courtney; Shinde, Arti V.; Van De Water, Livingston; Lukomski, Slawomir

    2012-01-01

    Summary Wounds are known to serve as portals of entry for group A Streptococcus (GAS). Subsequent tissue colonization is mediated by interactions between GAS surface proteins and host extracellular matrix components. We recently reported that the streptococcal collagen-like protein-1, Scl1, selectively binds the cellular form of fibronectin (cFn) and also contributes to GAS biofilm formation on abiotic surfaces. One structural feature of cFn, which is predominantly expressed in response to tissue injury, is the presence of a spliced variant containing extra domain A (EDA/EIIIA). We now report that GAS biofilm formation is mediated by the Scl1 interaction with EDA-containing cFn. Recombinant Scl1 proteins that bound cFn also bound recombinant EDA within the C-C′ loop region recognized by the α9β1 integrin. The extracellular 2-D matrix derived from human dermal fibroblasts supports GAS adherence and biofilm formation. Altogether, this work identifies and characterizes a novel molecular mechanism by which GAS utilizes Scl1 to specifically target an extracellular matrix component that is predominantly expressed at the site of injury in order to secure host tissue colonization. PMID:23217101

  16. Characterizing the optical properties of human brain tissue with high numerical aperture optical coherence tomography.

    Wang, Hui; Magnain, Caroline; Sakadžić, Sava; Fischl, Bruce; Boas, David A

    2017-12-01

    Quantification of tissue optical properties with optical coherence tomography (OCT) has proven to be useful in evaluating structural characteristics and pathological changes. Previous studies primarily used an exponential model to analyze low numerical aperture (NA) OCT measurements and obtain the total attenuation coefficient for biological tissue. In this study, we develop a systematic method that includes the confocal parameter for modeling the depth profiles of high NA OCT, when the confocal parameter cannot be ignored. This approach enables us to quantify tissue optical properties with higher lateral resolution. The model parameter predictions for the scattering coefficients were tested with calibrated microsphere phantoms. The application of the model to human brain tissue demonstrates that the scattering and back-scattering coefficients each provide unique information, allowing us to differentially identify laminar structures in primary visual cortex and distinguish various nuclei in the midbrain. The combination of the two optical properties greatly enhances the power of OCT to distinguish intricate structures in the human brain beyond what is achievable with measured OCT intensity information alone, and therefore has the potential to enable objective evaluation of normal brain structure as well as pathological conditions in brain diseases. These results represent a promising step for enabling the quantification of tissue optical properties from high NA OCT.

  17. A computational modeling approach for the characterization of mechanical properties of 3D alginate tissue scaffolds.

    Nair, K; Yan, K C; Sun, W

    2008-01-01

    Scaffold guided tissue engineering is an innovative approach wherein cells are seeded onto biocompatible and biodegradable materials to form 3-dimensional (3D) constructs that, when implanted in the body facilitate the regeneration of tissue. Tissue scaffolds act as artificial extracellular matrix providing the environment conducive for tissue growth. Characterization of scaffold properties is necessary to understand better the underlying processes involved in controlling cell behavior and formation of functional tissue. We report a computational modeling approach to characterize mechanical properties of 3D gellike biomaterial, specifically, 3D alginate scaffold encapsulated with cells. Alginate inherent nonlinearity and variations arising from minute changes in its concentration and viscosity make experimental evaluation of its mechanical properties a challenging and time consuming task. We developed an in silico model to determine the stress-strain relationship of alginate based scaffolds from experimental data. In particular, we compared the Ogden hyperelastic model to other hyperelastic material models and determined that this model was the most suitable to characterize the nonlinear behavior of alginate. We further propose a mathematical model that represents the alginate material constants in Ogden model as a function of concentrations and viscosity. This study demonstrates the model capability to predict mechanical properties of 3D alginate scaffolds.

  18. Cellular properties of principal neurons in the rat entorhinal cortex. II. The medial entorhinal cortex

    Canto, C.B.; Witter, M.P.

    2012-01-01

    Principal neurons in different medial entorhinal cortex (MEC) layers show variations in spatial modulation that stabilize between 15 and 30 days postnatally. These in vivo variations are likely due to differences in intrinsic membrane properties and integrative capacities of neurons. The latter

  19. A Comprehensive Review of Punica granatum (Pomegranate) Properties in Toxicological, Pharmacological, Cellular and Molecular Biology Researches

    Rahimi, Hamid Reza; Arastoo, Mohammad; Ostad, Seyed Nasser

    2012-01-01

    Punica granatum (Pg), commonly known as pomegranate (Pg), is a member of the monogeneric family, Punicaceae, and is mainly found in Iran which is considered to be its primary centre of origin. Pg and its chemical components possess various pharmacological and toxicological properties including antioxidant, anti-inflammatory (by inhibiting pro-inflammatory cytokines), anti-cancer and anti-angiogenesis activities. They also show inhibitory effects on invasion/motility, cell cycle, apoptosis, and vital enzymes such as cyclooxygenase (COX), lipooxygenase (LOX), cytochrome P450 (CYP450), phospholipase A2 (PLA2), ornithine decarboxylase (ODC), carbonic anhydrase (CA), 17beta-hydroxysteroid dehydrogenase (17β-HSDs) and serine protease (SP). Furthermore, they can stimulate cell differentiation and possess anti-mutagenic effects. Pg can also interfere with several signaling pathways including PI3K/AKT, mTOR, PI3K, Bcl-X, Bax, Bad, MAPK, ERK1/2, P38, JNK, and caspase. However, the exact mechanisms for its pharmacological and toxicological properties remain to be unclear and need further evaluation. These properties strongly suggest a wide range use of Pg for clinical applications. This review will discuss the areas for which Pg has shown therapeutic properties in different mechanisms. PMID:24250463

  20. Refinement of elastic, poroelastic, and osmotic tissue properties of intervertebral disks to analyze behavior in compression.

    Stokes, Ian A F; Laible, Jeffrey P; Gardner-Morse, Mack G; Costi, John J; Iatridis, James C

    2011-01-01

    Intervertebral disks support compressive forces because of their elastic stiffness as well as the fluid pressures resulting from poroelasticity and the osmotic (swelling) effects. Analytical methods can quantify the relative contributions, but only if correct material properties are used. To identify appropriate tissue properties, an experimental study and finite element analytical simulation of poroelastic and osmotic behavior of intervertebral disks were combined to refine published values of disk and endplate properties to optimize model fit to experimental data. Experimentally, nine human intervertebral disks with adjacent hemi-vertebrae were immersed sequentially in saline baths having concentrations of 0.015, 0.15, and 1.5 M and the loss of compressive force at constant height (force relaxation) was recorded over several hours after equilibration to a 300-N compressive force. Amplitude and time constant terms in exponential force-time curve-fits for experimental and finite element analytical simulations were compared. These experiments and finite element analyses provided data dependent on poroelastic and osmotic properties of the disk tissues. The sensitivities of the model to alterations in tissue material properties were used to obtain refined values of five key material parameters. The relaxation of the force in the three bath concentrations was exponential in form, expressed as mean compressive force loss of 48.7, 55.0, and 140 N, respectively, with time constants of 1.73, 2.78, and 3.40 h. This behavior was analytically well represented by a model having poroelastic and osmotic tissue properties with published tissue properties adjusted by multiplying factors between 0.55 and 2.6. Force relaxation and time constants from the analytical simulations were most sensitive to values of fixed charge density and endplate porosity.

  1. Enhanced mechanical properties and biocompatibility of novel hydroxyapatite/TOPAS hybrid composite for bone tissue engineering applications.

    Ain, Qurat Ul; Khan, Ahmad Nawaz; Nabavinia, Mahboubeh; Mujahid, Mohammad

    2017-06-01

    The bioactivity and mechanical properties of hybrid composites of hydroxyapatite (HA) in cyclic olefinic copolymer (COC) also known commercially as TOPAS are investigated, first time, for regeneration and repair of the bone tissues. HA is synthesized to obtain the spherically shaped nanoparticles in the size range of 60±20nm. Various concentrations of HA ranging from 1 to 30wt% are dispersed in TOPAS using sodium dodecyl sulfate (SDS) coupling agent for better dispersion and interaction of hydrophilic HA with hydrophobic TOPAS. Scanning electron microscope shows the uniform dispersion of HA≤10wt% in TOPAS and at higher concentrations >10wt%, agglomeration occurs in the hybrid composites. Tunable mechanical properties are achieved as the compressive modulus and strength are increased around 140% from 6.4 to 15.3MPa and 185% from 0.26 to 0.74MPa, respectively. Such increase in the mechanical properties of TOPAS is attributed to the anchoring of the polymer chains in the vicinity of HA nanoparticles owing to better dispersion and interfacial interactions. In comparison to neat TOPAS, hybrid composites of TOPAS/HA promoted the cell adhesion and proliferation significantly. The cell density and proliferation of TOPAS/HA hybrid composites is enhanced 9 and 3 folds, respectively, after 1day culturing in preosteoblasts cells. Moreover, the morphology of cells changed from spherical to flattened spread morphology demonstrating clearly the migration of the cells for the formation of interconnected cellular network. Additionally, very few dead cells are found in hybrid composites showing their cytocompatibility. Overall, the hybrid composites of TOPAS/HA exhibited superior strength and stiffness along with enhanced cytocompatibility for bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Exercise decreases lipogenic gene expression in adipose tissue and alters adipocyte cellularity during weight regain after weight loss.

    Erin Danielle Giles

    2016-02-01

    Full Text Available Exercise is a potent strategy to facilitate long-term weight maintenance. In addition to increasing energy expenditure and reducing appetite, exercise also favors the oxidation of dietary fat, which likely helps prevent weight re-gain. It is unclear whether this exercise-induced metabolic shift is due to changes in energy balance, or whether exercise imparts additional adaptations in the periphery that limit the storage and favor the oxidation of dietary fat. To answer this question, adipose tissue lipid metabolism and related gene expression were studied in obese rats following weight loss and during the first day of relapse to obesity. Mature, obese rats were weight-reduced for 2 weeks with or without daily treadmill exercise (EX. Rats were weight maintained for 6 weeks, followed by relapse on: a ad libitum low fat diet (LFD, b ad libitum LFD plus EX, or c a provision of LFD to match the positive energy imbalance of exercised, relapsing animals. 24h retention of dietary- and de novo-derived fat were assessed directly using 14C palmitate/oleate and 3H20, respectively. Exercise decreased the size, but increased the number of adipocytes in both retroperitoneal (RP and subcutaneous (SC adipose depots, and prevented the relapse-induced increase in adipocyte size. Further, exercise decreased the expression of genes involved in lipid uptake (CD36 & LPL, de novo lipogenesis (FAS, ACC1, and triacylglycerol synthesis (MGAT & DGAT in RP adipose during relapse following weight loss. This was consistent with the metabolic data, whereby exercise reduced retention of de novo-derived fat even when controlling for the positive energy imbalance. The decreased trafficking of dietary fat to adipose tissue with exercise was explained by reduced energy intake which attenuated energy imbalance during refeeding. Despite having decreased expression of lipogenic genes, the net retention of de novo-derived lipid was higher in both the RP and SC adipose of exercising

  3. Altered distributions of bone tissue mineral and collagen properties in women with fragility fractures.

    Wang, Zhen Xiang; Lloyd, Ashley A; Burket, Jayme C; Gourion-Arsiquaud, Samuel; Donnelly, Eve

    2016-03-01

    Heterogeneity of bone tissue properties is emerging as a potential indicator of altered bone quality in pathologic tissue. The objective of this study was to compare the distributions of tissue properties in women with and without histories of fragility fractures using Fourier transform infrared (FTIR) imaging. We extended a prior study that examined the relationship of the mean FTIR properties to fracture risk by analyzing in detail the widths and the tails of the distributions of FTIR properties in biopsies from fracture and non-fracture cohorts. The mineral and matrix properties of cortical and trabecular iliac crest tissue were compared in biopsies from women with a history of fragility fracture (+Fx; n=21, age: mean 54±SD 15y) and with no history of fragility fracture (-Fx; n=12, age: 57±5y). A subset of the patients included in the -Fx group were taking estrogen-plus-progestin hormone replacement therapy (HRT) (-Fx+HRT n=8, age: 58±5y) and were analyzed separately from patients with no history of HRT (-Fx-HRT n=4, age: 56±7y). When the FTIR parameter mean values were examined by treatment group, the trabecular tissue of -Fx-HRT patients had a lower mineral:matrix ratio (M:M) and collagen maturity (XLR) than that of -Fx+HRT patients (-22% M:M, -18% XLR) and +Fx patients (-17% M:M, -18% XLR). Across multiple FTIR parameters, tissue from the -Fx-HRT group had smaller low-tail (5th percentile) values than that from the -Fx+HRT or +Fx groups. In trabecular collagen maturity and crystallinity (XST), the -Fx-HRT group had smaller low-tail values than those in the -Fx+HRT group (-16% XLR, -5% XST) and the +Fx group (-17% XLR, -7% XST). The relatively low values of trabecular mineral:matrix ratio and collagen maturity and smaller low-tail values of collagen maturity and crystallinity observed in the -Fx-HRT group are characteristic of younger tissue. Taken together, our data suggest that the presence of newly formed tissue that includes small/imperfect crystals

  4. Modeling material-degradation-induced elastic property of tissue engineering scaffolds.

    Bawolin, N K; Li, M G; Chen, X B; Zhang, W J

    2010-11-01

    The mechanical properties of tissue engineering scaffolds play a critical role in the success of repairing damaged tissues/organs. Determining the mechanical properties has proven to be a challenging task as these properties are not constant but depend upon time as the scaffold degrades. In this study, the modeling of the time-dependent mechanical properties of a scaffold is performed based on the concept of finite element model updating. This modeling approach contains three steps: (1) development of a finite element model for the effective mechanical properties of the scaffold, (2) parametrizing the finite element model by selecting parameters associated with the scaffold microstructure and/or material properties, which vary with scaffold degradation, and (3) identifying selected parameters as functions of time based on measurements from the tests on the scaffold mechanical properties as they degrade. To validate the developed model, scaffolds were made from the biocompatible polymer polycaprolactone (PCL) mixed with hydroxylapatite (HA) nanoparticles and their mechanical properties were examined in terms of the Young modulus. Based on the bulk degradation exhibited by the PCL/HA scaffold, the molecular weight was selected for model updating. With the identified molecular weight, the finite element model developed was effective for predicting the time-dependent mechanical properties of PCL/HA scaffolds during degradation.

  5. The Effect of Structural Design on Mechanical Properties and Cellular Response of Additive Manufactured Titanium Scaffolds

    Jan Wieding

    2012-08-01

    Full Text Available Restoration of segmental defects in long bones remains a challenging task in orthopedic surgery. Although autologous bone is still the ‘Gold Standard’ because of its high biocompatibility, it has nevertheless been associated with several disadvantages. Consequently, artificial materials, such as calcium phosphate and titanium, have been considered for the treatment of bone defects. In the present study, the mechanical properties of three different scaffold designs were investigated. The scaffolds were made of titanium alloy (Ti6Al4V, fabricated by means of an additive manufacturing process with defined pore geometry and porosities of approximately 70%. Two scaffolds exhibited rectangular struts, orientated in the direction of loading. The struts for the third scaffold were orientated diagonal to the load direction, and featured a circular cross-section. Material properties were calculated from stress-strain relationships under axial compression testing. In vitro cell testing was undertaken with human osteoblasts on scaffolds fabricated using the same manufacturing process. Although the scaffolds exhibited different strut geometry, the mechanical properties of ultimate compressive strength were similar (145–164 MPa and in the range of human cortical bone. Test results for elastic modulus revealed values between 3.7 and 6.7 GPa. In vitro testing demonstrated proliferation and spreading of bone cells on the scaffold surface.

  6. Characterization of a Fasciola gigantica protein carrying two DM9 domains reveals cellular relocalization property.

    Phadungsil, Wansika; Smooker, Peter M; Vichasri-Grams, Suksiri; Grams, Rudi

    2016-01-01

    Even at the present age of whole-organism analysis, e.g., genomics, transcriptomics, and proteomics, the biological roles of many proteins remain unresolved. Classified among the proteins of unknown function is a family of proteins harboring repeats of the DM9 domain, a 60-75 amino acids motif first described in a small number of Drosophila melanogaster proteins. Proteins may carry two or more DM9 domains either in combination with other domains or as their sole constituent. Here we have characterized a 16.8 kDa Fasciola gigantica protein comprising two tandem repeated DM9 domains (FgDM9-1). The protein was located in the parenchyma of the immature and mature parasite and consequently it was not detected in the ES product of the parasite but only in the whole worm extract. Interestingly, extraction with SDS yielded a substantially higher amount of the protein suggesting association with insoluble cell components. In Sf9 insect cells a heterologously expressed EGFP-FgDM9-1 chimera showed cell-wide distribution but relocated to vesicle-like structures in the cytoplasm after stimulating cellular stress by bacteria, heat shock or chloroquine. These structures did not colocalize with the markers of endocytosis/phagocytosis ubiquitin, RAB7, GABARAP. The same behavior was noted for Aedes aegypti PRS1, a homologous mosquito DM9 protein as a positive control while EGFP did not exhibit such relocation in the insect cells. Cross-linking experiments on soluble recombinant FgDM9-1 indicated that the protein can undergo specific oligomerization. It is speculated that proteins carrying the DM9 domain have a role in vesicular transport in flatworms and insects. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Effect of solid distribution on elastic properties of open-cell cellular solids using numerical and experimental methods.

    Zargarian, A; Esfahanian, M; Kadkhodapour, J; Ziaei-Rad, S

    2014-09-01

    Effect of solid distribution between edges and vertices of three-dimensional cellular solid with an open-cell structure was investigated both numerically and experimentally. Finite element analysis (FEA) with continuum elements and appropriate periodic boundary condition was employed to calculate the elastic properties of cellular solids using tetrakaidecahedral (Kelvin) unit cell. Relative densities between 0.01 and 0.1 and various values of solid fractions were considered. In order to validate the numerical model, three scaffolds with the relative density of 0.08, but different amounts of solid in vertices, were fabricated via 3-D printing technique. Good agreement was observed between numerical simulation and experimental results. Results of numerical simulation showed that, at low relative densities (solid fraction in vertices. By fitting a curve to the data obtained from the numerical simulation and considering the relative density and solid fraction in vertices, empirical relations were derived for Young׳s modulus and Poisson׳s ratio. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. A cellular uptake and cytotoxicity properties study of gallic acid-loaded mesoporous silica nanoparticles on Caco-2 cells

    Rashidi, Ladan; Vasheghani-Farahani, Ebrahim; Soleimani, Masoud; Atashi, Amir; Rostami, Khosrow; Gangi, Fariba; Fallahpour, Masoud; Tahouri, Mohammad Taher

    2014-03-01

    In this study, the effects of intracellular delivery of various concentrations of gallic acid (GA) as a semistable antioxidant, gallic acid-loaded mesoporous silica nanoparticles (MSNs-GA), and cellular uptake of nanoparticles into Caco-2 cells were investigated. MSNs were synthesized and loaded with GA, then characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, N2 adsorption isotherms, X-ray diffraction, and thermal gravimetric analysis. The cytotoxicity of MSNs and MSNs-GA at low and high concentrations were studied by means of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test and flow cytometry. MSNs did not show significant toxicity in various concentrations (0-500 μg/ml) on Caco-2 cells. For MSNs-GA, cell viability was reduced as a function of incubation time and different concentrations of nanoparticles. The in vitro GA release from MSNs-GA exhibited the same antitumor properties as free GA on Caco-2 cells. Flow cytometry results confirmed those obtained using MTT assay. TEM and fluorescent microscopy confirmed the internalization of MSNs by Caco-2 cells through nonspecific cellular uptake. MSNs can easily internalize into Caco-2 cells without deleterious effects on cell viability. The cell viability of Caco-2 cells was affected during MSNs-GA uptake. MSNs could be designed as suitable nanocarriers for antioxidants delivery.

  9. Cellular properties of slug flow in vertical co-current gas-liquid flow: slug-churn transition

    Lusseyran, Francois

    1990-01-01

    This research thesis reports the study and description of the structure of a slug flow regime in a co-current vertical cylindrical duct, and the characterization and prediction of its transition towards a slug-churn (de-structured) regime. Flow physical mechanisms highlighted by the measurement of two important dynamics variables (wall friction and thickness of liquid films) are related to hypotheses of cellular models. The author first proposes an overview of slug flow regimes: theoretical steady and one-dimensional analysis, mass assessment equations of cellular models, application to the assessment of the flow rate and of the thickness of the film surrounding the gas slug. In the second part, the author addresses the slug flow regime transition towards the slug-churn regime: assessment of the evolution of flow dynamic properties, use of average wall friction analysis to obtain a relevant transition criterion. The third part presents experimental conditions, and measurement methods: conductometry for thickness measurement, polarography for wall friction measurement, and gas phase detection by using an optic barrier or optic fibres [fr

  10. Ex vivo investigation of tissue optical properties using an optical fibre sensor

    Warncke, Dennis

    2014-01-01

    peer-reviewed Biomedical research has become a strong growing sector in recent years. Moreover the interdisciplinary background involves novel possibilities and measurement techniques. Light propagation in turbid media like human tissue is a central aspect to many medical and biomedical applications. This is a very complex process and depends on parameters, which are called optical properties. The spatial distribution of light is determined by those optical properties. A maj...

  11. Tissue

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  12. Measurement of the hyperelastic properties of 44 pathological ex vivo breast tissue samples

    O'Hagan, Joseph J; Samani, Abbas

    2009-01-01

    The elastic and hyperelastic properties of biological soft tissues have been of interest to the medical community. There are several biomedical applications where parameters characterizing such properties are critical for a reliable clinical outcome. These applications include surgery planning, needle biopsy and brachtherapy where tissue biomechanical modeling is involved. Another important application is interpreting nonlinear elastography images. While there has been considerable research on the measurement of the linear elastic modulus of small tissue samples, little research has been conducted for measuring parameters that characterize the nonlinear elasticity of tissues included in tissue slice specimens. This work presents hyperelastic measurement results of 44 pathological ex vivo breast tissue samples. For each sample, five hyperelastic models have been used, including the Yeoh, N = 2 polynomial, N = 1 Ogden, Arruda-Boyce, and Veronda-Westmann models. Results show that the Yeoh, polynomial and Ogden models are the most accurate in terms of fitting experimental data. The results indicate that almost all of the parameters corresponding to the pathological tissues are between two times to over two orders of magnitude larger than those of normal tissues, with C 11 showing the most significant difference. Furthermore, statistical analysis indicates that C 02 of the Yeoh model, and C 11 and C 20 of the polynomial model have very good potential for cancer classification as they show statistically significant differences for various cancer types, especially for invasive lobular carcinoma. In addition to the potential for use in cancer classification, the presented data are very important for applications such as surgery planning and virtual reality based clinician training systems where accurate nonlinear tissue response modeling is required.

  13. Measurement of the hyperelastic properties of 44 pathological ex vivo breast tissue samples

    O' Hagan, Joseph J; Samani, Abbas [Department of Electrical and Computer Engineering, University of Western Ontario, London, ON (Canada)], E-mail: asamani@uwo.ca

    2009-04-21

    The elastic and hyperelastic properties of biological soft tissues have been of interest to the medical community. There are several biomedical applications where parameters characterizing such properties are critical for a reliable clinical outcome. These applications include surgery planning, needle biopsy and brachtherapy where tissue biomechanical modeling is involved. Another important application is interpreting nonlinear elastography images. While there has been considerable research on the measurement of the linear elastic modulus of small tissue samples, little research has been conducted for measuring parameters that characterize the nonlinear elasticity of tissues included in tissue slice specimens. This work presents hyperelastic measurement results of 44 pathological ex vivo breast tissue samples. For each sample, five hyperelastic models have been used, including the Yeoh, N = 2 polynomial, N = 1 Ogden, Arruda-Boyce, and Veronda-Westmann models. Results show that the Yeoh, polynomial and Ogden models are the most accurate in terms of fitting experimental data. The results indicate that almost all of the parameters corresponding to the pathological tissues are between two times to over two orders of magnitude larger than those of normal tissues, with C{sub 11} showing the most significant difference. Furthermore, statistical analysis indicates that C{sub 02} of the Yeoh model, and C{sub 11} and C{sub 20} of the polynomial model have very good potential for cancer classification as they show statistically significant differences for various cancer types, especially for invasive lobular carcinoma. In addition to the potential for use in cancer classification, the presented data are very important for applications such as surgery planning and virtual reality based clinician training systems where accurate nonlinear tissue response modeling is required.

  14. Measurement of the hyperelastic properties of 44 pathological ex vivo breast tissue samples

    O'Hagan, Joseph J.; Samani, Abbas

    2009-04-01

    The elastic and hyperelastic properties of biological soft tissues have been of interest to the medical community. There are several biomedical applications where parameters characterizing such properties are critical for a reliable clinical outcome. These applications include surgery planning, needle biopsy and brachtherapy where tissue biomechanical modeling is involved. Another important application is interpreting nonlinear elastography images. While there has been considerable research on the measurement of the linear elastic modulus of small tissue samples, little research has been conducted for measuring parameters that characterize the nonlinear elasticity of tissues included in tissue slice specimens. This work presents hyperelastic measurement results of 44 pathological ex vivo breast tissue samples. For each sample, five hyperelastic models have been used, including the Yeoh, N = 2 polynomial, N = 1 Ogden, Arruda-Boyce, and Veronda-Westmann models. Results show that the Yeoh, polynomial and Ogden models are the most accurate in terms of fitting experimental data. The results indicate that almost all of the parameters corresponding to the pathological tissues are between two times to over two orders of magnitude larger than those of normal tissues, with C11 showing the most significant difference. Furthermore, statistical analysis indicates that C02 of the Yeoh model, and C11 and C20 of the polynomial model have very good potential for cancer classification as they show statistically significant differences for various cancer types, especially for invasive lobular carcinoma. In addition to the potential for use in cancer classification, the presented data are very important for applications such as surgery planning and virtual reality based clinician training systems where accurate nonlinear tissue response modeling is required.

  15. Integrated automated nanomanipulation and real-time cellular surface imaging for mechanical properties characterization

    Eslami, Sohrab; Zareian, Ramin; Jalili, Nader

    2012-10-01

    Surface microscopy of individual biological cells is essential for determining the patterns of cell migration to study the tumor formation or metastasis. This paper presents a correlated and effective theoretical and experimental technique to automatically address the biophysical and mechanical properties and acquire live images of biological cells which are of interest in studying cancer. In the theoretical part, a distributed-parameters model as the comprehensive representation of the microcantilever is presented along with a model of the contact force as a function of the indentation depth and mechanical properties of the biological sample. Analysis of the transfer function of the whole system in the frequency domain is carried out to characterize the stiffness and damping coefficients of the sample. In the experimental section, unlike the conventional atomic force microscope techniques basically using the laser for determining the deflection of microcantilever's tip, a piezoresistive microcantilever serving as a force sensor is implemented to produce the appropriate voltage and measure the deflection of the microcantilever. A micromanipulator robotic system is integrated with the MATLAB® and programmed in such a way to automatically control the microcantilever mounted on the tip of the micromanipulator to achieve the topography of biological samples including the human corneal cells. For this purpose, the human primary corneal fibroblasts are extracted and adhered on a sterilized culture dish and prepared to attain their topographical image. The proposed methodology herein allows an approach to obtain 2D quality images of cells being comparatively cost effective and extendable to obtain 3D images of individual cells. The characterized mechanical properties of the human corneal cell are furthermore established by comparing and validating the phase shift of the theoretical and experimental results of the frequency response.

  16. Bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles: preparation, cellular uptake, tissue distribution, and anticancer activity

    Duan YR

    2012-07-01

    Full Text Available Peihao Yin,1,* Yan Wang,1,* YanYan Qiu,1 LiLi Hou,1 Xuan Liu,1 Jianmin Qin,1 Yourong Duan,2 Peifeng Liu,2 Ming Qiu,3 Qi Li11Department of Clinical Oncology, Putuo Hospital and Interventional Cancer Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Shanghai Cancer Institute, Jiaotong University, Shanghai, China; 3Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China *These authors contributed equally to this workBackground: Recent studies have shown that bufalin has a good antitumor effect but has high toxicity, poor water solubility, a short half-life, a narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study aimed to determine the targeting efficacy of nanoparticles (NPs made of methoxy polyethylene glycol (mPEG, polylactic-co-glycolic acid (PLGA, poly-L-lysine (PLL, and cyclic arginine-glycine-aspartic acid (cRGD loaded with bufalin, ie, bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles (BNPs, in SW620 colon cancer-bearing mice.Methods: BNPs showed uniform size. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these nanoparticles were studied in vitro. The tumor targeting, cellular uptake, and growth-inhibitory effect of BNPs in vivo were tested.Results: BNPs were of uniform size with an average particle size of 164 ± 84 nm and zeta potential of 2.77 mV. The encapsulation efficiency was 81.7% ± 0.89%, and the drug load was 3.92% ± 0.16%. The results of in vitro cytotoxicity studies showed that although the blank NPs were nontoxic, they enhanced the cytotoxicity of bufalin in BNPs. Drug release experiments showed that the release of the drug was prolonged and sustained. The results of confocal laser scanning microscopy indicated that BNPs could effectively bind to human umbilical vein endothelial cells. In the SW620

  17. Ultrasound Imaging Techniques for Spatiotemporal Characterization of Composition, Microstructure, and Mechanical Properties in Tissue Engineering.

    Deng, Cheri X; Hong, Xiaowei; Stegemann, Jan P

    2016-08-01

    Ultrasound techniques are increasingly being used to quantitatively characterize both native and engineered tissues. This review provides an overview and selected examples of the main techniques used in these applications. Grayscale imaging has been used to characterize extracellular matrix deposition, and quantitative ultrasound imaging based on the integrated backscatter coefficient has been applied to estimating cell concentrations and matrix morphology in tissue engineering. Spectral analysis has been employed to characterize the concentration and spatial distribution of mineral particles in a construct, as well as to monitor mineral deposition by cells over time. Ultrasound techniques have also been used to measure the mechanical properties of native and engineered tissues. Conventional ultrasound elasticity imaging and acoustic radiation force imaging have been applied to detect regions of altered stiffness within tissues. Sonorheometry and monitoring of steady-state excitation and recovery have been used to characterize viscoelastic properties of tissue using a single transducer to both deform and image the sample. Dual-mode ultrasound elastography uses separate ultrasound transducers to produce a more potent deformation force to microscale characterization of viscoelasticity of hydrogel constructs. These ultrasound-based techniques have high potential to impact the field of tissue engineering as they are further developed and their range of applications expands.

  18. RESEARCH ON THE INFLUENCE OF BLOWING AGENT ON SELECTED PROPERTIES OF EXTRUDED CELLULAR PRODUCTS

    Tomasz Garbacz

    2015-11-01

    Full Text Available As a part of a more comprehensive research project, the present study was undertaken to investigate the effect of the type and content of blowing agents in the polymeric materials being processed on the structure and selected physical and mechanical properties of the obtained extrusion parts. In the experiment, the content of the blowing agent (0–2.0% by mass, fed into the processed polymer were adopted as a variable factor. In the studies presented in the article, the blowing agents of endothermic decomposition characteristics (Hydrocerol BIH 70, Hydrocerol BM 70 and the exothermic decomposition characteristics (PLC 751 occurring in the granulated form with a diameter of 1.2 to 1.8 mm were used. Based on the results of investigating porosity, porous structure image analysis as well as microscopic examination of the structure, it has been found that the favorable content of the blowing agent in the polymeric material should be of up to 0.8% by mass. With such a content of the blowing agent in the polymeric material, favorable strength properties are retained in porous parts, the pore distribution is uniform and the pores have similar sizes.

  19. Cellular organization of pre-mRNA splicing factors in several tissues. Changes in the uterus by hormone action.

    George-Téllez, R; Segura-Valdez, M L; González-Santos, L; Jiménez-García, L F

    2002-05-01

    In the mammalian cell nucleus, splicing factors are distributed in nuclear domains known as speckles or splicing factor compartments (SFCs). In cultured cells, these domains are dynamic and reflect transcriptional and splicing activities. We used immunofluorescence and confocal microscopy to monitor whether splicing factors in differentiated cells display similar features. Speckled patterns are observed in rat hepatocytes, beta-cells, bronchial and intestine epithelia and also in three cell types of the uterus. Moreover, the number, distribution and sizes of the speckles vary among them. In addition, we studied variations in the circular form (shape) of speckles in uterine cells that are transcriptionally modified by a hormone action. During proestrus of the estral cycle, speckles are irregular in shape while in diestrus I they are circular. Experimentally, in castrated rats luminal epithelial cells show a pattern where speckles are dramatically rounded, but they recover their irregular shape rapidly after an injection of estradiol. The same results were observed in muscle and gland epithelial cells of the uterus. We concluded that different speckled patterns are present in various cells types in differentiated tissues and that these patterns change in the uterus depending upon the presence or absence of hormones such as estradiol.

  20. Correlation between tissue metabolism and cellularity assessed by standardized uptake value and apparent diffusion coefficient in peritoneal metastasis.

    Yu, Xue; Lee, Elaine Yuen Phin; Lai, Vincent; Chan, Queenie

    2014-07-01

    To evaluate the correlation between standardized uptake value (SUV) (tissue metabolism) and apparent diffusion coefficient (ADC) (water diffusivity) in peritoneal metastases. Patients with peritoneal dissemination detected on (18)F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) were prospectively recruited for MRI examinations with informed consent and the study was approved by the local Institutional Review Board. FDG-PET/CT, diffusion-weighted imaging (DWI), MRI, and DWI/MRI images were independently reviewed by two radiologists based on visual analysis. SUVmax/SUVmean and ADCmin/ADCmean were obtained manually by drawing ROIs over the peritoneal metastases on FDG-PET/CT and DWI, respectively. Diagnostic characteristics of each technique were evaluated. Pearson's coefficient and McNemar and Kappa tests were used for statistical analysis. Eight patients were recruited for this prospective study and 34 peritoneal metastases were evaluated. ADCmean was significantly and negatively correlated with SUVmax (r = -0.528, P = 0.001) and SUVmean (r = -0.548, P = 0.001). ADCmin had similar correlation with SUVmax (r = -0.508, P = 0.002) and SUVmean (r = -0.513, P = 0.002). DWI/MRI had high diagnostic performance (accuracy = 98%) comparable to FDG-PET/CT, in peritoneal metastasis detection. Kappa values were excellent for all techniques. There was a significant inverse correlation between SUV and ADC. © 2013 Wiley Periodicals, Inc.

  1. Design of Xylose-Based Semisynthetic Polyurethane Tissue Adhesives with Enhanced Bioactivity Properties.

    Balcioglu, Sevgi; Parlakpinar, Hakan; Vardi, Nigar; Denkbas, Emir Baki; Karaaslan, Merve Goksin; Gulgen, Selam; Taslidere, Elif; Koytepe, Suleyman; Ates, Burhan

    2016-02-01

    Developing biocompatible tissue adhesives with high adhesion properties is a highly desired goal of the tissue engineering due to adverse effects of the sutures. Therefore, our work involves synthesis, characterization, adhesion properties, protein adsorption, in vitro biodegradation, in vitro and in vivo biocompatibility properties of xylose-based semisynthetic polyurethane (NPU-PEG-X) bioadhesives. Xylose-based semisynthetic polyurethanes were developed by the reaction among 4,4'-methylenebis(cyclohexyl isocyanate) (MCI), xylose and polyethylene glycol 200 (PEG). Synthesized polyurethanes (PUs) showed good thermal stability and high adhesion strength. The highest values in adhesion strength were measured as 415.0 ± 48.8 and 94.0 ± 2.8 kPa for aluminum substrate and muscle tissue in 15% xylose containing PUs (NPU-PEG-X-15%), respectively. The biodegradation of NPU-PEG-X-15% was also determined as 19.96 ± 1.04% after 8 weeks of incubation. Relative cell viability of xylose containing PU was above 86%. Moreover, 10% xylose containing NPU-PEG-X (NPU-PEG-X-10%) sample has favorable tissue response, and inflammatory reaction between 1 and 6 weeks implantation period. With high adhesiveness and biocompatibility properties, NPU-PEG-X can be used in the medical field as supporting materials for preventing the fluid leakage after abdominal surgery or wound closure.

  2. In vitro double-integrating-sphere optical properties of tissues between 630 and 1064 nm

    Beek, J. F.; Blokland, P.; Posthumus, P.; Aalders, M.; Pickering, J. W.; Sterenborg, H. J. C. M.; van Gemert, M. J. C.

    1997-11-01

    The optical properties (absorption and scattering coefficients and the scattering anisotropy factor) were measured in vitro for cartilage, liver, lung, muscle, myocardium, skin, and tumour (colon adenocarcinoma CC 531) at 630, 632.8, 790, 850 and 1064 nm. Rabbits, rats, piglets, goats, and dogs were used to obtain the tissues. A double-integrating-sphere setup with an intervening sample was used to determine the reflectance, and the diffuse and collimated transmittances of the sample. The inverse adding - doubling algorithm was used to determine the optical properties from the measurements. The overall results were comparable to those available in the literature, although only limited data are available at 790 - 850 nm. The results were reproducible for a specific sample at a specific wavelength. However, when comparing the results of different samples of the same tissue or different lasers with approximately the same wavelength (e.g. argon dye laser at 630 nm and HeNe laser at 632.8 nm) variations are large. We believe these variations in optical properties should be explained by biological variations of the tissues. In conclusion, we report on an extensive set of in vitro absorption and scattering properties of tissues measured with the same equipment and software, and by the same group. Although the accuracy of the method requires further improvement, it is highly likely that the other existing data in the literature have a similar level of accuracy.

  3. Comments on the paper 'Optical properties of bovine muscle tissue in vitro; a comparison of methods'

    Marchesini, R.

    1999-01-01

    In reply to R. Marchesini's comments that optical values derived by himself and other authors given in the paper entitled 'Optical properties of bovine muscle tissue in vitro; a comparison of methods' were incorrectly cited, the author, J.R. Zijp, apologizes for this mistake and explains the reasons for this misinterpretation. Letter-to-the-editor

  4. Determination of optical properties of tissue and other bio-materials

    Singh, A

    2008-11-01

    Full Text Available appears less diffusively scattered. Determination of optical properties of tissue and other bio-materials A SINGH, AE KARSTEN, JS DAM CSIR National Laser Centre, Biophotonics Group PO Box 395, Pretoria, 0001, South Africa Email: ASingh1@csir.co.za K...

  5. Imaging the spectral reflectance properties of bipolar radiofrequency-fused bowel tissue

    Clancy, Neil T.; Arya, Shobhit; Stoyanov, Danail; Du, Xiaofei; Hanna, George B.; Elson, Daniel S.

    2015-07-01

    Delivery of radiofrequency (RF) electrical energy is used during surgery to heat and seal tissue, such as vessels, allowing resection without blood loss. Recent work has suggested that this approach may be extended to allow surgical attachment of larger tissue segments for applications such as bowel anastomosis. In a large series of porcine surgical procedures bipolar RF energy was used to resect and re-seal the small bowel in vivo with a commercial tissue fusion device (Ligasure; Covidien PLC, USA). The tissue was then imaged with a multispectral imaging laparoscope to obtain a spectral datacube comprising both fused and healthy tissue. Maps of blood volume, oxygen saturation and scattering power were derived from the measured reflectance spectra using an optimised light-tissue interaction model. A 60% increase in reflectance of visible light (460-700 nm) was observed after fusion, with the tissue taking on a white appearance. Despite this the distinctive shape of the haemoglobin absorption spectrum was still noticeable in the 460-600 nm wavelength range. Scattering power increased in the fused region in comparison to normal serosa, while blood volume and oxygen saturation decreased. Observed fusion-induced changes in the reflectance spectrum are consistent with the biophysical changes induced through tissue denaturation and increased collagen cross-linking. The multispectral imager allows mapping of the spatial extent of these changes and classification of the zone of damaged tissue. Further analysis of the spectral data in parallel with histopathological examination of excised specimens will allow correlation of the optical property changes with microscopic alterations in tissue structure.

  6. Quantitative methods for reconstructing tissue biomechanical properties in optical coherence elastography: a comparison study

    Han, Zhaolong; Li, Jiasong; Singh, Manmohan; Wu, Chen; Liu, Chih-hao; Wang, Shang; Idugboe, Rita; Raghunathan, Raksha; Sudheendran, Narendran; Larin, Kirill V; Aglyamov, Salavat R; Twa, Michael D

    2015-01-01

    We present a systematic analysis of the accuracy of five different methods for extracting the biomechanical properties of soft samples using optical coherence elastography (OCE). OCE is an emerging noninvasive technique, which allows assessment of biomechanical properties of tissues with micrometer spatial resolution. However, in order to accurately extract biomechanical properties from OCE measurements, application of a proper mechanical model is required. In this study, we utilize tissue-mimicking phantoms with controlled elastic properties and investigate the feasibilities of four available methods for reconstructing elasticity (Young’s modulus) based on OCE measurements of an air-pulse induced elastic wave. The approaches are based on the shear wave equation (SWE), the surface wave equation (SuWE), Rayleigh-Lamb frequency equation (RLFE), and finite element method (FEM), Elasticity values were compared with uniaxial mechanical testing. The results show that the RLFE and the FEM are more robust in quantitatively assessing elasticity than the other simplified models. This study provides a foundation and reference for reconstructing the biomechanical properties of tissues from OCE data, which is important for the further development of noninvasive elastography methods. (paper)

  7. Cellular Interaction and Tumoral Penetration Properties of Cyclodextrin Nanoparticles on 3D Breast Tumor Model

    Gamze Varan

    2018-01-01

    Full Text Available Amphiphilic cyclodextrins are biocompatible oligosaccharides that can be used for drug delivery especially for the delivery of drugs with solubility problems thanks to their unique molecular structures. In this paper, Paclitaxel was used as a model anticancer drug to determine the inclusion complex properties of amphiphilic cyclodextrins with different surface charge. Paclitaxel-loaded cyclodextrin nanoparticles were characterized in terms of mean particle diameter, zeta potential, encapsulation efficacy, drug release profile and cell culture studies. It was determined that the nanoparticles prepared from the inclusion complex according to characterization studies have a longer release profile than the conventionally prepared nanoparticles. In order to mimic the tumor microenvironment, breast cancer cells and healthy fibroblast cells were used in 3-dimensional (3D cell culture studies. It was determined that the activities of nanoparticles prepared by conventional methods behave differently in 2-dimensional (2D and 3D cell cultures. In addition, it was observed that the nanoparticles prepared from the inclusion complex have a stronger anti-tumoral activity in the 3D multicellular tumor model than the drug solution. Furthermore, polycationic amphiphilic cyclodextrin nanoparticles can diffuse and penetrate through multilayer cells in a 3D tumor model, which is crucial for an eventual antitumor effect.

  8. Organ and tissue level properties are more sensitive to age than osteocyte lacunar characteristics in rat cortical bone

    Wittig, Nina; Bach-Gansmo, Fiona Linnea; Birkbak, Mie Elholm

    2016-01-01

    orientation with animal age. Hence, the evolution of organ and tissue level properties with age in rat cortical bone is not accompanied by related changes in osteocyte lacunar properties. This suggests that bone microstructure and bone matrix material properties and not the geometric properties...... of bone on the organ and tissue level, whereas features on the nano- and micrometer scale are much less explored. We investigated the age-related development of organ and tissue level bone properties such as bone volume, bone mineral density, and load to fracture and correlated these with osteocyte...

  9. Effect of dispersion capability of organoclay on cellular structure and physical properties of PMMA/clay nanocomposite foams

    Yeh, Jui-Ming; Chang, Kung-Chin; Peng, Chih-Wei; Lai, Mei-Chun; Hung, Chih-Bing; Hsu, Sheng-Chieh; Hwang, Shyh-Shin; Lin, Hong-Ru

    2009-01-01

    In this study, PMMA/clay nanocomposite (PCN) materials with two kinds of organoclay were prepared via in situ bulk polymerization. The as-prepared PCN materials were then characterized by Fourier transformation infrared (FTIR) spectroscopy, wide-angle X-ray diffraction (WAXRD) and transmission electron microscopy (TEM). WAXRD and TEM analysis revealed that combination of both intercalated and exfoliated nanocomposites was formed and the silicate layers of the clay were uniformly dispersed at a nanometer scale in PMMA matrix. The molecular weights of PMMA extracted from PCN materials and bulk PMMA were determined by gel permeation chromatography (GPC) with THF used as the eluant. The PCN materials were used to produce foams by a batch process in an autoclave using nitrogen as foaming agent. The cellular structure analysis of foams was examined by SEM. The effect of dispersion capability of organoclay on the dielectric and thermal transport properties of PCN materials and foams and mechanical properties of PCN foams were investigated by LCR meter, transient plane source (TPS) technique and dynamic mechanical analysis (DMA), respectively.

  10. Determining the influence of calcification on the failure properties of abdominal aortic aneurysm (AAA) tissue.

    O'Leary, Siobhan A; Mulvihill, John J; Barrett, Hilary E; Kavanagh, Eamon G; Walsh, Michael T; McGloughlin, Tim M; Doyle, Barry J

    2015-02-01

    Varying degrees of calcification are present in most abdominal aortic aneurysms (AAAs). However, their impact on AAA failure properties and AAA rupture risk is unclear. The aim of this work is evaluate and compare the failure properties of partially calcified and predominantly fibrous AAA tissue and investigate the potential reasons for failure. Uniaxial mechanical testing was performed on AAA samples harvested from 31 patients undergoing open surgical repair. Individual tensile samples were divided into two groups: fibrous (n=31) and partially calcified (n=38). The presence of calcification was confirmed by fourier transform infrared spectroscopy (FTIR). A total of 69 mechanical tests were performed and the failure stretch (λf), failure stress (σf) and failure tension (Tf) were recorded for each test. Following mechanical testing, the failure sites of a subset of both tissue types were examined using scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) to investigate the potential reasons for failure. It has been shown that the failure properties of partially calcified tissue are significantly reduced compared to fibrous tissue and SEM and EDS results suggest that the junction between a calcification deposit and the fibrous matrix is highly susceptible to failure. This study implicates the presence of calcification as a key player in AAA rupture risk and provides further motivation for the development of non-invasive methods of measuring calcification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Age-related changes in dynamic compressive properties of trochanteric soft tissues over the hip.

    Choi, W J; Russell, C M; Tsai, C M; Arzanpour, S; Robinovitch, S N

    2015-02-26

    Hip fracture risk increases dramatically with age, and 90% of fractures are due to falls. During a fall on the hip, the soft tissues overlying the hip region (skin, fat, and muscle) act as shock absorbers to absorb energy and reduce the peak force applied to the underlying bone. We conducted dynamic indentation experiments with young women (aged 19-30; n=17) and older women (aged 65-81; n=17) to test the hypothesis that changes occur with age in the stiffness and damping properties of these tissues. Tissue stiffness and damping were derived from experiments where subjects lay sideways on a bed with the greater trochanter contacting a 3.8cm diameter indenter, which applied sinusoidal compression between 5 to 30Hz with a peak-to-peak amplitude of 1mm. Soft tissue thickness was measured using ultrasound. On average, stiffness was 2.9-fold smaller in older than young women (5.7 versus 16.8kN/m, p=0.0005) and damping was 3.5-fold smaller in older than young women (81 versus 282Ns/m, p=0.001). Neither parameter associated with soft tissue thickness. Our results indicate substantial age-related reductions in the stiffness and damping of soft tissues over the hip region, which likely reduce their capacity to absorb and dissipate energy (before "bottoming out") during a fall. Strategies such as wearable hip protectors or compliant flooringmay compensate for age-related reductions in the shock-absorbing properties of soft tissues and decrease the injury potential of falls. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts

    Eom, Young Woo [Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Biomedical Research Institute, Lifeliver Co., Ltd., Suwon (Korea, Republic of); Lee, Jong Eun; Yang, Mal Sook; Jang, In Keun; Kim, Hyo Eun; Lee, Doo Hoon; Kim, Young Jin [Biomedical Research Institute, Lifeliver Co., Ltd., Suwon (Korea, Republic of); Park, Won Jin [Dr. Park' s Aesthetic Clinic, Seoul (Korea, Republic of); Kong, Jee Hyun; Shim, Kwang Yong [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Lee, Jong In, E-mail: oncochem@yonsei.ac.kr [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of); Kim, Hyun Soo, E-mail: khsmd@unitel.co.kr [Department of Hematology-Oncology, Wonju College of Medicine, Yonsei Univ., Wonju (Korea, Republic of)

    2011-04-29

    Highlights: {yields} hASCs were differentiated into skeletal muscle cells by treatment with 5-azacytidine, FGF-2, and the supernatant of cultured hASCs. {yields} Dystrophin and MyHC were expressed in late differentiation step by treatment with the supernatant of cultured hASCs. {yields} hASCs expressing dystrophin and MyHC contributed to myotube formation during co-culture with mouse myoblast C2C12 cells. -- Abstract: Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of human adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin.

  13. Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts

    Eom, Young Woo; Lee, Jong Eun; Yang, Mal Sook; Jang, In Keun; Kim, Hyo Eun; Lee, Doo Hoon; Kim, Young Jin; Park, Won Jin; Kong, Jee Hyun; Shim, Kwang Yong; Lee, Jong In; Kim, Hyun Soo

    2011-01-01

    Highlights: → hASCs were differentiated into skeletal muscle cells by treatment with 5-azacytidine, FGF-2, and the supernatant of cultured hASCs. → Dystrophin and MyHC were expressed in late differentiation step by treatment with the supernatant of cultured hASCs. → hASCs expressing dystrophin and MyHC contributed to myotube formation during co-culture with mouse myoblast C2C12 cells. -- Abstract: Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of human adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin.

  14. Chitosan fibers with improved biological and mechanical properties for tissue engineering applications.

    Albanna, Mohammad Z; Bou-Akl, Therese H; Blowytsky, Oksana; Walters, Henry L; Matthew, Howard W T

    2013-04-01

    The low mechanical properties of hydrogel materials such as chitosan hinder their broad utility for tissue engineering applications. Previous research efforts improved the mechanical properties of chitosan fiber through chemical and physical modifications; however, unfavorable toxicity effects on cells were reported. In this paper, we report the preparation of chitosan fibers with improved mechanical and biocompatibility properties. The structure-property relationships of extruded chitosan fibers were explored by varying acetic acid (AA) concentration, ammonia concentration, annealing temperature and degree of heparin crosslinking. Results showed that optimizing AA concentration to 2vol% improved fiber strength and stiffness by 2-fold. Extruding chitosan solution into 25wt% of ammonia solution reduced fiber diameters and improved fiber strength by 2-fold and stiffness by 3-fold, due to an increase in crystallinity as confirmed by XRD. Fiber annealing further reduced fiber diameter and improved fiber strength and stiffness as temperature increased. Chitosan fibers crosslinked with heparin had increased diameter but lower strength and stiffness properties and higher breaking strain values. When individual parameters were combined, further improvement in fiber mechanical properties was achieved. All mechanically improved fibers and heparin crosslinked fibers promoted valvular interstitial cells (VIC) attachment and growth over 10 day cultures. Our results demonstrate the ability to substantially improve the mechanical properties of chitosan fibers without adversely affecting their biological properties. The investigated treatments offer numerous advantages over previous physical/chemical modifications and thus are expected to expand the utility of chitosan fibers with tunable mechanical properties in various tissue engineering applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Changes in diffusion properties of biological tissues associated with mechanical strain

    Tanaka, Kenichiro; Imae, T.; Mima, Kazuo; Sekino, Masaki; Ohsaki, Hiroyuki; Ueno, Shogo

    2007-01-01

    Mechanical strain in biological tissues causes a change in the diffusion properties of water molecules. This paper proposes a method of estimating mechanical strain in biological tissues using diffusion magnetic resonance imaging (MRI). Measurements were carried out on uncompressed and compressed chicken skeletal muscles. A theoretical model of the diffusion of water molecules in muscle fibers was derived based on Tanner's equation. Diameter of the muscle fibers was estimated by fitting the model equation to the measured signals. Changes in the mean diffusivity (MD), the fractional anisotropy (FA), and diameter of the muscle fiber did not have any statistical significance. The intracellular diffusion coefficient (D int ) was changed by mechanical strain (p<.05). This method has potential applications in the quantitative evaluation of strain in biological tissues, a though it poses several technical challenges. (author)

  16. Effect of mechanical tissue properties on thermal damage in skin after IR-laser ablation

    Frenz, M.; Romano, V.; Forrer, M.; Weber, H.P. (Inst. of Applied Physics, Bern Univ. (Switzerland)); Mischler, C.; Mueller, O.M. (Anatomical Inst., Bern Univ. (Switzerland))

    1991-04-01

    The damage created instantaneously in dorsal skin and in the subjacent skeletal muscle layer after CO{sub 2} and Er{sup 3+} laser incisions is histologically and ultrastructurally investigated. Light microscopical examinations show an up to three times larger damage zone in the subcutaneous layer of skeletal muscle than in the connective tissue above. The extent of thermally altered muscle tissue is classified by different zones and characterized by comparison to long time heating injuries. The unexpectedly large damage is a result of the change of elastic properties occurring abruptly at the transition between different materials. This leads to a discontinuity of the cutting dynamics that reduces the ejection of tissue material. We show that the degree of thermal damage originates from the amount of hot material that is not ejected out of the crater acting as a secondary heat source. (orig.).

  17. Determination of optical properties, drug concentration, and tissue oxygenation in human pleural tissue before and after Photofrin-mediated photodynamic therapy

    Ong, Yi Hong; Padawer-Curry, Jonah; Finlay, Jarod C.; Kim, Michele M.; Dimofte, Andreea; Cengel, Keith; Zhu, Timothy C.

    2018-02-01

    PDT efficacy depends on the concentration of photosensitizer, oxygen, and light delivery in patient tissues. In this study, we measure the in-vivo distribution of important dosimetric parameters, namely the tissue optical properties (absorption μa (λ) and scattering μs ' (λ) coefficients), photofrin concentration (cphotofrin), blood oxygen saturation (%StO2), and total hemoglobin concentration (THC), before and after PDT. We characterize the inter- and intra-patient heterogeneity of these quantities and explore how these properties change as a result of PDT treatment. The result suggests the need for real-time dosimetry during PDT to optimize the treatment condition depending on the optical and physiological properties.

  18. Longitudinal elastic properties and porosity of cortical bone tissue vary with age in human proximal femur.

    Malo, M K H; Rohrbach, D; Isaksson, H; Töyräs, J; Jurvelin, J S; Tamminen, I S; Kröger, H; Raum, K

    2013-04-01

    Tissue level structural and mechanical properties are important determinants of bone strength. As an individual ages, microstructural changes occur in bone, e.g., trabeculae and cortex become thinner and porosity increases. However, it is not known how the elastic properties of bone change during aging. Bone tissue may lose its elasticity and become more brittle and prone to fractures as it ages. In the present study the age-dependent variation in the spatial distributions of microstructural and microelastic properties of the human femoral neck and shaft were evaluated by using acoustic microscopy. Although these properties may not be directly measured in vivo, there is a major interest to investigate their relationships with the linear elastic measurements obtained by diagnostic ultrasound at the most severe fracture sites, e.g., the femoral neck. However, before the validity of novel in vivo techniques can be established, it is essential to understand the age-dependent variation in tissue elastic properties and porosity at different skeletal sites. A total of 42 transverse cross-sectional bone samples were obtained from the femoral neck (Fn) and proximal femoral shaft (Ps) of 21 men (mean±SD age 47.1±17.8, range 17-82years). Samples were quantitatively imaged using a scanning acoustic microscope (SAM) equipped with a 50MHz ultrasound transducer. Distributions of the elastic coefficient (c33) of cortical (Ct) and trabecular (Tr) tissues and microstructure of cortex (cortical thickness Ct.Th and porosity Ct.Po) were determined. Variations in c33 were observed with respect to tissue type (c33Trc33(Ct.Fn)=35.3GPa>c33(Tr.Ps)=33.8GPa>c33(Tr.Fn)=31.9GPa), and cadaver age (R(2)=0.28-0.46, pbone tissue were observed. These findings may explain in part the increase in susceptibility to suffer low energy fractures during aging and highlight the potential of ultrasound in clinical osteoporosis diagnostics. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries.

    Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

    2007-05-21

    The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at the University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties.

  20. A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries

    Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

    2007-01-01

    The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties

  1. A genetic algorithm for optimizing multi-pole Debye models of tissue dielectric properties

    Clegg, J; Robinson, M P

    2012-01-01

    Models of tissue dielectric properties (permittivity and conductivity) enable the interactions of tissues and electromagnetic fields to be simulated, which has many useful applications in microwave imaging, radio propagation, and non-ionizing radiation dosimetry. Parametric formulae are available, based on a multi-pole model of tissue dispersions, but although they give the dielectric properties over a wide frequency range, they do not convert easily to the time domain. An alternative is the multi-pole Debye model which works well in both time and frequency domains. Genetic algorithms are an evolutionary approach to optimization, and we found that this technique was effective at finding the best values of the multi-Debye parameters. Our genetic algorithm optimized these parameters to fit to either a Cole–Cole model or to measured data, and worked well over wide or narrow frequency ranges. Over 10 Hz–10 GHz the best fits for muscle, fat or bone were each found for ten dispersions or poles in the multi-Debye model. The genetic algorithm is a fast and effective method of developing tissue models that compares favourably with alternatives such as the rational polynomial fit. (paper)

  2. Nonlinear and anisotropic tensile properties of graft materials used in soft tissue applications.

    Yoder, Jonathon H; Elliott, Dawn M

    2010-05-01

    The mechanical properties of extracellular matrix grafts that are intended to augment or replace soft tissues should be comparable to the native tissue. Such grafts are often used in fiber-reinforced tissue applications that undergo multi-axial loading and therefore knowledge of the anisotropic and nonlinear properties are needed, including the moduli and Poisson's ratio in two orthogonal directions within the plane of the graft. The objective of this study was to measure the tensile mechanical properties of several marketed grafts: Alloderm, Restore, CuffPatch, and OrthADAPT. The degree of anisotropy and non-linearity within each graft was evaluated from uniaxial tensile tests and compared to their native tissue. The Alloderm graft was anisotropic in both the toe- and linear-region of the stress-strain response, was highly nonlinear, and generally had low properties. The Restore and CuffPatch grafts had similar stress-strain responses, were largely isotropic, had a linear-region modulus of 18MPa, and were nonlinear. OrthADAPT was anisotropic in the linear-region (131 MPA vs 47MPa in the toe-region) and was highly nonlinear. The Poisson ratio for all grafts was between 0.4 and 0.7, except for the parallel orientation of Restore which was greater than 1.0. Having an informed understanding of how the available grafts perform mechanically will allow for better assessment by the physician for which graft to apply depending upon its application. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering.

    Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song

    2017-08-17

    Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

  4. Toxicity of functional nano-micro zinc oxide tetrapods: impact of cell culture conditions, cellular age and material properties.

    Papavlassopoulos, Heike; Mishra, Yogendra K; Kaps, Sören; Paulowicz, Ingo; Abdelaziz, Ramzy; Elbahri, Mady; Maser, Edmund; Adelung, Rainer; Röhl, Claudia

    2014-01-01

    With increasing production and applications of nanostructured zinc oxide, e.g., for biomedical and consumer products, the question of safety is getting more and more important. Different morphologies of zinc oxide structures have been synthesized and accordingly investigated. In this study, we have particularly focused on nano-micro ZnO tetrapods (ZnO-T), because their large scale fabrication has been made possible by a newly introduced flame transport synthesis approach which will probably lead to several new applications. Moreover, ZnO-T provide a completely different morphology then classical spherical ZnO nanoparticles. To get a better understanding of parameters that affect the interactions between ZnO-T and mammalian cells, and thus their biocompatibility, we have examined the impact of cell culture conditions as well as of material properties on cytotoxicity. Our results demonstrate that the cell density of fibroblasts in culture along with their age, i.e., the number of preceding cell divisions, strongly affect the cytotoxic potency of ZnO-T. Concerning the material properties, the toxic potency of ZnO-T is found to be significantly lower than that of spherical ZnO nanoparticles. Furthermore, the morphology of the ZnO-T influenced cellular toxicity in contrast to surface charges modified by UV illumination or O2 treatment and to the material age. Finally, we have observed that direct contact between tetrapods and cells increases their toxicity compared to transwell culture models which allow only an indirect effect via released zinc ions. The results reveal several parameters that can be of importance for the assessment of ZnO-T toxicity in cell cultures and for particle development.

  5. Assessment of tissue polarimetric properties using Stokes polarimetric imaging with circularly polarized illumination.

    Qi, Ji; He, Honghui; Lin, Jianyu; Dong, Yang; Chen, Dongsheng; Ma, Hui; Elson, Daniel S

    2018-04-01

    Tissue-depolarization and linear-retardance are the main polarization characteristics of interest for bulk tissue characterization, and are normally interpreted from Mueller polarimetry. Stokes polarimetry can be conducted using simpler instrumentation and in a shorter time. Here, we use Stokes polarimetric imaging with circularly polarized illumination to assess the circular-depolarization and linear-retardance properties of tissue. Results obtained were compared with Mueller polarimetry in transmission and reflection geometry, respectively. It is found that circular-depolarization obtained from these 2 methods is very similar in both geometries, and that linear-retardance is highly quantitatively similar for transmission geometry and qualitatively similar for reflection geometry. The majority of tissue circular-depolarization and linear-retardance image information (represented by local image contrast features) obtained from Mueller polarimetry is well preserved from Stokes polarimetry in both geometries. These findings can be referred to for further understanding tissue Stokes polarimetric data, and for further application of Stokes polarimetry under the circumstances where short acquisition time or low optical system complexity is a priority, such as polarimetric endoscopy and microscopy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Dielectric properties of biological tissues in which cells are connected by communicating junctions

    Asami, Koji

    2007-01-01

    The frequency dependence of the complex permittivity of biological tissues has been simulated using a simple model that is a cubic array of spherical cells in a parallel plate capacitor. The cells are connected by two types of communicating junctions: one is a membrane-lined channel for plasmodesmata in plant tissues, and the other is a conducting patch of adjoining plasma membranes for gap junctions in animal tissues. Both junctions provided similar effects on the dielectric properties of the tissue model. The model without junction showed a dielectric relaxation (called β-dispersion) that was expected from an interfacial polarization theory for a concentrated suspension of spherical cells. The dielectric relaxation was the same as that of the model in which neighbouring cells were connected by junctions perpendicular to the applied electric field. When neighbouring cells were connected by junctions parallel to the applied electric field or in all directions, a dielectric relaxation appeared at a lower frequency side in addition to the β-dispersion, corresponding to the so called α-dispersion. When junctions were randomly introduced at varied probabilities P j , the low-frequency (LF) relaxation curve became broader, especially at P j of 0.2-0.5, and its intensity was proportional to P j up to 0.7. The intensity and the characteristic frequency of the LF relaxation both decreased with decreasing junction conductance. The simulations indicate that communicating junctions are important for understanding the LF dielectric relaxation in tissues

  7. Dielectric properties of biological tissues in which cells are connected by communicating junctions

    Asami, Koji

    2007-06-01

    The frequency dependence of the complex permittivity of biological tissues has been simulated using a simple model that is a cubic array of spherical cells in a parallel plate capacitor. The cells are connected by two types of communicating junctions: one is a membrane-lined channel for plasmodesmata in plant tissues, and the other is a conducting patch of adjoining plasma membranes for gap junctions in animal tissues. Both junctions provided similar effects on the dielectric properties of the tissue model. The model without junction showed a dielectric relaxation (called β-dispersion) that was expected from an interfacial polarization theory for a concentrated suspension of spherical cells. The dielectric relaxation was the same as that of the model in which neighbouring cells were connected by junctions perpendicular to the applied electric field. When neighbouring cells were connected by junctions parallel to the applied electric field or in all directions, a dielectric relaxation appeared at a lower frequency side in addition to the β-dispersion, corresponding to the so called α-dispersion. When junctions were randomly introduced at varied probabilities Pj, the low-frequency (LF) relaxation curve became broader, especially at Pj of 0.2-0.5, and its intensity was proportional to Pj up to 0.7. The intensity and the characteristic frequency of the LF relaxation both decreased with decreasing junction conductance. The simulations indicate that communicating junctions are important for understanding the LF dielectric relaxation in tissues.

  8. Time-domain scanning optical mammography: II. Optical properties and tissue parameters of 87 carcinomas

    Grosenick, Dirk; Wabnitz, Heidrun; Moesta, K Thomas; Mucke, Joerg; Schlag, Peter M; Rinneberg, Herbert

    2005-01-01

    Within a clinical trial on scanning time-domain optical mammography reported on in a companion publication (part I), craniocaudal and mediolateral projection optical mammograms were recorded from 154 patients, suspected of having breast cancer. Here we report on in vivo optical properties of the subset of 87 histologically validated carcinomas which were visible in optical mammograms recorded at two or three near-infrared wavelengths. Tumour absorption and reduced scattering coefficients were derived from distributions of times of flight of photons recorded at the tumour site employing the model of diffraction of photon density waves by a spherical inhomogeneity, located in an otherwise homogeneous tissue slab. Effective tumour radii, taken from pathology, and tumour location along the compression direction, deduced from off-axis optical scans of the tumour region, were included in the analysis as prior knowledge, if available. On average, tumour absorption coefficients exceeded those of surrounding healthy breast tissue by a factor of about 2.5 (670 nm), whereas tumour reduced scattering coefficients were larger by about 20% (670 nm). From absorption coefficients at 670 nm and 785 nm total haemoglobin concentration and blood oxygen saturation were deduced for tumours and surrounding healthy breast tissue. Apart from a few outliers total haemoglobin concentration was observed to be systematically larger in tumours compared to healthy breast tissue. In contrast, blood oxygen saturation was found to be a poor discriminator for tumours and healthy breast tissue; both median values of blood oxygen saturation are the same within their statistical uncertainties. However, the ratio of total haemoglobin concentration over blood oxygen saturation further improves discrimination between tumours and healthy breast tissue. For 29 tumours detected in optical mammograms recorded at three wavelengths (670 nm, 785 nm, 843 nm or 884 nm), scatter power was derived from transport

  9. Biomechanics of cellular solids.

    Gibson, Lorna J

    2005-03-01

    Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

  10. Label-free 3D visualization of cellular and tissue structures in intact muscle with second and third harmonic generation microscopy.

    Markus Rehberg

    Full Text Available Second and Third Harmonic Generation (SHG and THG microscopy is based on optical effects which are induced by specific inherent physical properties of a specimen. As a multi-photon laser scanning approach which is not based on fluorescence it combines the advantages of a label-free technique with restriction of signal generation to the focal plane, thus allowing high resolution 3D reconstruction of image volumes without out-of-focus background several hundred micrometers deep into the tissue. While in mammalian soft tissues SHG is mostly restricted to collagen fibers and striated muscle myosin, THG is induced at a large variety of structures, since it is generated at interfaces such as refraction index changes within the focal volume of the excitation laser. Besides, colorants such as hemoglobin can cause resonance enhancement, leading to intense THG signals. We applied SHG and THG microscopy to murine (Mus musculus muscles, an established model system for physiological research, to investigate their potential for label-free tissue imaging. In addition to collagen fibers and muscle fiber substructure, THG allowed us to visualize blood vessel walls and erythrocytes as well as white blood cells adhering to vessel walls, residing in or moving through the extravascular tissue. Moreover peripheral nerve fibers could be clearly identified. Structure down to the nuclear chromatin distribution was visualized in 3D and with more detail than obtainable by bright field microscopy. To our knowledge, most of these objects have not been visualized previously by THG or any label-free 3D approach. THG allows label-free microscopy with inherent optical sectioning and therefore may offer similar improvements compared to bright field microscopy as does confocal laser scanning microscopy compared to conventional fluorescence microscopy.

  11. Effects of surface modification on the mechanical and structural properties of nanofibrous poly(ε-caprolactone)/forsterite scaffold for tissue engineering applications

    Kharaziha, M., E-mail: Kharaziha.ma@yahoo.com [Biomaterials Research Group, Department of Materials Engineering, Isfahan University of Technology, Isfahan 8415683111 (Iran, Islamic Republic of); Department of Materials Engineering, Isfahan University of Technology, Isfahan 8415683111 (Iran, Islamic Republic of); Fathi, M.H. [Biomaterials Research Group, Department of Materials Engineering, Isfahan University of Technology, Isfahan 8415683111 (Iran, Islamic Republic of); Dental Materials Research Center, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Edris, H. [Biomaterials Research Group, Department of Materials Engineering, Isfahan University of Technology, Isfahan 8415683111 (Iran, Islamic Republic of); Department of Materials Engineering, Isfahan University of Technology, Isfahan 8415683111 (Iran, Islamic Republic of)

    2013-12-01

    Composite scaffolds consisting of polymers reinforced with ceramic nanoparticles are widely applied for hard tissue engineering. However, due to the incompatible polarity of ceramic nanoparticles with polymers, they tend to agglomerate in the polymer matrix which results in undesirable effects on the integral properties of composites. In this research, forsterite (Mg{sub 2}SiO{sub 4}) nanoparticles was surface esterified by dodecyl alcohol and nanofibrous poly(ε-caprolactone)(PCL)/modified forsterite scaffolds were developed through electrospinning technique. The aim of this research was to investigate the properties of surface modified forsterite nanopowder and PCL/modified forsterite scaffolds, before and after hydrolytic treatment, as well as the cellular attachment and proliferation. Results demonstrated that surface modification of nanoparticles significantly enhanced the tensile strength and toughness of scaffolds upon 1.5- and 4-folds compared to unmodified samples, respectively, due to improved compatibility between matrix and filler. Hydrolytic treatment of scaffolds also modified the bioactivity and cellular attachment and proliferation due to greatly enhanced hydrophilicity of the forsterite nanoparticles after this process compared to surface modified samples. Results suggested that surface modification of forsterite nanopowder and hydrolytic treatment of the developed scaffolds were effective approaches to address the issues in the formation of composite fibers and resulted in development of bioactive composite scaffolds with ideal mechanical and structural properties for bone tissue engineering applications. - Highlights: • Forsterite nanopowder was surface modified with dodecyl alcohol. • Nanofibrous PCL/forsterite scaffolds were developed through electrospinning. • Composite scaffolds were treated in boiled water to remove the dodecyl chains. • Surface modification resulted in improved mechanical properties. • Hydrolytic treatment

  12. Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level.

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2014-08-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by an increase in bone fragility on the macroscopic scale, but few data are available to describe the mechanisms involved on the tissue scale and the possible correlations between these scales. To better understand the effects of OI on the properties of human bone, we studied the mechanical and chemical properties of eight bone samples from children suffering from OI and compared them to the properties of three controls. High-resolution computed tomography, nanoindentation and Raman microspectroscopy were used to assess those properties. A higher tissue mineral density was found for OI bone (1.131 gHA/cm3 vs. 1.032 gHA/cm3, p=0.032), along with a lower Young's modulus (17.6 GPa vs. 20.5 GPa, p=0.024). Obviously, the mutation-induced collagen defects alter the collagen matrix, thereby affecting the mineralization. Raman spectroscopy showed that the mineral-to-matrix ratio was higher in the OI samples, while the crystallinity was lower, suggesting that the mineral crystals were smaller but more abundant in the case of OI. This change in crystal size, distribution and composition contributes to the observed decrease in mechanical strength. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Nanoreinforced Hydrogels for Tissue Engineering: Biomaterials that are Compatible with Load-Bearing and Electroactive Tissues

    Mehrali, Mehdi; Thakur, Ashish; Pennisi, Christian Pablo

    2017-01-01

    , mechanical, and electrical properties. Here, recent advances in the fabrication and application of nanocomposite hydrogels in tissue engineering applications are described, with specific attention toward skeletal and electroactive tissues, such as cardiac, nerve, bone, cartilage, and skeletal muscle......Given their highly porous nature and excellent water retention, hydrogel-based biomaterials can mimic critical properties of the native cellular environment. However, their potential to emulate the electromechanical milieu of native tissues or conform well with the curved topology of human organs...

  14. Multilayered phantoms with tunable optical properties for a better understanding of light/tissue interactions

    Roig, Blandine; Koenig, Anne; Perraut, François; Piot, Olivier; Vignoud, Séverine; Lavaud, Jonathan; Manfait, Michel; Dinten, Jean-Marc

    2015-03-01

    Light/tissue interactions, like diffuse reflectance, endogenous fluorescence and Raman scattering, are a powerful means for providing skin diagnosis. Instrument calibration is an important step. We thus developed multilayered phantoms for calibration of optical systems. These phantoms mimic the optical properties of biological tissues such as skin. Our final objective is to better understand light/tissue interactions especially in the case of confocal Raman spectroscopy. The phantom preparation procedure is described, including the employed method to obtain a stratified object. PDMS was chosen as the bulk material. TiO2 was used as light scattering agent. Dye and ink were adopted to mimic, respectively, oxy-hemoglobin and melanin absorption spectra. By varying the amount of the incorporated components, we created a material with tunable optical properties. Monolayer and multilayered phantoms were designed to allow several characterization methods. Among them, we can name: X-ray tomography for structural information; Diffuse Reflectance Spectroscopy (DRS) with a homemade fibered bundle system for optical characterization; and Raman depth profiling with a commercial confocal Raman microscope for structural information and for our final objective. For each technique, the obtained results are presented and correlated when possible. A few words are said on our final objective. Raman depth profiles of the multilayered phantoms are distorted by elastic scattering. The signal attenuation through each single layer is directly dependent on its own scattering property. Therefore, determining the optical properties, obtained here with DRS, is crucial to properly correct Raman depth profiles. Thus, it would be permitted to consider quantitative studies on skin for drug permeation follow-up or hydration assessment, for instance.

  15. Cellular mechanics and motility

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  16. Biphasic Finite Element Modeling Reconciles Mechanical Properties of Tissue-Engineered Cartilage Constructs Across Testing Platforms.

    Meloni, Gregory R; Fisher, Matthew B; Stoeckl, Brendan D; Dodge, George R; Mauck, Robert L

    2017-07-01

    Cartilage tissue engineering is emerging as a promising treatment for osteoarthritis, and the field has progressed toward utilizing large animal models for proof of concept and preclinical studies. Mechanical testing of the regenerative tissue is an essential outcome for functional evaluation. However, testing modalities and constitutive frameworks used to evaluate in vitro grown samples differ substantially from those used to evaluate in vivo derived samples. To address this, we developed finite element (FE) models (using FEBio) of unconfined compression and indentation testing, modalities commonly used for such samples. We determined the model sensitivity to tissue radius and subchondral bone modulus, as well as its ability to estimate material parameters using the built-in parameter optimization tool in FEBio. We then sequentially tested agarose gels of 4%, 6%, 8%, and 10% weight/weight using a custom indentation platform, followed by unconfined compression. Similarly, we evaluated the ability of the model to generate material parameters for living constructs by evaluating engineered cartilage. Juvenile bovine mesenchymal stem cells were seeded (2 × 10 7 cells/mL) in 1% weight/volume hyaluronic acid hydrogels and cultured in a chondrogenic medium for 3, 6, and 9 weeks. Samples were planed and tested sequentially in indentation and unconfined compression. The model successfully completed parameter optimization routines for each testing modality for both acellular and cell-based constructs. Traditional outcome measures and the FE-derived outcomes showed significant changes in material properties during the maturation of engineered cartilage tissue, capturing dynamic changes in functional tissue mechanics. These outcomes were significantly correlated with one another, establishing this FE modeling approach as a singular method for the evaluation of functional engineered and native tissue regeneration, both in vitro and in vivo.

  17. Development of Chitosan Scaffolds with Enhanced Mechanical Properties for Intestinal Tissue Engineering Applications.

    Zakhem, Elie; Bitar, Khalil N

    2015-10-13

    Massive resections of segments of the gastrointestinal (GI) tract lead to intestinal discontinuity. Functional tubular replacements are needed. Different scaffolds were designed for intestinal tissue engineering application. However, none of the studies have evaluated the mechanical properties of the scaffolds. We have previously shown the biocompatibility of chitosan as a natural material in intestinal tissue engineering. Our scaffolds demonstrated weak mechanical properties. In this study, we enhanced the mechanical strength of the scaffolds with the use of chitosan fibers. Chitosan fibers were circumferentially-aligned around the tubular chitosan scaffolds either from the luminal side or from the outer side or both. Tensile strength, tensile strain, and Young's modulus were significantly increased in the scaffolds with fibers when compared with scaffolds without fibers. Burst pressure was also increased. The biocompatibility of the scaffolds was maintained as demonstrated by the adhesion of smooth muscle cells around the different kinds of scaffolds. The chitosan scaffolds with fibers provided a better candidate for intestinal tissue engineering. The novelty of this study was in the design of the fibers in a specific alignment and their incorporation within the scaffolds.

  18. Mesenchymal Stem/Stromal Cells from Discarded Neonatal Sternal Tissue: In Vitro Characterization and Angiogenic Properties

    Shuyun Wang

    2016-01-01

    Full Text Available Autologous and nonautologous bone marrow mesenchymal stem/stromal cells (MSCs are being evaluated as proangiogenic agents for ischemic and vascular disease in adults but not in children. A significant number of newborns and infants with critical congenital heart disease who undergo cardiac surgery already have or are at risk of developing conditions related to inadequate tissue perfusion. During neonatal cardiac surgery, a small amount of sternal tissue is usually discarded. Here we demonstrate that MSCs can be isolated from human neonatal sternal tissue using a nonenzymatic explant culture method. Neonatal sternal bone MSCs (sbMSCs were clonogenic, had a surface marker expression profile that was characteristic of bone marrow MSCs, were multipotent, and expressed pluripotency-related genes at low levels. Neonatal sbMSCs also demonstrated in vitro proangiogenic properties. Sternal bone MSCs cooperated with human umbilical vein endothelial cells (HUVECs to form 3D networks and tubes in vitro. Conditioned media from sbMSCs cultured in hypoxia also promoted HUVEC survival and migration. Given the neonatal source, ease of isolation, and proangiogenic properties, sbMSCs may have relevance to therapeutic applications.

  19. Dielectric property measurement of ocular tissues up to 110 GHz using 1 mm coaxial sensor

    Sasaki, K; Isimura, Y; Fujii, K; Wake, K; Watanabe, S; Kojima, M; Suga, R; Hashimoto, O

    2015-01-01

    Measurement of the dielectric properties of ocular tissues up to 110 GHz was performed by the coaxial probe method. A coaxial sensor was fabricated to allow the measurement of small amounts of biological tissues. Four-standard calibration was applied in the dielectric property measurement to obtain more accurate data than that obtained with conventional three-standard calibration, especially at high frequencies. Novel data of the dielectric properties of several ocular tissues are presented and compared with data from the de facto database. (paper)

  20. The importance of the biomimetic composites components for recreating the optical properties and molecular composition of intact dental tissues.

    Seredin, P. V.; Goloshchapov, D. L.; Gushchin, M. S.; Ippolitov, Y. A.; Prutskij, T.

    2017-11-01

    The objective of this paper was to investigate whether it is possible to obtain biomimetic materials recreating the luminescent properties and molecular composition of intact dental tissues. Biomimetic materials were produced and their properties compared with native dental tissues. In addition, the overall contribution of the organic and non-organic components in the photoluminescence band was investigated. The results showed that it is possible to develop biomimetic materials with similar molecular composition and optical properties to native dental tissues for the early identification of dental caries.

  1. In vitro assessment of the agonist properties of the novel 5-HT1A receptor ligand, CUMI-101 (MMP), in rat brain tissue

    Hendry, Nicola; Christie, Isabel; Rabiner, Eugenii Alfredovich; Laruelle, Marc; Watson, Jeannette

    2011-01-01

    Introduction: Development of agonist positron emission tomography (PET) radioligands for the 5-HT neurotransmitter system is an important target to enable the understanding of human 5-HT function in vivo. [ 11 C]CUMI-101, proposed as the first 5-HT 1A receptor agonist PET ligand, has been reported to behave as a potent 5-HT 1A agonist in a cellular system stably expressing human recombinant 5-HT 1A receptors. In this study, we investigate the agonist properties of CUMI-101 in rat brain tissue. Methods: [ 35 S]-GTPγS binding studies were used to determine receptor function in HEK (human embryonic kidney) 293 cells transfected with human recombinant 5-HT 1A receptors and in rat cortex and rat hippocampal tissue, following administration of CUMI-101 and standard 5-HT1A antagonists (5-HT, 5-CT and 8-OH-DPAT). Results: CUMI-101 behaved as an agonist at human recombinant 5-HT 1A receptors (pEC 50 9.2). However, CUMI-101 did not show agonist activity in either rat cortex or hippocampus at concentrations up to 10 μM. In these tissues, CUMI-behaved as an antagonist with pK B s of 9.2 and 9.3, respectively. Conclusions: Our studies demonstrate that as opposed to its behavior in human recombinant system, in rat brain tissue CUMI-101 behaves as a potent 5-HT 1A receptor antagonist.

  2. Quantitative assessment of the mechanical properties of prostate tissue with optical coherence elastography

    Ling, Yuting; Li, Chunhui; Zhou, Kanheng; Guan, Guangying; Lang, Stephen; McGloin, David; Nabi, Ghulam; Huang, Zhihong

    2018-02-01

    Prostate cancer (PCa) is a heterogeneous disease with multifocal origin. In current clinical care, the Gleason scoring system is the well-established diagnosis by microscopic evaluation of the tissue from trans-rectal ultrasound (TRUS) guided biopsies. Nevertheless, the sensitivity and specificity in detecting PCa can range from 40 to 50% for conventional TRUS B-mode imaging. Tissue elasticity is associated with the disease progression and elastography technique has recently shown promise in aiding PCa diagnosis. However, many cancer foci in the prostate gland has very small size less than 1 mm and those detected by medical elastography were larger than 2 mm. Hereby, we introduce optical coherence elastography (OCE) to quantify the prostate stiffness with high resolution in the magnitude of 10 µm. Following our feasibility study of 10 patients reported previously, we recruited 60 more patients undergoing 12-core TRUS guided biopsies for suspected PCa with a total of 720 biopsies. The stiffness of cancer tissue was approximately 57.63% higher than that of benign ones. Using histology as reference standard and cut-off threshold of 600kPa, the data analysis showed sensitivity and specificity of 89.6% and 99.8% respectively. The method also demonstrated potential in characterising different grades of PCa based on the change of tissue morphology and quantitative mechanical properties. In conclusion, quantitative OCE can be a reliable technique to identify PCa lesion and differentiate indolent from aggressive cancer.

  3. Spatial organization and correlation properties quantify structural changes on mesoscale of parenchymatous plant tissue

    Valous, N. A.; Delgado, A.; Sun, D.-W., E-mail: dawen.sun@ucd.ie [School of Biosystems Engineering, University College Dublin, National University of Ireland, Belfield, Dublin 4, Dublin (Ireland); Drakakis, K. [Complex and Adaptive Systems Laboratory, University College Dublin, National University of Ireland, Belfield, Dublin 4, Dublin (Ireland)

    2014-02-14

    The study of plant tissue parenchyma's intercellular air spaces contributes to the understanding of anatomy and physiology. This is challenging due to difficulty in making direct measurements of the pore space and the complex mosaic of parenchymatous tissue. The architectural complexity of pore space has shown that single geometrical measurements are not sufficient for characterization. The inhomogeneity of distribution depends not only on the percentage content of phase, but also on how the phase fills the space. The lacunarity morphometric, as multiscale measure, provides information about the distribution of gaps that correspond to degree of spatial organization in parenchyma. Additionally, modern theories have suggested strategies, where the focus has shifted from the study of averages and histograms to the study of patterns in data fluctuations. Detrended fluctuation analysis provides information on the correlation properties of the parenchyma at different spatial scales. The aim is to quantify (with the aid of the aforementioned metrics), the mesostructural changes—that occur from one cycle of freezing and thawing—in the void phase of pome fruit parenchymatous tissue, acquired with X-ray microcomputed tomography. Complex systems methods provide numerical indices and detailed insights regarding the freezing-induced modifications upon the arrangement of cells and voids. These structural changes have the potential to lead to physiological disorders. The work can further stimulate interest for the analysis of internal plant tissue structures coupled with other physico-chemical processes or phenomena.

  4. Spatial organization and correlation properties quantify structural changes on mesoscale of parenchymatous plant tissue

    Valous, N. A.; Delgado, A.; Sun, D.-W.; Drakakis, K.

    2014-01-01

    The study of plant tissue parenchyma's intercellular air spaces contributes to the understanding of anatomy and physiology. This is challenging due to difficulty in making direct measurements of the pore space and the complex mosaic of parenchymatous tissue. The architectural complexity of pore space has shown that single geometrical measurements are not sufficient for characterization. The inhomogeneity of distribution depends not only on the percentage content of phase, but also on how the phase fills the space. The lacunarity morphometric, as multiscale measure, provides information about the distribution of gaps that correspond to degree of spatial organization in parenchyma. Additionally, modern theories have suggested strategies, where the focus has shifted from the study of averages and histograms to the study of patterns in data fluctuations. Detrended fluctuation analysis provides information on the correlation properties of the parenchyma at different spatial scales. The aim is to quantify (with the aid of the aforementioned metrics), the mesostructural changes—that occur from one cycle of freezing and thawing—in the void phase of pome fruit parenchymatous tissue, acquired with X-ray microcomputed tomography. Complex systems methods provide numerical indices and detailed insights regarding the freezing-induced modifications upon the arrangement of cells and voids. These structural changes have the potential to lead to physiological disorders. The work can further stimulate interest for the analysis of internal plant tissue structures coupled with other physico-chemical processes or phenomena

  5. Correlation of particle properties with cytotoxicity and cellular uptake of hydroxyapatite nanoparticles in human gastric cancer cells

    Cui, Xinhui [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China); Liang, Tong [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Liu, Changsheng [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China); Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Yuan, Yuan, E-mail: yyuan@ecust.edu.cn [Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Qian, Jiangchao, E-mail: jiangchaoqian@ecust.edu.cn [State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2016-10-01

    Three types of hydroxyapatite nanoparticles (HAPNs) were synthesized employing a sonochemistry-assisted microwave method by changing microwave power (from 200 to 300 W) or using calcination treatment: L200 (200 W, lyophilization), L300 (300 W, lyophilization) and C200 (200 W, lyophilization & calcination). Their physiochemical properties were characterized and correlated with cytotoxicity to human gastric cancer cells (MGC80-3). The major differences among these HAPN preparations were their size and specific surface area, with the L200 showing a smaller size and higher specific surface area. Although all HAPNs inhibited cell proliferation and induced apoptosis of cancer cells, L200 exhibited the greatest toxicity. All types of HAPNs were internalized through energy-dependent pathways, but the L200 nanoparticles were more efficiently uptaken by MGC80-3 cells. Inhibitor studies with dynasore and methyl-β-cyclodextrin suggested that caveolae-mediated endocytosis and, to a much lesser extent, clathrin-mediated endocytosis, were involved in cellular uptake of the various preparations, whereas the inhibition of endocytosis was more obvious for L200. Using fluorescein isothiocyanate-labeled HAPNs and laser-scanning confocal microscopy, we found that all forms of nanoparticles were present in the cytoplasm, and some L200 HAPNs were even found within nuclei. Treatment with all HAPN preparations led to the increase in the intracellular calcium level with the highest level detected for L200. - Highlights: • Three types of HAPNs (L200, L300 and C200) were synthesized employing a sonochemistry-assisted microwave method. • L200 exhibited the greatest cytotoxicity to human gastric cancer (MGC80-3) cells. • L200 showed a smaller size and higher specific surface area. • The L200 nanoparticles were more efficiently uptaken by MGC80-3 cells through energy-dependent pathways. • L200 caused the most significant increase in the intracellular calcium level.

  6. Polyvinyl chloride as a multimodal tissue-mimicking material with tuned mechanical and medical imaging properties.

    Li, Weisi; Belmont, Barry; Greve, Joan M; Manders, Adam B; Downey, Brian C; Zhang, Xi; Xu, Zhen; Guo, Dongming; Shih, Albert

    2016-10-01

    The mechanical and imaging properties of polyvinyl chloride (PVC) can be adjusted to meet the needs of researchers as a tissue-mimicking material. For instance, the hardness can be adjusted by changing the ratio of softener to PVC polymer, mineral oil can be added for lubrication in needle insertion, and glass beads can be added to scatter acoustic energy similar to biological tissue. Through this research, the authors sought to develop a regression model to design formulations of PVC with targeted mechanical and multimodal medical imaging properties. The design of experiment was conducted by varying three factors-(1) the ratio of softener to PVC polymer, (2) the mass fraction of mineral oil, and (3) the mass fraction of glass beads-and measuring the mechanical properties (elastic modulus, hardness, viscoelastic relaxation time constant, and needle insertion friction force) and the medical imaging properties [speed of sound, acoustic attenuation coefficient, magnetic resonance imaging time constants T 1 and T 2 , and the transmittance of the visible light at wavelengths of 695 nm (T λ695 ) and 532 nm (T λ532 )] on twelve soft PVC samples. A regression model was built to describe the relationship between the mechanical and medical imaging properties and the values of the three composition factors of PVC. The model was validated by testing the properties of a PVC sample with a formulation distinct from the twelve samples. The tested soft PVC had elastic moduli from 6 to 45 kPa, hardnesses from 5 to 50 Shore OOO-S, viscoelastic stress relaxation time constants from 114.1 to 191.9 s, friction forces of 18 gauge needle insertion from 0.005 to 0.086 N/mm, speeds of sound from 1393 to 1407 m/s, acoustic attenuation coefficients from 0.38 to 0.61 (dB/cm)/MHz, T 1 relaxation times from 426.3 to 450.2 ms, T 2 relaxation times from 21.5 to 28.4 ms, T λ695 from 46.8% to 92.6%, and T λ532 from 41.1% to 86.3%. Statistically significant factors of each property were

  7. Characterization, corrosion behavior, cellular response and in vivo bone tissue compatibility of titanium–niobium alloy with low Young's modulus

    Bai, Yanjie; Deng, Yi; Zheng, Yunfei; Li, Yongliang; Zhang, Ranran; Lv, Yalin; Zhao, Qiang; Wei, Shicheng

    2016-01-01

    β-Type titanium alloys with a low elastic modulus are a potential strategy to enhance bone remodeling and to mitigate the concern over the risks of osteanabrosis and bone resorption caused by stress shielding, when used to substitute irreversibly impaired hard tissue. Hence, in this study, a Ti–45Nb alloy with low Young's modulus and high strength was developed, and microstructure, mechanical properties, corrosion behaviors, cytocompatibility and in vivo osteo-compatibility of the alloy were systematically investigated for the first time. The results of mechanical tests showed that Young's modulus of the Ti–Nb alloy was reduced to about 64.3 GPa (close to human cortical bone) accompanied with higher tensile strength and hardness compared with those of pure Ti. Importantly, the Ti–Nb alloy exhibited superior corrosion resistance to Ti in different solutions including SBF, MAS and FAAS (MAS containing NaF) media. In addition, the Ti–Nb alloy produced no deleterious effect to L929 and MG-63 cells, and cells performed excellent cell attachment onto Ti–Nb surface, indicating a good in vitro cytocompatibility. In vivo evaluations indicated that Ti–Nb had comparable bone tissue compatibility to Ti determined from micro-CT and histological evaluations. The Ti–Nb alloy with an elasticity close to human bone, thus, could be suitable for orthopedic/dental applications. - Highlights: • A β-type Ti–45Nb alloy was developed with low Young's modulus close to human bone. • Ti–Nb alloy had superior corrosion resistance to pure Ti in different solutions. • Ti–Nb alloy displayed good cytocompatibility and in vivo bone tissue compatibility. • Ti–Nb alloy could be suitable for orthopedic/dental application based on the study.

  8. Characterization, corrosion behavior, cellular response and in vivo bone tissue compatibility of titanium–niobium alloy with low Young's modulus

    Bai, Yanjie [Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Department of Stomatology, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Science, Beijing 100012 (China); Deng, Yi [Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Zheng, Yunfei; Li, Yongliang [Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Zhang, Ranran; Lv, Yalin [Department of Stomatology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029 (China); Zhao, Qiang, E-mail: 15911025865@139.com [Department of Stomatology, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Science, Beijing 100012 (China); Wei, Shicheng, E-mail: sc-wei@pku.edu.cn [Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China)

    2016-02-01

    β-Type titanium alloys with a low elastic modulus are a potential strategy to enhance bone remodeling and to mitigate the concern over the risks of osteanabrosis and bone resorption caused by stress shielding, when used to substitute irreversibly impaired hard tissue. Hence, in this study, a Ti–45Nb alloy with low Young's modulus and high strength was developed, and microstructure, mechanical properties, corrosion behaviors, cytocompatibility and in vivo osteo-compatibility of the alloy were systematically investigated for the first time. The results of mechanical tests showed that Young's modulus of the Ti–Nb alloy was reduced to about 64.3 GPa (close to human cortical bone) accompanied with higher tensile strength and hardness compared with those of pure Ti. Importantly, the Ti–Nb alloy exhibited superior corrosion resistance to Ti in different solutions including SBF, MAS and FAAS (MAS containing NaF) media. In addition, the Ti–Nb alloy produced no deleterious effect to L929 and MG-63 cells, and cells performed excellent cell attachment onto Ti–Nb surface, indicating a good in vitro cytocompatibility. In vivo evaluations indicated that Ti–Nb had comparable bone tissue compatibility to Ti determined from micro-CT and histological evaluations. The Ti–Nb alloy with an elasticity close to human bone, thus, could be suitable for orthopedic/dental applications. - Highlights: • A β-type Ti–45Nb alloy was developed with low Young's modulus close to human bone. • Ti–Nb alloy had superior corrosion resistance to pure Ti in different solutions. • Ti–Nb alloy displayed good cytocompatibility and in vivo bone tissue compatibility. • Ti–Nb alloy could be suitable for orthopedic/dental application based on the study.

  9. Portable, Fiber-Based, Diffuse Reflection Spectroscopy (DRS) Systems for Estimating Tissue Optical Properties.

    Vishwanath, Karthik; Chang, Kevin; Klein, Daniel; Deng, Yu Feng; Chang, Vivide; Phelps, Janelle E; Ramanujam, Nimmi

    2011-02-01

    Steady-state diffuse reflection spectroscopy is a well-studied optical technique that can provide a noninvasive and quantitative method for characterizing the absorption and scattering properties of biological tissues. Here, we compare three fiber-based diffuse reflection spectroscopy systems that were assembled to create a light-weight, portable, and robust optical spectrometer that could be easily translated for repeated and reliable use in mobile settings. The three systems were built using a broadband light source and a compact, commercially available spectrograph. We tested two different light sources and two spectrographs (manufactured by two different vendors). The assembled systems were characterized by their signal-to-noise ratios, the source-intensity drifts, and detector linearity. We quantified the performance of these instruments in extracting optical properties from diffuse reflectance spectra in tissue-mimicking liquid phantoms with well-controlled optical absorption and scattering coefficients. We show that all assembled systems were able to extract the optical absorption and scattering properties with errors less than 10%, while providing greater than ten-fold decrease in footprint and cost (relative to a previously well-characterized and widely used commercial system). Finally, we demonstrate the use of these small systems to measure optical biomarkers in vivo in a small-animal model cancer therapy study. We show that optical measurements from the simple portable system provide estimates of tumor oxygen saturation similar to those detected using the commercial system in murine tumor models of head and neck cancer.

  10. Hydrogels for lung tissue engineering: Biomechanical properties of thin collagen-elastin constructs.

    Dunphy, Siobhán E; Bratt, Jessica A J; Akram, Khondoker M; Forsyth, Nicholas R; El Haj, Alicia J

    2014-10-01

    In this study, collagen-elastin constructs were prepared with the aim of producing a material capable of mimicking the mechanical properties of a single alveolar wall. Collagen has been used in a wide range of tissue engineering applications; however, due to its low mechanical properties its use is limited to non load-bearing applications without further manipulation using methods such as cross-linking or mechanical compression. Here, it was hypothesised that the addition of soluble elastin to a collagen hydrogel could improve its mechanical properties. Hydrogels made from collagen only and collagen plus varying amounts elastin were prepared. Young׳s modulus of each membrane was measured using the combination of a non-destructive indentation and a theoretical model previously described. An increase in Young׳s modulus was observed with increasing concentration of elastin. The use of non-destructive indentation allowed for online monitoring of the elastic moduli of cell-seeded constructs over 8 days. The addition of lung fibroblasts into the membrane increased the stiffness of the hydrogels further and cell-seeded collagen hydrogels were found to have a stiffness equal to the theoretical value for a single alveolar wall (≈5kPa). Through provision of some of the native extracellular matrix components of the lung parenchyma these scaffolds may be able to provide an initial building block toward the regeneration of new functional lung tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Preparation and properties of polyvinyl alcohol (PVA) and hydroxylapatite (HA) hydrogels for cartilage tissue engineering.

    Yuan, F; Ma, M; Lu, L; Pan, Z; Zhou, W; Cai, J; Luo, S; Zeng, W; Yin, F

    2017-05-20

    A novel bioactive hydrogel for cartilage tissue based on polyvinyl alcohol (PVA) and hydroxylapatite (HA) were prepared, the effects of its component contents on the mechanical properties and microstructure of the hydrogel were investigated. The important properties of the scaffold composites, such as density, porosity, compressive modulus and microstructure were studied and analyzed through various measurements and methods. The biodegradability of hydrogel was evaluated by soaking the samples into artificial degradation solution at body temperature (36 - 37 oC) in vitro. Experimental results showed that the PVA/HA hydrogels had a density of 0.572 - 0.683 g/cm3, a porosity of 63.25 - 96.14% and a compressive modulus of 5.62 - 8.24 MP. The HA compound in the hydrogels enhanced the biodegradation significantly and linearly increased the rate of biodegradation by 2.3 - 8.5 %. The compressive modulus of PVA/HA exhibited a linear reduce to 0.86 - 1.53 MP with the time of degradation. The scaffold composites PVA/HA possess a high porosity, decent compressive modulus and good biodegradability. After further optimizing the structure and properties, this composite might be considered as novel hydrogel biomaterials to be applied in the field of cartilage tissue engineering.

  12. Improving the mechanical properties of collagen-based membranes using silk fibroin for corneal tissue engineering.

    Long, Kai; Liu, Yang; Li, Weichang; Wang, Lin; Liu, Sa; Wang, Yingjun; Wang, Zhichong; Ren, Li

    2015-03-01

    Although collagen with outstanding biocompatibility has promising application in corneal tissue engineering, the mechanical properties of collagen-based scaffolds, especially suture retention strength, must be further improved to satisfy the requirements of clinical applications. This article describes a toughness reinforced collagen-based membrane using silk fibroin. The collagen-silk fibroin membranes based on collagen [silk fibroin (w/w) ratios of 100:5, 100:10, and 100:20] were prepared by using silk fibroin and cross-linking by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. These membranes were analyzed by scanning electron microscopy and their optical property, and NaCl and tryptophan diffusivity had been tested. The water content was found to be dependent on the content of silk fibroin, and CS10 membrane (loading 10 wt % of silk fibroin) performed the optimal mechanical properties. Also the suture experiments have proved CS10 has high suture retention strength, which can be sutured in rabbit eyes integrally. Moreover, the composite membrane proved good biocompatibility for the proliferation of human corneal epithelial cells in vitro. Lamellar keratoplasty shows that CS10 membrane promoted complete epithelialization in 35 ± 5 days, and their transparency is restored quickly in the first month. Corneal rejection reaction, neovascularization, and keratoconus are not observed. The composite films show potential for use in the field of corneal tissue engineering. © 2014 Wiley Periodicals, Inc.

  13. The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.

    Ohri, Chandra M; Shikotra, Aarti; Green, Ruth H; Waller, David A; Bradding, Peter

    2011-01-01

    We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM) expression of proteins associated with M1 and M2 macrophages in NSCLC. Using immunohistochemistry, CD68(+) macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14), or a non-cytotoxic M2 phenotype (CD163 and VEGF) were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES) (median 92.7 months) and 20 patients with poor survival (PS) (median 7.7 months). The NM expression of NM-HLA-DR (pMRP 8/14 (p = 0.02) was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (pMRP 8/14 (p = 0.01) expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR pMRP 8/14 p = 0.04), as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41) and 19.4% versus 59.0% (NM-VEGF p = 0.001). Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

  14. Chondroprotective supplementation promotes the mechanical properties of injectable scaffold for human nucleus pulposus tissue engineering.

    Foss, Berit L; Maxwell, Thomas W; Deng, Ying

    2014-01-01

    A result of intervertebral disc (IVD) degeneration, the nucleus pulposus (NP) is no longer able to withstand applied load leading to pain and disability. The objective of this study is to fabricate a tissue-engineered injectable scaffold with chondroprotective supplementation in vitro to improve the mechanical properties of a degenerative NP. Tissue-engineered scaffolds were fabricated using different concentrations of alginate and calcium chloride and mechanically evaluated. Fabrication conditions were based on structural and mechanical resemblance to the native NP. Chondroprotective supplementation, glucosamine (GCSN) and chondroitin sulfate (CS), were added to scaffolds at concentrations of 0:0µg/mL (0:0-S), 125:100µg/mL (125:100-S), 250:200µg/mL (250:200-S), and 500:400µg/mL (500:400-S), GCSN and CS, respectively. Scaffolds were used to fabricate tissue-engineered constructs through encapsulation of human nucleus pulposus cells (HNPCs). The tissue-engineered constructs were collected at days 1, 14, and 28 for biochemical and biomechanical evaluations. Confocal microscopy showed HNPC viability and rounded morphology over the 28 day period. MTT analysis resulted in significant increases in cell proliferation for each group. Collagen type II ELISA quantification and compressive aggregate moduli (HA) showed increasing trends for both 250:200-S and the 500:400-S groups on Day 28 with significantly greater HA compared to 0:0-S group. Glycosaminoglycan and water content decreased for all groups. Results indicate the increased mechanical properties of the 250:200-S and the 500:400-S was due to production of a functional matrix. This study demonstrated potential for a chondroprotective supplemented injectable scaffold to restore biomechanical function of a degenerative disc through the production of a mechanically functional matrix. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Cosserat modeling of cellular solids

    Onck, P.R.

    Cellular solids inherit their macroscopic mechanical properties directly from the cellular microstructure. However, the characteristic material length scale is often not small compared to macroscopic dimensions, which limits the applicability of classical continuum-type constitutive models. Cosserat

  16. Evaluation of Structural Cellular Glass

    Adams, M. A.; Zwissler, J. G.

    1984-01-01

    Preliminary design information presented. First report discusses state of structural-cellular-glass programs as of June 1979. Second report gives further details of program to develop improved cellular glasses and to characterize properties of glasses and commercially available materials.

  17. Changes of Dielectric Properties induced by Fast neutrons in Tissue Equivalent Plastic A-150

    Abdou, M.S.

    2000-01-01

    Tissue equivalent plastic A-150 (TEP A-150) samples are exposed to fast neutrons. Dielectric studies for TEP A-150 are carried out in the frequency range from 40 Hz to 4 MHz in the temperature range 295-343 K. The obtained data revealed that, both the dielectric properties and conductivity sigma ac (omega) of TEP A-150 are altered when irradiated by a relatively high fast neutron dose (15 Sv). The values of dielectric constant and conductivity are increased for the irradiated samples to about 24% than the blank samples

  18. effect of electromagnetic fields from cellular phone base stations on some physiological and biophysical properties of rats

    Mahmoud, A.H.

    2006-01-01

    the hazards of exposure to EMFs are observed on different tissues, the mechanistic by which EMFs can produce such effect still need to be delineated. the present study aims to monitor the possibility of modulation in the different physiological and biophysical properties of the organs after exposure to microwave produced from mobile phone base station at frequency of 900 MHz. one hundred and ten pregnant rats were exposed for periods of 5 and 12 week's at distances of 8,15 and 25 meter from the station antenna (0.01,0.05 and 0.036 MW/cm 2 ) the groups exposed for 5 weeks classified into two halves, one half was used for direct effect studies and the other was used for delayed effects studies (45 days post irradiation). haematological investigations demonstrated non significant changes in (RBC's), (Hb),(PCV) and (MCV)of exposed and delayed rats for 5,12 weeks. the young's of exposed rats show non considerable increase in RBC's, Hb and PCV. significant increases were observed in serum total protein , albumin and globulin levels in 5 and 12 weeks exposed rats and more significant increase in delayed rats

  19. Luminescent cyclometalated iridium(III) polypyridine indole complexes--synthesis, photophysics, electrochemistry, protein-binding properties, cytotoxicity, and cellular uptake.

    Lau, Jason Shing-Yip; Lee, Pui-Kei; Tsang, Keith Hing-Kit; Ng, Cyrus Ho-Cheong; Lam, Yun-Wah; Cheng, Shuk-Han; Lo, Kenneth Kam-Wing

    2009-01-19

    A series of luminescent cyclometalated iridium(III) polypyridine indole complexes, [Ir(N--C)(2)(N--N)](PF(6)) (HN--C = 2-phenylpyridine (Hppy), N--N = 4-((2-(indol-3-yl)ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine (bpy-ind) (1a), N--N = 4-((5-((2-(indol-3-yl)ethyl)aminocarbonyl)pentyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine (bpy-C6-ind) (1b); HN--C = 7,8-benzoquinoline (Hbzq), N--N = bpy-ind (2a), N--N = bpy-C6-ind (2b); and HN--C = 2-phenylquinoline (Hpq), N--N = bpy-ind (3a), N--N = bpy-C6-ind (3b)), have been synthesized, characterized, and their photophysical and electrochemical properties and lipophilicity investigated. Photoexcitation of the complexes in fluid solutions at 298 K and in alcohol glass at 77 K resulted in intense and long-lived luminescence (lambda(em) = 540-616 nm, tau(o) = 0.13-5.15 mus). The emission of the complexes has been assigned to a triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir) --> pi*(N--N)) excited state, probably with some mixing of triplet intraligand ((3)IL) (pi --> pi*) (pq) character for complexes 3a,b. Electrochemical measurements revealed that all the complexes showed an irreversible indole oxidation wave at ca. +1.1 V versus SCE, a quasi-reversible iridium(IV/III) couple at ca. +1.3 V, and a reversible diimine reduction couple at ca. -1.3 V. The interactions of these complexes with an indole-binding protein, bovine serum albumin (BSA), have been studied by emission titrations, and the K(a) values are on the order of 10(4) M(-1). Additionally, the cytotoxicity of the complexes toward human cervix epithelioid carcinoma (HeLa) cells has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC(50) values of the complexes ranged from 1.1 to 6.3 microM, which are significantly smaller than that of cisplatin (30.7 microM) under the same experimental conditions. Furthermore, the cellular uptake of the complexes has been investigated by flow cytometry and laser

  20. Decreased mechanical properties of heart valve tissue constructs cultured in platelet lysate as compared to fetal bovine serum

    Geemen, van D.; Riem Vis, P.W.; Soekhradj - Soechit, R.S.; Sluijter, J.P.G.; Liefde - van Beest, de M.; Kluin, J.; Bouten, C.V.C.

    2011-01-01

    In autologous heart valve tissue engineering, there is an ongoing search for alternatives of fetal bovine serum (FBS). Human platelet-lysate (PL) might be a promising substitute. In the present article, we aimed to examine the tissue formation, functionality, and mechanical properties of engineered

  1. Influence of Various Pulp Properties on the Adhesion Between Tissue Paper and Yankee Cylinder Surface

    Jonna Boudreau

    2014-02-01

    Full Text Available The strength of the adhesion between the paper and the drying Yankee cylinder is of great importance with respect to the final properties of a tissue paper product. Therefore, the effects of a few potentially important pulp properties have been evaluated in laboratory experiments. Four highly different kraft pulps were used, and the adhesion strength was measured by means of the force required when scraping off a paper from a metal surface with a specifically designed knife mounted on a moving cart. The adhesion strength was observed to increase with increasing grammage and increasing degree of beating of the pulp. It was also found that pulps containing more fines, or with higher hemicellulose content, gave rise to higher adhesion strength.

  2. Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

    Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D; Marini, Joan C; Caird, Michelle S; Morris, Michael D; Kozloff, Kenneth M

    2016-03-01

    Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and

  3. Poly (Ethylene Glycol)-Based Hydrogels as Self-Inflating Tissue Expanders with Tunable Mechanical and Swelling Properties.

    Jamadi, Mahsa; Shokrollahi, Parvin; Houshmand, Behzad; Joupari, Mortaza Daliri; Mashhadiabbas, Fatemeh; Khademhosseini, Ali; Annabi, Nasim

    2017-08-01

    Tissue expansion is used by plastic/reconstructive surgeons to grow additional skin/tissue for replacing or repairing lost or damaged soft tissues. Recently, hydrogels have been widely used for tissue expansion applications. Herein, a self-inflating tissue expander blend composition from three different molecular weights (2, 6, and 10 kDa) of poly (ethylene glycol) diacrylate (PEGDA) hydrogel with tunable mechanical and swelling properties is presented. The in vitro results demonstrate that, of the eight studied compositions, P6 (PEGDA 6 kDa:10 kDa (50:50)) and P8 (PEGDA 6 kDa:10 kDa (35:65)) formulations provide a balance of mechanical property and swelling capability suitable for tissue expansion. Furthermore, these expanders can be compressed up to 60% of their original height and can be loaded and unloaded cyclically at least ten times with no permanent deformation. The in vivo results indicate that these two engineered blend compositions are capable to generate a swelling pressure sufficient to dilate the surrounding tissue while retaining their original shape. The histological analyses reveal the formation of fibrous capsule at the interface between the implant and the subcutaneous tissue with no signs of inflammation. Ultimately, controlling the PEGDA chain length shows potential for the development of self-inflating tissue expanders with tunable mechanical and swelling properties. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. A novel bioreactor to simulate urinary bladder mechanical properties and compliance for bladder functional tissue engineering.

    Wei, Xin; Li, Dao-bing; Xu, Feng; Wang, Yan; Zhu, Yu-chun; Li, Hong; Wang, Kun-jie

    2011-02-01

    Bioreactors are pivotal tools for generating mechanical stimulation in functional tissue engineering study. This study aimed to create a bioreactor that can simulate urinary bladder mechanical properties, and to investigate the effects of a mechanically stimulated culture on urothelial cells and bladder smooth muscle cells. We designed a bioreactor to simulate the mechanical properties of bladder. A pressure-record system was used to evaluate the mechanical properties of the bioreactor by measuring the pressure in culture chambers. To test the biocompatibility of the bioreactor, viabilities of urothelial cells and smooth muscle cells cultured in the bioreactor under static and mechanically changed conditions were measured after 7-day culture. To evaluate the effect of mechanical stimulations on the vital cells, urethral cells and smooth muscle cells were cultured in the simulated mechanical conditions. After that, the viability and the distribution pattern of the cells were observed and compared with cells cultured in non-mechanical stimulated condition. The bioreactor system successfully generated waveforms similar to the intended programmed model while maintaining a cell-seeded elastic membrane between the chambers. There were no differences between viabilities of urothelial cells ((91.90 ± 1.22)% vs. (93.14 ± 1.78)%, P > 0.05) and bladder smooth muscle cells ((93.41 ± 1.49)% vs. (92.61 ± 1.34)%, P > 0.05). The viability of cells and tissue structure observation after cultured in simulated condition showed that mechanical stimulation was the only factor affected cells in the bioreactor and improved the arrangement of cells on silastic membrane. This bioreactor can effectively simulate the physiological and mechanical properties of the bladder. Mechanical stimulation is the only factor that affected the viability of cells cultured in the bioreactor. The bioreactor can change the growth behavior of urothelial cells and bladder smooth muscle cells, resulting in

  5. Experimental evaluation of the thermal properties of two tissue equivalent phantom materials.

    Craciunescu, O I; Howle, L E; Clegg, S T

    1999-01-01

    Tissue equivalent radio frequency (RF) phantoms provide a means for measuring the power deposition of various hyperthermia therapy applicators. Temperature measurements made in phantoms are used to verify the accuracy of various numerical approaches for computing the power and/or temperature distributions. For the numerical simulations to be accurate, the electrical and thermal properties of the materials that form the phantom should be accurately characterized. This paper reports on the experimentally measured thermal properties of two commonly used phantom materials, i.e. a rigid material with the electrical properties of human fat, and a low concentration polymer gel with the electrical properties of human muscle. Particularities of the two samples required the design of alternative measuring techniques for the specific heat and thermal conductivity. For the specific heat, a calorimeter method is used. For the thermal diffusivity, a method derived from the standard guarded comparative-longitudinal heat flow technique was used for both materials. For the 'muscle'-like material, the thermal conductivity, density and specific heat at constant pressure were measured as: k = 0.31 +/- 0.001 W(mK)(-1), p = 1026 +/- 7 kgm(-3), and c(p) = 4584 +/- 107 J(kgK)(-1). For the 'fat'-like material, the literature reports on the density and specific heat such that only the thermal conductivity was measured as k = 0.55 W(mK)(-1).

  6. Poly(amido-amine)-based hydrogels with tailored mechanical properties and degradation rates for tissue engineering.

    Martello, Federico; Tocchio, Alessandro; Tamplenizza, Margherita; Gerges, Irini; Pistis, Valentina; Recenti, Rossella; Bortolin, Monica; Del Fabbro, Massimo; Argentiere, Simona; Milani, Paolo; Lenardi, Cristina

    2014-03-01

    Poly(amido-amine) (PAA) hydrogels containing the 2,2-bisacrylamidoacetic acid-4-amminobutyl guanidine monomeric unit have a known ability to enhance cellular adhesion by interacting with the arginin-glycin-aspartic acid (RGD)-binding αVβ3 integrin, expressed by a wide number of cell types. Scientific interest in this class of materials has traditionally been hampered by their poor mechanical properties and restricted range of degradation rate. Here we present the design of novel biocompatible, RGD-mimic PAA-based hydrogels with wide and tunable degradation rates as well as improved mechanical and biological properties for biomedical applications. This is achieved by radical polymerization of acrylamide-terminated PAA oligomers in both the presence and absence of 2-hydroxyethylmethacrylate. The degradation rate is found to be precisely tunable by adjusting the PAA oligomer molecular weight and acrylic co-monomer concentration in the starting reaction mixture. Cell adhesion and proliferation tests on Madin-Darby canine kidney epithelial cells show that PAA-based hydrogels have the capacity to promote cell adhesion up to 200% compared to the control. Mechanical tests show higher compressive strength of acrylic chain containing hydrogels compared to traditional PAA hydrogels. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  7. The influence of supercritical foaming conditions on properties of polymer scaffolds for tissue engineering

    Kosowska Katarzyna

    2017-12-01

    Full Text Available The results of experimental investigations into foaming process of poly(ε-caprolactone using supercritical CO2 are presented. The objective of the study was to explore the aspects of fabrication of biodegradable and biocompatible scaffolds that can be applied as a temporary three-dimensional extracellular matrix analog for cells to grow into a new tissue. The influence of foaming process parameters, which have been proven previously to affect significantly scaffold bioactivity, such as pressure (8-18 MPa, temperature (323-373 K and time of saturation (1-6 h on microstructure and mechanical properties of produced polymer porous structures is presented. The morphology and mechanical properties of considered materials were analyzed using a scanning electron microscope (SEM, x-ray microtomography (μ-CT and a static compression test. A precise control over porosity and morphology of obtained polymer porous structures by adjusting the foaming process parameters has been proved. The obtained poly(ε-caprolactone solid foams prepared using scCO2 have demonstrated sufficient mechanical strength to be applied as scaffolds in tissue engineering.

  8. High-resolution optical polarimetric elastography for measuring the mechanical properties of tissue

    Hudnut, Alexa W.; Armani, Andrea M.

    2018-02-01

    Traditionally, chemical and molecular markers have been the predominate method in diagnostics. Recently, alternate methods of determining tissue and disease characteristics have been proposed based on testing the mechanical behavior of biomaterials. Existing methods for performing elastography measurements, such as atomic force microscopy, compression testing, and ultrasound elastography, require either extensive sample processing or have poor resolution. In the present work, we demonstrate an optical polarimetric elastography device to characterize the mechanical properties of salmon skeletal muscle. A fiber-coupled 1550nm laser paired with an optical polarizer is used to create a fiber optic sensing region. By measuring the change in polarization from the initial state to the final state within the fiber sensing region with a polarimeter, the loading-unloading curves can be determined for the biomaterial. The device is used to characterize the difference between samples with a range of collagen membranes. The loading-unloading curves are used to determine the change in polarization phase and energy loss of the samples at 10%, 20% and 30% strain. As expected, the energy loss is a better metric for measuring the mechanical properties of the tissues because it incorporates the entire loading-unloading curve rather than a single point. Using this metric, it is demonstrated the device can repeatedly differentiate between the different membrane configurations.

  9. Mathematical Modeling of Uniaxial Mechanical Properties of Collagen Gel Scaffolds for Vascular Tissue Engineering

    Ramiro M. Irastorza

    2015-01-01

    Full Text Available Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.. When Akaike criterion is used, the best is the Mooney-Rivlin inspired model.

  10. Mathematical modeling of uniaxial mechanical properties of collagen gel scaffolds for vascular tissue engineering.

    Irastorza, Ramiro M; Drouin, Bernard; Blangino, Eugenia; Mantovani, Diego

    2015-01-01

    Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.). When Akaike criterion is used, the best is the Mooney-Rivlin inspired model.

  11. A numerical investigation into the influence of the properties of cobalt chrome cellular structures on the load transfer to the periprosthetic femur following total hip arthroplasty.

    Hazlehurst, Kevin Brian; Wang, Chang Jiang; Stanford, Mark

    2014-04-01

    Stress shielding of the periprosthetic femur following total hip arthroplasty is a problem that can promote the premature loosening of femoral stems. In order to reduce the need for revision surgery it is thought that more flexible implant designs need to be considered. In this work, the mechanical properties of laser melted square pore cobalt chrome molybdenum cellular structures have been incorporated into the design of a traditional monoblock femoral stem. The influence of incorporating the properties of cellular structures on the load transfer to the periprosthetic femur was investigated using a three dimensional finite element model. Eleven different stiffness configurations were investigated by using fully porous and functionally graded approaches. This investigation confirms that the periprosthetic stress values depend on the stiffness configuration of the stem. The numerical results showed that stress shielding is reduced in the periprosthetic Gruen zones when the mechanical properties of cobalt chrome molybdenum cellular structures are used. This work identifies that monoblock femoral stems manufactured using a laser melting process, which are designed for reduced stiffness, have the potential to contribute towards reducing stress shielding. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

  12. Raman spectral properties of squamous cell carcinoma of oral tissues and cells

    Su, L.; Sun, Y. F.; Chen, Y.; Chen, P.; Shen, A. G.; Wang, X. H.; Jia, J.; Zhao, Y. F.; Zhou, X. D.; Hu, J. M.

    2012-01-01

    Early diagnosis is the key of the improved survival rates of oral cancer. Raman spectroscopy is sensitive to the early changes of molecular composition and structure that occur in benign lesion during carcinogenesis. In this study, in situ Raman analysis provided distinct spectra that can be used to discriminate between normal and malignant tissues, as well as normal and cancer cells. The biochemical variations between different groups were analyzed by the characteristic bands by comparing the normalized mean spectra. Spectral profiles of normal, malignant conditions show pronounced differences between one another, and multiple Raman markers associated with DNA and protein vibrational modes have been identified that exhibit excellent discrimination power for cancer sample identification. Statistical analyses of the Raman data and classification using principal component analysis (PCA) are shown to be effective for the Raman spectral diagnosis of oral mucosal diseases. The results indicate that the biomolecular differences between normal and malignant conditions are more obviously at the cellular level. This technique could provide a research foundation for the Raman spectral diagnosis of oral mucosal diseases.

  13. The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.

    Chandra M Ohri

    Full Text Available BACKGROUND: We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM expression of proteins associated with M1 and M2 macrophages in NSCLC. METHODS: Using immunohistochemistry, CD68(+ macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14, or a non-cytotoxic M2 phenotype (CD163 and VEGF were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES (median 92.7 months and 20 patients with poor survival (PS (median 7.7 months. RESULTS: The NM expression of NM-HLA-DR (p<0.001, NM-iNOS (p = 0.02 and NM-MRP 8/14 (p = 0.02 was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001. There was more NM-CD163 expression (p = 0.04 but less NM-iNOS (p = 0.002 and MRP 8/14 (p = 0.01 expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001, 65.0% versus 14.6% (NM-iNOS p = 0.003, and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04, as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41 and 19.4% versus 59.0% (NM-VEGF p = 0.001. CONCLUSIONS: Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

  14. A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition.

    Krishnan, Anuradha; Abdullah, Tasduq Sheikh; Mounajjed, Taofic; Hartono, Stella; McConico, Andrea; White, Thomas; LeBrasseur, Nathan; Lanza, Ian; Nair, Sreekumaran; Gores, Gregory; Charlton, Michael

    2017-06-01

    The sequence of events that lead to inflammation and fibrosing nonalcoholic steatohepatitis (NASH) is incompletely understood. Hence, we investigated the chronology of whole body, tissue, and cellular events that occur during the evolution of diet-induced NASH. Male C57Bl/6 mice were assigned to a fast-food (FF; high calorie, high cholesterol, high fructose) or standard-chow (SC) diet over a period of 36 wk. Liver histology, body composition, mitochondrial respiration, metabolic rate, gene expression, and hepatic lipid content were analyzed. Insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] increased 10-fold after 4 wk. Fibrosing NASH was fully established by 16 wk. Total hepatic lipids increased by 4 wk and remained two- to threefold increased throughout. Hepatic triglycerides declined from sixfold increase at 8 wk to threefold increase by 36 wk. In contrast, hepatic cholesterol levels steadily increased from baseline at 8 wk to twofold by 36 wk. The hepatic immune cell population altered over time with macrophages persisting beyond 16 wk. Mitochondrial oxygen flux rates of FF mice diet were uniformly lower with all the tested substrates (13-276 pmol·s -1 ·ml -1 per unit citrate synthase) than SC mice (17-394 pmol·s -1 ·ml -1 per unit citrate synthase) and was accompanied by decreased mitochondrial:nuclear gene copy number ratios after 4 wk. Metabolic rate was lower in FF mice. Mitochondrial glutathione was significantly decreased at 24 wk in FF mice. Expression of dismutases and catalase was also decreased in FF mice. The evolution of NASH in the FF diet-induced model is multiphasic, particularly in terms of hepatic lipid composition. Insulin resistance precedes hepatic inflammation and fibrosis. Mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. Collectively, these observations provide a unique overview of the sequence of changes that coevolve with the histological evolution of

  15. Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child.

    Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

    2015-01-01

    Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters.

  16. Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child

    Shihai Cui

    2015-01-01

    Full Text Available Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters.

  17. Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

    Fraenzel, W.; Gerlach, R.; Hein, H.J.; Schaller, H.G.

    2006-01-01

    Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 registered or elmex gelee registered . The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In non-irradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 registered or elmex gelee registered led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected, by remineralization than the dentine. (orig.)

  18. Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

    Fraenzel, W. [Dept. of Physics, Martin Luther Univ. Halle (Germany); Gerlach, R. [Univ. Clinic and Policlinic for Radiation Therapy, Martin Luther Univ. Halle (Germany); Hein, H.J. [Univ. Clinic and Policlinic for Orthopaedics and Physical Medicine, Martin Luther Univ. Halle (Germany); Schaller, H.G. [Dept. of Operative Dentistry and Periodontology, Martin Luther Univ. Halle (Germany)

    2006-07-01

    Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 {sup registered} or elmex gelee {sup registered}. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In non-irradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 {sup registered} or elmex gelee {sup registered} led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected, by remineralization than the dentine. (orig.)

  19. Skeletal muscle connective tissue

    Brüggemann, Dagmar Adeline

    in the structure of fibrous collagen and myofibers at high-resolution. The results demonstrate that the collagen composition in the extra cellular matrix of Gadus morhua fish muscle is much more complex than previously anticipated, as it contains type III, IV, V  and VI collagen in addition to type I. The vascular....... Consequently, functional structures, ensuring "tissue maintenance" must form a major role of connective tissue, in addition that is to the force transmitting structures one typically finds in muscle. Vascular structures have also been shown to change their mechanical properties with age and it has been shown...

  20. Estimation of anisotropy factor spectrum for determination of optical properties in biological tissues

    Iwamoto, Misako; Honda, Norihiro; Ishii, Katsunori; Awazu, Kunio

    2017-07-01

    Spectroscopic setup for measuring anisotropy factor g spectrum of biological tissues was constructed. g of chicken liver tissue was lower than chicken breast tissue. High absorption of hemoglobin can have an influence on g spectrum.

  1. Cytoskeletal remodeling of connective tissue fibroblasts in response to static stretch is dependent on matrix material properties

    Abbott, Rosalyn D; Koptiuch, Cathryn; Iatridis, James C; Howe, Alan K; Badger, Gary J; Langevin, Helene M

    2012-01-01

    In areolar “loose” connective tissue, fibroblasts remodel their cytoskeleton within minutes in response to static stretch resulting in increased cell body cross-sectional area that relaxes the tissue to a lower state of resting tension. It remains unknown whether the loosely arranged collagen matrix, characteristic of areolar connective tissue, is required for this cytoskeletal response to occur. The purpose of this study was to evaluate cytoskeletal remodeling of fibroblasts in and dissociated from areolar and dense connective tissue in response to 2 hours of static stretch in both native tissue and collagen gels of varying crosslinking. Rheometric testing indicated that the areolar connective tissue had a lower dynamic modulus and was more viscous than the dense connective tissue. In response to stretch, cells within the more compliant areolar connective tissue adopted a large “sheet-like” morphology that was in contrast to the smaller dendritic morphology in the dense connective tissue. By adjusting the in vitro collagen crosslinking, and the resulting dynamic modulus, it was demonstrated that cells dissociated from dense connective tissue are capable of responding when seeded into a compliant matrix, while cells dissociated from areolar connective tissue can lose their ability to respond when their matrix becomes stiffer. This set of experiments indicated stretch-induced fibroblast expansion was dependent on the distinct matrix material properties of areolar connective tissues as opposed to the cells’ tissue of origin. These results also suggest that disease and pathological processes with increased crosslinks, such as diabetes and fibrosis, could impair fibroblast responsiveness in connective tissues. PMID:22552950

  2. Optical properties of bovine muscle tissue in vitro; a comparison of methods

    Zijp, Jaap R.; Bosch, Jaap J. ten

    1998-01-01

    We measured the optical properties of muscular tissue using several methods. Collimated transmission measurements of thin slabs showed spatial anisotropy of the scattering processes. Surface roughness of the sample disables the calculation of the extinction coefficient from these measurements. From angular intensity measurements we found a scattering asymmetry parameter g 0.96. In fresh samples the optical diffusion constant D depends on the orientation with respect to the longitudinal direction of the muscular cells. From the D values we calculated s' perpendicular to the longitudinal direction as 0.19 mm -1 (at 543 nm), 0.39 mm -1 (at 594 nm) and 0.59 mm -1 (at 632 nm). The values for D which we measured from samples that were frozen and thawed did not show dependence on orientation. From spectral dependent reflectance measurements we found an oxygenation degree of 0.61 and a reduced scattering coefficient s'=0.85mm -1 around 560 nm. (author)

  3. Measuring the linear and nonlinear elastic properties of brain tissue with shear waves and inverse analysis.

    Jiang, Yi; Li, Guoyang; Qian, Lin-Xue; Liang, Si; Destrade, Michel; Cao, Yanping

    2015-10-01

    We use supersonic shear wave imaging (SSI) technique to measure not only the linear but also the nonlinear elastic properties of brain matter. Here, we tested six porcine brains ex vivo and measured the velocities of the plane shear waves induced by acoustic radiation force at different states of pre-deformation when the ultrasonic probe is pushed into the soft tissue. We relied on an inverse method based on the theory governing the propagation of small-amplitude acoustic waves in deformed solids to interpret the experimental data. We found that, depending on the subjects, the resulting initial shear modulus [Formula: see text] varies from 1.8 to 3.2 kPa, the stiffening parameter [Formula: see text] of the hyperelastic Demiray-Fung model from 0.13 to 0.73, and the third- [Formula: see text] and fourth-order [Formula: see text] constants of weakly nonlinear elasticity from [Formula: see text]1.3 to [Formula: see text]20.6 kPa and from 3.1 to 8.7 kPa, respectively. Paired [Formula: see text] test performed on the experimental results of the left and right lobes of the brain shows no significant difference. These values are in line with those reported in the literature on brain tissue, indicating that the SSI method, combined to the inverse analysis, is an efficient and powerful tool for the mechanical characterization of brain tissue, which is of great importance for computer simulation of traumatic brain injury and virtual neurosurgery.

  4. Design and properties of 3D scaffolds for bone tissue engineering.

    Gómez, S; Vlad, M D; López, J; Fernández, E

    2016-09-15

    In this study, the Voronoi tessellation method has been used to design novel bone like three dimension (3D) porous scaffolds. The Voronoi method has been processed with computer design software to obtain 3D virtual isotropic porous interconnected models, exactly matching the main histomorphometric indices of trabecular bone (trabecular thickness, trabecular separation, trabecular number, bone volume to total volume ratio, bone surface to bone volume ratio, etc.). These bone like models have been further computed for mechanical (elastic modulus) and fluid mass transport (permeability) properties. The results show that the final properties of the scaffolds can be controlled during their microstructure and histomorphometric initial design stage. It is also shown that final properties can be tuned during the design stage to exactly match those of trabecular natural bone. Moreover, identical total porosity models can be designed with quite different specific bone surface area and thus, this specific microstructural feature can be used to favour cell adhesion, migration and, ultimately, new bone apposition (i.e. osteoconduction). Once the virtual models are fully characterized and optimized, these can be easily 3D printed by additive manufacturing and/or stereolitography technologies. The significance of this article goes far beyond the specific objectives on which it is focussed. In fact, it shows, in a guided way, the entire novel process that can be followed to design graded porous implants, whatever its external shape and geometry, but internally tuned to the exact histomorphometric indices needed to match natural human tissues microstructures and, consequently, their mechanical and fluid properties, among others. The significance is even more relevant nowadays thanks to the available new computing and design software that is easily linked to the 3D printing new technologies. It is this transversality, at the frontier of different disciplines, the main characteristic

  5. Effect of eccentric training on the plantar flexor muscle-tendon tissue properties.

    Mahieu, Nele Nathalie; McNair, Peter; Cools, Ann; D'Haen, Caroline; Vandermeulen, Katrien; Witvrouw, Erik

    2008-01-01

    It has been shown that eccentric training can be effective in the rehabilitation of patients with Achilles tendonopathy. The mechanism behind these results is not clear. However, there is evidence that tendons are able to respond to repeated forces by altering their structure and composition, and, thus, their mechanical properties change. In this regard, the objective of the present study was to investigate whether eccentric training affects the mechanical properties of the plantar flexor's muscle-tendon tissue properties. Seventy-four healthy subjects were randomized into two groups: an eccentric training group and a control group. The eccentric training group performed a 6-wk eccentric training program for the calf muscles. Before and after this period, all subjects were evaluated for dorsiflexion range of motion using universal goniometry, passive resistive torque of the plantar flexors, and stiffness of the Achilles tendon. Passive resistive torque was measured during ankle dorsiflexion on an isokinetic dynamometer. Stiffness of the Achilles tendon was assessed using a dynamometer, in combination with ultrasonography. The results of the study reveal that the dorsiflexion range of motion was significantly increased only in the eccentric training group. The eccentric heel drop program also resulted in a significant decrease of the passive resistive torque of the plantar flexors (from 16.423 +/- 0.827 to 12.651 +/- 0.617 N.m). The stiffness of the Achilles tendon did not change significantly as a result of training. These findings provide evidence that an eccentric training program results in changes to some of the mechanical properties of the plantar flexor muscles. These changes were thought to be associated with modifications to structure rather than to stretch tolerance.

  6. Preparation and Properties of 3D Printed Alginate–Chitosan Polyion Complex Hydrogels for Tissue Engineering

    Qiongqiong Liu

    2018-06-01

    Full Text Available Three-dimensional (3D printing holds great potential for preparing sophisticated scaffolds for tissue engineering. As a result of the shear thinning properties of an alginate solution, it is often used as 3D printing ink. However, it is difficult to prepare scaffolds with complexity structure and high fidelity, because the alginate solution has a low viscosity and alginate hydrogels prepared with Ca2+ crosslinking are mechanically weak. In this work, chitosan powders were dispersed and swelled in an alginate solution, which could effectively improve the viscosity of an alginate solution by 1.5–4 times. With the increase of chitosan content, the shape fidelity of the 3D printed alginate–chitosan polyion complex (AlCh PIC hydrogels were improved. Scanning electron microscope (SEM photographs showed that the lateral pore structure of 3D printed hydrogels was becoming more obvious. As a result of the increased reaction ion pairs in comparison to the alginate hydrogels that were prepared with Ca2+ crosslinking, AlCh PIC hydrogels were mechanically strong, and the compression stress of hydrogels at a 90% strain could achieve 1.4 MPa without breaking. In addition, human adipose derived stem cells (hASCs adhered to the 3D printed AlCh PIC hydrogels and proliferated with time, which indicated that the obtained hydrogels were biocompatible and could potentially be used as scaffolds for tissue engineering.

  7. Mechanical properties and biocompatibility of porous titanium scaffolds for bone tissue engineering.

    Chen, Yunhui; Frith, Jessica Ellen; Dehghan-Manshadi, Ali; Attar, Hooyar; Kent, Damon; Soro, Nicolas Dominique Mathieu; Bermingham, Michael J; Dargusch, Matthew S

    2017-11-01

    Synthetic scaffolds are a highly promising new approach to replace both autografts and allografts to repair and remodel damaged bone tissue. Biocompatible porous titanium scaffold was manufactured through a powder metallurgy approach. Magnesium powder was used as space holder material which was compacted with titanium powder and removed during sintering. Evaluation of the porosity and mechanical properties showed a high level of compatibility with human cortical bone. Interconnectivity between pores is higher than 95% for porosity as low as 30%. The elastic moduli are 44.2GPa, 24.7GPa and 15.4GPa for 30%, 40% and 50% porosity samples which match well to that of natural bone (4-30GPa). The yield strengths for 30% and 40% porosity samples of 221.7MPa and 117MPa are superior to that of human cortical bone (130-180MPa). In-vitro cell culture tests on the scaffold samples using Human Mesenchymal Stem Cells (hMSCs) demonstrated their biocompatibility and indicated osseointegration potential. The scaffolds allowed cells to adhere and spread both on the surface and inside the pore structures. With increasing levels of porosity/interconnectivity, improved cell proliferation is obtained within the pores. It is concluded that samples with 30% porosity exhibit the best biocompatibility. The results suggest that porous titanium scaffolds generated using this manufacturing route have excellent potential for hard tissue engineering applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Chitosan-Based Matrices Prepared by Gamma Irradiation for Tissue Regeneration: Structural Properties vs. Preparation Method.

    Casimiro, Maria Helena; Lancastre, Joana J H; Rodrigues, Alexandra P; Gomes, Susana R; Rodrigues, Gabriela; Ferreira, Luís M

    2017-02-01

    In the last decade, new generations of biopolymer-based materials have attracted attention, aiming its application as scaffolds for tissue engineering. These engineered three-dimensional scaffolds are designed to improve or replace damaged, missing, or otherwise compromised tissues or organs. Despite the number of promising methods that can be used to generate 3D cell-instructive matrices, the innovative nature of the present work relies on the application of ionizing radiation technology to form and modify surfaces and matrices with advantage over more conventional technologies (room temperature reaction, absence of harmful initiators or solvents, high penetration through the bulk materials, etc.), and the possibility of preparation and sterilization in one single step. The current chapter summarizes the work done by the authors in the gamma radiation processing of biocompatible and biodegradable chitosan-based matrices for skin regeneration. Particular attention is given to the correlation between the different preparation conditions and the final polymeric matrices' properties. We therefore expect to demonstrate that instructive matrices produced and improved by radiation technology bring to the field of skin regenerative medicine a supplemental advantage over more conservative techniques.

  9. The correlation of in vivo and ex vivo tissue dielectric properties to validate electromagnetic breast imaging: initial clinical experience

    Halter, Ryan J; Zhou, Tian; Meaney, Paul M; Hartov, Alex; Barth, Richard J Jr; Rosenkranz, Kari M; Wells, Wendy A; Kogel, Christine A; Borsic, Andrea; Rizzo, Elizabeth J; Paulsen, Keith D

    2009-01-01

    Electromagnetic (EM) breast imaging provides low-cost, safe and potentially a more specific modality for cancer detection than conventional imaging systems. A primary difficulty in validating these EM imaging modalities is that the true dielectric property values of the particular breast being imaged are not readily available on an individual subject basis. Here, we describe our initial experience in seeking to correlate tomographic EM imaging studies with discrete point spectroscopy measurements of the dielectric properties of breast tissue. The protocol we have developed involves measurement of in vivo tissue properties during partial and full mastectomy procedures in the operating room (OR) followed by ex vivo tissue property recordings in the same locations in the excised tissue specimens in the pathology laboratory immediately after resection. We have successfully applied all of the elements of this validation protocol in a series of six women with cancer diagnoses. Conductivity and permittivity gauged from ex vivo samples over the frequency range 100 Hz–8.5 GHz are found to be similar to those reported in the literature. A decrease in both conductivity and permittivity is observed when these properties are gauged from ex vivo samples instead of in vivo. We present these results in addition to a case study demonstrating how discrete point spectroscopy measurements of the tissue can be correlated and used to validate EM imaging studies

  10. An optical coherence tomography (OCT)-based air jet indentation system for measuring the mechanical properties of soft tissues

    Huang, Yan-Ping; Zheng, Yong-Ping; Wang, Shu-Zhe; Huang, Qing-Hua; Chen, Zhong-Ping; He, Yong-Hong

    2009-01-01

    A novel noncontact indentation system with the combination of an air jet and optical coherence tomography (OCT) was presented in this paper for the quantitative measurement of the mechanical properties of soft tissues. The key idea of this method is to use a pressure-controlled air jet as an indenter to compress the soft tissue in a noncontact way and utilize the OCT signals to extract the deformation induced. This indentation system provides measurement and mapping of tissue elasticity for small specimens with high scanning speed. Experiments were performed on 27 silicone tissue-mimicking phantoms with different Young's moduli, which were also measured by uniaxial compression tests. The regression coefficient of the indentation force to the indentation depth (N mm −1 ) was used as an indicator of the stiffness of tissue under air jet indentation. Results showed that the stiffness coefficients measured by the current system correlated well with the corresponding Young's moduli obtained by conventional mechanical testing (r = 0.89, p < 0.001). Preliminary in vivo tests also showed that the change of soft tissue stiffness with and without the contraction of the underlying muscles in the hand could be differentiated by the current measurement. This system may have broad applications in tissue assessment and characterization where alterations of mechanical properties are involved, in particular with the potential of noncontact micro-indentation for tissues

  11. Highly roughened polycaprolactone surfaces using oxygen plasma-etching and in vitro mineralization for bone tissue regeneration: fabrication, characterization, and cellular activities.

    Kim, YongBok; Kim, GeunHyung

    2015-01-01

    Herein, poly(ɛ-caprolactone) (PCL) surfaces were treated to form various roughness values (R(a)=290-445 nm) and polar functional groups on the surfaces using a plasma-etching process, followed by immersion into simulated body fluid (SBF) for apatite formation. The surface morphology, chemical composition, and mean roughness of the plasma-etched PCL surfaces were measured, and various physical and morphological properties (water contact angles, protein absorption ability, and crystallite size of the apatite layer) of the in vitro mineralized PCL surfaces were evaluated. The roughened PCL surface P-3, which was treated with a sufficient plasma exposure time (4 h), achieved homogeneously distributed apatite formation after soaking in SBF for 7 days, as compared with other surfaces that were untreated or plasma-treated for 30 min or 2 h. Furthermore, to demonstrate their feasibility as a biomimetic surface, pre-osteoblast cells (MC3T3-E1) were cultured on the mineralized PCL surfaces, and cell viability, DAPI-phalloidin fluorescence assay, and alizarin red-staining of the P-3 surface were highly improved compared to the P-1 surface treated with a 30-min plasma exposure time; compared to untreated mineralized PCL surface (N-P), P-3 showed even greater improvements in cell viability and DAPI-phalloidin fluorescence assay. Based on these results, we found that the mineralized PCL surface supplemented with the appropriate plasma treatment can be implicitly helpful to achieve rapid hard tissue regeneration. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Low Immunogenic Endothelial Cells Maintain Morphological and Functional Properties Required for Vascular Tissue Engineering.

    Lau, Skadi; Eicke, Dorothee; Carvalho Oliveira, Marco; Wiegmann, Bettina; Schrimpf, Claudia; Haverich, Axel; Blasczyk, Rainer; Wilhelmi, Mathias; Figueiredo, Constança; Böer, Ulrike

    2018-03-01

    functional properties required for vascular tissue engineering. This extends the spectrum of available cell sources from autologous to allogeneic sources, thereby accelerating the generation of tissue-engineered vascular grafts in acute clinical cases.

  13. A study on improving mechanical properties of porous HA tissue engineering scaffolds by hot isostatic pressing

    Zhao Jing; Xiao Suguang; Lu Xiong; Wang Jianxin; Weng Jie

    2006-01-01

    Various interconnected porous hydroxyapatite (HA) ceramic scaffolds are universally used to induct the tissue growth for bone repair and replacement, and serve to support the adhesion, transfer, proliferation and differentiation of cells. Impregnation of polyurethane sponges with a ceramic slurry is adopted to produce highly porous HA ceramic scaffolds with a 3D interconnected structure. However, high porosity always accompanies a decrease in the strength of the HA ceramic scaffolds. Therefore, it is significant to improve the strength of the HA ceramic scaffolds with highly interconnected porosity so that they are more suitable in clinical applications. In this work, highly porous HA ceramic scaffolds are first produced by the polymer impregnation approach, and subsequently further sintered by hot isostatic pressing (HIP). The phase composition, macro- and micro-porous structure, sintering and mechanical properties of the porous HA scaffolds are investigated by x-ray diffraction (XRD), scanning electron microscopy (SEM), nanoindentation analysis and compressive test. The experimental results show that the nanohardness and compressive strength of HIP-sintered porous HA ceramics are higher than those of commonly sintered HA scaffolds. The HIP technique can effectively improve the sintering property and densification of porous HA ceramic scaffolds, so inducing an increase in the compression strength

  14. Cellular gravity

    F.C. Gruau; J.T. Tromp (John)

    1999-01-01

    textabstractWe consider the problem of establishing gravity in cellular automata. In particular, when cellular automata states can be partitioned into empty, particle, and wall types, with the latter enclosing rectangular areas, we desire rules that will make the particles fall down and pile up on

  15. Cellular decomposition in vikalloys

    Belyatskaya, I.S.; Vintajkin, E.Z.; Georgieva, I.Ya.; Golikov, V.A.; Udovenko, V.A.

    1981-01-01

    Austenite decomposition in Fe-Co-V and Fe-Co-V-Ni alloys at 475-600 deg C is investigated. The cellular decomposition in ternary alloys results in the formation of bcc (ordered) and fcc structures, and in quaternary alloys - bcc (ordered) and 12R structures. The cellular 12R structure results from the emergence of stacking faults in the fcc lattice with irregular spacing in four layers. The cellular decomposition results in a high-dispersion structure and magnetic properties approaching the level of well-known vikalloys [ru

  16. Mechanotransduction mechanisms in growing spherically structured tissues

    Littlejohns, Euan; Dunlop, Carina M.

    2018-04-01

    There is increasing experimental interest in mechanotransduction in multi-cellular tissues as opposed to single cells. This is driven by a growing awareness of the importance of physiologically relevant three-dimensional culture and of cell–cell and cell–gel interactions in directing growth and development. The paradigm biophysical technique for investigating tissue level mechanobiology in this context is to grow model tissues in artificial gels with well-defined mechanical properties. These studies often indicate that the stiffness of the encapsulating gel can significantly alter cellular behaviours. We demonstrate here potential mechanisms linking tissue growth with stiffness-mediated mechanotransduction. We show how tissue growth in gel systems generates points at which there is a significant qualitative change in the cellular stress and strain experienced. We show analytically how these potential switching points depend on the mechanical properties of the constraining gel and predict when they will occur. Significantly, we identify distinct mechanisms that act separately in each of the stress and strain fields at different times. These observations suggest growth as a potential physical mechanism coupling gel stiffness with cellular mechanotransduction in three-dimensional tissues. We additionally show that non-proliferating areas, in the case that the constraining gel is soft compared with the tissue, will expand and contract passively as a result of growth. Central compartment size is thus seen to not be a reliable indicator on its own for growth initiation or active behaviour.

  17. Quantifying the motion of magnetic particles in excised tissue: Effect of particle properties and applied magnetic field

    Kulkarni, Sandip, E-mail: sandip.d.kulkarni@gmail.com [Fischell Department of Bioengineering, University of Maryland at College Park, MD 20742 (United States); Ramaswamy, Bharath; Horton, Emily; Gangapuram, Sruthi [Fischell Department of Bioengineering, University of Maryland at College Park, MD 20742 (United States); Nacev, Alek [Weinberg Medical Physics, LLC (United States); Depireux, Didier [The Institute for Systems Research, University of Maryland at College Park, MD 20742 (United States); Otomagnetics, LLC (United States); Shimoji, Mika [Fischell Department of Bioengineering, University of Maryland at College Park, MD 20742 (United States); Otomagnetics, LLC (United States); Shapiro, Benjamin [Fischell Department of Bioengineering, University of Maryland at College Park, MD 20742 (United States); The Institute for Systems Research, University of Maryland at College Park, MD 20742 (United States); Otomagnetics, LLC (United States)

    2015-11-01

    This article presents a method to investigate how magnetic particle characteristics affect their motion inside tissues under the influence of an applied magnetic field. Particles are placed on top of freshly excised tissue samples, a calibrated magnetic field is applied by a magnet underneath each tissue sample, and we image and quantify particle penetration depth by quantitative metrics to assess how particle sizes, their surface coatings, and tissue resistance affect particle motion. Using this method, we tested available fluorescent particles from Chemicell of four sizes (100 nm, 300 nm, 500 nm, and 1 μm diameter) with four different coatings (starch, chitosan, lipid, and PEG/P) and quantified their motion through freshly excised rat liver, kidney, and brain tissues. In broad terms, we found that the applied magnetic field moved chitosan particles most effectively through all three tissue types (as compared to starch, lipid, and PEG/P coated particles). However, the relationship between particle properties and their resulting motion was found to be complex. Hence, it will likely require substantial further study to elucidate the nuances of transport mechanisms and to select and engineer optimal particle properties to enable the most effective transport through various tissue types under applied magnetic fields.

  18. Cellular distribution, purification and electrophoretic properties of malate dehydrogenase in Trichuris ovis and inhibition by benzimidazoles and pyrimidine derivatives.

    Sanchez-Moreno, M; Ortega, J E; Valero, A

    1989-12-01

    High levels of malate dehydrogenase were found in Trichuris ovis. Two molecular forms of the enzyme, of different cellular location and electrophoretic pattern, were isolated and purified. The activity of soluble malate dehydrogenase was greater than that of mitochondrial malate dehydrogenase. Both forms also displayed different electrophoretic profiles in comparison with purified extracts from goat (Capra hircus) liver. Substrate concentration directly affected enzyme activity. Host and parasite malate dehydrogenase activity were both inhibited by a series of benzimidazoles and pyrimidine-derived compounds, some of which markedly reduced parasite enzyme activity, but not host enzyme activity. Percentage inhibition by some pyrimidine derivatives was greater than that produced by benzimidazoles.

  19. Differences in the mechanical properties of the developing cerebral cortical proliferative zone between mice and ferrets at both the tissue and single-cell levels

    Arata Nagasaka

    2016-11-01

    actually greater in mice (720 Pa than in ferrets (450 Pa. Adherens junction was ultrastructurally comparable between mice and ferrets. These results show that the horizontally denser packing of neuroepithelial cell processes is a major contributor to the increased tissue-level apical stiffness in ferrets, and suggest that tissue-level mechanical properties may be achieved by balancing cellular densification and the physical properties of single cells.

  20. Antioxidant properties of Taraxacum officinale fruit extract are involved in the protective effect against cellular death induced by sodium nitroprusside in brain of rats.

    Colle, Dirleise; Arantes, Letícia Priscilla; Rauber, Ricardo; de Mattos, Sérgio Edgar Campos; Rocha, João Batista Teixeira da; Nogueira, Cristina Wayne; Soares, Félix Alexandre Antunes

    2012-07-01

    Taraxacum officinale Weber (Asteraceae), known as dandelion, is used for medicinal purposes due to its choleretic, diuretic, antitumor, antioxidant, antiinflammatory, and hepatoprotective properties. We sought to investigate the protective activity of T. officinale fruit extract against sodium nitroprusside (SNP)-induced decreased cellular viability and increased lipid peroxidation in the cortex, hippocampus, and striatum of rats in vitro. To explain the mechanism of the extract's antioxidant activity, its putative scavenger activities against NO, DPPH·, OH·, and H(2)O(2) were determined. Slices of cortex, hippocampus, and striatum were treated with 50 μM SNP and T. officinale fruit ethanolic extract (1-20 µg/mL) to determine cellular viability by MTT reduction assay. Lipid peroxidation was measure in cortical, hippocampal and striatal slices incubates with SNP (5 µM) and T. officinale fruit extract (1-20 µg/mL). We also determined the scavenger activities of T. officinale fruit extract against NO·, DPPH·, OH·, and H(2)O(2), as well as its iron chelating capacity. The extract (1, 5, 10, and 20 μg/mL) protected against SNP-induced decreases in cellular viability and increases in lipid peroxidation in the cortex, hippocampus, and striatum of rats. The extract had scavenger activity against DPPH· and NO· at low concentrations and was able to protect against H(2)O(2) and Fe(2+)-induced deoxyribose oxidation. T. officinale fruit extract has antioxidant activity and protects brain slices against SNP-induced cellular death. Possible mechanisms of action include its scavenger activities against reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are attributed to the presence of phenolic compounds in the extract.

  1. Input and output for surgical simulation: devices to measure tissue properties in vivo and a haptic interface for laparoscopy simulators.

    Ottensmeyer, M P; Ben-Ur, E; Salisbury, J K

    2000-01-01

    Current efforts in surgical simulation very often focus on creating realistic graphical feedback, but neglect some or all tactile and force (haptic) feedback that a surgeon would normally receive. Simulations that do include haptic feedback do not typically use real tissue compliance properties, favoring estimates and user feedback to determine realism. When tissue compliance data are used, there are virtually no in vivo property measurements to draw upon. Together with the Center for Innovative Minimally Invasive Therapy at the Massachusetts General Hospital, the Haptics Group is developing tools to introduce more comprehensive haptic feedback in laparoscopy simulators and to provide biological tissue material property data for our software simulation. The platform for providing haptic feedback is a PHANToM Haptic Interface, produced by SensAble Technologies, Inc. Our devices supplement the PHANToM to provide for grasping and optionally, for the roll axis of the tool. Together with feedback from the PHANToM, which provides the pitch, yaw and thrust axes of a typical laparoscopy tool, we can recreate all of the haptic sensations experienced during laparoscopy. The devices integrate real laparoscopy toolhandles and a compliant torso model to complete the set of visual and tactile sensations. Biological tissues are known to exhibit non-linear mechanical properties, and change their properties dramatically when removed from a living organism. To measure the properties in vivo, two devices are being developed. The first is a small displacement, 1-D indenter. It will measure the linear tissue compliance (stiffness and damping) over a wide range of frequencies. These data will be used as inputs to a finite element or other model. The second device will be able to deflect tissues in 3-D over a larger range, so that the non-linearities due to changes in the tissue geometry will be measured. This will allow us to validate the performance of the model on large tissue

  2. Functionally graded electrospun scaffolds with tunable mechanical properties for vascular tissue regeneration

    Thomas, Vinoy [Center for Nanoscale Materials and Biointegration (CNMB), Department of Physics, University of Alabama at Birmingham (UAB), AL 35294 (United States); Zhang Xing [Department of Biomedical Engineering, School of Engineering, University of Alabama at Birmingham (UAB), AL 35294 (United States); Catledge, Shane A [Center for Nanoscale Materials and Biointegration (CNMB), Department of Physics, University of Alabama at Birmingham (UAB), AL 35294 (United States); Vohra, Yogesh K [Center for Nanoscale Materials and Biointegration (CNMB), Department of Physics, University of Alabama at Birmingham (UAB), AL 35294 (United States)

    2007-12-15

    Electrospun tubular scaffolds (4 mm inner diameter) based on bio-artificial blends of polyglyconate (Maxon (registered) ) and proteins such as gelatin and elastin having a spatially designed multilayer structure were prepared for use as vascular tissue scaffolds. Scanning electron microscopy analysis of scaffolds showed a random nanofibrous morphology with fiber diameter in the range of 200-400 nm for protein-blended Maxon, which mimics the nanoscale dimensions of collagen (50-500 nm). The scaffolds have a well interconnected pore structure and porosity up to 82%, with protein blending and multi-layering in contrast to electrospun Maxon (registered) scaffolds (67%). Fourier-transform infrared spectroscopy, x-ray diffraction and differential scanning calorimetry results confirmed the blended composition and crystallinity of fibers. Uniaxial tensile testing revealed a strength of 14.46 {+-} 0.42 MPa and a modulus of 15.44 {+-} 2.53 MPa with a failure strain of 322.5 {+-} 10% for a pure Maxon (registered) scaffold. The blending of polyglyconate with biopolymers decreased the tensile properties in general, with an exception of the tensile modulus (48.38 {+-} 2 MPa) of gelatin/Maxon mesh, which was higher than that of the pure Maxon (registered) scaffold. Trilayered tubular scaffolds of gelatin/elastin, gelatin/elastin/Maxon and gelatin/Maxon (GE-GEM-GM) that mimic the complex trilayer matrix structure of natural artery have been prepared by sequential electrospinning. Tensile testing under dry conditions revealed a tensile strength of 2.71 {+-} 0.2 MPa and a modulus of 20.4 {+-} 3 MPa with a failure strain of 140 {+-} 10%. However, GE-GEM-GM scaffolds tested under wet conditions after soaking in a phosphate buffered saline medium at 37 {sup 0}C for 24 h exhibited mechanical properties (2.5 MPa tensile strength and 9 MPa tensile modulus) comparable to those of native femoral artery.

  3. Functionally graded electrospun scaffolds with tunable mechanical properties for vascular tissue regeneration

    Thomas, Vinoy; Zhang Xing; Catledge, Shane A; Vohra, Yogesh K

    2007-01-01

    Electrospun tubular scaffolds (4 mm inner diameter) based on bio-artificial blends of polyglyconate (Maxon (registered) ) and proteins such as gelatin and elastin having a spatially designed multilayer structure were prepared for use as vascular tissue scaffolds. Scanning electron microscopy analysis of scaffolds showed a random nanofibrous morphology with fiber diameter in the range of 200-400 nm for protein-blended Maxon, which mimics the nanoscale dimensions of collagen (50-500 nm). The scaffolds have a well interconnected pore structure and porosity up to 82%, with protein blending and multi-layering in contrast to electrospun Maxon (registered) scaffolds (67%). Fourier-transform infrared spectroscopy, x-ray diffraction and differential scanning calorimetry results confirmed the blended composition and crystallinity of fibers. Uniaxial tensile testing revealed a strength of 14.46 ± 0.42 MPa and a modulus of 15.44 ± 2.53 MPa with a failure strain of 322.5 ± 10% for a pure Maxon (registered) scaffold. The blending of polyglyconate with biopolymers decreased the tensile properties in general, with an exception of the tensile modulus (48.38 ± 2 MPa) of gelatin/Maxon mesh, which was higher than that of the pure Maxon (registered) scaffold. Trilayered tubular scaffolds of gelatin/elastin, gelatin/elastin/Maxon and gelatin/Maxon (GE-GEM-GM) that mimic the complex trilayer matrix structure of natural artery have been prepared by sequential electrospinning. Tensile testing under dry conditions revealed a tensile strength of 2.71 ± 0.2 MPa and a modulus of 20.4 ± 3 MPa with a failure strain of 140 ± 10%. However, GE-GEM-GM scaffolds tested under wet conditions after soaking in a phosphate buffered saline medium at 37 0 C for 24 h exhibited mechanical properties (2.5 MPa tensile strength and 9 MPa tensile modulus) comparable to those of native femoral artery

  4. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering

    Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

    2013-01-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. - Highlights: • Chitosan hydrogel composites fabricated by two forms of silk fiber • Silk fibers provide structural support for the hydrogel matrix. • The mechanical properties of hydrogel significantly improved by associating with silk. • Production of GAG and collagen type II was demonstrated within the scaffolds

  5. Comparison of mechanical compressive properties of commercial and autologous fibrin glues for tissue engineering applications.

    Cravens, Matthew G; Behn, Anthony W; Dragoo, Jason L

    2017-11-01

    Fibrin glues are widely used in orthopedic surgery as adhesives and hemostatic agents. We evaluated the compressive properties of selected fibrin glues in order to identify which are appropriate for tissue regeneration applications subject to compression. Uniaxial unconfined compression tests were performed on fibrin gels prepared from commercial and autologous products: (1) Evicel (Ethicon), (2) Tisseel (Baxter), (3) Angel (Arthrex), and (4) ProPlaz (Biorich). Cyclic loads were applied from 0 to 30% strain for 100cycles at 0.5Hz. Following cyclic testing, specimens were subjected to ramp displacement of 1% strain per second to 80% strain. Throughout cyclic loading, Evicel and Tisseel deformed (shortened) less than Angel at all but one time point, and deformed less than ProPlaz at cycles 10 and 20. The dynamic moduli, peak stress, and strain energy were significantly greater in Tisseel than all other groups. Evicel displayed significantly greater dynamic moduli, peak stress, and strain energy than Angel and ProPlaz. Following cyclic testing, Tisseel and Evicel were significantly less deformed than Angel. No specimens exhibited gross failure during ramp loading to 80% strain. Ramp loading trends mirrored those of cyclic loading. The tested commercial glues were significantly more resistant to compression than the autologous products. The compressive properties of Tisseel were approximately twice those of Evicel. All preparations displayed moduli multiple orders of magnitude less than that of native articular cartilage. We conclude that in knee surgeries requiring fibrin glue to undergo compression of daily activity, commercial products are preferable to autologous preparations from platelet-poor plasma, though both will deform significantly. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering

    Mirahmadi, Fereshteh [Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad, E-mail: Tafazoli@aut.ac.ir [Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Shokrgozar, Mohammad Ali, E-mail: mashokrgozar@pasteur.ac.ir [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Bonakdar, Shahin [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of)

    2013-12-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. - Highlights: • Chitosan hydrogel composites fabricated by two forms of silk fiber • Silk fibers provide structural support for the hydrogel matrix. • The mechanical properties of hydrogel significantly improved by associating with silk. • Production of GAG and collagen type II was demonstrated within the scaffolds.

  7. Determination of the axial and circumferential mechanical properties of the skin tissue using experimental testing and constitutive modeling.

    Karimi, Alireza; Navidbakhsh, Mahdi; Haghighatnama, Maedeh; Haghi, Afsaneh Motevalli

    2015-01-01

    The skin, being a multi-layered material, is responsible for protecting the human body from the mechanical, bacterial, and viral insults. The skin tissue may display different mechanical properties according to the anatomical locations of a body. However, these mechanical properties in different anatomical regions and at different loading directions (axial and circumferential) of the mice body to date have not been determined. In this study, the axial and circumferential loads were imposed on the mice skin samples. The elastic modulus and maximum stress of the skin tissues were measured before the failure occurred. The nonlinear mechanical behavior of the skin tissues was also computationally investigated through a suitable constitutive equation. Hyperelastic material model was calibrated using the experimental data. Regardless of the anatomic locations of the mice body, the results revealed significantly different mechanical properties in the axial and circumferential directions and, consequently, the mice skin tissue behaves like a pure anisotropic material. The highest elastic modulus was observed in the back skin under the circumferential direction (6.67 MPa), while the lowest one was seen in the abdomen skin under circumferential loading (0.80 MPa). The Ogden material model was narrowly captured the nonlinear mechanical response of the skin at different loading directions. The results help to understand the isotropic/anisotropic mechanical behavior of the skin tissue at different anatomical locations. They also have implications for a diversity of disciplines, i.e., dermatology, cosmetics industry, clinical decision making, and clinical intervention.

  8. Analysis of 3D Printed Diopside Scaffolds Properties for Tissue Engineering

    Tingting LIU

    2015-11-01

    Full Text Available Diopside exhibits favorable potential for bone repair on account of the good mechanical performance, bioactivity and biocompatibility. In this paper, diopside scaffolds with high pore interconnectivity were successfully fabricated by laser three-dimensional (3D printing. The microstructure and mechanical performance of the diopside scaffolds were studied. The experimental analysis indicated that diopside particles gradually fused together until a dense structure was built with an energy density increasing in the range between 2.4 and 4.8 J·mm-2. Meanwhile, compressive strength and fracture toughness increased gradually from 5.96 ± 0.88 MPa to 10.87 ± 0.55 MPa. However, mechanical properties decreased due to the appearance of voids when energy density were 5.4 and 6 J·mm-2. Simulated body fluid (SBF tests showed that apatite crystals formed on the diopside scaffolds surface, and the apatite crystals increased with soaking time. Cell culture tests indicated the scaffolds supported the adhesion and growth of MG-63 cells. The study suggested that diopside scaffolds fabricated by laser 3D printing are promising candidates for bone tissue engineering.DOI: http://dx.doi.org/10.5755/j01.ms.21.4.9845

  9. Mechanical properties of electrospun bilayer fibrous membranes as potential scaffolds for tissue engineering.

    Pu, Juan; Komvopoulos, Kyriakos

    2014-06-01

    Bilayer fibrous membranes of poly(l-lactic acid) (PLLA) were fabricated by electrospinning, using a parallel-disk mandrel configuration that resulted in the sequential deposition of a layer with fibers aligned across the two parallel disks and a layer with randomly oriented fibers, both layers deposited in a single process step. Membrane structure and fiber alignment were characterized by scanning electron microscopy and two-dimensional fast Fourier transform. Because of the intricacies of the generated electric field, bilayer membranes exhibited higher porosity than single-layer membranes consisting of randomly oriented fibers fabricated with a solid-drum collector. However, despite their higher porosity, bilayer membranes demonstrated generally higher elastic modulus, yield strength and toughness than single-layer membranes with random fibers. Bilayer membrane deformation at relatively high strain rates comprised multiple abrupt microfracture events characterized by discontinuous fiber breakage. Bilayer membrane elongation yielded excessive necking of the layer with random fibers and remarkable fiber stretching (on the order of 400%) in the layer with fibers aligned in the stress direction. In addition, fibers in both layers exhibited multiple localized necking, attributed to the nonuniform distribution of crystalline phases in the fibrillar structure. The high membrane porosity, good mechanical properties, and good biocompatibility and biodegradability of PLLA (demonstrated in previous studies) make the present bilayer membranes good scaffold candidates for a wide range of tissue engineering applications. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering.

    Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

    2013-12-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber-hydrogel composite for GAG content and in two-layer electrospun fiber-hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. © 2013.

  11. Experimental testing and constitutive modeling of the mechanical properties of the swine skin tissue.

    Łagan, Sylwia D; Liber-Kneć, Aneta

    2017-01-01

    The aim of the study was an estimation of the possibility of using hyperelastic material models to fit experimental data obtained in the tensile test for the swine skin tissue. The uniaxial tensile tests of samples taken from the abdomen and back of a pig was carried out. The mechanical properties of the skin such as the mean Young's modulus, the mean maximum stress and the mean maximum elongation were calculated. The experimental data have been used to identify the parameters in specific strain-energy functions given in seven constitutive models of hyperelastic materials: neo-Hookean, Mooney-Rivlin, Ogden, Yeoh, Martins, Humphrey and Veronda-Westmann. An analysis of errors in fitting of theoretical and experimental data was done. Comparison of load -displacement curves for the back and abdomen regions of skin taken showed a different scope of both the mean maximum loading forces and the mean maximum elongation. Samples which have been prepared from the abdominal area had lower values of the mean maximum load compared to samples from the spine area. The reverse trend was observed during the analysis of the values of elongation. An analysis of the accuracy of model fitting to the experimental data showed that, the least accurate were the model of neo- -Hookean, model of Mooney-Rivlin for the abdominal region and model of Veronda-Westmann for the spine region. An analysis of seven hyperelastic material models showed good correlations between the experimental and the theoretical data for five models.

  12. The validity and reliability of modelled neural and tissue properties of the ankle muscles in children with cerebral palsy

    Sloot, L.H.; van der Krogt, M.M.; de Gooijer-van Groep, K.; van Eesbeek, S.; de Groot, J.; Buizer, A.I.; Meskers, C.; Becher, J.G.; de Vlugt, E.; Harlaar, J.

    2015-01-01

    Spastic cerebral palsy (CP) is characterized by increased joint resistance, caused by a mix of increased tissue stiffness, as well as involuntary reflex and background muscle activity. These properties can be quantified using a neuromechanical model of the musculoskeletal complex and instrumented

  13. Influence of the temporal deposition of extracellular matrix on the mechanical properties of tissue-engineered cartilage

    Khoshgoftar, M.; Wilson, W.; Ito, K.; Donkelaar, van C.C.

    2014-01-01

    Enhancement of the load-bearing capacity of tissue engineered (TE) cartilage is expected to improve the clinical outcome of implantations. Generally, cartilage TE studies aim to increase the total extracellular matrix (ECM) content to improve implant mechanical properties. Besides the ECM content,

  14. Dielectric properties of porcine cerebrospinal tissues at microwave frequencies: in vivo, in vitro and systematic variation with age

    Peyman, A; Holden, S J; Watts, S; Perrott, R; Gabriel, C

    2007-01-01

    The dielectric properties of pig cerebrospinal tissues were measured in vivo and in vitro, in the frequency range of 50 MHz-20 GHz. The total combined measurement uncertainty was calculated at each frequency point and is reported over representative frequency regions. Comparisons were made for each tissue between the two sets of data and with the literature of the past decade. The in vitro study was extended to include tissue from pigs weighing approximately 10, 50 and 250 kg to re-visit the question of the variation of dielectric properties with age. White matter and spinal chord showed significant variation as function of animal age, no age-related variations were recorded for grey matter

  15. MODELLING OF RING-SHAPED ULTRASONIC WAVEGUIDES FOR TESTING OF MECHANICAL PROPERTIES AND THERAPEUTIC TREATMENT OF BIOLOGICAL TISSUES

    V. T. Minchenya

    2011-01-01

    Full Text Available The article presents results of modelling of ring-shaped waveguide tool for ultrasonic treatment of biological materials, particularly malignant tumours, and testing of their mechanical properties. Harmonic analysis of forced flexural vibration of the waveguide using ANSYS software and APDL programming language was implemented for determination of waveguide geometric parameters providing its resonance for the given excitation frequency. The developed finite element model accounts for interaction between the waveguide and tumour tissue as well as initial prestressing of tissue radially compressed by the waveguide. Resonant curves of the waveguide in terms of its thickness and diameter are calculated and presented. Principle of application of the developed modeling technique for extraction of diagnostic data on mechanical properties of biological tissues is described.

  16. Properties of soils and tree-wood tissue across a Lake States sulfate-deposition gradient. Forest Service resource bulletin

    Ohmann, L.F.; Grigal, D.F.

    1991-01-01

    There is general concern that atmospheric pollutants may be affecting the health of forests in the USA. The hypotheses tested were that the wet sulfate deposition gradient across the Lake States: (1) is reflected in the amount of accumulated sulfur in the forest floor-soil system and tree woody tissue and (2) is related to differences in tree radial increment. The authors present the properties of the soil and tree woody tissue (mostly chemical) on the study plots. Knowledge of the properties of soil and woody tree tissue is needed for understanding and interpreting relations between sulfate deposition, sulfur accumulation in the ecosystem, soil and tree chemistry, and tree growth and climatic variation. The report provides a summary of those data for study, analysis, and interpretation

  17. A chondroitinase-ABC and TGF-β1 treatment regimen for enhancing the mechanical properties of tissue engineered fibrocartilage

    MacBarb, Regina F.; Makris, Eleftherios A.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2012-01-01

    The development of functionally equivalent fibrocartilage remains elusive despite efforts to engineer tissues such as the knee menisci, intervertebral disc, and TMJ disc. Attempts to engineer these structures often fail to create tissues with mechanical properties on par with native tissue, resulting in constructs unsuitable for clinical applications. The objective of this study was to engineer a spectrum of biomimetic fibrocartilages representative of the distinct functional properties found in native tissues. Using the self-assembly process, different co-cultures of meniscus cells (MCs) and articular chondrocytes (ACs) were seeded into agarose wells and treated with the catabolic agent chondroitinase-ABC (C-ABC) and the anabolic agent transforming growth factor-β1 (TGF-β1) via a two-factor (cell ratio and bioactive treatment), full factorial study design. Application of both C-ABC and TGF-β1 resulted in a beneficial or positive increase in the collagen content of treated constructs compared to controls. Significant increases in both the collagen density and fiber diameter were also seen with this treatment, increasing these values 32% and 15%, respectively, over control values. Mechanical testing found the combined bioactive treatment to synergistically increase the Young’s modulus and ultimate tensile strength of the engineered fibrocartilages compared to controls, with values reaching the lower spectrum of those found in native tissues. Together, these data demonstrate that C-ABC and TGF-β1 interact to develop a denser collagen matrix better able to withstand tensile loading. This study highlights a way to optimize the tensile properties of engineered fibrocartilage using a biochemical and biophysical agent together to create distinct fibrocartilages with functional properties mimicking those of native tissue. PMID:23041782

  18. Membrane Lipid Replacement for chronic illnesses, aging and cancer using oral glycerolphospholipid formulations with fructooligosaccharides to restore phospholipid function in cellular membranes, organelles, cells and tissues.

    Nicolson, Garth L; Ash, Michael E

    2017-09-01

    Membrane Lipid Replacement is the use of functional, oral supplements containing mixtures of cell membrane glycerolphospholipids, plus fructooligosaccharides (for protection against oxidative, bile acid and enzymatic damage) and antioxidants, in order to safely replace damaged, oxidized, membrane phospholipids and restore membrane, organelle, cellular and organ function. Defects in cellular and intracellular membranes are characteristic of all chronic medical conditions, including cancer, and normal processes, such as aging. Once the replacement glycerolphospholipids have been ingested, dispersed, complexed and transported, while being protected by fructooligosaccharides and several natural mechanisms, they can be inserted into cell membranes, lipoproteins, lipid globules, lipid droplets, liposomes and other carriers. They are conveyed by the lymphatics and blood circulation to cellular sites where they are endocytosed or incorporated into or transported by cell membranes. Inside cells the glycerolphospholipids can be transferred to various intracellular membranes by lipid globules, liposomes, membrane-membrane contact or by lipid carrier transfer. Eventually they arrive at their membrane destinations due to 'bulk flow' principles, and there they can stimulate the natural removal and replacement of damaged membrane lipids while undergoing further enzymatic alterations. Clinical trials have shown the benefits of Membrane Lipid Replacement in restoring mitochondrial function and reducing fatigue in aged subjects and chronically ill patients. Recently Membrane Lipid Replacement has been used to reduce pain and other symptoms as well as removing hydrophobic chemical contaminants, suggesting that there are additional new uses for this safe, natural medicine supplement. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights

  19. Effects of silicon treatment and inoculation with Fusarium oxysporum f. sp. vasinfectum on cellular defences in root tissues of two cotton cultivars.

    Whan, Jennifer A; Dann, Elizabeth K; Aitken, Elizabeth A B

    2016-08-01

    Silicon has been shown to enhance the resistance of plants to fungal and bacterial pathogens. Here, the effect of potassium silicate was assessed on two cotton (Gossypium hirsutum) cultivars subsequently inoculated with Fusarium oxysporum f. sp. vasinfectum (Fov). Sicot 189 is moderately resistant whilst Sicot F-1 is the second most resistant commercial cultivar presently available in Australia. Transmission and light microscopy were used to compare cellular modifications in root cells after these different treatments. The accumulation of phenolic compounds and lignin was measured. Cellular alterations including the deposition of electron-dense material, degradation of fungal hyphae and occlusion of endodermal cells were more rapidly induced and more intense in endodermal and vascular regions of Sicot F-1 plants supplied with potassium silicate followed by inoculation with Fov than in similarly treated Sicot 189 plants or in silicate-treated plants of either cultivar not inoculated with Fov. Significantly more phenolic compounds were present at 7 d post-infection (dpi) in root extracts of Sicot F-1 plants treated with potassium silicate followed by inoculation with Fov compared with plants from all other treatments. The lignin concentration at 3 dpi in root material from Sicot F-1 treated with potassium silicate and inoculated with Fov was significantly higher than that from water-treated and inoculated plants. This study demonstrates that silicon treatment can affect cellular defence responses in cotton roots subsequently inoculated with Fov, particularly in Sicot F-1, a cultivar with greater inherent resistance to this pathogen. This suggests that silicon may interact with or initiate defence pathways faster in this cultivar than in the less resistant cultivar. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Cellular and molecular properties of 90Y-labeled cetuximab in combination with radiotherapy on human tumor cells in vitro

    Saki, M.; Toulany, M.; Rodemann, H.P.; Sihver, W.; Zenker, M.; Heldt, J.M.; Mosch, B.; Pietzsch, H.J.; Steinbach, J.; Baumann, M.

    2012-01-01

    Purpose: Anti-EGFR antibody cetuximab (C225) is used in combination with radiotherapy of head and neck squamous cell carcinoma (HNSCC) patients. We investigated whether conjugation of cetuximab with trans-cyclohexyl-diethylene-triamine-pentaacetic acid (CHX-A''-DTPA) and radiolabeling with 90 Yttrium affect the molecular and cellular function of cetuximab and improve its combined effect with external-beam irradiation (EBI). Methods: The following cell lines were used: HNSCC UT5, SAS, FaDu, as well as A43, Chinese hamster ovary cells (CHO), and human skin fibroblast HSF7. Binding affinity and kinetics, specificity, retention, and the combination of 90 Y-cetuximab with EBI were evaluated. Results: Control cetuximab and CHX-A''-DTPA-cetuximab blocked the proliferation activity of UT5 cells. In combination with EBI, CHX-A''-DTPA-cetuximab increased the radiosensitivity of UT5 to a similar degree as control cetuximab did. In contrast, in SAS and HSF7 cells neither proliferation nor radiosensitivity was affected by either of the antibodies. Binding [ 90 Y]Y-CHX-A''-DTPA-cetuximab ( 90 Y-cetuximab) to EGFR in HNSCC cells occurred time dependently with a maximum binding at 24 h. Retention of 90 Y-cetuximab was similar in both HNSCC cell lines; 24 h after treatment, approximately 90% of bound activity remained in the cell layer. Competition assays, using cell membranes in the absence of an internalized fraction of cetuximab, showed that the cetuximab affinity is not lost as a result of conjugation with CHX-A''-DTPA. Cetuximab and CHX-A''-DTPA-cetuximab blocked EGF-induced Y1068 phosphorylation of EGFR. The lack of an effect of cetuximab on EGF-induced Akt and ERK1/2 phosphorylation and the inhibition of irradiation (IR)-induced Akt and ERK1/2 phosphorylation by cetuximab were not affected by DTPA conjugation. 90 Y-cetuximab in combination with EBI resulted in a pronounced inhibition of colony formation of HNSCC cells. Conclusions: Conjugation of CHX-A''-DTPA to cetuximab

  1. The role of mechanical loading in ligament tissue engineering.

    Benhardt, Hugh A; Cosgriff-Hernandez, Elizabeth M

    2009-12-01

    Tissue-engineered ligaments have received growing interest as a promising alternative for ligament reconstruction when traditional transplants are unavailable or fail. Mechanical stimulation was recently identified as a critical component in engineering load-bearing tissues. It is well established that living tissue responds to altered loads through endogenous changes in cellular behavior, tissue organization, and bulk mechanical properties. Without the appropriate biomechanical cues, new tissue formation lacks the necessary collagenous organization and alignment for sufficient load-bearing capacity. Therefore, tissue engineers utilize mechanical conditioning to guide tissue remodeling and improve the performance of ligament grafts. This review provides a comparative analysis of the response of ligament and tendon fibroblasts to mechanical loading in current bioreactor studies. The differential effect of mechanical stimulation on cellular processes such as protease production, matrix protein synthesis, and cell proliferation is examined in the context of tissue engineering design.

  2. Fatigue and biological properties of Ti-6Al-4V ELI cellular structures with variously arranged cubic cells made by selective laser melting.

    Dallago, M; Fontanari, V; Torresani, E; Leoni, M; Pederzolli, C; Potrich, C; Benedetti, M

    2018-02-01

    Traditional implants made of bulk titanium are much stiffer than human bone and this mismatch can induce stress shielding. Although more complex to produce and with less predictable properties compared to bulk implants, implants with a highly porous structure can be produced to match the bone stiffness and at the same time favor bone ingrowth and regeneration. This paper presents the results of the mechanical and dimensional characterization of different regular cubic open-cell cellular structures produced by Selective Laser Melting (SLM) of Ti6Al4V alloy, all with the same nominal elastic modulus of 3GPa that matches that of human trabecular bone. The main objective of this research was to determine which structure has the best fatigue resistance through fully reversed fatigue tests on cellular specimens. The quality of the manufacturing process and the discrepancy between the actual measured cell parameters and the nominal CAD values were assessed through an extensive metrological analysis. The results of the metrological assessment allowed us to discuss the effect of manufacturing defects (porosity, surface roughness and geometrical inaccuracies) on the mechanical properties. Half of the specimens was subjected to a stress relief thermal treatment while the other half to Hot Isostatic Pressing (HIP), and we compared the effect of the treatments on porosity and on the mechanical properties. Fatigue strength seems to be highly dependent on the surface irregularities and notches introduced during the manufacturing process. In fully reversed fatigue tests, the high performances of stretching dominated structures compared to bending dominated structures are not found. In fact, with thicker struts, such structures proved to be more resistant, even if bending actions were present. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. A new approach to fabrication of Cs/BG/CNT nanocomposite scaffold towards bone tissue engineering and evaluation of its properties

    Shokri, S. [Department of Nanotechnology Engineering, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Movahedi, B., E-mail: b.movahedi@ast.ui.ac.ir [Department of Nanotechnology Engineering, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Rafieinia, M. [Biosensor Research Center, Department of Advanced Medical Technology, Isfahan University of Medical Sciences, Isfahan, 64716 (Iran, Islamic Republic of); Salehi, H. [Department of Anatomical Sciences, Isfahan University of Medical Sciences, Isfahan, 64716 (Iran, Islamic Republic of)

    2015-12-01

    Graphical abstract: - Highlights: • Nanocomposite scaffold was produced using a novel technique. • Bioactive glass, carbon nanotube and chitosan were used for fabrication of nanocomposite scaffold. • The compressive strength of the scaffold was near to the cancellous bone. • Biodegradability of the scaffolds in PBS shows the slow destruction. - Abstract: In the present study, bioactive glass (BG), carbon nanotube (CNT), and chitosan (Cs) were used with different ratios for the fabrication of nanocomposite scaffold for bone tissue engineering. BG was synthesized by sol–gel process and CNT was functionalized by immersing in sulfuric acid as well as nitric acid. Nanocomposite scaffold was produced using a novel technique, hot press, and salt leaching process and cross-linked by Hexamethylene diisocyanate (HDI). The optimum porosity of the scaffold with respect to the ratio of salt and precursor was kept around 70%. Mechanical properties of the scaffolds were increased by the addition of CNT and hence, the compressive strength of them with 4 wt% CNT was increased up to 5.95 ± 0.5 MPa. The nanocomposite scaffolds were characterized by FT-IR, SEM, XRD, and electrochemical analysis. Furthermore, scaffolds were immersed in PBS for evaluating the biodegradability, water absorption, and CNT release. The results indicated that water absorption of the scaffolds was increased by adding CNT to the scaffold. The amount of released CNT after 30 days was measured within 6 × 10{sup −4} and 1 × 10{sup −3} mg/ml. Attachment and proliferation of MG63 osteoblast cell line on Cs/BG/CNT scaffolds were investigated by MTT assay indicating no toxicity for this nanocomposite scaffolds. According to the results of the experiments, the nanocomposite scaffold with modified composition (Cs/BG/CNT, 80:20:2 wt%) was the best one in matters of mechanical, chemical, and cellular properties and also the most appropriate for trabecular bone tissue.

  4. Microstructure and mechanical properties of open-cellular biomaterials prototypes for total knee replacement implants fabricated by electron beam melting.

    Murr, L E; Amato, K N; Li, S J; Tian, Y X; Cheng, X Y; Gaytan, S M; Martinez, E; Shindo, P W; Medina, F; Wicker, R B

    2011-10-01

    Total knee replacement implants consisting of a Co-29Cr-6Mo alloy femoral component and a Ti-6Al-4V tibial component are the basis for the additive manufacturing of novel solid, mesh, and foam monoliths using electron beam melting (EBM). Ti-6Al-4V solid prototype microstructures were primarily α-phase acicular platelets while the mesh and foam structures were characterized by α(')-martensite with some residual α. The Co-29Cr-6Mo containing 0.22% C formed columnar (directional) Cr(23)C(6) carbides spaced ~2 μm in the build direction, while HIP-annealed Co-Cr alloy exhibited an intrinsic stacking fault microstructure. A log-log plot of relative stiffness versus relative density for Ti-6Al-4V and Co-29Cr-6Mo open-cellular mesh and foams resulted in a fitted line with a nearly ideal slope, n = 2.1. A stress shielding design graph constructed from these data permitted mesh and foam implant prototypes to be fabricated for compatible bone stiffness. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Two-color cytofluorometry and cellular properties of the urokinase receptor associated with a human metastatic carcinomatous cell line

    Takahashi, K.; Gojobori, T.; Tanifuji, M.

    1991-01-01

    Purified human urokinase was labeled with either fluorescein isothiocyanate or iodine-125 and used as a probe for binding to the human metastatic carcinomatous cell line, Detroit 562. Cytofluorometry showed that the ligand bound preferentially to cells that had been exposed to acidic pH. The binding was competitive and decreased after mild tryptic digestion. The bound ligand could be removed by restoration of the cells to a low pH. Therefore, the cells had specific binding sites. The bound urokinase was involved in the breakdown of fibrin. Two-color cytofluorometric maps were constructed by counterstaining with propidium iodide. Results suggested that there were different cell populations that had different numbers of receptors and amounts of DNA. We cloned cells and found that single clones had homogeneous levels of receptors with different dissociation constants (from 10(-13) to 10(-11) mol/mg protein) for different clones. Cells of one clone, C5, which had high levels of receptor production, moved characteristically on a glass substratum coated with gold particles and reacted with wheat germ agglutinin, but not with concanavalin A. The receptors were found together with adhesion proteins at the sites where the cells adhered to the substrate. These results and the data obtained by zymography of the cellular proteins suggested that the urokinase-type plasminogen activators were bound to the receptors. The membrane-associated activator may stimulate local proteolysis, facilitating the migration of the tumor cell across the substrate

  6. Two-color cytofluorometry and cellular properties of the urokinase receptor associated with a human metastatic carcinomatous cell line

    Takahashi, K.; Gojobori, T.; Tanifuji, M. (Shimane Medical Univ., Izumo (Japan))

    1991-02-01

    Purified human urokinase was labeled with either fluorescein isothiocyanate or iodine-125 and used as a probe for binding to the human metastatic carcinomatous cell line, Detroit 562. Cytofluorometry showed that the ligand bound preferentially to cells that had been exposed to acidic pH. The binding was competitive and decreased after mild tryptic digestion. The bound ligand could be removed by restoration of the cells to a low pH. Therefore, the cells had specific binding sites. The bound urokinase was involved in the breakdown of fibrin. Two-color cytofluorometric maps were constructed by counterstaining with propidium iodide. Results suggested that there were different cell populations that had different numbers of receptors and amounts of DNA. We cloned cells and found that single clones had homogeneous levels of receptors with different dissociation constants (from 10(-13) to 10(-11) mol/mg protein) for different clones. Cells of one clone, C5, which had high levels of receptor production, moved characteristically on a glass substratum coated with gold particles and reacted with wheat germ agglutinin, but not with concanavalin A. The receptors were found together with adhesion proteins at the sites where the cells adhered to the substrate. These results and the data obtained by zymography of the cellular proteins suggested that the urokinase-type plasminogen activators were bound to the receptors. The membrane-associated activator may stimulate local proteolysis, facilitating the migration of the tumor cell across the substrate.

  7. Multiple-level porous polymer monoliths with interconnected cellular topology prepared by combining hard sphere and emulsion templating for use in bone tissue engineering

    Paljevac, M.; Gradišnik, L.; Lipovšek, S.; Maver, U.; Kotek, Jiří; Krajnc, P.

    2018-01-01

    Roč. 18, č. 2 (2018), s. 1-8, č. článku 1700306. ISSN 1616-5187 R&D Projects: GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : bone tissue engineering * hierarchical materials * polymer scaffolds Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 3.238, year: 2016

  8. Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

    Eneh, C. T. M., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Töyräs, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Jurvelin, J. S., E-mail: jukka.jurvelin@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, Finland and Diagnostic Imaging Center, Kuopio University Hospital, P.O. Box 100, Kuopio FI-70029 (Finland); Malo, M. K. H., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Liukkonen, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211 (Finland); Karjalainen, J. P., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Bone Index Finland Ltd., P.O. Box 1188, Kuopio FI-70211 (Finland)

    2016-05-15

    Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R{sup 2} ≥ 0.493, p < 0.01 and R{sup 2} ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated

  9. Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

    Eneh, C. T. M.; Töyräs, J.; Jurvelin, J. S.; Malo, M. K. H.; Liukkonen, J.; Karjalainen, J. P.

    2016-01-01

    Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R"2 ≥ 0.493, p < 0.01 and R"2 ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated in vivo

  10. Anomalous properties of heat diffusion in living tissue caused by branching artery network. Qualitative description

    Lubashevsky, I. A.; Gafiychuk, V. V.; Datsko, B. Y.

    2002-01-01

    We analyze the effect of blood flow through large arteries of peripheral circulation on heat transfer in living tissue. Blood flow in such arteries gives rise to fast heat propagation over large scales, which is described in terms of heat superdiffusion. The corresponding bioheat heat equation is derived. In particular, we show that under local strong heating of a small tissue domain the temperature distribution inside the surrounding tissue is affected substantially by heat superdiffusion.

  11. [Therapeutic applications and promises of cellular and tissue engineering. What strategic choice for the Etablissement Français du Sang?].

    Hervé, Patrick

    2007-05-01

    A new medical field, known as regeneration medicine, is developing and attracting more and more researchers and practitioners. Whereas hematopoietic cell-based therapies have already proven their efficacy in numerous--malignant or not--diseases, non-hematopoietic cell-based therapies have not. They can be useful to dozens, if not hundreds, of patients with various disorders, such as cardiopathy, diabetes, some types of cancer, osteoarticular and neurodegenerative disorders. In these fields, numerous clinical applications are possible for mesenchymal stem cells. Cell and tissue (corneas, bone, skin) therapy products require the definition of pharmaceutical standards with new European requirements in terms of quality and safety. The legitimacy of the Etablissement Français du Sang (EFS) in cell and tissue engineering activities is established, it is recognized by most specialists and by regulatory authorities and has been asserted by the orientations of its "contrat d'objectifs et de moyens". An independent committee has been set up by the EFS President to define an EFS-specific strategy. This committee made up of qualified specialists was required to draw up a rational organization plan for these activities, in order for EFS to be in a position to produce cells and tissues according to pharmaceutical standards. The committee proposals are based on economic data and an inventory of existing cell and tissue engineering activities. Public/private partnerships are required and efforts must focus towards the industrial valorization of EFS expertise in R&D activities and staff know-how. Implementing such a new organization requires national management and the cooperation of institutional actors (university hospitals, cancer treatment centers, universities). For the success of this approach, EFS personnel must be convinced of its legitimacy and new skills must be encouraged. With its numerous assets, EFS can be ambitious and assert itself as a major actor in cell and

  12. Sensitivity of microwave ablation models to tissue biophysical properties: A first step toward probabilistic modeling and treatment planning.

    Sebek, Jan; Albin, Nathan; Bortel, Radoslav; Natarajan, Bala; Prakash, Punit

    2016-05-01

    Computational models of microwave ablation (MWA) are widely used during the design optimization of novel devices and are under consideration for patient-specific treatment planning. The objective of this study was to assess the sensitivity of computational models of MWA to tissue biophysical properties. The Morris method was employed to assess the global sensitivity of the coupled electromagnetic-thermal model, which was implemented with the finite element method (FEM). The FEM model incorporated temperature dependencies of tissue physical properties. The variability of the model was studied using six different outputs to characterize the size and shape of the ablation zone, as well as impedance matching of the ablation antenna. Furthermore, the sensitivity results were statistically analyzed and absolute influence of each input parameter was quantified. A framework for systematically incorporating model uncertainties for treatment planning was suggested. A total of 1221 simulations, incorporating 111 randomly sampled starting points, were performed. Tissue dielectric parameters, specifically relative permittivity, effective conductivity, and the threshold temperature at which they transitioned to lower values (i.e., signifying desiccation), were identified as the most influential parameters for the shape of the ablation zone and antenna impedance matching. Of the thermal parameters considered in this study, the nominal blood perfusion rate and the temperature interval across which the tissue changes phase were identified as the most influential. The latent heat of tissue water vaporization and the volumetric heat capacity of the vaporized tissue were recognized as the least influential parameters. Based on the evaluation of absolute changes, the most important parameter (perfusion) had approximately 40.23 times greater influence on ablation area than the least important parameter (volumetric heat capacity of vaporized tissue). Another significant input parameter

  13. Quantifying dynamic mechanical properties of human placenta tissue using optimization techniques with specimen-specific finite-element models.

    Hu, Jingwen; Klinich, Kathleen D; Miller, Carl S; Nazmi, Giseli; Pearlman, Mark D; Schneider, Lawrence W; Rupp, Jonathan D

    2009-11-13

    Motor-vehicle crashes are the leading cause of fetal deaths resulting from maternal trauma in the United States, and placental abruption is the most common cause of these deaths. To minimize this injury, new assessment tools, such as crash-test dummies and computational models of pregnant women, are needed to evaluate vehicle restraint systems with respect to reducing the risk of placental abruption. Developing these models requires accurate material properties for tissues in the pregnant abdomen under dynamic loading conditions that can occur in crashes. A method has been developed for determining dynamic material properties of human soft tissues that combines results from uniaxial tensile tests, specimen-specific finite-element models based on laser scans that accurately capture non-uniform tissue-specimen geometry, and optimization techniques. The current study applies this method to characterizing material properties of placental tissue. For 21 placenta specimens tested at a strain rate of 12/s, the mean failure strain is 0.472+/-0.097 and the mean failure stress is 34.80+/-12.62 kPa. A first-order Ogden material model with ground-state shear modulus (mu) of 23.97+/-5.52 kPa and exponent (alpha(1)) of 3.66+/-1.90 best fits the test results. The new method provides a nearly 40% error reduction (p<0.001) compared to traditional curve-fitting methods by considering detailed specimen geometry, loading conditions, and dynamic effects from high-speed loading. The proposed method can be applied to determine mechanical properties of other soft biological tissues.

  14. Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties.

    Mabilleau, Guillaume; Mieczkowska, Aleksandra; Irwin, Nigel; Simon, Yannick; Audran, Maurice; Flatt, Peter R; Chappard, Daniel

    2014-06-01

    Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed, with N-AcGIP being the most promising. The aims of the present study were to investigate the effects of N-AcGIP on bone at the micro-level using trabecular and cortical microstructural morphology, and at the tissue-level in rats. Copenhagen rats were randomly assigned into control or N-AcGIP-treated groups and received daily injection for 4 weeks. Bone microstructural morphology was assessed by microCT and dynamic histomorphometry and tissue-level properties by nanoindentation, qBEI and infra-red microscopy. Four week treatment with N-AcGIP did not alter trabecular or cortical microstructural morphology. In addition, no significant modifications of mechanical response and properties at the tissue-level were observed in trabecular bone. However, significant augmentations in maximum load (12%), hardness (14%), indentation modulus (13%) and dissipated energy (16%) were demonstrated in cortical bone. These beneficial modifications of mechanical properties at the tissue-level were associated with increased mineralization (22%) and collagen maturity (13%) of the bone matrix. Taken together, the results support a beneficial role of GIP, and particularly stable analogs such as N-AcGIP, on tissue material properties of bone. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

    Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

    2017-01-01

    Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

  16. The effect of magnetic nanoparticles on the acoustic properties of tissue-mimicking agar-gel phantoms

    Józefczak, A., E-mail: aras@amu.edu.pl [Institute of Acoustics, Faculty of Physics, Adam Mickiewicz University, Poznań (Poland); Kaczmarek, K. [Institute of Acoustics, Faculty of Physics, Adam Mickiewicz University, Poznań (Poland); Kubovčíková, M. [Institute of Experimental Physics, Slovak Academy of Sciences, Košice (Slovakia); Rozynek, Z.; Hornowski, T. [Institute of Acoustics, Faculty of Physics, Adam Mickiewicz University, Poznań (Poland)

    2017-06-01

    In ultrasonic hyperthermia, ultrasound-induced heating is achieved by the absorption of wave energy and its conversion into heat. The effectiveness of ultrasounds can be improved by using sonosensitisers that greatly attenuate ultrasonic waves and then dissipate the acquired energy in the form of heat. One possible candidate for such a sonosensitiser are superparamagnetic iron oxide nanoparticles. Here, we used magnetic nanoparticles embedded in a tissue-mimicking agar-gel matrix. Such tissue-mimicking phantoms possess acoustic properties similar to those of real tissues, and are used as a tool for performance testing and optimisation of medical ultrasound systems. In this work, we studied the effect of magnetic nanoparticles on the acoustic properties of agar-gel phantoms, including the attenuation of ultrasonic waves. - Highlights: • Ultrasonic insertion technique is used to study acoustic properties of agar-gel phantoms with and without magnetic particles. • The addition of magnetic nanoparticles improves effectiveness of ultrasound heating in agar phantoms. • Acoustics properties of a pure agar-gel phantom are altered by adding nanoparticles.

  17. Biophysical properties and functional significance of stem water storage tissues in Neotropical savanna trees.

    F.G. Scholz; S.J. Bucci; G. Goldstein; F.C. Meinzer; A.C. Franco; F. Miralles-Wilhelm

    2007-01-01

    Biophysical characteristics of sapwood and outer parenchyma water storage compartments were studied in stems of eight dominant Brazilian Cerrado tree species to assess the impact of differences in tissue capacitance on whole-plant water relations. Both the sapwood and outer parenchyma tissues played an important role in regulation of internal water deficits of Cerrado...

  18. Nondestructive and noninvasive assessment of mechanical properties in heart valve tissue engineering

    Kortsmit, J.; Driessen, N.J.B.; Rutten, M.C.M.; Baaijens, F.P.T.

    2009-01-01

    Despite recent progress, mechanical behavior of tissue-engineered heart valves still needs improvement when native aortic valves are considered as a benchmark. Although it is known that cyclic straining enhances tissue formation, optimal loading protocols have not been defined yet. To obtain a

  19. Photophysical properties and localization of chlorins substituted with methoxy groups, hydroxyl groups and alkyl chains in liposome-like cellular membrane

    Al-Omari, S [Department of Physics, Hashemite University, Zarqa 13115 (Jordan)

    2007-06-01

    Some of the photophysical properties (stationary absorbance and fluorescence, fluorescence decay times and singlet oxygen quantum yields) of chlorins substituted with methoxy groups, hydroxyl groups and hydrocarbonic chains were studied in ethanol and dipalmitoyl-phosphatidylcholine (DPPC) liposomes using steady-state and time-resolved fluorescence spectroscopies. The photophysical behaviors of the chlorins in liposomes like cellular membrane were compared with those obtained from chlorin-liposome systems delivered to Jurkat cells in order to select potent photosensitizers for the photodynamic treatment of cancer. The localization of the studied chlorins inside liposomes was found to depend strongly on the substituents of chlorins. Absorption spectra of chlorins embedded in DPPC-liposomes have been recorded in the temperature range of 20-70 deg. C. It is demonstrated that the location of the chlorin molecules depends on the phase state of the phospholipids. These observations are confirmed by the fluorescence lifetimes, singlet oxygen lifetimes and singlet oxygen quantum yields results.

  20. Membrane transport properties of equine and macaque ovarian tissues frozen in mixtures of dimethylsulfoxide and ethylene glycol.

    Kardak, A; Leibo, S P; Devireddy, R

    2007-10-01

    /mole. The parameters for both equine and macaque tissue samples suspended in the DMSO+EG mixture and first cooled at 0.5 degrees C/min between +25 degrees C and +4 degrees C were very similar to the corresponding values for samples cooled at 40 degrees C/min. In contrast, the membrane parameters of equine and macaque samples first cooled at 0.5 degrees C/min in single-component solutions were significantly different from the corresponding values for samples cooled at 40 degrees C/min. These results show that the membrane properties of ovarian cells from two species are different, and that the membrane properties are significantly affected both by the solution in which the tissue is suspended and by the rate at which the tissue is cooled from +25 degrees C to +4 degrees C before being frozen. These observations suggest that these variables ought to be considered in the derivation of methods to cryopreserve ovarian tissues.

  1. Effects of collagen microstructure and material properties on the deformation of the neural tissues of the lamina cribrosa.

    Voorhees, A P; Jan, N-J; Sigal, I A

    2017-08-01

    It is widely considered that intraocular pressure (IOP)-induced deformation within the neural tissue pores of the lamina cribrosa (LC) contributes to neurodegeneration and glaucoma. Our goal was to study how the LC microstructure and mechanical properties determine the mechanical insult to the neural tissues within the pores of the LC. Polarized light microscopy was used to measure the collagen density and orientation in histology sections of three sheep optic nerve heads (ONH) at both mesoscale (4.4μm) and microscale (0.73μm) resolutions. Mesoscale fiber-aware FE models were first used to calculate ONH deformations at an IOP of 30mmHg. The results were then used as boundary conditions for microscale models of LC regions. Models predicted large insult to the LC neural tissues, with 95th percentile 1st principal strains ranging from 7 to 12%. Pores near the scleral boundary suffered significantly higher stretch compared to pores in more central regions (10.0±1.4% vs. 7.2±0.4%; p=0.014; mean±SD). Variations in material properties altered the minimum, median, and maximum levels of neural tissue insult but largely did not alter the patterns of pore-to-pore variation, suggesting these patterns are determined by the underlying structure and geometry of the LC beams and pores. To the best of our knowledge, this is the first computational model that reproduces the highly heterogeneous neural tissue strain fields observed experimentally. The loss of visual function associated with glaucoma has been attributed to sustained mechanical insult to the neural tissues of the lamina cribrosa due to elevated intraocular pressure. Our study is the first computational model built from specimen-specific tissue microstructure to consider the mechanics of the neural tissues of the lamina separately from the connective tissue. We found that the deformation of the neural tissue was much larger than that predicted by any recent microstructure-aware models of the lamina. These results

  2. Exploring emergent properties in cellular homeostasis using OnGuard to model K+ and other ion transport in guard cells.

    Blatt, Michael R; Wang, Yizhou; Leonhardt, Nathalie; Hills, Adrian

    2014-05-15

    It is widely recognized that the nature and characteristics of transport across eukaryotic membranes are so complex as to defy intuitive understanding. In these circumstances, quantitative mathematical modeling is an essential tool, both to integrate detailed knowledge of individual transporters and to extract the properties emergent from their interactions. As the first, fully integrated and quantitative modeling environment for the study of ion transport dynamics in a plant cell, OnGuard offers a unique tool for exploring homeostatic properties emerging from the interactions of ion transport, both at the plasma membrane and tonoplast in the guard cell. OnGuard has already yielded detail sufficient to guide phenotypic and mutational studies, and it represents a key step toward 'reverse engineering' of stomatal guard cell physiology, based on rational design and testing in simulation, to improve water use efficiency and carbon assimilation. Its construction from the HoTSig libraries enables translation of the software to other cell types, including growing root hairs and pollen. The problems inherent to transport are nonetheless challenging, and are compounded for those unfamiliar with conceptual 'mindset' of the modeler. Here we set out guidelines for the use of OnGuard and outline a standardized approach that will enable users to advance quickly to its application both in the classroom and laboratory. We also highlight the uncanny and emergent property of OnGuard models to reproduce the 'communication' evident between the plasma membrane and tonoplast of the guard cell. Copyright © 2014 The Authors. Published by Elsevier GmbH.. All rights reserved.

  3. Uncovering the Design Principle of Amino Acid-Derived Photoluminescent Biodots with Tailor-Made Structure-Properties and Applications for Cellular Bioimaging.

    Xu, Hesheng Victor; Zheng, Xin Ting; Zhao, Yanli; Tan, Yen Nee

    2018-06-01

    Natural amino acids possess side chains with different functional groups (R groups), which make them excellent precursors for programmable synthesis of biomolecule-derived nanodots (biodots) with desired properties. Herein, we report the first systematic study to uncover the material design rules of biodot synthesis from 20 natural α-amino acids via a green hydrothermal approach. The as-synthesized amino acid biodots (AA dots) are comprehensively characterized to establish a structure-property relationship between the amino acid precursors and the corresponding photoluminescent properties of AA dots. It was found that the amino acids with reactive R groups, including amine, hydroxyl, and carboxyl functional groups form unique C-O-C/C-OH and N-H bonds in the AA dots which stabilize the surface defects, giving rise to brightly luminescent AA dots. Furthermore, the AA dots were found to be amorphous and the length of the R group was observed to affect the final morphology (e.g., disclike nanostructure, nanowire, or nanomesh) of the AA dots, which in turn influence their photoluminescent properties. It is noteworthy to highlight that the hydroxyl-containing amino acids, that is, Ser and Thr, form the brightest AA dots with a quantum yield of 30.44% and 23.07%, respectively, and possess high photostability with negligible photobleaching upon continuous UV exposure for 3 h. Intriguingly, by selective mixing of Ser or Thr with another amino acid precursor, the resulting mixed AA dots could inherit unique properties such as improved photostability and significant red shift in their emission wavelength, producing enhanced green and red fluorescent intensity. Moreover, our cellular studies demonstrate that the as-synthesized AA dots display outstanding biocompatibility and excellent intracellular uptake, which are highly desirable for imaging applications. We envision that the material design rules discovered in this study will be broadly applicable for the rational

  4. Nitrogen and phosphorus co-doped graphene quantum dots: synthesis from adenosine triphosphate, optical properties, and cellular imaging.

    Ananthanarayanan, Arundithi; Wang, Yue; Routh, Parimal; Sk, Mahasin Alam; Than, Aung; Lin, Ming; Zhang, Jie; Chen, Jie; Sun, Handong; Chen, Peng

    2015-05-07

    Graphene quantum dots (GQDs) are emerging zero-dimensional materials promising a wide spectrum of applications, particularly, as superior fluorescent reporters for bio-imaging and optical sensing. Heteroatom doping can endow GQDs with new or improved photoluminescence properties. Here, we demonstrate a simple strategy for the synthesis of nitrogen and phosphorus co-doped GQDs from a single biomolecule precursor (adenosine triphosphate - ATP). Such ATP-GQDs exhibit high fluorescence quantum yield, strong two-photon upconversion, small molecular weight, high photostability, and good biocompatibility. Furthermore, transferrin conjugated ATP-GQDs have been used for imaging and real-time tracking of transferrin receptors in live cells.

  5. Nutrient-deprivation autophagy factor-1 (NAF-1: biochemical properties of a novel cellular target for anti-diabetic drugs.

    Sagi Tamir

    Full Text Available Nutrient-deprivation autophagy factor-1 (NAF-1 (synonyms: Cisd2, Eris, Miner1, and Noxp70 is a [2Fe-2S] cluster protein immune-detected both in endoplasmic reticulum (ER and mitochondrial outer membrane. It was implicated in human pathology (Wolfram Syndrome 2 and in BCL-2 mediated antagonization of Beclin 1-dependent autophagy and depression of ER calcium stores. To gain insights about NAF-1 functions, we investigated the biochemical properties of its 2Fe-2S cluster and sensitivity of those properties to small molecules. The structure of the soluble domain of NAF-1 shows that it forms a homodimer with each protomer containing a [2Fe-2S] cluster bound by 3 Cys and one His. NAF-1 has shown the unusual abilities to transfer its 2Fe-2S cluster to an apo-acceptor protein (followed in vitro by spectrophotometry and by native PAGE electrophoresis and to transfer iron to intact mitochondria in cell models (monitored by fluorescence imaging with iron fluorescent sensors targeted to mitochondria. Importantly, the drug pioglitazone abrogates NAF-1's ability to transfer the cluster to acceptor proteins and iron to mitochondria. Similar effects were found for the anti-diabetes and longevity-promoting antioxidant resveratrol. These results reveal NAF-1 as a previously unidentified cell target of anti-diabetes thiazolidinedione drugs like pioglitazone and of the natural product resveratrol, both of which interact with the protein and stabilize its labile [2Fe-2S] cluster.

  6. Mineral density and biomechanical properties of bone tissue from male Arctic foxes (Vulpes lagopus) exposed to organochlorine contaminants and emaciation

    Sonne, Christian; Wolkers, Hans; Rigét, Frank F

    2008-01-01

    We investigated the impact from dietary OC (organochlorine) exposure and restricted feeding (emaciation) on bone mineral density (BMD; g hydroxy-apatite cm(-2)) in femoral, vertebrate, skull and baculum osteoid tissue from farmed Arctic blue foxes (Vulpes lagopus). For femur, also biomechanical......), energy absorption (J) and time (s) biomechanical properties than fat winter foxes (all pbones from fasting which is in agreement with previous studies. Further, it should be kept in mind when studying bone tissues in Arctic mammals also in order to avoid...... tissue of ca. 1700 ng/g live mass in the 8 EXP fat foxes euthanized after 16 months. A control group (CON) composed of 15 foxes were fed equal daily caloric amounts of clean pork (Sus scrofa) fat. After 16 months, 8 EXP and 7 CON foxes were euthanized (mean body mass=9.25 kg) while the remaining 8 EXP...

  7. An examination of the elastic properties of tissue-mimicking phantoms using vibro-acoustography and a muscle motor system

    Maccabi, A.; Taylor, Z.; Bajwa, N.; Mallen-St. Clair, J.; St. John, M.; Sung, S.; Grundfest, W.; Saddik, G.

    2016-02-01

    Tissue hardness, often quantified in terms of elasticity, is an important differentiating criterion for pathological identity and is extensively used by surgeons for tumor localization. Delineation of malignant regions from benign regions is typically performed by visual inspection and palpation. Although practical, this method is highly subjective and does not provide quantitative metrics. We have previously reported on Vibro-Acoustography (VA) for tumor delineation. VA is unique in that it uses the specific, non-linear properties of tumor tissue in response to an amplitude modulated ultrasound beam to generate spatially resolved, high contrast maps of tissue. Although the lateral and axial resolutions (sub-millimeter and sub-centimeter, respectively) of VA have been extensively characterized, the relationship between static stiffness assessment (palpation) and dynamic stiffness characterization (VA) has not been explicitly established. Here we perform a correlative exploration of the static and dynamic properties of tissue-mimicking phantoms, specifically elasticity, using VA and a muscle motor system. Muscle motor systems, commonly used to probe the mechanical properties of materials, provide absolute, quantitative point measurements of the elastic modulus, analogous to Young's modulus, of a target. For phantoms of varying percent-by-weight concentrations, parallel VA and muscle motor studies conducted on 18 phantoms reveal a negative correlation (p < - 0.85) between mean signal amplitude levels observed with VA and calculated elastic modulus values from force vs. indentation depth curves. Comparison of these elasticity measurements may provide additional information to improve tissue modeling, system characterization, as well as offer valuable insights for in vivo applications, specifically surgical extirpation of tumors.

  8. Serotoninergic receptors in brain tissue: properties and identification of various 3H-ligand binding sites in vitro

    Leysen, J.E.

    1981-01-01

    In vitro binding studies to serotoninergic receptors were performed using 3 H-LSD, 3 H-5-HT and 3 H-spiperone. An overwiew is given on findings using these three ligands with respect to the following: localization of specific binding sites, in various animal species, the regional distribution in the brain and periphery, the subcellular and cellular distribution. Properties of the binding sites, influence of the composition of the assay medium, binding kinetic properties, receptor regulation in vivo. Identity of the binding sites, differences between site for various 3 H-ligands, pharmacological specificity of the membranous binding sites, chemical composition of the macromolecular complex constituting the binding site. Function of the receptor. Binding affinities of 44 compounds were measured in binding assays using 3 H-spiperone and 3 H-LSD with rat frontal cortex membrane preparations and using 3 H-5-HT and 3 H-LSD with rat hippocampal membrane preparations

  9. Mechanical and biological properties of the micro-/nano-grain functionally graded hydroxyapatite bioceramics for bone tissue engineering.

    Zhou, Changchun; Deng, Congying; Chen, Xuening; Zhao, Xiufen; Chen, Ying; Fan, Yujiang; Zhang, Xingdong

    2015-08-01

    Functionally graded materials (FGM) open the promising approach for bone tissue repair. In this study, a novel functionally graded hydroxyapatite (HA) bioceramic with micrograin and nanograin structure was fabricated. Its mechanical properties were tailored by composition of micrograin and nanograin. The dynamic mechanical analysis (DMA) indicated that the graded HA ceramics had similar mechanical property compared to natural bones. Their cytocompatibility was evaluated via fluorescent microscopy and MTT colorimetric assay. The viability and proliferation of rabbit bone marrow mesenchymal stem cells (BMSCs) on ceramics indicated that this functionally graded HA ceramic had better cytocompatibility than conventional HA ceramic. This study demonstrated that functionally graded HA ceramics create suitable structures to satisfy both the mechanical and biological requirements of bone tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Methods of Assessing Human Tendon Metabolism and Tissue Properties in Response to Changes in Mechanical Loading

    Heinemeier, Katja M; Kjaer, Michael; Magnusson, S Peter

    2016-01-01

    expression as well as protein synthesis rate. Further the (14)C bomb-pulse method has provided data on long-term tissue turnover in human tendon. Non-invasive techniques allow measurement of tendon metabolism (positron emission tomography (PET)), tendon morphology (magnetic resonance imaging (MRI......In recent years a number of methodological developments have improved the opportunities to study human tendon. Microdialysis enables sampling of interstitial fluid in the peritendon tissue, while sampling of human tendon biopsies allows direct analysis of tendon tissue for gene- and protein...

  11. An experimental study on the mechanical properties of rat brain tissue using different stress-strain definitions.

    Karimi, Alireza; Navidbakhsh, Mahdi

    2014-07-01

    There are different stress-strain definitions to measure the mechanical properties of the brain tissue. However, there is no agreement as to which stress-strain definition should be employed to measure the mechanical properties of the brain tissue at both the longitudinal and circumferential directions. It is worth knowing that an optimize stress-strain definition of the brain tissue at different loading directions may have implications for neuronavigation and surgery simulation through haptic devices. This study is aimed to conduct a comparative study on different results are given by the various definitions of stress-strain and to recommend a specific definition when testing brain tissues. Prepared cylindrical samples are excised from the parietal lobes of rats' brains and experimentally tested by applying load on both the longitudinal and circumferential directions. Three stress definitions (second Piola-Kichhoff stress, engineering stress, and true stress) and four strain definitions (Almansi-Hamel strain, Green-St. Venant strain, engineering strain, and true strain) are used to determine the elastic modulus, maximum stress and strain. The highest non-linear stress-strain relation is observed for the Almansi-Hamel strain definition and it may overestimate the elastic modulus at different stress definitions at both the longitudinal and circumferential directions. The Green-St. Venant strain definition fails to address the non-linear stress-strain relation using different definitions of stress and triggers an underestimation of the elastic modulus. The results suggest the application of the true stress-true strain definition for characterization of the brain tissues mechanics since it gives more accurate measurements of the tissue's response using the instantaneous values.

  12. Impact of O-glycosylation on the molecular and cellular adhesion properties of the Escherichia coli autotransporter protein Ag43.

    Reidl, Sebastian; Lehmann, Annika; Schiller, Roswitha; Salam Khan, A; Dobrindt, Ulrich

    2009-08-01

    Antigen 43 (Ag43) represents an entire family of closely related autotransporter proteins in Escherichia coli and has been described to confer aggregation and fluffing of cells, to promote biofilm formation, uptake and survival in macrophages as well as long-term persistence of uropathogenic E. coli in the murine urinary tract. Furthermore, it has been reported that glycosylation of the Ag43 passenger domain (alpha(43)) stabilizes its conformation and increases adhesion to Hep-2 cells. We characterized the role of Ag43 as an adhesin and the impact of O-glycosylation on the function of Ag43. To analyze whether structural variations in the alpha(43) domain correlate with different functional properties, we cloned 5 different agn43 alleles from different E. coli subtypes and tested them for autoaggregation, biofilm formation, adhesion to different eukaryotic cell lines as well as to purified components of the extracellular matrix. These experiments were performed with nonglycosylated and O-glycosylated Ag43 variants. We show for the first time that Ag43 mediates bacterial adhesion in a cell line-specific manner and that structural variations of the alpha(43) domain correlate with increased adhesive properties to proteins of the extracellular matrix such as collagen and laminin. Whereas O-glycosylation of many alpha(43) domains led to impaired autoaggregation and a significantly reduced adhesion to eukaryotic cell lines, their interaction with collagen was significantly increased. These data demonstrate that O-glycosylation is not a prerequisite for Ag43 function and that the different traits mediated by Ag43, i.e., biofilm formation, autoaggregation, adhesion to eukaryotic cells and extracellular matrix proteins, rely on distinct mechanisms.

  13. Cellular response of healing tissue to DegraPol tube implantation in rabbit Achilles tendon rupture repair: an in vivo histomorphometric study.

    Buschmann, Johanna; Meier-Bürgisser, Gabriella; Bonavoglia, Eliana; Neuenschwander, Peter; Milleret, Vincent; Giovanoli, Pietro; Calcagni, Maurizio

    2013-05-01

    In tendon rupture repair, improvements such as higher primary repair strength, anti-adhesion and accelerated healing are needed. We developed a potential carrier system of an electrospun DegraPol tube, which was tightly implanted around a transected and conventionally sutured rabbit Achilles tendon. Histomorphometric analysis of the tendon tissue 12 weeks postoperation showed that the tenocyte density, tenocyte morphology and number of inflammation zones were statistically equivalent, whether or not DegraPol tube was implanted; only the collagen fibres were slightly less parallelly orientated in the tube-treated case. Comparison of rabbits that were operated on both hind legs with ones that were operated on only one hind leg showed that there were significantly more inflammation zones in the two-leg cases compared to the one-leg cases, while the implantation of a DegraPol tube had no such adverse effects. These findings are a prerequisite for using DegraPol tube as a carrier system for growth factors, cytokines or stem cells in order to accelerate the healing process of tendon tissue. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Biocompatibility of a novel cyanoacrylate based tissue adhesive: cytotoxicity and biochemical property evaluation.

    Young Ju Lee

    Full Text Available Cyanoacrylate (CA is most widely used as a medical and commercial tissue adhesive because of easier wound closure, good cosmetic results and little discomfort. But, CA-based tissue adhesives have some limitations including the release of cytotoxic chemicals during biodegradation. In previous study, we made prepolymerized allyl 2-CA (PACA based tissue adhesive, resulting in longer chain structure. In this study, we investigated a biocompatibility of PACA as alternative tissue adhesive for medical application, comparing with that of Dermabond® as commercial tissue adhesive. The biocompatibility of PACA was evaluated for short-term (24 hr and long-term (3 and 7 days using conventional cytotoxicity (WST, neutral red, LIVE/DEAD and TUNEL assays, hematoxylin-eosin (H&E and Masson trichrome (MT staining. Besides we examined the biochemical changes in cells and DNA induced by PACA and Dermabond® utilizing Raman spectroscopy which could observe the denaturation and conformational changes in protein, as well as disintegration of the DNA/RNA by cell death. In particular, we analyzed Raman spectrum using the multivariate statistical methods including principal component analysis (PCA and support vector machine (SVM. As a result, PACA and Dermabond® tissue adhesive treated cells and tissues showed no difference of the cell viability values, histological analysis and Raman spectral intensity. Also, the classification analysis by means of PCA-SVM classifier could not discriminate the difference between the PACA and Dermabond® treated cells and DNA. Therefore we suggest that novel PACA might be useful as potential tissue adhesive with effective biocompatibility.

  15. Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner.

    Munir, Hafsa; Ward, Lewis S C; Sheriff, Lozan; Kemble, Samuel; Nayar, Saba; Barone, Francesca; Nash, Gerard B; McGettrick, Helen M

    2017-06-01

    Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage-induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC isolated from bone marrow or adipose tissue on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue. Bone marrow derived MSC were immunosuppressive, inhibiting neutrophil recruitment to TNFα-treated endothelial cells (EC), but MSC-derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL-6 and TGFβ1 signalling appeared critical for the loss of the immunosuppressive phenotype. In contrast, native stromal cells, adipocytes derived from them, and mature adipocytes from adipose tissue were all immunoprotective. Thus disruption of normal tissue stroma homeostasis, as occurs in chronic inflammatory diseases, might drive "abnormal" adipogenesis which adversely influences the behavior of MSC and contributes to pathogenic recruitment of leukocytes. Interestingly, stromal cells programmed in native fat tissue retain an immunoprotective phenotype. Stem Cells 2017;35:1636-1646. © 2017 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  16. The properties of connective tissue membrane and pig skin as raw materials for cooked sausage.

    Puolanne, E; Ruusunen, M

    1981-09-01

    Pig skin and epimysial membrane from young bulls were comminuted in a colloid grinder and mixed with water and additives. The resultant mixture was heated in a water bath to give an internal temperature of 72°C, and centrifuged while still hot. Such variations in the amount of water added, the salt content, the phosphate content and the pH value as are possible in cooked sausage heated to over 65°C during processing did not cause marked changes in the amount of water bound by the connective tissues, the amount of dissolved protein or the gel strength of the liquid released from the connective tissues. As the temperature rose the amount of bound water dropped, but the amount of dissolved protein and the gel strength increased. The liquid released from the connective tissue membranes formed a gel at 32°C and re-melted at 49°C. For pig skin, the corresponding temperatures were 23°C and 47°C. On the basis of this study it appears that connective tissue may be important for the water-binding capacity and firmness of cold sausage. The connective tissue membranes obtained from young bulls and pig skin are of roughly equal value in this respect, although the gel formed from connective tissue membrane is tougher. Copyright © 1981. Published by Elsevier Ltd.

  17. The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental Tissue Engineering

    Ratajczak, Jessica; Bronckaers, Annelies; Dillen, Yörg; Gervois, Pascal; Vangansewinkel, Tim; Driesen, Ronald B.; Wolfs, Esther; Lambrichts, Ivo

    2016-01-01

    Within the field of tissue engineering, natural tissues are reconstructed by combining growth factors, stem cells, and different biomaterials to serve as a scaffold for novel tissue growth. As adequate vascularization and innervation are essential components for the viability of regenerated tissues, there is a high need for easily accessible stem cells that are capable of supporting these functions. Within the human tooth and its surrounding tissues, different stem cell populations can be distinguished, such as dental pulp stem cells, stem cells from human deciduous teeth, stem cells from the apical papilla, dental follicle stem cells, and periodontal ligament stem cells. Given their straightforward and relatively easy isolation from extracted third molars, dental stem cells (DSCs) have become an attractive source of mesenchymal-like stem cells. Over the past decade, there have been numerous studies supporting the angiogenic, neuroprotective, and neurotrophic effects of the DSC secretome. Together with their ability to differentiate into endothelial cells and neural cell types, this makes DSCs suitable candidates for dental tissue engineering and nerve injury repair. PMID:27688777

  18. The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental Tissue Engineering

    Jessica Ratajczak

    2016-01-01

    Full Text Available Within the field of tissue engineering, natural tissues are reconstructed by combining growth factors, stem cells, and different biomaterials to serve as a scaffold for novel tissue growth. As adequate vascularization and innervation are essential components for the viability of regenerated tissues, there is a high need for easily accessible stem cells that are capable of supporting these functions. Within the human tooth and its surrounding tissues, different stem cell populations can be distinguished, such as dental pulp stem cells, stem cells from human deciduous teeth, stem cells from the apical papilla, dental follicle stem cells, and periodontal ligament stem cells. Given their straightforward and relatively easy isolation from extracted third molars, dental stem cells (DSCs have become an attractive source of mesenchymal-like stem cells. Over the past decade, there have been numerous studies supporting the angiogenic, neuroprotective, and neurotrophic effects of the DSC secretome. Together with their ability to differentiate into endothelial cells and neural cell types, this makes DSCs suitable candidates for dental tissue engineering and nerve injury repair.

  19. Elastin density: Link between histological and biomechanical properties of vaginal tissue in women with pelvic organ prolapse?

    de Landsheere, Laurent; Brieu, Mathias; Blacher, Silvia; Munaut, Carine; Nusgens, Betty; Rubod, Chrystèle; Noel, Agnès; Foidart, Jean-Michel; Nisolle, Michelle; Cosson, Michel

    2016-04-01

    The aim of the study was to correlate histological and biomechanical characteristics of the vaginal wall in women with pelvic organ prolapse (POP). Tissue samples were collected from the anterior [point Ba; POP Questionnaire (POP-Q)] and/or posterior (point Bp; POP-Q) vaginal wall of 15 women who underwent vaginal surgery for POP. Both histological and biomechanical assessments were performed from the same tissue samples in 14 of 15 patients. For histological assessment, the density of collagen and elastin fibers was determined by combining high-resolution virtual imaging and computer-assisted digital image analysis. For biomechanical testing, uniaxial tension tests were performed to evaluate vaginal tissue stiffness at low (C0) and high (C1) deformation rates. Biomechanical testing highlights the hyperelastic behavior of the vaginal wall. At low strains (C0), vaginal tissue appeared stiffer when elastin density was low. We found a statistically significant inverse relationship between C0 and the elastin/collagen ratio (p = 0.048) in the lamina propria. However, at large strain levels (C1), no clear relationship was observed between elastin density or elastin/collagen ratio and stiffness, likely reflecting the large dispersion of the mechanical behavior of the tissue samples. Histological and biomechanical properties of the vaginal wall vary from patient to patient. This study suggests that elastin density deserves consideration as a relevant factor of vaginal stiffness in women with POP.

  20. Cellular metabolism

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  1. Best Signal Quality in Cellular Networks: Asymptotic Properties and Applications to Mobility Management in Small Cell Networks

    Baccelli François

    2010-01-01

    Full Text Available The quickly increasing data traffic and the user demand for a full coverage of mobile services anywhere and anytime are leading mobile networking into a future of small cell networks. However, due to the high-density and randomness of small cell networks, there are several technical challenges. In this paper, we investigate two critical issues: best signal quality and mobility management. Under the assumptions that base stations are uniformly distributed in a ring-shaped region and that shadowings are lognormal, independent, and identically distributed, we prove that when the number of sites in the ring tends to infinity, then (i the maximum signal strength received at the center of the ring tends in distribution to a Gumbel distribution when properly renormalized, and (ii it is asymptotically independent of the interference. Using these properties, we derive the distribution of the best signal quality. Furthermore, an optimized random cell scanning scheme is proposed, based on the evaluation of the optimal number of sites to be scanned for maximizing the user data throughput.

  2. Temperature simulations in hyperthermia treatment planning of the head and neck region. Rigorous optimization of tissue properties

    Verhaart, Rene F.; Rijnen, Zef; Verduijn, Gerda M.; Paulides, Margarethus M.; Fortunati, Valerio; Walsum, Theo van; Veenland, Jifke F.

    2014-01-01

    Hyperthermia treatment planning (HTP) is used in the head and neck region (H and N) for pretreatment optimization, decision making, and real-time HTP-guided adaptive application of hyperthermia. In current clinical practice, HTP is based on power-absorption predictions, but thermal dose-effect relationships advocate its extension to temperature predictions. Exploitation of temperature simulations requires region- and temperature-specific thermal tissue properties due to the strong thermoregulatory response of H and N tissues. The purpose of our work was to develop a technique for patient group-specific optimization of thermal tissue properties based on invasively measured temperatures, and to evaluate the accuracy achievable. Data from 17 treated patients were used to optimize the perfusion and thermal conductivity values for the Pennes bioheat equation-based thermal model. A leave-one-out approach was applied to accurately assess the difference between measured and simulated temperature (∇T). The improvement in ∇T for optimized thermal property values was assessed by comparison with the ∇T for values from the literature, i.e., baseline and under thermal stress. The optimized perfusion and conductivity values of tumor, muscle, and fat led to an improvement in simulation accuracy (∇T: 2.1 ± 1.2 C) compared with the accuracy for baseline (∇T: 12.7 ± 11.1 C) or thermal stress (∇T: 4.4 ± 3.5 C) property values. The presented technique leads to patient group-specific temperature property values that effectively improve simulation accuracy for the challenging H and N region, thereby making simulations an elegant addition to invasive measurements. The rigorous leave-one-out assessment indicates that improvements in accuracy are required to rely only on temperature-based HTP in the clinic. (orig.) [de

  3. Effect of bioglass 45S5 addition on properties, microstructure and cellular response of tetracalcium phosphate/monetite cements

    Stulajterova, R., E-mail: rstulajterova@saske.sk; Medvecky, L.; Giretova, M.; Sopcak, T.; Kovalcikova, A.

    2017-04-15

    Tetracalcium phosphate/nanomonetite (TTCPMH) cement composites with 7.5 and 15 wt% addition of melt-derived 45S5 bioactive glass were prepared by mechanical homogenization of powder components and 2% NaH{sub 2}PO{sub 4} solution was used as a hardening liquid. The properties of composites with the acidic (Ca/P ratio equal 1.5) or basic (Ca/P ratio equal 1.67) TTCPMH component were compared. Addition of glass component caused rapid rise in pH of composites up to 10. In microstructure of basic cement composite, the large bioglass particles weakly bounded to surrounding cement matrix were found contrary to a more compact microstructure of acidic cement composites with the high number of spherical silica particles. Both the significant refinement of hydroxyapatite particles and the change to needle-like morphology with rise in the content of bioglass were identified in hydroxyapatite coatings created during soaking of composites in phosphate buffered saline. In acidic cement mixtures, the increase of compressive strength with an amount of bioglass was found whereas the opposite tendency was revealed in the case of basic cement mixtures. The higher concentrations of ions were verified in solutions after immersion of acidic cement composites. The severe cytotoxicity of extracts and composite cement substrates containing 15 wt% of bioglass demonstrated adverse effects of both the ionic concentrations and unappropriate surface texture on proliferation of mesenchymal stem cells. The enhanced ALP activities of cells cultured on composite cements confirmed the positive effect of bioactive glass addition on differentiation of mesenchymal stem cells. - Highlights: • Novel B45S5 bioglass/tetracalcium phosphate/nanomonetite cement composites • Cement basicity negatively affected their microstructure. • Acid composite cements had higher compressive strengths than basic composites. • Fast differentiation of MSC to osteoblast line on composite with 7.5 wt% of bioglass

  4. A model of the effects of cancer cell motility and cellular adhesion properties on tumour-immune dynamics.

    Frascoli, Federico; Flood, Emelie; Kim, Peter S

    2017-06-01

    We present a three-dimensional model simulating the dynamics of an anti-cancer T-cell response against a small, avascular, early-stage tumour. Interactions at the tumour site are accounted for using an agent-based model (ABM), while immune cell dynamics in the lymph node are modelled as a system of delay differential equations (DDEs). We combine these separate approaches into a two-compartment hybrid ABM-DDE system to capture the T-cell response against the tumour. In the ABM at the tumour site, movement of tumour cells is modelled using effective physical forces with a specific focus on cell-to-cell adhesion properties and varying levels of tumour cell motility, thus taking into account the ability of cancer cells to spread and form clusters. We consider the effectiveness of the immune response over a range of parameters pertaining to tumour cell motility, cell-to-cell adhesion strength and growth rate. We also investigate the dependence of outcomes on the distribution of tumour cells. Low tumour cell motility is generally a good indicator for successful tumour eradication before relapse, while high motility leads, almost invariably, to relapse and tumour escape. In general, the effect of cell-to-cell adhesion on prognosis is dependent on the level of tumour cell motility, with an often unpredictable cross influence between adhesion and motility, which can lead to counterintuitive effects. In terms of overall tumour shape and structure, the spatial distribution of cancer cells in clusters of various sizes has shown to be strongly related to the likelihood of extinction. © The authors 2016. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  5. A crosstalk between muscarinic and CRF2 receptors regulates cellular adhesion properties of human colon cancer cells.

    Pelissier-Rota, M; Chartier, N T; Bonaz, B; Jacquier-Sarlin, M R

    2017-07-01

    Patients with inflammatory bowel disease often suffer from chronic and relapsing intestinal inflammation that favor the development of colitis associated cancer. An alteration of the epithelial intestinal barrier function observed in IBD is supposed to be a consequence of stress. It has been proposed that corticotrophin-releasing factor receptor (CRF2), one of the two receptors of CRF, the principal neuromediator of stress, acts on cholinergic nerves to induce stress-mediated epithelial barrier dysfunction. Non-neuronal acetylcholine (Ach) and muscarinic receptors (mAchR) also contribute to alterations of epithelial cell functions. In this study, we investigated the mechanisms through which stress and Ach modulate epithelial cell adhesive properties. We show that Ach-induced activation of mAchR in HT-29 cells results in cell dissociation together with changes in cell-matrix contacts, which correlates with the acquisition of invasive potential consistent with a matrix metalloproteinase (MMP) mode of invasion. These processes result from mAchR subsequent stimulation of the cascade of src/Erk and FAK activation. Ach-induced secretion of laminin 332 leads to α3β1 integrin activation and RhoA-dependent reorganization of the actin cytoskeleton. We show that Ach-mediated effects on cell adhesion are blocked by astressin 2b, a CRF2 antagonist, suggesting that Ach action depends partly on CRF2 signaling. This is reinforced by the fact that Ach-mediated activation of mAchR stimulates both the synthesis and the release of CRF2 ligands in HT-29 cells (effects blocked by atropine). In summary, our data provides evidence for a novel intracellular circuit involving mAchR acting on CRF2-signaling that could mediate colonic mucosal barrier dysfunction and exacerbate mucosal inflammation. Copyright © 2017. Published by Elsevier B.V.

  6. Determination of tenogenic differentiation in human mesenchymal stem cells by terahertz waves for measurement of the optical property of cellular suspensions

    Morita, Yasuyuki; Azuchi, Kosuke; Ju, Yang; Suzuki, Satoshi; Xu, Baiyao; Yamamoto, Shuhei

    2014-01-01

    Technology for identifying stem cell-to-tenocyte differentiation that is non-contact and non-destructive in vitro is essential in tissue engineering. It has been found that expression of various RNA and proteins produced by differentiated cells is elevated when human bone marrow mesenchymal stem cells (hBMSCs) differentiate into tenocytes. Also, such biomolecules have absorption bands in the terahertz range. Thus, we attempted to evaluate whether terahertz waves could be used to distinguish hBMSC-to-tenocyte differentiation. Terahertz time-domain spectroscopy (THz-TDS) using femtosecond laser pulses was used for terahertz measurements. HBMSCs differentiated into tenocytes with mechanical stimulation: 10% cyclical uniaxial stretching at 1 Hz for 24 or 48 h. Cellular suspensions before and after differentiation were measured with terahertz waves. Complex refractive index, consisting of a refractive index (real) and an extinction coefficient (imaginary) obtained from the transmitted terahertz signals, was evaluated before and after differentiation at 1.0 THz. As a result, the THz-TDS system enabled discrimination of hBMSC-to-tenocyte differentiation due to the marked contrast in optical parameter before and after differentiation. This is the first report of the potential of a THz-TDS system for the detection of tenogenic differentiation using a non-contact and non-destructive in vitro technique. (paper)

  7. Determination of tenogenic differentiation in human mesenchymal stem cells by terahertz waves for measurement of the optical property of cellular suspensions

    Morita, Yasuyuki; Azuchi, Kosuke; Ju, Yang; Suzuki, Satoshi; Xu, Baiyao; Yamamoto, Shuhei

    2014-06-01

    Technology for identifying stem cell-to-tenocyte differentiation that is non-contact and non-destructive in vitro is essential in tissue engineering. It has been found that expression of various RNA and proteins produced by differentiated cells is elevated when human bone marrow mesenchymal stem cells (hBMSCs) differentiate into tenocytes. Also, such biomolecules have absorption bands in the terahertz range. Thus, we attempted to evaluate whether terahertz waves could be used to distinguish hBMSC-to-tenocyte differentiation. Terahertz time-domain spectroscopy (THz-TDS) using femtosecond laser pulses was used for terahertz measurements. HBMSCs differentiated into tenocytes with mechanical stimulation: 10% cyclical uniaxial stretching at 1 Hz for 24 or 48 h. Cellular suspensions before and after differentiation were measured with terahertz waves. Complex refractive index, consisting of a refractive index (real) and an extinction coefficient (imaginary) obtained from the transmitted terahertz signals, was evaluated before and after differentiation at 1.0 THz. As a result, the THz-TDS system enabled discrimination of hBMSC-to-tenocyte differentiation due to the marked contrast in optical parameter before and after differentiation. This is the first report of the potential of a THz-TDS system for the detection of tenogenic differentiation using a non-contact and non-destructive in vitro technique.

  8. Tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors are the cellular source of fibrofatty infiltration in arrhythmogenic cardiomyopathy [v1; ref status: indexed, http://f1000r.es/17s

    Ben Paylor

    2013-06-01

    Full Text Available Arrhythmogenic cardiomyopathy (AC is a disease of the heart involving myocardial dystrophy leading to fibrofatty scarring of the myocardium and is associated with an increased risk of both ventricular arrhythmias and sudden cardiac death. It often affects the right ventricle but may also involve the left. Although there has been significant progress in understanding the role of underlying desmosomal genetic defects in AC, there is still a lack of data regarding the cellular processes involved in its progression. The development of cardiac fibrofatty scarring is known to be a principal pathological process associated with ventricular arrhythmias, and it is vital that we elucidate the role of various cell populations involved in the disease if targeted therapeutics are to be developed. The known role of mesenchymal progenitor cells in the reparative process of both the heart and skeletal muscle has provided inspiration for the identification of the cellular basis of fibrofatty infiltration in AC. Here we hypothesize that reparative processes triggered by myocardial degeneration lead to the differentiation of tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors into adipocytes and fibroblasts, which compose the fibrofatty lesions characteristic of AC.

  9. Multifunctional Hydrogel with Good Structure Integrity, Self-Healing, and Tissue-Adhesive Property Formed by Combining Diels-Alder Click Reaction and Acylhydrazone Bond.

    Yu, Feng; Cao, Xiaodong; Du, Jie; Wang, Gang; Chen, Xiaofeng

    2015-11-04

    Hydrogel, as a good cartilage tissue-engineered scaffold, not only has to possess robust mechanical property but also has to have an intrinsic self-healing property to integrate itself or the surrounding host cartilage. In this work a double cross-linked network (DN) was designed and prepared by combining Diels-Alder click reaction and acylhydrazone bond. The DA reaction maintained the hydrogel's structural integrity and mechanical strength in physiological environment, while the dynamic covalent acylhydrazone bond resulted in hydrogel's self-healing property and controlled the on-off switch of network cross-link density. At the same time, the aldehyde groups contained in hydrogel further promote good integration of the hydrogel to surrounding tissue based on aldehyde-amine Schiff-base reaction. This kind of hydrogel has good structural integrity, autonomous self-healing, and tissue-adhesive property and simultaneously will have a good application in tissue engineering and tissue repair field.

  10. Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering

    Chengdong Xiong

    2009-07-01

    Full Text Available Abstract In this study, we report the physico-chemical and biological properties of a novel biodegradable composite scaffold made of nano-hydroxyapatite and natural derived polymers of chitosan and carboxymethyl cellulose, namely, n-HA/CS/CMC, which was prepared by freeze-drying method. The physico-chemical properties of n-HA/CS/CMC scaffold were tested by infrared absorption spectra (IR, transmission electron microscope(TEM, scanning electron microscope(SEM, universal material testing machine and phosphate buffer solution (PBS soaking experiment. Besides, the biological properties were evaluated by MG63 cells and Mesenchymal stem cells (MSCs culture experiment in vitro and a short period implantation study in vivo. The results show that the composite scaffold is mainly formed through the ionic crossing-linking of the two polyions between CS and CMC, and n-HA is incorporated into the polyelectrolyte matrix of CS-CMC without agglomeration, which endows the scaffold with good physico-chemical properties such as highly interconnected porous structure, high compressive strength and good structural stability and degradation. More important, the results of cells attached, proliferated on the scaffold indicate that the scaffold is non-toxic and has good cell biocompatibility, and the results of implantation experiment in vivo further confirm that the scaffold has good tissue biocompatibility. All the above results suggest that the novel degradable n-HA/CS/CMC composite scaffold has a great potential to be used as bone tissue engineering material.

  11. Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering

    Liuyun, Jiang; Yubao, Li; Chengdong, Xiong

    2009-01-01

    In this study, we report the physico-chemical and biological properties of a novel biodegradable composite scaffold made of nano-hydroxyapatite and natural derived polymers of chitosan and carboxymethyl cellulose, namely, n-HA/CS/CMC, which was prepared by freeze-drying method. The physico-chemical properties of n-HA/CS/CMC scaffold were tested by infrared absorption spectra (IR), transmission electron microscope(TEM), scanning electron microscope(SEM), universal material testing machine and phosphate buffer solution (PBS) soaking experiment. Besides, the biological properties were evaluated by MG63 cells and Mesenchymal stem cells (MSCs) culture experiment in vitro and a short period implantation study in vivo. The results show that the composite scaffold is mainly formed through the ionic crossing-linking of the two polyions between CS and CMC, and n-HA is incorporated into the polyelectrolyte matrix of CS-CMC without agglomeration, which endows the scaffold with good physico-chemical properties such as highly interconnected porous structure, high compressive strength and good structural stability and degradation. More important, the results of cells attached, proliferated on the scaffold indicate that the scaffold is non-toxic and has good cell biocompatibility, and the results of implantation experiment in vivo further confirm that the scaffold has good tissue biocompatibility. All the above results suggest that the novel degradable n-HA/CS/CMC composite scaffold has a great potential to be used as bone tissue engineering material. PMID:19594953

  12. Preparation of a Carbon Doped Tissue-Mimicking Material with High Dielectric Properties for Microwave Imaging Application

    Siang-Wen Lan

    2016-07-01

    Full Text Available In this paper, the oil-in-gelatin based tissue-mimicking materials (TMMs doped with carbon based materials including carbon nanotube, graphene ink or lignin were prepared. The volume percent for gelatin based mixtures and oil based mixtures were both around 50%, and the doping amounts were 2 wt %, 4 wt %, and 6 wt %. The effect of doping material and amount on the microwave dielectric properties including dielectric constant and conductivity were investigated over an ultra-wide frequency range from 2 GHz to 20 GHz. The coaxial open-ended reflection technology was used to evaluate the microwave dielectric properties. Six measured values in different locations of each sample were averaged and the standard deviations of all the measured dielectric properties, including dielectric constant and conductivity, were less than one, indicating a good uniformity of the prepared samples. Without doping, the dielectric constant was equal to 23 ± 2 approximately. Results showed with doping of carbon based materials that the dielectric constant and conductivity both increased about 5% to 20%, and the increment was dependent on the doping amount. By proper selection of doping amount of the carbon based materials, the prepared material could map the required dielectric properties of special tissues. The proposed materials were suitable for the phantom used in the microwave medical imaging system.

  13. A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

    Lazebnik, Mariya [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Popovic, Dijana [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); McCartney, Leah [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); Watkins, Cynthia B [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Lindstrom, Mary J [Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI (United States); Harter, Josephine [Department of Pathology, University of Wisconsin, Madison, WI (United States); Sewall, Sarah [Department of Pathology, University of Wisconsin, Madison, WI (United States); Ogilvie, Travis [Department of Pathology, University of Calgary, Calgary, AB (Canada); Magliocco, Anthony [Department of Pathology, University of Calgary, Calgary, AB (Canada); Breslin, Tara M [Department of Surgery, University of Wisconsin, Madison, WI (United States); Temple, Walley [Department of Surgery and Oncology, University of Calgary, Calgary, AB (Canada); Mew, Daphne [Department of Surgery and Oncology, University of Calgary, Calgary, AB (Canada); Booske, John H [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Okoniewski, Michal [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); Hagness, Susan C [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States)

    2007-10-21

    The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

  14. A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

    Lazebnik, Mariya; Popovic, Dijana; McCartney, Leah; Watkins, Cynthia B.; Lindstrom, Mary J.; Harter, Josephine; Sewall, Sarah; Ogilvie, Travis; Magliocco, Anthony; Breslin, Tara M.; Temple, Walley; Mew, Daphne; Booske, John H.; Okoniewski, Michal; Hagness, Susan C.

    2007-10-01

    The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

  15. A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

    Lazebnik, Mariya; Popovic, Dijana; McCartney, Leah; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Ogilvie, Travis; Magliocco, Anthony; Breslin, Tara M; Temple, Walley; Mew, Daphne; Booske, John H; Okoniewski, Michal; Hagness, Susan C

    2007-01-01

    The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%

  16. Negative-ion beam surface modification of tissue-culture polystyrene dishes for changing hydrophilic and cell-attachment properties

    Tsuji, H.; Satoh, H.; Ikeda, S.; Ikemura, S.; Gotoh, Y.; Ishikawa, J.

    1999-01-01

    Negative-silver-ion implantation into tissue-culture polystyrene (TCPS) dishes was investigated and it was found to modify hydrophilic and cell attachment properties of the dishes. Negative-ion implantation has an advantage of being almost free of surface charging, and is a suitable method for implantation into insulators such as polymers. Negative silver ions are used due to the antibacterial property of silver. Ag-implanted TCPS dishes had a contact angle larger than the normal value of 66 deg. of unimplanted dishes. The contact angle of water had a strong dependence on the ion energy rather than the dose. As a cell-culture experiment, human umbilical vascular endothelial cell (HUVEC) was used in unimplanted and Ag-implanted TCPS dishes, the implantation removed the cell-attachment property of the surface. In implantation with a mask with a striped pattern, most attached cells of HUVEC were in the unimplanted region aligned along a stripe direction

  17. Statistical mechanics of cellular automata

    Wolfram, S.

    1983-01-01

    Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of ''elementary'' cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to p definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions approx. =1.59 or approx. =1.69. With ''random'' initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed

  18. Porous Nb-Ti-Ta alloy scaffolds for bone tissue engineering: Fabrication, mechanical properties and in vitro/vivo biocompatibility.

    Liu, Jue; Ruan, Jianming; Chang, Lin; Yang, Hailin; Ruan, Wei

    2017-09-01

    Porous Nb-Ti-Ta (at.%) alloys with the pore size of 100-600μm and the porosity of 50%-80% were fabricated by the combination of the sponge impregnation technique and sintering method. The results revealed that the pores were well connected with three-dimensional (3D) network structure, which showed morphological similarity to the anisotropic porous structure of human bones. The results also showed that the alloys could provide the compressive Young's modulus of 0.11±0.01GPa to 2.08±0.09GPa and the strength of 17.45±2.76MPa to 121.67±1.76MPa at different level of porosity, indicating that the mechanical properties of the alloys are similar to those of human bones. Pore structure on the compressive properties was also discussed on the basis of the deformation mode. The relationship between compressive properties and porosity was well consistent with the Gibson-Ashby model. The mechanical properties could be tailored to match different requirements of the human bones. Moreover, the alloys had good biocompatibility due to the porous structure with higher surface, which were suitable for apatite formation and cell adhesion. In conclusion, the porous Nb-Ti-Ta alloy is potentially useful in the hard tissue implants for the appropriate mechanical properties as well as the good biocompatible properties. Copyright © 2017. Published by Elsevier B.V.

  19. Human rights and human tissue : The case of sperm as property

    Goodwin, Morag; Brownsword, Roger; Yeung, Karen; Scotford, Eloise

    2016-01-01

    In a 2012 case from Canada, the Supreme Court of British Columbia held that sperm acquired and stored for the purposes of IVF could be considered shared marital property in the event of a separation. This case followed on from similar cases that accepted sperm as capable of being property. This

  20. Impact of tissue surface properties on the desorption electrospray ionization imaging of organic acids in grapevine stem.

    Dong, Yonghui; Guella, Graziano; Franceschi, Pietro

    2016-03-30

    Desorption electrospray ionization (DESI) imaging is a fast analytical technique used to assess spatially resolved biological processes over unmodified sample surfaces. Although DESI profiling experiments have demonstrated that the properties of the sample surface significantly affect the outcomes of DESI analyses, the potential implications of these phenomena in imaging applications have not yet been explored extensively. The distribution of endogenous and exogenous organic acids in pith and out pith region of grapevine stems was investigated by using DESI imaging, ion chromatography and direct infusion methods. Several common normalization strategies to account for the surface effect, including TIC normalization, addition of the internal standard in the spray solvent and deposition of the standard over the sample surface, were critically evaluated. DESI imaging results show that, in our case, the measured distributions of these small organic acids are not consistent with their 'true' localizations within the tissues. Furthermore, our results indicate that the common normalization strategies are not able to completely compensate for the observed surface effect. Variations in the tissue surface properties across the tissue sample can greatly affect the semi-quantitative detection of organic acids. Attention should be paid when interpreting DESI imaging results and an independent analytical validation step is important in untargeted DESI imaging investigations. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Pathogen Inactivating Properties and Increased Sensitivity in Molecular Diagnostics by PAXgene, a Novel Non-Crosslinking Tissue Fixative.

    Martina Loibner

    Full Text Available Requirements on tissue fixatives are getting more demanding as molecular analysis becomes increasingly relevant for routine diagnostics. Buffered formaldehyde in pathology laboratories for tissue fixation is known to cause chemical modifications of biomolecules which affect molecular testing. A novel non-crosslinking tissue preservation technology, PAXgene Tissue (PAXgene, was developed to preserve the integrity of nucleic acids in a comparable way to cryopreservation and also to preserve morphological features comparable to those of formalin fixed samples.Because of the excellent preservation of biomolecules by PAXgene we investigated its pathogen inactivation ability and biosafety in comparison to formalin by in-vitro testing of bacteria, human relevant fungi and human cytomegalovirus (CMV. Guidelines for testing disinfectants served as reference for inactivation assays. Furthermore, we tested the properties of PAXgene for detection of pathogens by PCR based assays.All microorganisms tested were similarly inactivated by PAXgene and formalin except Clostridium sporogenes, which remained viable in seven out of ten assays after PAXgene treatment and in three out of ten assays after formalin fixation. The findings suggest that similar biosafety measures can be applied for PAXgene and formalin fixed samples. Detection of pathogens in PCR-based diagnostics using two CMV assays resulted in a reduction of four to ten quantification cycles of PAXgene treated samples which is a remarkable increase of sensitivity.PAXgene fixation might be superior to formalin fixation when molecular diagnostics and highly sensitive detection of pathogens is required in parallel to morphology assessment.

  2. Pathogen Inactivating Properties and Increased Sensitivity in Molecular Diagnostics by PAXgene, a Novel Non-Crosslinking Tissue Fixative.

    Loibner, Martina; Buzina, Walter; Viertler, Christian; Groelz, Daniel; Hausleitner, Anja; Siaulyte, Gintare; Kufferath, Iris; Kölli, Bettina; Zatloukal, Kurt

    2016-01-01

    Requirements on tissue fixatives are getting more demanding as molecular analysis becomes increasingly relevant for routine diagnostics. Buffered formaldehyde in pathology laboratories for tissue fixation is known to cause chemical modifications of biomolecules which affect molecular testing. A novel non-crosslinking tissue preservation technology, PAXgene Tissue (PAXgene), was developed to preserve the integrity of nucleic acids in a comparable way to cryopreservation and also to preserve morphological features comparable to those of formalin fixed samples. Because of the excellent preservation of biomolecules by PAXgene we investigated its pathogen inactivation ability and biosafety in comparison to formalin by in-vitro testing of bacteria, human relevant fungi and human cytomegalovirus (CMV). Guidelines for testing disinfectants served as reference for inactivation assays. Furthermore, we tested the properties of PAXgene for detection of pathogens by PCR based assays. All microorganisms tested were similarly inactivated by PAXgene and formalin except Clostridium sporogenes, which remained viable in seven out of ten assays after PAXgene treatment and in three out of ten assays after formalin fixation. The findings suggest that similar biosafety measures can be applied for PAXgene and formalin fixed samples. Detection of pathogens in PCR-based diagnostics using two CMV assays resulted in a reduction of four to ten quantification cycles of PAXgene treated samples which is a remarkable increase of sensitivity. PAXgene fixation might be superior to formalin fixation when molecular diagnostics and highly sensitive detection of pathogens is required in parallel to morphology assessment.

  3. Tensile properties in collagen-rich tissues of Quarter Horses with hereditary equine regional dermal asthenia (HERDA).

    Bowser, J E; Elder, S H; Pasquali, M; Grady, J G; Rashmir-Raven, A M; Wills, R; Swiderski, C E

    2014-03-01

    Hereditary equine regional dermal asthenia (HERDA) is an autosomal recessive disorder of Quarter Horses characterised by skin fragility. Horses with HERDA have a missense mutation in peptidyl-prolyl cis-trans isomerase B (PPIB), which encodes cyclophilin B and alters folding and post translational modifications of fibrillar collagen. The study aimed to test the hypothesis that tendons, ligaments and great vessels, which, like skin, are rich in fibrillar collagen, will also have abnormal biomechanical properties in horses with HERDA. Ex vivo biomechanical study comparing horses with and without a diagnosis of HERDA. Forelimb suspensory ligament, superficial and deep digital flexor tendons; withers, forelimb and abdominal skin; the main pulmonary artery and the aortic arch were harvested from 6 horses with HERDA and 6 control horses without the HERDA allele. Tissues were distracted to failure. Tensile strength (TS), elastic modulus (EM) and energy to failure (ETF) were compared. Horses with HERDA had significantly lower TS and EM in tendinoligamentous tissues and great vessels, respectively. The TS, EM and ETF were significantly lower in skin from horses with HERDA. Differences in TS and ETF were more extreme at the withers than at the forelimb or abdomen. Tendinoligamentous tissue, great vessels and skin are significantly weaker in horses with HERDA than in horses lacking the PPIB mutation, substantiating that diverse tissues with high fibrillar collagen content are abnormal in HERDA and that the HERDA phenotype is not limited to the integument. © 2013 EVJ Ltd.

  4. Carbon nanotubes reinforced chitosan films: mechanical properties and cell response of a novel biomaterial for cardiovascular tissue engineering.

    Kroustalli, A; Zisimopoulou, A E; Koch, S; Rongen, L; Deligianni, D; Diamantouros, S; Athanassiou, G; Kokozidou, M; Mavrilas, D; Jockenhoevel, S

    2013-12-01

    Carbon nanotubes have been proposed as fillers to reinforce polymeric biomaterials for the strengthening of their structural integrity to achieve better biomechanical properties. In this study, a new polymeric composite material was introduced by incorporating various low concentrations of multiwalled carbon nanotubes (MWCNTs) into chitosan (CS), aiming at achieving a novel composite biomaterial with superior mechanical and biological properties compared to neat CS, in order to be used in cardiovascular tissue engineering applications. Both mechanical and biological characteristics in contact with the two relevant cell types (endothelial cells and vascular myofibroblasts) were studied. Regarding the mechanical behavior of MWCNT reinforced CS (MWCNT/CS), 5 and 10 % concentrations of MWCNTs enhanced the mechanical behavior of CS, with that of 5 % exhibiting a superior mechanical strength compared to 10 % concentration and neat CS. Regarding biological properties, MWCNT/CS best supported proliferation of endothelial and myofibroblast cells, MWCNTs and MWCNT/CS caused no apoptosis and were not toxic of the examined cell types. Conclusively, the new material could be suitable for tissue engineering (TE) and particularly for cardiovascular TE applications.

  5. Supplementation of exogenous adenosine 5'-triphosphate enhances mechanical properties of 3D cell-agarose constructs for cartilage tissue engineering.

    Gadjanski, Ivana; Yodmuang, Supansa; Spiller, Kara; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana

    2013-10-01

    Formation of tissue-engineered cartilage is greatly enhanced by mechanical stimulation. However, direct mechanical stimulation is not always a suitable method, and the utilization of mechanisms underlying mechanotransduction might allow for a highly effective and less aggressive alternate means of stimulation. In particular, the purinergic, adenosine 5'-triphosphate (ATP)-mediated signaling pathway is strongly implicated in mechanotransduction within the articular cartilage. We investigated the effects of transient and continuous exogenous ATP supplementation on mechanical properties of cartilaginous constructs engineered using bovine chondrocytes and human mesenchymal stem cells (hMSCs) encapsulated in an agarose hydrogel. For both cell types, we have observed significant increases in equilibrium and dynamic compressive moduli after transient ATP treatment applied in the fourth week of cultivation. Continuous ATP treatment over 4 weeks of culture only slightly improved the mechanical properties of the constructs, without major changes in the total glycosaminoglycan (GAG) and collagen content. Structure-function analyses showed that transiently ATP-treated constructs, and in particular those based on hMSCs, had the highest level of correlation between compositional and mechanical properties. Transiently treated groups showed intense staining of the territorial matrix for GAGs and collagen type II. These results indicate that transient ATP treatment can improve functional mechanical properties of cartilaginous constructs based on chondrogenic cells and agarose hydrogels, possibly by improving the structural organization of the bulk phase and territorial extracellular matrix (ECM), that is, by increasing correlation slopes between the content of the ECM components (GAG, collagen) and mechanical properties of the construct.

  6. High seeding density of human chondrocytes in agarose produces tissue-engineered cartilage approaching native mechanical and biochemical properties.

    Cigan, Alexander D; Roach, Brendan L; Nims, Robert J; Tan, Andrea R; Albro, Michael B; Stoker, Aaron M; Cook, James L; Vunjak-Novakovic, Gordana; Hung, Clark T; Ateshian, Gerard A

    2016-06-14

    Animal cells have served as highly controllable model systems for furthering cartilage tissue engineering practices in pursuit of treating osteoarthritis. Although successful strategies for animal cells must ultimately be adapted to human cells to be clinically relevant, human chondrocytes are rarely employed in such studies. In this study, we evaluated the applicability of culture techniques established for juvenile bovine and adult canine chondrocytes to human chondrocytes obtained from fresh or expired osteochondral allografts. Human chondrocytes were expanded and encapsulated in 2% agarose scaffolds measuring ∅3-4mm×2.3mm, with cell seeding densities ranging from 15 to 90×10(6)cells/mL. Subsets of constructs were subjected to transient or sustained TGF-β treatment, or provided channels to enhance nutrient transport. Human cartilaginous constructs physically resembled native human cartilage, and reached compressive Young's moduli of up to ~250kPa (corresponding to the low end of ranges reported for native knee cartilage), dynamic moduli of ~950kPa (0.01Hz), and contained 5.7% wet weight (%/ww) of glycosaminoglycans (≥ native levels) and 1.5%/ww collagen. We found that the initial seeding density had pronounced effects on tissue outcomes, with high cell seeding densities significantly increasing nearly all measured properties. Transient TGF-β treatment was ineffective for adult human cells, and tissue construct properties plateaued or declined beyond 28 days of culture. Finally, nutrient channels improved construct mechanical properties, presumably due to enhanced rates of mass transport. These results demonstrate that our previously established culture system can be successfully translated to human chondrocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Fabrication method, structure, mechanical, and biological properties of decellularized extracellular matrix for replacement of wide bone tissue defects.

    Anisimova, N Y; Kiselevsky, M V; Sukhorukova, I V; Shvindina, N V; Shtansky, D V

    2015-09-01

    The present paper was focused on the development of a new method of decellularized extracellular matrix (DECM) fabrication via a chemical treatment of a native bone tissue. Particular attention was paid to the influence of chemical treatment on the mechanical properties of native bones, sterility, and biological performance in vivo using the syngeneic heterotopic and orthotopic implantation models. The obtained data indicated that after a chemical decellularization treatment in 4% aqueous sodium chlorite, no noticeable signs of the erosion of compact cortical bone surface or destruction of trabeculae of spongy bone in spinal channel were observed. The histological studies showed that the chemical treatment resulted in the decellularization of both bone and cartilage tissues. The DECM samples demonstrated no signs of chemical and biological degradation in vivo. Thorough structural characterization revealed that after decellularization, the mineral frame retained its integrity with the organic phase; however clotting and destruction of organic molecules and fibers were observed. FTIR studies revealed several structural changes associated with the destruction of organic molecules, although all organic components typical of intact bone were preserved. The decellularization-induced structural changes in the collagen constituent resulted changed the deformation under compression mechanism: from the major fracture by crack propagation throughout the sample to the predominantly brittle fracture. Although the mechanical properties of radius bones subjected to decellularization were observed to degrade, the mechanical properties of ulna bones in compression and humerus bones in bending remained unchanged. The compressive strength of both the intact and decellularized ulna bones was 125-130 MPa and the flexural strength of humerus bones was 156 and 145 MPa for the intact and decellularized samples, respectively. These results open new avenues for the use of DECM samples as

  8. The effects of preferred and non-preferred running strike patterns on tissue vibration properties.

    Enders, Hendrik; von Tscharner, Vinzenz; Nigg, Benno M

    2014-03-01

    To characterize soft tissue vibrations during running with a preferred and a non-preferred strike pattern in shoes and barefoot. Cross-sectional study. Participants ran at 3.5 m s(-1) on a treadmill in shoes and barefoot using a rearfoot and a forefoot strike for each footwear condition. The preferred strike patterns for the subjects were a rearfoot strike and a forefoot strike for shod and barefoot running, respectively. Vibrations were recorded with an accelerometer overlying the belly of the medial gastrocnemius. Thirteen non-linearly scaled wavelets were used for the analysis. Damping was calculated as the overall decay of power in the acceleration signal post ground contact. A higher damping coefficient indicates higher damping capacities of the soft tissue. The shod rearfoot strike showed a 93% lower damping coefficient than the shod forefoot strike (pforefoot strike showed a trend toward a lower damping coefficient compared to a barefoot rearfoot strike. Running barefoot with a forefoot strike resulted in a significantly lower damping coefficient than a forefoot strike when wearing shoes (pstrike showed lower damping compared to a barefoot rearfoot strike (p<0.001). While rearfoot striking showed lower vibration frequencies in shod and barefoot running, it did not consistently result in lower damping coefficients. This study showed that the use of a preferred movement resulted in lower damping coefficients of running related soft tissue vibrations. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  9. Ultrasonic modulation of tissue optical properties in ex vivo porcine skin to improve transmitted transdermal laser intensity.

    Whiteside, Paul J D; Qian, Chenxi; Golda, Nicholas; Hunt, Heather K

    2017-09-01

    Applications of light-based energy devices involving optical targets within the dermis frequently experience negative side-effects resultant from surface scattering and excess optical absorption by epidermal melanin. As a broadband optical absorber, melanin decreases the efficacy of light-based treatments throughout the ultraviolet, visible, and near-infrared spectra while also generating additional heat within the surface tissue that can lead to inflammation or tissue damage. Consequently, procedures may be performed using greater energy densities to ensure that the target receives a clinically relevant dose of light; however, such practices are limited, as doing so tends to exacerbate the detrimental complications resulting from melanin absorption of treatment light. The technique presented herein represents an alternative method of operation aimed at increasing epidermal energy fluence while mitigating excess absorption by unintended chromophores. The approach involves the application of continuously pulsed ultrasound to modulate the tissue's optical properties and thereby improve light transmission through the epidermis. To demonstrate the change in optical properties, pulsed light at a wavelength of 532 nm from a Q-switched Nd:YAG laser was transmitted into 4 mm thick samples of porcine skin, comprised of both epidermal and dermal tissue. The light was transmitted using an optical waveguide, which allowed for an ultrasonic transducer to be incorporated for simultaneous paraxial pulsation in parallel with laser operation. Light transmitted through the tissue was measured by a photodiode attached to an integrating sphere. Increasing the driving voltage of ultrasonic pulsation resulted in an increase in mean transmitted optical power of up to a factor of 1.742 ± 0.0526 times the control, wherein no ultrasound was applied, after which the optical power increase plateaued to an average amplification factor of 1.733 ± 0.549 times the control. The

  10. Age dependence of dielectric properties of bovine brain and ocular tissues in the frequency range of 400 MHz to 18 GHz

    Schmid, Gernot; Ueberbacher, Richard

    2005-01-01

    In order to identify possible age-dependent dielectric properties of brain and eye tissues in the frequency range of 400 MHz to 18 GHz, measurements on bovine grey and white matter as well as on cornea, lens (cortical) and the vitreous body were performed using a commercially available open-ended coaxial probe and a computer-controlled vector network analyser. Freshly excised tissues of 52 animals of two age groups (42 adult animals, i.e. 16-24 month old and 10 young animals, i.e. 4-6 month old calves) were examined within 8 min (brain tissue) and 15