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Sample records for quantify engineered tissue

  1. Computational Modeling in Tissue Engineering

    CERN Document Server

    2013-01-01

    One of the major challenges in tissue engineering is the translation of biological knowledge on complex cell and tissue behavior into a predictive and robust engineering process. Mastering this complexity is an essential step towards clinical applications of tissue engineering. This volume discusses computational modeling tools that allow studying the biological complexity in a more quantitative way. More specifically, computational tools can help in:  (i) quantifying and optimizing the tissue engineering product, e.g. by adapting scaffold design to optimize micro-environmental signals or by adapting selection criteria to improve homogeneity of the selected cell population; (ii) quantifying and optimizing the tissue engineering process, e.g. by adapting bioreactor design to improve quality and quantity of the final product; and (iii) assessing the influence of the in vivo environment on the behavior of the tissue engineering product, e.g. by investigating vascular ingrowth. The book presents examples of each...

  2. QEEN Workshop: "Quantifying Exposure to Engineered Nano-materials from Manufactured Products": Write Up Biological Tissues and Media

    Science.gov (United States)

    The measurement and characterization of nanomaterials in biological tissues is complicated by a number of factors including: the sensitivity of the assay to small sized particles or low concentrations of materials; the ability to distinguish different forms and transformations of...

  3. Vascularization in tissue engineering

    NARCIS (Netherlands)

    Rouwkema, Jeroen; Rivron, Nicolas C.; Blitterswijk, van Clemens A.

    2008-01-01

    Tissue engineering has been an active field of research for several decades now. However, the amount of clinical applications in the field of tissue engineering is still limited. One of the current limitations of tissue engineering is its inability to provide sufficient blood supply in the initial p

  4. Prevascularized bone tissue engineering

    NARCIS (Netherlands)

    Rouwkema, Jeroen

    2007-01-01

    Tissue engineering has been an active field of research for several decades now. However, the number of successful clinical applications in the field of tissue engineering are limited and can mainly be found in thin or avascular tissues like skin and cartilage. One of the current limitations of tiss

  5. Cell and Tissue Engineering

    CERN Document Server

    2012-01-01

    “Cell and Tissue Engineering” introduces the principles and new approaches in cell and tissue engineering. It includes both the fundamentals and the current trends in cell and tissue engineering, in a way useful both to a novice and an expert in the field. The book is composed of 13 chapters all of which are written by the leading experts. It is organized to gradually assemble an insight in cell and tissue function starting form a molecular nano-level, extending to a cellular micro-level and finishing at the tissue macro-level. In specific, biological, physiological, biophysical, biochemical, medical, and engineering aspects are covered from the standpoint of the development of functional substitutes of biological tissues for potential clinical use. Topics in the area of cell engineering include cell membrane biophysics, structure and function of the cytoskeleton, cell-extracellular matrix interactions, and mechanotransduction. In the area of tissue engineering the focus is on the in vitro cultivation of ...

  6. Tissue engineering in dentistry.

    Science.gov (United States)

    Abou Neel, Ensanya Ali; Chrzanowski, Wojciech; Salih, Vehid M; Kim, Hae-Won; Knowles, Jonathan C

    2014-08-01

    of this review is to inform practitioners with the most updated information on tissue engineering and its potential applications in dentistry. The authors used "PUBMED" to find relevant literature written in English and published from the beginning of tissue engineering until today. A combination of keywords was used as the search terms e.g., "tissue engineering", "approaches", "strategies" "dentistry", "dental stem cells", "dentino-pulp complex", "guided tissue regeneration", "whole tooth", "TMJ", "condyle", "salivary glands", and "oral mucosa". Abstracts and full text articles were used to identify causes of craniofacial tissue loss, different approaches for craniofacial reconstructions, how the tissue engineering emerges, different strategies of tissue engineering, biomaterials employed for this purpose, the major attempts to engineer different dental structures, finally challenges and future of tissue engineering in dentistry. Only those articles that dealt with the tissue engineering in dentistry were selected. There have been a recent surge in guided tissue engineering methods to manage periodontal diseases beyond the traditional approaches. However, the predictable reconstruction of the innate organisation and function of whole teeth as well as their periodontal structures remains challenging. Despite some limited progress and minor successes, there remain distinct and important challenges in the development of reproducible and clinically safe approaches for oral tissue repair and regeneration. Clearly, there is a convincing body of evidence which confirms the need for this type of treatment, and public health data worldwide indicates a more than adequate patient resource. The future of these therapies involving more biological approaches and the use of dental tissue stem cells is promising and advancing. Also there may be a significant interest of their application and wider potential to treat disorders beyond the craniofacial region. Considering the

  7. Vascularised Tissue Engineering Construct

    Directory of Open Access Journals (Sweden)

    Irza Sukmana

    2012-01-01

    Full Text Available The guidance of endothelial cell organization into a capillary network has been a long-standing challenge in tissue engineering. Some research efforts have been made to develop methods to promote capillary networks inside engineered tissue constructs. Capillary and vascular networks that would mimic blood microvessel function can be used to subsequently facilitate oxygen and nutrient transfer as well as waste removal. Vascularization of engineering tissue construct is one of the most favorable strategies to overpass nutrient and oxygen supply limitation, which is often the major hurdle in developing thick and complex tissue and artificial organ. This paper addresses recent advances and future challenges in developing three-dimensional culture systems to promote tissue construct vascularization allowing mimicking blood microvessel development and function encountered in vivo. Bioreactors systems that have been used to create fully vascularized functional tissue constructs will also be outlined.

  8. Tissue engineered periodontal products.

    Science.gov (United States)

    Bartold, P M; Gronthos, S; Ivanovski, S; Fisher, A; Hutmacher, D W

    2016-02-01

    Attainment of periodontal regeneration is a significant clinical goal in the management of advanced periodontal defects arising from periodontitis. Over the past 30 years numerous techniques and materials have been introduced and evaluated clinically and have included guided tissue regeneration, bone grafting materials, growth and other biological factors and gene therapy. With the exception of gene therapy, all have undergone evaluation in humans. All of the products have shown efficacy in promoting periodontal regeneration in animal models but the results in humans remain variable and equivocal concerning attaining complete biological regeneration of damaged periodontal structures. In the early 2000s, the concept of tissue engineering was proposed as a new paradigm for periodontal regeneration based on molecular and cell biology. At this time, tissue engineering was a new and emerging field. Now, 14 years later we revisit the concept of tissue engineering for the periodontium and assess how far we have come, where we are currently situated and what needs to be done in the future to make this concept a reality. In this review, we cover some of the precursor products, which led to our current position in periodontal tissue engineering. The basic concepts of tissue engineering with special emphasis on periodontal tissue engineering products is discussed including the use of mesenchymal stem cells in bioscaffolds and the emerging field of cell sheet technology. Finally, we look into the future to consider what CAD/CAM technology and nanotechnology will have to offer.

  9. Advances in tissue engineering

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Tissue engineering is a newly developed specialty involved in the construction of tissues and organs either in vitro or in vivo. Tremendous progress has been achieved over the past decade in tisse construction as well as in other related areas, such as bone marrow stromal cells, embryonic stem cells and tissue progenitor cells. In our laboratory, tissues of full-thickness skin, bone, cartilage and tendon have been successfully engineered, and the engineered tissues have repaired full-thickness skin wound, cranial bone defects, articular cartilage defects and tendon defects in animals. In basic research areas, bone marrow stromal cells have been induced and transformed into osteoblasts and chondrocytes in vitro. Mouse embryo stem cell lines we established have differentiated into neuron precursor, cardiac muscle cells and epithelial cells. Genetic modifications of seed cells for promoting cell proliferation, delaying cell aging and inducing immune tolerance have also been investigated.

  10. DENTAL PULP TISSUE ENGINEERING

    Science.gov (United States)

    Demarco, FF; Conde, MCM; Cavalcanti, B; Casagrande, L; Sakai, V; Nör, JE

    2013-01-01

    Dental pulp is a highly specialized mesenchymal tissue, which have a restrict regeneration capacity due to anatomical arrangement and post-mitotic nature of odontoblastic cells. Entire pulp amputation followed by pulp-space disinfection and filling with an artificial material cause loss of a significant amount of dentin leaving as life-lasting sequelae a non-vital and weakened tooth. However, regenerative endodontics is an emerging field of modern tissue engineering that demonstrated promising results using stem cells associated with scaffolds and responsive molecules. Thereby, this article will review the most recent endeavors to regenerate pulp tissue based on tissue engineering principles and providing insightful information to readers about the different aspects enrolled in tissue engineering. Here, we speculate that the search for the ideal combination of cells, scaffolds, and morphogenic factors for dental pulp tissue engineering may be extended over future years and result in significant advances in other areas of dental and craniofacial research. The finds collected in our review showed that we are now at a stage in which engineering a complex tissue, such as the dental pulp, is no longer an unachievable and the next decade will certainly be an exciting time for dental and craniofacial research. PMID:21519641

  11. Regulating tissue engineering

    Directory of Open Access Journals (Sweden)

    Meredith Lloyd-Evans

    2004-05-01

    Full Text Available Tissue engineering is a radical new approach to the repair and replacement of damaged or diseased body tissues. Cells, often seeded into or shaped around a biomaterial matrix, are used to replace damaged or diseased tissue or stimulate repair by the body. Because it is an area of tremendous focus and achievement, there is a risk that technical developments will outstrip the capacity of existing regulatory frameworks to cope with these novel products. Australia, the USA, and Canada are somewhat ahead of Japan in establishing a feasible regulatory approach. All four are currently ahead of the European Union (EU, but individual European countries and the EU as a whole are catching up. However, for the foreseeable future, it may still be possible in certain European countries to use autologous cell therapies in hospitals and market allogeneic tissue-engineered products, especially skin replacements, without regulatory control.

  12. Quantifying lateral tissue heterogeneities in hadron therapy.

    Science.gov (United States)

    Pflugfelder, D; Wilkens, J J; Szymanowski, H; Oelfke, U

    2007-04-01

    In radiotherapy with scanned particle beams, tissue heterogeneities lateral to the beam direction are problematic in two ways: they pose a challenge to dose calculation algorithms, and they lead to a high sensitivity to setup errors. In order to quantify and avoid these problems, a heterogeneity number H(i) as a method to quantify lateral tissue heterogeneities of single beam spot i is introduced. To evaluate this new concept, two kinds of potential errors were investigated for single beam spots: First, the dose calculation error has been obtained by comparing the dose distribution computed by a simple pencil beam algorithm to more accurate Monte Carlo simulations. The resulting error is clearly correlated with H(i). Second, the analysis of the sensitivity to setup errors of single beam spots also showed a dependence on H(i). From this data it is concluded that H(i) can be used as a criterion to assess the risks of a compromised delivered dose due to lateral tissue heterogeneities. Furthermore, a method how to incorporate this information into the inverse planning process for intensity modulated proton therapy is presented. By suppressing beam spots with a high value of H(i), the unfavorable impact of lateral tissue heterogeneities can be reduced, leading to treatment plans which are more robust to dose calculation errors of the pencil beam algorithm. Additional possibilities to use the information of H(i) are outlined in the discussion.

  13. Engineering graded tissue interfaces.

    Science.gov (United States)

    Phillips, Jennifer E; Burns, Kellie L; Le Doux, Joseph M; Guldberg, Robert E; García, Andrés J

    2008-08-26

    Interfacial zones between tissues provide specialized, transitional junctions central to normal tissue function. Regenerative medicine strategies focused on multiple cell types and/or bi/tri-layered scaffolds do not provide continuously graded interfaces, severely limiting the integration and biological performance of engineered tissue substitutes. Inspired by the bone-soft tissue interface, we describe a biomaterial-mediated gene transfer strategy for spatially regulated genetic modification and differentiation of primary dermal fibroblasts within tissue-engineered constructs. We demonstrate that zonal organization of osteoblastic and fibroblastic cellular phenotypes can be engineered by a simple, one-step seeding of fibroblasts onto scaffolds containing a spatial distribution of retrovirus encoding the osteogenic transcription factor Runx2/Cbfa1. Gradients of immobilized retrovirus, achieved via deposition of controlled poly(L-lysine) densities, resulted in spatial patterns of transcription factor expression, osteoblastic differentiation, and mineralized matrix deposition. Notably, this graded distribution of mineral deposition and mechanical properties was maintained when implanted in vivo in an ectopic site. Development of this facile and robust strategy is significant toward the regeneration of continuous interfacial zones that mimic the cellular and microstructural characteristics of native tissue.

  14. Stereolithography in tissue engineering.

    Science.gov (United States)

    Skoog, Shelby A; Goering, Peter L; Narayan, Roger J

    2014-03-01

    Several recent research efforts have focused on use of computer-aided additive fabrication technologies, commonly referred to as additive manufacturing, rapid prototyping, solid freeform fabrication, or three-dimensional printing technologies, to create structures for tissue engineering. For example, scaffolds for tissue engineering may be processed using rapid prototyping technologies, which serve as matrices for cell ingrowth, vascularization, as well as transport of nutrients and waste. Stereolithography is a photopolymerization-based rapid prototyping technology that involves computer-driven and spatially controlled irradiation of liquid resin. This technology enables structures with precise microscale features to be prepared directly from a computer model. In this review, use of stereolithography for processing trimethylene carbonate, polycaprolactone, and poly(D,L-lactide) poly(propylene fumarate)-based materials is considered. In addition, incorporation of bioceramic fillers for fabrication of bioceramic scaffolds is reviewed. Use of stereolithography for processing of patient-specific implantable scaffolds is also discussed. In addition, use of photopolymerization-based rapid prototyping technology, known as two-photon polymerization, for production of tissue engineering scaffolds with smaller features than conventional stereolithography technology is considered.

  15. Cardiac tissue engineering

    Directory of Open Access Journals (Sweden)

    MILICA RADISIC

    2005-03-01

    Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

  16. Skin tissue engineering.

    Science.gov (United States)

    Mansbridge, Jonathan

    2008-01-01

    The major applications of tissue-engineered skin substitutes are in promoting the healing of acute and chronic wounds. Several approaches have been taken by commercial companies to develop products to address these conditions. Skin substitutes include both acellular and cellular devices. While acellular skin substitutes act as a template for dermal formation, this discussion mainly covers cellular devices. In addressing therapeutic applications in tissue engineering generally, a valuable precursor is an understanding of the mechanism of the underlying pathology. While this is straightforward in many cases, it has not been available for wound healing. Investigation of the mode of action of the tissue-engineered skin substitutes has led to considerable insight into the mechanism of formation, maintenance and treatment of chronic wounds. Four aspects mediating healing are considered here for their mechanism of action: (i) colonization of the wound bed by live fibroblasts in the implant, (ii) the secretion of growth factors, (iii) provision of a suitable substrate for cell migration, particularly keratinocytes and immune cells, and (iv) modification of the immune system by secretion of neutrophil recruiting chemokines. An early event in acute wound healing is an influx of neutrophils that destroy planktonic bacteria. However, if the bacteria are able to form biofilm, they become resistant to neutrophil action and prevent reepithelialization. In this situation the wound becomes chronic. In chronic wounds, fibroblasts show a senescence-like phenotype with decreased secretion of neutrophil chemoattractants that make it more likely that biofilms become established. Treatment of the chronic wounds involves debridement to eliminate biofilm, and the use of antimicrobials. A role of skin substitutes is to provide non-senescent fibroblasts that attract and activate neutrophils to prevent biofilm re-establishment. The emphasis of the conclusion is the importance of preventing

  17. Tissue engineering the kidney.

    Science.gov (United States)

    Hammerman, Marc R

    2003-04-01

    The means by which kidney function can be replaced in humans include dialysis and renal allotransplantation. Dialytic therapies are lifesaving, but often poorly tolerated. Transplantation of human kidneys is limited by the availability of donor organs. During the past decades, a number of different approaches have been applied toward tissue engineering the kidney as a means to replace renal function. The goals of one or another of them included the recapitulation of renal filtration, reabsorptive and secretory functions, and replacement of endocrine/metabolic activities. This review will delineate the progress to date recorded for five approaches: (1) integration of new nephrons into the kidney; (2) growing new kidneys in situ; (3) use of stem cells; (4) generation of histocompatible tissues using nuclear transplantation; and (5) bioengineering of an artificial kidney. All five approaches utilize cellular therapy. The first four employ transplantation as well, and the fifth uses dialysis.

  18. Tissue engineering for clinical applications.

    Science.gov (United States)

    Bhatia, Sujata K

    2010-12-01

    Tissue engineering is increasingly being recognized as a beneficial means for lessening the global disease burden. One strategy of tissue engineering is to replace lost tissues or organs with polymeric scaffolds that contain specialized populations of living cells, with the goal of regenerating tissues to restore normal function. Typical constructs for tissue engineering employ biocompatible and degradable polymers, along with organ-specific and tissue-specific cells. Once implanted, the construct guides the growth and development of new tissues; the polymer scaffold degrades away to be replaced by healthy functioning tissue. The ideal biomaterial for tissue engineering not only defends against disease and supports weakened tissues or organs, it also provides the elements required for healing and repair, stimulates the body's intrinsic immunological and regenerative capacities, and seamlessly interacts with the living body. Tissue engineering has been investigated for virtually every organ system in the human body. This review describes the potential of tissue engineering to alleviate disease, as well as the latest advances in tissue regeneration. The discussion focuses on three specific clinical applications of tissue engineering: cardiac tissue regeneration for treatment of heart failure; nerve regeneration for treatment of stroke; and lung regeneration for treatment of chronic obstructive pulmonary disease. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Tissue bionics: examples in biomimetic tissue engineering.

    Science.gov (United States)

    Green, David W

    2008-09-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

  20. Integrated Biomaterials in Tissue Engineering

    CERN Document Server

    Ramalingam, Murugan; Ramakrishna, Seeram; Kobayashi, Hisatoshi; Haikel, Youssef

    2012-01-01

    "Integrated Biomaterials in Tissue Engineering" features all aspects from fundamental principles to current technological advances in biomaterials at the macro/micro/nano/molecular scales suitable for tissue engineering and regenerative medicine. The book is unique as it provides all important aspects dealing with the basic science involved in structure and properties, techniques and technological innovations in material processing and characterizations, and applications of biomaterials in tissue engineering and regenerative medicine.

  1. Electrospun multifunctional tissue engineering scaffolds

    Science.gov (United States)

    Wang, Chong; Wang, Min

    2014-03-01

    Tissue engineering holds great promises in providing successful treatments of human body tissue loss that current methods are unable to treat or unable to achieve satisfactory clinical outcomes. In scaffold-based tissue engineering, a highperformance scaffold underpins the success of a tissue engineering strategy and a major direction in the field is to create multifunctional tissue engineering scaffolds for enhanced biological performance and for regenerating complex body tissues. Electrospinning can produce nanofibrous scaffolds that are highly desirable for tissue engineering. The enormous interest in electrospinning and electrospun fibrous structures by the science, engineering and medical communities has led to various developments of the electrospinning technology and wide investigations of electrospun products in many industries, including biomedical engineering, over the past two decades. It is now possible to create novel, multicomponent tissue engineering scaffolds with multiple functions. This article provides a concise review of recent advances in the R & D of electrospun multifunctional tissue engineering scaffolds. It also presents our philosophy and research in the designing and fabrication of electrospun multicomponent scaffolds with multiple functions.

  2. Mechanical Aspects of Tissue Engineering

    OpenAIRE

    Liebschner, Michael; Bucklen, Brandon; Wettergreen, Matthew

    2005-01-01

    Tissue engineering describes an initiative whereby a deficit of tissue may be replaced with an engineered construct, typically thought to be some combination of a structural support element and a cellular element. There are several mechanical aspects that come into play during the design of such a construct. First, the way in which the mechanical behavior of a tissue is characterized varies depending on the tissue type. For example, one would not consider the ultimate strength of a non–load-b...

  3. Vascularization strategies for tissue engineers.

    Science.gov (United States)

    Dew, Lindsey; MacNeil, Sheila; Chong, Chuh Khiun

    2015-01-01

    All tissue-engineered substitutes (with the exception of cornea and cartilage) require a vascular network to provide the nutrient and oxygen supply needed for their survival in vivo. Unfortunately the process of vascular ingrowth into an engineered tissue can take weeks to occur naturally and during this time the tissues become starved of essential nutrients, leading to tissue death. This review initially gives a brief overview of the processes and factors involved in the formation of new vasculature. It then summarizes the different approaches that are being applied or developed to overcome the issue of slow neovascularization in a range of tissue-engineered substitutes. Some potential future strategies are then discussed.

  4. Molecular, cellular, and tissue engineering

    CERN Document Server

    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...

  5. Biomaterials & scaffolds for tissue engineering

    Directory of Open Access Journals (Sweden)

    Fergal J. O'Brien

    2011-03-01

    Full Text Available Every day thousands of surgical procedures are performed to replace or repair tissue that has been damaged through disease or trauma. The developing field of tissue engineering (TE aims to regenerate damaged tissues by combining cells from the body with highly porous scaffold biomaterials, which act as templates for tissue regeneration, to guide the growth of new tissue. This article describes the functional requirements, and types, of materials used in developing state of the art of scaffolds for tissue engineering applications. Furthermore, it describes the challenges and where future research and direction is required in this rapidly advancing field.

  6. Strategic directions in tissue engineering.

    NARCIS (Netherlands)

    Johnson, P.C.; Mikos, A.G.; Fisher, J.P.; Jansen, J.A.

    2007-01-01

    The field of tissue engineering is developing rapidly. Given its ultimate importance to clinical care, the time is appropriate to assess the field's strategic directions to optimize research and development activities. To characterize strategic directions in tissue engineering, a distant but reachab

  7. Tissue Engineering of the Penis

    Directory of Open Access Journals (Sweden)

    Manish N. Patel

    2011-01-01

    Full Text Available Congenital disorders, cancer, trauma, or other conditions of the genitourinary tract can lead to significant organ damage or loss of function, necessitating eventual reconstruction or replacement of the damaged structures. However, current reconstructive techniques are limited by issues of tissue availability and compatibility. Physicians and scientists have begun to explore tissue engineering and regenerative medicine strategies for repair and reconstruction of the genitourinary tract. Tissue engineering allows the development of biological substitutes which could potentially restore normal function. Tissue engineering efforts designed to treat or replace most organs are currently being undertaken. Most of these efforts have occurred within the past decade. However, before these engineering techniques can be applied to humans, further studies are needed to ensure the safety and efficacy of these new materials. Recent progress suggests that engineered urologic tissues and cell therapy may soon have clinical applicability.

  8. Engineering vascularized skeletal muscle tissue

    NARCIS (Netherlands)

    Levenberg, Shulamit; Rouwkema, Jeroen; Macdonald, Mara; Garfein, Evan S.; Kohane, Daniel S.; Darland, Diane C.; Marini, Robert; van Blitterswijk, Clemens; Mulligan, Richard C.; D'Amore, Patricia A.; Langer, Robert

    2005-01-01

    One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe

  9. Tissue engineering for periodontal regeneration.

    Science.gov (United States)

    Kao, Richard T; Conte, Greg; Nishimine, Dee; Dault, Scott

    2005-03-01

    As a result of periodontal regeneration research, a series of clinical techniques have emerged that permit tissue engineering to be performed for more efficient regeneration and repair of periodontal defects and improved implant site development. Historically, periodontal regeneration research has focused on a quest for "magic filler" material. This search has led to the development of techniques utilizing autologous bone and bone marrow, allografts, xenografts, and various man-made bone substitutes. Though these techniques have had limited success, the desire for a more effective regenerative approach has resulted in the development of tissue engineering techniques. Tissue engineering is a relatively new field of reconstructive biology which utilizes mechanical, cellular, or biologic mediators to facilitate reconstruction/regeneration of a particular tissue. In periodontology, the concept of tissue engineering had its beginnings with guided tissue regeneration, a mechanical approach utilizing nonresorbable membranes to obtain regeneration in defects. In dental implantology, guided bone regeneration membranes +/- mechanical support are used for bone augmentation of proposed implant placement sites. With the availability of partially purified protein mixture from developing teeth and growth factors from recombinant technology, a new era of tissue engineering whereby biologic mediators can be used for periodontal regeneration. The advantage of recombinant growth factors is this tissue engineering device is consistent in its regenerative capacity, and variations in regenerative response are due to individual healing response and/or poor surgical techniques. In this article, the authors review how tissue engineering has advanced and discuss its impact on the clinical management of both periodontal and osseous defects in preparation for implant placement. An understanding of these new tissue engineering techniques is essential for comprehending today's ever

  10. Tissue Engineering Initiative

    Science.gov (United States)

    2000-08-01

    skin and certain specialized tissues such as umbilical cord and rooster comb, during fetal development, and in tissue repair and regeneration...hylan preparations precluded testing by tensile stress-strain methods because of the difficulty in clamping ends of the pliant materials. Thus, only...analysis), histology (decalcified histology), and oxygen tension history (early environment and rate of revascularization). Briefly, four identical (1

  11. Chitin Scaffolds in Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Tetsuya Furuike

    2011-03-01

    Full Text Available Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine.

  12. Commercial considerations in tissue engineering.

    Science.gov (United States)

    Mansbridge, Jonathan

    2006-10-01

    Tissue engineering is a field with immense promise. Using the example of an early tissue-engineered skin implant, Dermagraft, factors involved in the successful commercial development of devices of this type are explored. Tissue engineering has to strike a balance between tissue culture, which is a resource-intensive activity, and business considerations that are concerned with minimizing cost and maximizing customer convenience. Bioreactor design takes place in a highly regulated environment, so factors to be incorporated into the concept include not only tissue culture considerations but also matters related to asepsis, scaleup, automation and ease of use by the final customer. Dermagraft is an allogeneic tissue. Stasis preservation, in this case cryopreservation, is essential in allogeneic tissue engineering, allowing sterility testing, inventory control and, in the case of Dermagraft, a cellular stress that may be important for hormesis following implantation. Although the use of allogeneic cells provides advantages in manufacturing under suitable conditions, it raises the spectre of immunological rejection. Such rejection has not been experienced with Dermagraft. Possible reasons for this and the vision of further application of allogeneic tissues are important considerations in future tissue-engineered cellular devices. This review illustrates approaches that indicate some of the criteria that may provide a basis for further developments. Marketing is a further requirement for success, which entails understanding of the mechanism of action of the procedure, and is illustrated for Dermagraft. The success of a tissue-engineered product is dependent on many interacting operations, some discussed here, each of which must be performed simultaneously and well.

  13. Skeletal muscle tissue engineering

    National Research Council Canada - National Science Library

    Bach, A. D; Beier, J. P; Stern‐Staeter, J; Horch, R. E

    2004-01-01

    The reconstruction of skeletal muscle tissue either lost by traumatic injury or tumor ablation or functional damage due to myopathies is hampered by the lack of availability of functional substitution...

  14. Scaffolds in Tendon Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Umile Giuseppe Longo

    2012-01-01

    Full Text Available Tissue engineering techniques using novel scaffold materials offer potential alternatives for managing tendon disorders. Tissue engineering strategies to improve tendon repair healing include the use of scaffolds, growth factors, cell seeding, or a combination of these approaches. Scaffolds have been the most common strategy investigated to date. Available scaffolds for tendon repair include both biological scaffolds, obtained from mammalian tissues, and synthetic scaffolds, manufactured from chemical compounds. Preliminary studies support the idea that scaffolds can provide an alternative for tendon augmentation with an enormous therapeutic potential. However, available data are lacking to allow definitive conclusion on the use of scaffolds for tendon augmentation. We review the current basic science and clinical understanding in the field of scaffolds and tissue engineering for tendon repair.

  15. Synthetic biology meets tissue engineering.

    Science.gov (United States)

    Davies, Jamie A; Cachat, Elise

    2016-06-15

    Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the 'embryological cycle' of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. © 2016 Authors; published by Portland Press Limited.

  16. Multiphoton tomography for tissue engineering

    Science.gov (United States)

    König, Karsten

    2008-02-01

    Femtosecond laser multiphoton tomography has been employed in the field of tissue engineering to perform 3D high-resolution imaging of the extracellular matrix proteins elastin and collagen as well as of living cells without any fixation, slicing, and staining. Near infrared 80 MHz picojoule femtosecond laser pulses are able to excite the endogenous fluorophores NAD(P)H, flavoproteins, melanin, and elastin via a non-resonant two-photon excitation process. In addition, collagen can be imaged by second harmonic generation. Using a two-PMT detection system, the ratio of elastin to collagen was determined during optical sectioning. A high submicron spatial resolution and 50 picosecond temporal resolution was achieved using galvoscan mirrors and piezodriven focusing optics as well as a time-correlated single photon counting module with a fast microchannel plate detector and fast photomultipliers. Multiphoton tomography has been used to optimize the tissue engineering of heart valves and vessels in bioincubators as well as to characterize artificial skin. Stem cell characterization and manipulation are of major interest for the field of tissue engineering. Using the novel sub-20 femtosecond multiphoton nanoprocessing laser microscope FemtOgene, the differentiation of human stem cells within spheroids has been in vivo monitored with submicron resolution. In addition, the efficient targeted transfection has been demonstrated. Clinical studies on the interaction of tissue-engineered products with the natural tissue environment can be performed with in vivo multiphoton tomograph DermaInspect.

  17. Carbon nanotubes in tissue engineering.

    Science.gov (United States)

    Bosi, Susanna; Ballerini, Laura; Prato, Maurizio

    2014-01-01

    As a result of their peculiar features, carbon nanotubes (CNTs) are emerging in many areas of nanotechnology applications. CNT-based technology has been increasingly proposed for biomedical applications, to develop biomolecule nanocarriers, bionanosensors and smart material for tissue engineering purposes. In the following chapter this latter application will be explored, describing why CNTs can be considered an ideal material able to support and boost the growth and the proliferation of many kinds of tissues.

  18. Bioactive glass in tissue engineering

    Science.gov (United States)

    Rahaman, Mohamed N.; Day, Delbert E.; Bal, B. Sonny; Fu, Qiang; Jung, Steven B.; Bonewald, Lynda F.; Tomsia, Antoni P.

    2011-01-01

    This review focuses on recent advances in the development and use of bioactive glass for tissue engineering applications. Despite its inherent brittleness, bioactive glass has several appealing characteristics as a scaffold material for bone tissue engineering. New bioactive glasses based on borate and borosilicate compositions have shown the ability to enhance new bone formation when compared to silicate bioactive glass. Borate-based bioactive glasses also have controllable degradation rates, so the degradation of the bioactive glass implant can be more closely matched to the rate of new bone formation. Bioactive glasses can be doped with trace quantities of elements such as Cu, Zn and Sr, which are known to be beneficial for healthy bone growth. In addition to the new bioactive glasses, recent advances in biomaterials processing have resulted in the creation of scaffold architectures with a range of mechanical properties suitable for the substitution of loaded as well as non-loaded bone. While bioactive glass has been extensively investigated for bone repair, there has been relatively little research on the application of bioactive glass to the repair of soft tissues. However, recent work has shown the ability of bioactive glass to promote angiogenesis, which is critical to numerous applications in tissue regeneration, such as neovascularization for bone regeneration and the healing of soft tissue wounds. Bioactive glass has also been shown to enhance neocartilage formation during in vitro culture of chondrocyte-seeded hydrogels, and to serve as a subchondral substrate for tissue-engineered osteochondral constructs. Methods used to manipulate the structure and performance of bioactive glass in these tissue engineering applications are analyzed. PMID:21421084

  19. Engineering Students Designing a Statistical Procedure for Quantifying Variability

    Science.gov (United States)

    Hjalmarson, Margret A.

    2007-01-01

    The study examined first-year engineering students' responses to a statistics task that asked them to generate a procedure for quantifying variability in a data set from an engineering context. Teams used technological tools to perform computations, and their final product was a ranking procedure. The students could use any statistical measures,…

  20. Engineering functionally graded tissue engineering scaffolds.

    Science.gov (United States)

    Leong, K F; Chua, C K; Sudarmadji, N; Yeong, W Y

    2008-04-01

    Tissue Engineering (TE) aims to create biological substitutes to repair or replace failing organs or tissues due to trauma or ageing. One of the more promising approaches in TE is to grow cells on biodegradable scaffolds, which act as temporary supports for the cells to attach, proliferate and differentiate; after which the scaffold will degrade, leaving behind a healthy regenerated tissue. Tissues in nature, including human tissues, exhibit gradients across a spatial volume, in which each identifiable layer has specific functions to perform so that the whole tissue/organ can behave normally. Such a gradient is termed a functional gradient. A good TE scaffold should mimic such a gradient, which fulfils the biological and mechanical requirements of the target tissue. Thus, the design and fabrication process of such scaffolds become more complex and the introduction of computer-aided tools will lend themselves well to ease these challenges. This paper reviews the needs and characterization of these functional gradients and the computer-aided systems used to ease the complexity of the scaffold design stage. These include the fabrication techniques capable of building functionally graded scaffolds (FGS) using both conventional and rapid prototyping (RP) techniques. They are able to fabricate both continuous and discrete types of FGS. The challenge in fabricating continuous FGS using RP techniques lies in the development of suitable computer aided systems to facilitate continuous FGS design. What have been missing are the appropriate models that relate the scaffold gradient, e.g. pore size, porosity or material gradient, to the biological and mechanical requirements for the regeneration of the target tissue. The establishment of these relationships will provide the foundation to develop better computer-aided systems to help design a suitable customized FGS.

  1. [DEVELOPMENT OF CELL SHEET ENGINEERING TECHNOLOGY IN ENGINEERING VASCULARIZED TISSUE].

    Science.gov (United States)

    Chen, Jia; Ma, Dongyang; Ren, Liling

    2015-03-01

    To review the development of cell sheet engineering technology in engineering vascularized tissue. The literature about cell sheet engineering technology and engineering vascularized tissue was reviewed, analyzed, and summarized. Although there are many methods to engineer vascularized tissue, cell sheet engineering technology provides a promising potential to develop a vascularized tissue. Recently, cell sheet engineering technology has become a hot topic in engineering vascularized tissue. Co-culturing endothelial cells on a cell sheet, endothelial cells are able to form three-dimensional prevascularized networks and microvascular cavities in the cell sheet, which facilitate the formation of functional vascular networks in the transplanted tissue. Cell sheet engineering technology is a promising strategy to engineer vascularized tissue, which is still being studied to explore more potential.

  2. Developmental biology and tissue engineering.

    Science.gov (United States)

    Marga, Francoise; Neagu, Adrian; Kosztin, Ioan; Forgacs, Gabor

    2007-12-01

    Morphogenesis implies the controlled spatial organization of cells that gives rise to tissues and organs in early embryonic development. While morphogenesis is under strict genetic control, the formation of specialized biological structures of specific shape hinges on physical processes. Tissue engineering (TE) aims at reproducing morphogenesis in the laboratory, i.e., in vitro, to fabricate replacement organs for regenerative medicine. The classical approach to generate tissues/organs is by seeding and expanding cells in appropriately shaped biocompatible scaffolds, in the hope that the maturation process will result in the desired structure. To accomplish this goal more naturally and efficiently, we set up and implemented a novel TE method that is based on principles of developmental biology and employs bioprinting, the automated delivery of cellular composites into a three-dimensional (3D) biocompatible environment. The novel technology relies on the concept of tissue liquidity according to which multicellular aggregates composed of adhesive and motile cells behave in analogy with liquids: in particular, they fuse. We emphasize the major role played by tissue fusion in the embryo and explain how the parameters (surface tension, viscosity) that govern tissue fusion can be used both experimentally and theoretically to control and simulate the self-assembly of cellular spheroids into 3D living structures. The experimentally observed postprinting shape evolution of tube- and sheet-like constructs is presented. Computer simulations, based on a liquid model, support the idea that tissue liquidity may provide a mechanism for in vitro organ building.

  3. Methods to Quantify Nickel in Soils and Plant Tissues

    Directory of Open Access Journals (Sweden)

    Bruna Wurr Rodak

    2015-06-01

    Full Text Available In comparison with other micronutrients, the levels of nickel (Ni available in soils and plant tissues are very low, making quantification very difficult. The objective of this paper is to present optimized determination methods of Ni availability in soils by extractants and total content in plant tissues for routine commercial laboratory analyses. Samples of natural and agricultural soils were processed and analyzed by Mehlich-1 extraction and by DTPA. To quantify Ni in the plant tissues, samples were digested with nitric acid in a closed system in a microwave oven. The measurement was performed by inductively coupled plasma/optical emission spectrometry (ICP-OES. There was a positive and significant correlation between the levels of available Ni in the soils subjected to Mehlich-1 and DTPA extraction, while for plant tissue samples the Ni levels recovered were high and similar to the reference materials. The availability of Ni in some of the natural soil and plant tissue samples were lower than the limits of quantification. Concentrations of this micronutrient were higher in the soil samples in which Ni had been applied. Nickel concentration differed in the plant parts analyzed, with highest levels in the grains of soybean. The grain, in comparison with the shoot and leaf concentrations, were better correlated with the soil available levels for both extractants. The methods described in this article were efficient in quantifying Ni and can be used for routine laboratory analysis of soils and plant tissues.

  4. Extracellular matrix and tissue engineering applications

    NARCIS (Netherlands)

    Fernandes, Hugo; Moroni, Lorenzo; Blitterswijk, van Clemens; Boer, de Jan

    2009-01-01

    The extracellular matrix is a key component during regeneration and maintenance of tissues and organs, and it therefore plays a critical role in successful tissue engineering as well. Tissue engineers should recognise that engineering technology can be deduced from natural repair processes. Due to a

  5. Membrane supported scaffold : architectures for tissue engineering

    NARCIS (Netherlands)

    Bettahalli, Narasimha Murthy Srivatsa

    2011-01-01

    Tissue engineering aims at restoring or regenerating a damaged tissue. Often the tissue recreation occurs by combining cells, derived from a patient biopsy, onto a 3D porous matrix, functioning as a scaffold. One of the current limitations of tissue engineering is the inability to provide sufficie

  6. Photoacoustic microscopy in tissue engineering

    Directory of Open Access Journals (Sweden)

    Xin Cai

    2013-03-01

    Full Text Available Photoacoustic tomography (PAT is an attractive modality for noninvasive, volumetric imaging of scattering media such as biological tissues. By choosing the ultrasonic detection frequency, PAT enables scalable spatial resolution with an imaging depth of up to ∼7 cm while maintaining a high depth-to-resolution ratio of ∼200 and consistent optical absorption contrasts. Photoacoustic microscopy (PAM, the microscopic embodiment of PAT, aims to image at millimeter depth and micrometer-scale resolution. PAM is well-suited for characterizing three-dimensional scaffold-based samples, including scaffolds themselves, cells, and blood vessels, both qualitatively and quantitatively. Here we review our previous work on applications of PAM in tissue engineering and then discuss its future developments.

  7. Nanotechnology in bone tissue engineering.

    Science.gov (United States)

    Walmsley, Graham G; McArdle, Adrian; Tevlin, Ruth; Momeni, Arash; Atashroo, David; Hu, Michael S; Feroze, Abdullah H; Wong, Victor W; Lorenz, Peter H; Longaker, Michael T; Wan, Derrick C

    2015-07-01

    Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases. Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Microfabricated biomaterials for engineering 3D tissues.

    Science.gov (United States)

    Zorlutuna, Pinar; Annabi, Nasim; Camci-Unal, Gulden; Nikkhah, Mehdi; Cha, Jae Min; Nichol, Jason W; Manbachi, Amir; Bae, Hojae; Chen, Shaochen; Khademhosseini, Ali

    2012-04-10

    Mimicking natural tissue structure is crucial for engineered tissues with intended applications ranging from regenerative medicine to biorobotics. Native tissues are highly organized at the microscale, thus making these natural characteristics an integral part of creating effective biomimetic tissue structures. There exists a growing appreciation that the incorporation of similar highly organized microscale structures in tissue engineering may yield a remedy for problems ranging from vascularization to cell function control/determination. In this review, we highlight the recent progress in the field of microscale tissue engineering and discuss the use of various biomaterials for generating engineered tissue structures with microscale features. In particular, we will discuss the use of microscale approaches to engineer the architecture of scaffolds, generate artificial vasculature, and control cellular orientation and differentiation. In addition, the emergence of microfabricated tissue units and the modular assembly to emulate hierarchical tissues will be discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Biomechanics and mechanobiology in functional tissue engineering

    Science.gov (United States)

    Guilak, Farshid; Butler, David L.; Goldstein, Steven A.; Baaijens, Frank P.T.

    2014-01-01

    The field of tissue engineering continues to expand and mature, and several products are now in clinical use, with numerous other preclinical and clinical studies underway. However, specific challenges still remain in the repair or regeneration of tissues that serve a predominantly biomechanical function. Furthermore, it is now clear that mechanobiological interactions between cells and scaffolds can critically influence cell behavior, even in tissues and organs that do not serve an overt biomechanical role. Over the past decade, the field of “functional tissue engineering” has grown as a subfield of tissue engineering to address the challenges and questions on the role of biomechanics and mechanobiology in tissue engineering. Originally posed as a set of principles and guidelines for engineering of load-bearing tissues, functional tissue engineering has grown to encompass several related areas that have proven to have important implications for tissue repair and regeneration. These topics include measurement and modeling of the in vivo biomechanical environment; quantitative analysis of the mechanical properties of native tissues, scaffolds, and repair tissues; development of rationale criteria for the design and assessment of engineered tissues; investigation of the effects biomechanical factors on native and repair tissues, in vivo and in vitro; and development and application of computational models of tissue growth and remodeling. Here we further expand this paradigm and provide examples of the numerous advances in the field over the past decade. Consideration of these principles in the design process will hopefully improve the safety, efficacy, and overall success of engineered tissue replacements. PMID:24818797

  10. Systems biology characterization of engineered tissues.

    Science.gov (United States)

    Rajagopalan, Padmavathy; Kasif, Simon; Murali, T M

    2013-01-01

    Tissue engineering and molecular systems biology are inherently interdisciplinary fields that have been developed independently so far. In this review, we first provide a brief introduction to tissue engineering and to molecular systems biology. Next, we highlight some prominent applications of systems biology techniques in tissue engineering. Finally, we outline research directions that can successfully blend these two fields. Through these examples, we propose that experimental and computational advances in molecular systems biology can lead to predictive models of bioengineered tissues that enhance our understanding of bioengineered systems. In turn, the unique challenges posed by tissue engineering will usher in new experimental techniques and computational advances in systems biology.

  11. Informing tendon tissue engineering with embryonic development

    OpenAIRE

    Glass, Zachary A.; Schiele, Nathan R.; Kuo, Catherine K

    2014-01-01

    Tendon is a strong connective tissue that transduces muscle-generated forces into skeletal motion. In fulfilling this role, tendons are subjected to repeated mechanical loading and high stress, which may result in injury. Tissue engineering with stem cells offers the potential to replace injured/damaged tissue with healthy, new living tissue. Critical to tendon tissue engineering is the induction and guidance of stem cells towards the tendon phenotype. Typical strategies hav...

  12. Skeletal tissue engineering using embryonic stem cells

    NARCIS (Netherlands)

    Jukes, Jojanneke Maria

    2009-01-01

    Tissue engineering aims at repairing or replacing damaged or diseased tissue. In this thesis, we investigated the potential of embryonic stem cells (ESCs) for cartilage tissue engineering. After differentiation of mouse and human ESCs into the chondrogenic and osteogenic lineage had been established

  13. Tissue Engineered Human Skin Equivalents

    Directory of Open Access Journals (Sweden)

    Zheng Zhang

    2012-01-01

    Full Text Available Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery and/or the body (transdermal delivery. In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening. Several academic laboratories have developed their own human skin equivalent models and applied these models for studying skin permeation, corrosivity and irritation, compound toxicity, biochemistry, metabolism and cellular pharmacology. Various aspects of the state of the art of human skin equivalents are reviewed and discussed.

  14. Tissue engineering of cartilages using biomatrices

    DEFF Research Database (Denmark)

    Melrose, J.; Chuang, C.; Whitelock, J.

    2008-01-01

    Tissue engineering is an exciting new cross-disciplinary methodology which applies the principles of engineering and structure-function relationships between normal and pathological tissues to develop biological substitute to restore, maintain or improve tissue function. Tissue engineering...... engineering approaches and many of these are discussed and their in vitro and in vivo applications covered in this review. Tissue engineering is entering an exciting era; significant advances have been made; however, many technical challenges remain to be solved before this technology becomes widely...... therefore involves a melange of approaches encompassing developmental biology, tissue mechanics, medicine, cell differentiation and survival biology, mechanostransduction and nano-fabrication technology. The central tissue of interest in this review is cartilage. Traumatic injuries, congenital abnormalities...

  15. Adipose and mammary epithelial tissue engineering.

    Science.gov (United States)

    Zhu, Wenting; Nelson, Celeste M

    2013-01-01

    Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast.

  16. Nanomaterials for Cardiac Myocyte Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Rodolfo Amezcua

    2016-07-01

    Full Text Available Since their synthesizing introduction to the research community, nanomaterials have infiltrated almost every corner of science and engineering. Over the last decade, one such field has begun to look at using nanomaterials for beneficial applications in tissue engineering, specifically, cardiac tissue engineering. During a myocardial infarction, part of the cardiac muscle, or myocardium, is deprived of blood. Therefore, the lack of oxygen destroys cardiomyocytes, leaving dead tissue and possibly resulting in the development of arrhythmia, ventricular remodeling, and eventual heart failure. Scarred cardiac muscle results in heart failure for millions of heart attack survivors worldwide. Modern cardiac tissue engineering research has developed nanomaterial applications to combat heart failure, preserve normal heart tissue, and grow healthy myocardium around the infarcted area. This review will discuss the recent progress of nanomaterials for cardiovascular tissue engineering applications through three main nanomaterial approaches: scaffold designs, patches, and injectable materials.

  17. Biomechanics and mechanobiology in functional tissue engineering.

    Science.gov (United States)

    Guilak, Farshid; Butler, David L; Goldstein, Steven A; Baaijens, Frank P T

    2014-06-27

    The field of tissue engineering continues to expand and mature, and several products are now in clinical use, with numerous other preclinical and clinical studies underway. However, specific challenges still remain in the repair or regeneration of tissues that serve a predominantly biomechanical function. Furthermore, it is now clear that mechanobiological interactions between cells and scaffolds can critically influence cell behavior, even in tissues and organs that do not serve an overt biomechanical role. Over the past decade, the field of "functional tissue engineering" has grown as a subfield of tissue engineering to address the challenges and questions on the role of biomechanics and mechanobiology in tissue engineering. Originally posed as a set of principles and guidelines for engineering of load-bearing tissues, functional tissue engineering has grown to encompass several related areas that have proven to have important implications for tissue repair and regeneration. These topics include measurement and modeling of the in vivo biomechanical environment; quantitative analysis of the mechanical properties of native tissues, scaffolds, and repair tissues; development of rationale criteria for the design and assessment of engineered tissues; investigation of the effects biomechanical factors on native and repair tissues, in vivo and in vitro; and development and application of computational models of tissue growth and remodeling. Here we further expand this paradigm and provide examples of the numerous advances in the field over the past decade. Consideration of these principles in the design process will hopefully improve the safety, efficacy, and overall success of engineered tissue replacements. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. [Chondrocyte mecanobiology. Application in cartilage tissue engineering].

    Science.gov (United States)

    Stoltz, Jean François; Netter, Patrick; Huselstein, Céline; de Isla, Natalia; Wei Yang, Jing; Muller, Sylvaine

    2005-11-01

    Cartilage is a hydrated connective tissue that withstands and distributes mechanical forces within joints. Chondrocytes utilize mechanical signals to maintain cartilaginous tissue homeostasis. They regulate their metabolic activity through complex biological and biophysical interactions with the extracellular matrix (ECM). Some mechanotransduction mechanisms are known, while many others no doubt remain to be discovered. Various aspects of chondrocyte mechanobiology have been applied to tissue engineering, with the creation of replacement tissue in vitro from bioresorbable or non-bioresorbable scaffolds and harvested cells. The tissues are maintained in a near-physiologic mechanical and biochemical environment. This paper is an overview of both chondrocyte mechanobiology and cartilage tissue engineering

  19. Development of multilayer constructs for tissue engineering

    NARCIS (Netherlands)

    Bettahalli, N. M. S.; Groen, N.; Steg, H.; Unadkat, H.; de Boer, J.; van Blitterswijk, C. A.; Wessling, M.; Stamatialis, D.

    2014-01-01

    The rapidly developing field of tissue engineering produces living substitutes that restore, maintain or improve the function of tissues or organs. In contrast to standard therapies, the engineered products become integrated within the patient, affording a potentially permanent and specific cure of

  20. Using Polymeric Scaffolds for Vascular Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Alida Abruzzo

    2014-01-01

    Full Text Available With the high occurrence of cardiovascular disease and increasing numbers of patients requiring vascular access, there is a significant need for small-diameter (<6 mm inner diameter vascular graft that can provide long-term patency. Despite the technological improvements, restenosis and graft thrombosis continue to hamper the success of the implants. Vascular tissue engineering is a new field that has undergone enormous growth over the last decade and has proposed valid solutions for blood vessels repair. The goal of vascular tissue engineering is to produce neovessels and neoorgan tissue from autologous cells using a biodegradable polymer as a scaffold. The most important advantage of tissue-engineered implants is that these tissues can grow, remodel, rebuild, and respond to injury. This review describes the development of polymeric materials over the years and current tissue engineering strategies for the improvement of vascular conduits.

  1. Biodegradable polymeric fiber structures in tissue engineering.

    Science.gov (United States)

    Tuzlakoglu, Kadriye; Reis, Rui L

    2009-03-01

    Tissue engineering offers a promising new approach to create biological alternatives to repair or restore function of damaged or diseased tissues. To obtain three-dimensional tissue constructs, stem or progenitor cells must be combined with a highly porous three-dimensional scaffold, but many of the structures purposed for tissue engineering cannot meet all the criteria required by an adequate scaffold because of lack of mechanical strength and interconnectivity, as well as poor surface characteristics. Fiber-based structures represent a wide range of morphological and geometric possibilities that can be tailored for each specific tissue-engineering application. The present article overviews the research data on tissue-engineering therapies based on the use of biodegradable fiber architectures as a scaffold.

  2. PLA-based foams: tissue engineering

    OpenAIRE

    Velasco Perero, José Ignacio; Antunes, Marcelo de Sousa Pais

    2015-01-01

    Biodegradable porous scaffolds with or without bioactive molecules prepared by clean techniques attract an enormous interest for tissue engineering applications. Scaffolds work as structural support for both cell implantation and growth, favoring the regeneration or formation of new tissue. Scaffold requisites for tissue engineering applications include a proper material selection, which has to be biocompatible and biodegradable and with a good balance of mechanical properties, as...

  3. Tissue engineering of cartilages using biomatrices

    DEFF Research Database (Denmark)

    Melrose, J.; Chuang, C.; Whitelock, J.

    2008-01-01

    Tissue engineering is an exciting new cross-disciplinary methodology which applies the principles of engineering and structure-function relationships between normal and pathological tissues to develop biological substitute to restore, maintain or improve tissue function. Tissue engineering...... therefore involves a melange of approaches encompassing developmental biology, tissue mechanics, medicine, cell differentiation and survival biology, mechanostransduction and nano-fabrication technology. The central tissue of interest in this review is cartilage. Traumatic injuries, congenital abnormalities...... and age-related degenerative diseases can all lead to cartilage loss; however, the low cell density and very limited self-renewal capacity of cartilage necessitate the development of effective therapeutic repair strategies for this tissue. The ontogeny of the chondrocyte, which is the cell that provides...

  4. Towards improved scaffolds for bone tissue engineering

    NARCIS (Netherlands)

    Nandakumar, A.

    2012-01-01

    Tissue engineering aims to restore, maintain or improve tissue function of damaged tissues. In a classical set-up, a scaffold functions as a supporting structure and a carrier for growth factors and/or cells. Human mesenchymal stromal cells (hMSCs) have the ability to differentiate into bone, cartil

  5. Engineering vascular development for tissue regeneration

    NARCIS (Netherlands)

    Rivron, N.C.

    2010-01-01

    Tissue engineering and regenerative medicine aim at restoring a damaged tissue by recreating in vitro or promoting its regeneratin in vovo. The vasculature is central to these therapies for the irrigation of the defective tissue (oxygen, nutrients or circulating regenerative cells) and as an

  6. Optical Coherence Tomography in Tissue Engineering

    Science.gov (United States)

    Zhao, Youbo; Yang, Ying; Wang, Ruikang K.; Boppart, Stephen A.

    Tissue engineering holds the promise for a therapeutic solution in regenerative medicine. The primary goal of tissue engineering is the development of physiologically functional and biocompatible tissues/organs being implanted for the repair and replacement of damaged or diseased ones. Given the complexity in the developing processes of engineered tissues, which involves multi-dimensional interactions among cells of different types, three-dimensionally constructed scaffolds, and actively intervening bioreactors, a capable real-time imaging tool is critically required for expanding our knowledge about the developing process of desired tissues or organs. It has been recognized that optical coherence tomography (OCT), an emerging noninvasive imaging technique that provides high spatial resolution (up to the cellular level) and three-dimensional imaging capability, is a promising investigative tool for tissue engineering. This chapter discusses the existing and potential applications of OCT in tissue engineering. Example OCT investigations of the three major components of tissue engineering, i.e., cells, scaffolds, and bioreactors are overviewed. Imaging examples of OCT and its enabling functions and variants, e.g., Doppler OCT, polarization-sensitive OCT, optical coherence microscopy are emphasized. Remaining challenges in the application of OCT to tissue engineering are discussed, and the prospective solutions including the combination of OCT with other high-contrast and high-resolution modalities such as two-photon fluorescence microscopy are suggested as well. It is expected that OCT, along with its functional variants, will make important contributions toward revealing the complex cellular dynamics in engineered tissues as well as help us culture demanding tissue/organ implants that will advance regenerative medicine.

  7. Cardiac tissue engineering: state of the art.

    Science.gov (United States)

    Hirt, Marc N; Hansen, Arne; Eschenhagen, Thomas

    2014-01-17

    The engineering of 3-dimensional (3D) heart muscles has undergone exciting progress for the past decade. Profound advances in human stem cell biology and technology, tissue engineering and material sciences, as well as prevascularization and in vitro assay technologies make the first clinical application of engineered cardiac tissues a realistic option and predict that cardiac tissue engineering techniques will find widespread use in the preclinical research and drug development in the near future. Tasks that need to be solved for this purpose include standardization of human myocyte production protocols, establishment of simple methods for the in vitro vascularization of 3D constructs and better maturation of myocytes, and, finally, thorough definition of the predictive value of these methods for preclinical safety pharmacology. The present article gives an overview of the present state of the art, bottlenecks, and perspectives of cardiac tissue engineering for cardiac repair and in vitro testing.

  8. Aloe Vera for Tissue Engineering Applications.

    Science.gov (United States)

    Rahman, Shekh; Carter, Princeton; Bhattarai, Narayan

    2017-02-14

    Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers.

  9. Aloe Vera for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Shekh Rahman

    2017-02-01

    Full Text Available Aloe vera, also referred as Aloe barbadensis Miller, is a succulent plant widely used for biomedical, pharmaceutical and cosmetic applications. Aloe vera has been used for thousands of years. However, recent significant advances have been made in the development of aloe vera for tissue engineering applications. Aloe vera has received considerable attention in tissue engineering due to its biodegradability, biocompatibility, and low toxicity properties. Aloe vera has been reported to have many biologically active components. The bioactive components of aloe vera have effective antibacterial, anti-inflammatory, antioxidant, and immune-modulatory effects that promote both tissue regeneration and growth. The aloe vera plant, its bioactive components, extraction and processing, and tissue engineering prospects are reviewed in this article. The use of aloe vera as tissue engineering scaffolds, gels, and films is discussed, with a special focus on electrospun nanofibers.

  10. Imaging in cellular and tissue engineering

    CERN Document Server

    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

  11. Composite scaffolds for cartilage tissue engineering.

    Science.gov (United States)

    Moutos, Franklin T; Guilak, Farshid

    2008-01-01

    Tissue engineering remains a promising therapeutic strategy for the repair or regeneration of diseased or damaged tissues. Previous approaches have typically focused on combining cells and bioactive molecules (e.g., growth factors, cytokines and DNA fragments) with a biomaterial scaffold that functions as a template to control the geometry of the newly formed tissue, while facilitating the attachment, proliferation, and differentiation of embedded cells. Biomaterial scaffolds also play a crucial role in determining the functional properties of engineered tissues, including biomechanical characteristics such as inhomogeneity, anisotropy, nonlinearity or viscoelasticity. While single-phase, homogeneous materials have been used extensively to create numerous types of tissue constructs, there continue to be significant challenges in the development of scaffolds that can provide the functional properties of load-bearing tissues such as articular cartilage. In an attempt to create more complex scaffolds that promote the regeneration of functional engineered tissues, composite scaffolds comprising two or more distinct materials have been developed. This paper reviews various studies on the development and testing of composite scaffolds for the tissue engineering of articular cartilage, using techniques such as embedded fibers and textiles for reinforcement, embedded solid structures, multi-layered designs, or three-dimensionally woven composite materials. In many cases, the use of composite scaffolds can provide unique biomechanical and biological properties for the development of functional tissue engineering scaffolds.

  12. Rapid Prototyping Technology of Tissue Engineering Scaffold

    Institute of Scientific and Technical Information of China (English)

    管金鹏

    2014-01-01

    In the modern medicine field, the transplant of organ and tissue is a big problem due to serious shortage of donor organ. Artificial organ and tissue is one of solutions. With the development of science, various tissue manufacture techniques emerged. Hereinto, due to its versatility both in materials and structure, rapid prototyping technology has become one of the important methods for tissue engineering scaffold fabrication in this field.

  13. Tissue Engineering and Regenerative Medicine

    Science.gov (United States)

    2006-11-01

    Vessels - 5 years; Heart Valves – in progress Respiratory: Trachea – in progress Orthopedic : Cartilage, Bone, Skeletal Muscle, Digits Nephrology...interactions (bio-engineers) Small & large animal models (physiologists, biochemists, veterinarians ) Clinical trials (physicians, epidemiologists

  14. Tissue Engineering in Regenerative Dental Therapy

    Directory of Open Access Journals (Sweden)

    Hiral Jhaveri-Desai

    2011-01-01

    Full Text Available Tissue engineering is amongst the latest exciting technologies having impacted the field of dentistry. Initially considered as a futuristic approach, tissue engineering is now being successfully applied in regenerative surgery. This article reviews the important determinants of tissue engineering and how they contribute to the improvement of wound healing and surgical outcomes in the oral region. Furthermore, we shall address the clinical applications of engineering involving oral and maxillofacial surgical and periodontal procedures along with other concepts that are still in experimental phase of development. This knowledge will aid the surgical and engineering researchers to comprehend the collaboration between these fields leading to extounding dental applications and to ever-continuing man-made miracles in the field of human science.

  15. Introduction to tissue engineering applications and challenges

    CERN Document Server

    Birla, Ravi

    2014-01-01

    Covering a progressive medical field, Tissue Engineering describes the innovative process of regenerating human cells to restore or establish normal function in defective organs. As pioneering individuals look ahead to the possibility of generating entire organ systems, students may turn to this textbook for a comprehensive understanding and preparation for the future of regenerative medicine. This book explains chemical stimulations, the bioengineering of specific organs, and treatment plans for chronic diseases. It is a must-read for tissue engineering students and practitioners.

  16. Bone Tissue Engineering: Recent Advances and Challenges

    Science.gov (United States)

    Amini, Ami R.; Laurencin, Cato T.; Nukavarapu, Syam P.

    2013-01-01

    The worldwide incidence of bone disorders and conditions has trended steeply upward and is expected to double by 2020, especially in populations where aging is coupled with increased obesity and poor physical activity. Engineered bone tissue has been viewed as a potential alternative to the conventional use of bone grafts, due to their limitless supply and no disease transmission. However, bone tissue engineering practices have not proceeded to clinical practice due to several limitations or challenges. Bone tissue engineering aims to induce new functional bone regeneration via the synergistic combination of biomaterials, cells, and factor therapy. In this review, we discuss the fundamentals of bone tissue engineering, highlighting the current state of this field. Further, we review the recent advances of biomaterial and cell-based research, as well as approaches used to enhance bone regeneration. Specifically, we discuss widely investigated biomaterial scaffolds, micro- and nano-structural properties of these scaffolds, and the incorporation of biomimetic properties and/or growth factors. In addition, we examine various cellular approaches, including the use of mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), adult stem cells, induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), and their clinical application strengths and limitations. We conclude by overviewing the challenges that face the bone tissue engineering field, such as the lack of sufficient vascularization at the defect site, and the research aimed at functional bone tissue engineering. These challenges will drive future research in the field. PMID:23339648

  17. Multilayer scaffolds in orthopaedic tissue engineering.

    Science.gov (United States)

    Atesok, Kivanc; Doral, M Nedim; Karlsson, Jon; Egol, Kenneth A; Jazrawi, Laith M; Coelho, Paulo G; Martinez, Amaury; Matsumoto, Tomoyuki; Owens, Brett D; Ochi, Mitsuo; Hurwitz, Shepard R; Atala, Anthony; Fu, Freddie H; Lu, Helen H; Rodeo, Scott A

    2016-07-01

    The purpose of this study was to summarize the recent developments in the field of tissue engineering as they relate to multilayer scaffold designs in musculoskeletal regeneration. Clinical and basic research studies that highlight the current knowledge and potential future applications of the multilayer scaffolds in orthopaedic tissue engineering were evaluated and the best evidence collected. Studies were divided into three main categories based on tissue types and interfaces for which multilayer scaffolds were used to regenerate: bone, osteochondral junction and tendon-to-bone interfaces. In vitro and in vivo studies indicate that the use of stratified scaffolds composed of multiple layers with distinct compositions for regeneration of distinct tissue types within the same scaffold and anatomic location is feasible. This emerging tissue engineering approach has potential applications in regeneration of bone defects, osteochondral lesions and tendon-to-bone interfaces with successful basic research findings that encourage clinical applications. Present data supporting the advantages of the use of multilayer scaffolds as an emerging strategy in musculoskeletal tissue engineering are promising, however, still limited. Positive impacts of the use of next generation scaffolds in orthopaedic tissue engineering can be expected in terms of decreasing the invasiveness of current grafting techniques used for reconstruction of bone and osteochondral defects, and tendon-to-bone interfaces in near future.

  18. Mechanobiology and Cartilage Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    Céline; HUSELSTEIN; Natalia; de; ISLA; Sylvaine; MULLER; Jean-Franois; STOLTZ

    2005-01-01

    1 IntroductionThe cartilage is a hydrated connective tissue in joints that withstands and distributes mechanical forces. Chondrocytes utilize mechanical signals to maintain tissue homeostasis. They regulate their metabolic activity through complex biological and biophysical interactions with the extracellular matrix (ECM). Although some of the mechanisms of mechanotransduction are known today, there are certainly many others left unrevealed. Different topics of chondrocytes mechanobiology have led to the de...

  19. Single domain antibodies in tissue engineering

    NARCIS (Netherlands)

    Rodrigues, Emilie Dooms

    2014-01-01

    The aim of this thesis is to demonstrate the potential of VHH in tissue engineering applications, with a focus on bone and cartilage tissue regeneration. After a general introduction to this thesis in chapter 1, the selection of VHH targeting growth factors is described in chapter 2. VHH were select

  20. Hard-Soft Tissue Interface Engineering.

    Science.gov (United States)

    Armitage, Oliver E; Oyen, Michelle L

    2015-01-01

    The musculoskeletal system is comprised of three distinct tissue categories: structural mineralized tissues, actuating muscular soft tissues, and connective tissues. Where connective tissues - ligament, tendon and cartilage - meet with bones, a graded interface in mechanical properties occurs that allows the transmission of load without creating stress concentrations that would cause tissue damage. This interface typically occurs over less than 1 mm and contains a three order of magnitude difference in elastic stiffness, in addition to changes in cell type and growth factor concentrations among others. Like all engineered tissues, the replication of these interfaces requires the production of scaffolds that will provide chemical and mechanical cues, resulting in biologically accurate cellular differentiation. For interface tissues however, the scaffold must provide spatially graded chemical and mechanical cues over sub millimetre length scales. Naturally, this complicates the manufacture of the scaffolds and every stage of their subsequent cell seeding and growth, as each region has different optimal conditions. Given the higher degree of difficulty associated with replicating interface tissues compared to surrounding homogeneous tissues, it is likely that the development of complex musculoskeletal tissue systems will continue to be limited by the engineering of connective tissues interfaces with bone.

  1. Engineering skeletal muscle tissue in bioreactor systems

    Institute of Scientific and Technical Information of China (English)

    An Yang; Li Dong

    2014-01-01

    Objective To give a concise review of the current state of the art in tissue engineering (TE) related to skeletal muscle and kinds of bioreactor environment.Data sources The review was based on data obtained from the published articles and guidelines.Study selection A total of 106 articles were selected from several hundred original articles or reviews.The content of selected articles is in accordance with our purpose and the authors are authorized scientists in the study of engineered muscle tissue in bioreactor.Results Skeletal muscle TE is a promising interdisciplinary field which aims at the reconstruction of skeletal muscle loss.Although numerous studies have indicated that engineering skeletal muscle tissue may be of great importance in medicine in the near future,this technique still represents a limited degree of success.Since tissue-engineered muscle constructs require an adequate connection to the vascular system for efficient transport of oxygen,carbon dioxide,nutrients and waste products.Moreover,functional and clinically applicable muscle constructs depend on adequate neuromuscular junctions with neural calls.Third,in order to engineer muscle tissue successfully,it may be beneficial to mimic the in vivo environment of muscle through association with adequate stimuli from bioreactors.Conclusion Vascular system and bioreactors are necessary for development and maintenance of engineered muscle in order to provide circulation within the construct.

  2. Injectable, Biodegradable Hydrogels for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Huaping Tan

    2010-03-01

    Full Text Available Hydrogels have many different applications in the field of regenerative medicine. Biodegradable, injectable hydrogels could be utilized as delivery systems, cell carriers, and scaffolds for tissue engineering. Injectable hydrogels are an appealing scaffold because they are structurally similar to the extracellular matrix of many tissues, can often be processed under relatively mild conditions, and may be delivered in a minimally invasive manner. This review will discuss recent advances in the field of injectable hydrogels, including both synthetic and native polymeric materials, which can be potentially used in cartilage and soft tissue engineering applications.

  3. Conducting polypyrrole in tissue engineering applications

    Science.gov (United States)

    Huang, Zhong-Bing; Yin, Guang-Fu; Liao, Xiao-Ming; Gu, Jian-Wen

    2014-03-01

    Polypyrrole (PPy), the earliest prepared conducting polymer, has good biocompatibility, easy synthesis and flexibility in processing. Compared with metal and inorganic materials, doped PPy has better mechanical match with live tissue, resulting in its many applications in biomedical field. This mini-review presents some information on specific PPy properties for tissue engineering applications, including its synthesis, doping, bio-modification. Although some challenges and unanswered problems still remain, PPy as novel biomaterial has promoted the development tissue engineering for its clinical application in the future.

  4. Stem cells in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Jeong Min [Department of Preventive and Social Dentistry and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik [Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, College of Dentistry, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Mantalaris, Anathathios, E-mail: yshwang@khu.ac.k [Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom)

    2010-12-15

    Bone tissue engineering has been one of the most promising areas of research, providing a potential clinical application to cure bone defects. Recently, various stem cells including embryonic stem cells (ESCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs), adipose tissue-derived stem cells (ADSCs), muscle-derived stem cells (MDSCs) and dental pulp stem cells (DPSCs) have received extensive attention in the field of bone tissue engineering due to their distinct biological capability to differentiate into osteogenic lineages. The application of these stem cells to bone tissue engineering requires inducing in vitro differentiation of these cells into bone forming cells, osteoblasts. For this purpose, efficient in vitro differentiation towards osteogenic lineage requires the development of well-defined and proficient protocols. This would reduce the likelihood of spontaneous differentiation into divergent lineages and increase the available cell source for application to bone tissue engineering therapies. This review provides a critical examination of the various experimental strategies that could be used to direct the differentiation of ESC, BM-MSC, UCB-MSC, ADSC, MDSC and DPSC towards osteogenic lineages and their potential applications in tissue engineering, particularly in the regeneration of bone. (topical review)

  5. Tissue engineering chamber promotes adipose tissue regeneration in adipose tissue engineering models through induced aseptic inflammation.

    Science.gov (United States)

    Peng, Zhangsong; Dong, Ziqing; Chang, Qiang; Zhan, Weiqing; Zeng, Zhaowei; Zhang, Shengchang; Lu, Feng

    2014-11-01

    Tissue engineering chamber (TEC) makes it possible to generate significant amounts of mature, vascularized, stable, and transferable adipose tissue. However, little is known about the role of the chamber in tissue engineering. Therefore, to investigate the role of inflammatory response and the change in mechanotransduction started by TEC after implantation, we placed a unique TEC model on the surface of the groin fat pads in rats to study the expression of cytokines and tissue development in the TEC. The number of infiltrating cells was counted, and vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) expression levels in the chamber at multiple time points postimplantation were analyzed by enzyme-linked immunosorbent assay. Tissue samples were collected at various time points and labeled for specific cell populations. The result showed that new adipose tissue formed in the chamber at day 60. Also, the expression of MCP-1 and VEGF in the chamber decreased slightly from an early stage as well as the number of the infiltrating cells. A large number of CD34+/perilipin- perivascular cells could be detected at day 30. Also, the CD34+/perilipin+ adipose precursor cell numbers increased sharply by day 45 and then decreased by day 60. CD34-/perilipin+ mature adipocytes were hard to detect in the chamber content at day 30, but their number increased and then peaked at day 60. Ki67-positive cells could be found near blood vessels and their number decreased sharply over time. Masson's trichrome showed that collagen was the dominant component of the chamber content at early stage and was replaced by newly formed small adipocytes over time. Our findings suggested that the TEC implantation could promote the proliferation of adipose precursor cells derived from local adipose tissue, increase angiogenesis, and finally lead to spontaneous adipogenesis by inducing aseptic inflammation and changing local mechanotransduction.

  6. Trends in Tissue Engineering for Blood Vessels

    Directory of Open Access Journals (Sweden)

    Judee Grace Nemeno-Guanzon

    2012-01-01

    Full Text Available Over the years, cardiovascular diseases continue to increase and affect not only human health but also the economic stability worldwide. The advancement in tissue engineering is contributing a lot in dealing with this immediate need of alleviating human health. Blood vessel diseases are considered as major cardiovascular health problems. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient’s conditions. However, tissue-engineered blood vessels are promising alternatives as mode of treatment for blood vessel defects. The purpose of this paper is to show the importance of the advancement on biofabrication technology for treatment of soft tissue defects particularly for vascular tissues. This will also provide an overview and update on the current status of tissue reconstruction especially from autologous stem cells, scaffolds, and scaffold-free cellular transplantable constructs. The discussion of this paper will be focused on the historical view of cardiovascular tissue engineering and stem cell biology. The representative studies featured in this paper are limited within the last decade in order to trace the trend and evolution of techniques for blood vessel tissue engineering.

  7. Imaging challenges in biomaterials and tissue engineering.

    Science.gov (United States)

    Appel, Alyssa A; Anastasio, Mark A; Larson, Jeffery C; Brey, Eric M

    2013-09-01

    Biomaterials are employed in the fields of tissue engineering and regenerative medicine (TERM) in order to enhance the regeneration or replacement of tissue function and/or structure. The unique environments resulting from the presence of biomaterials, cells, and tissues result in distinct challenges in regards to monitoring and assessing the results of these interventions. Imaging technologies for three-dimensional (3D) analysis have been identified as a strategic priority in TERM research. Traditionally, histological and immunohistochemical techniques have been used to evaluate engineered tissues. However, these methods do not allow for an accurate volume assessment, are invasive, and do not provide information on functional status. Imaging techniques are needed that enable non-destructive, longitudinal, quantitative, and three-dimensional analysis of TERM strategies. This review focuses on evaluating the application of available imaging modalities for assessment of biomaterials and tissue in TERM applications. Included is a discussion of limitations of these techniques and identification of areas for further development.

  8. [Scaffold-based Bone Tissue Engineering].

    Science.gov (United States)

    Holzapfel, B M; Rudert, M; Hutmacher, D W

    2017-08-01

    Tissue engineering provides the possibility of regenerating damaged or lost osseous structures without the need for permanent implants. Within this context, biodegradable and bioresorbable scaffolds can provide structural and biomechanical stability until the body's own tissue can take over their function. Additive biomanufacturing makes it possible to design the scaffold's architectural characteristics to specifically guide tissue formation and regeneration. Its nano-, micro-, and macro-architectural properties can be tailored to ensure vascularization, oxygenation, nutrient supply, waste exchange, and eventually ossification not only in its periphery but also in its center, which is not in direct contact with osteogenic elements of the surrounding healthy tissue. In this article we provide an overview about our conceptual design and process of the clinical translation of scaffold-based bone tissue engineering applications.

  9. Informing tendon tissue engineering with embryonic development

    Science.gov (United States)

    Glass, Zachary A.; Schiele, Nathan R.; Kuo, Catherine K.

    2014-01-01

    Tendon is a strong connective tissue that transduces muscle-generated forces into skeletal motion. In fulfilling this role, tendons are subjected to repeated mechanical loading and high stress, which may result in injury. Tissue engineering with stem cells offers the potential to replace injured/damaged tissue with healthy, new living tissue. Critical to tendon tissue engineering is the induction and guidance of stem cells towards the tendon phenotype. Typical strategies have relied on adult tissue homeostatic and healing factors to influence stem cell differentiation, but have yet to achieve tissue regeneration. A novel paradigm is to use embryonic developmental factors as cues to promote tendon regeneration. Embryonic tendon progenitor cell differentiation in vivo is regulated by a combination of mechanical and chemical factors. We propose that these cues will guide stem cells to recapitulate critical aspects of tenogenesis and effectively direct the cells to differentiate and regenerate new tendon. Here, we review recent efforts to identify mechanical and chemical factors of embryonic tendon development to guide stem/progenitor cell differentiation toward new tendon formation, and discuss the role this work may have in the future of tendon tissue engineering. PMID:24484642

  10. Informing tendon tissue engineering with embryonic development.

    Science.gov (United States)

    Glass, Zachary A; Schiele, Nathan R; Kuo, Catherine K

    2014-06-27

    Tendon is a strong connective tissue that transduces muscle-generated forces into skeletal motion. In fulfilling this role, tendons are subjected to repeated mechanical loading and high stress, which may result in injury. Tissue engineering with stem cells offers the potential to replace injured/damaged tissue with healthy, new living tissue. Critical to tendon tissue engineering is the induction and guidance of stem cells towards the tendon phenotype. Typical strategies have relied on adult tissue homeostatic and healing factors to influence stem cell differentiation, but have yet to achieve tissue regeneration. A novel paradigm is to use embryonic developmental factors as cues to promote tendon regeneration. Embryonic tendon progenitor cell differentiation in vivo is regulated by a combination of mechanical and chemical factors. We propose that these cues will guide stem cells to recapitulate critical aspects of tenogenesis and effectively direct the cells to differentiate and regenerate new tendon. Here, we review recent efforts to identify mechanical and chemical factors of embryonic tendon development to guide stem/progenitor cell differentiation toward new tendon formation, and discuss the role this work may have in the future of tendon tissue engineering.

  11. Engineering Complex Orthopaedic Tissues via Strategic Biomimicry

    Science.gov (United States)

    Qu, Dovina; Mosher, Christopher Z.; Boushell, Margaret K.; Lu, Helen H.

    2014-01-01

    The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, whereby overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g. bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g. bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g. bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

  12. Engineering complex orthopaedic tissues via strategic biomimicry.

    Science.gov (United States)

    Qu, Dovina; Mosher, Christopher Z; Boushell, Margaret K; Lu, Helen H

    2015-03-01

    The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

  13. The materials used in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Tereshchenko, V. P., E-mail: tervp@ngs.ru; Kirilova, I. A.; Sadovoy, M. A.; Larionov, P. M. [Novosibirsk Research Institute of Traumatology and Orthopedics n.a. Ya.L. Tsivyan, Novosibirsk (Russian Federation)

    2015-11-17

    Bone tissue engineering looking for an alternative solution to the problem of skeletal injuries. The method is based on the creation of tissue engineered bone tissue equivalent with stem cells, osteogenic factors, and scaffolds - the carriers of these cells. For production of tissue engineered bone equivalent is advisable to create scaffolds similar in composition to natural extracellular matrix of the bone. This will provide optimal conditions for the cells, and produce favorable physico-mechanical properties of the final construction. This review article gives an analysis of the most promising materials for the manufacture of cell scaffolds. Biodegradable synthetic polymers are the basis for the scaffold, but it alone cannot provide adequate physical and mechanical properties of the construction, and favorable conditions for the cells. Addition of natural polymers improves the strength characteristics and bioactivity of constructions. Of the inorganic compounds, to create cell scaffolds the most widely used calcium phosphates, which give the structure adequate stiffness and significantly increase its osteoinductive capacity. Signaling molecules do not affect the physico-mechanical properties of the scaffold, but beneficial effect is on the processes of adhesion, proliferation and differentiation of cells. Biodegradation of the materials will help to fulfill the main task of bone tissue engineering - the ability to replace synthetic construct by natural tissues that will restore the original anatomical integrity of the bone.

  14. Nanomaterials for Tissue Engineering In Dentistry

    Science.gov (United States)

    Chieruzzi, Manila; Pagano, Stefano; Moretti, Silvia; Pinna, Roberto; Milia, Egle; Torre, Luigi; Eramo, Stefano

    2016-01-01

    The tissue engineering (TE) of dental oral tissue is facing significant changes in clinical treatments in dentistry. TE is based on a stem cell, signaling molecule, and scaffold triad that must be known and calibrated with attention to specific sectors in dentistry. This review article shows a summary of micro- and nanomorphological characteristics of dental tissues, of stem cells available in the oral region, of signaling molecules usable in TE, and of scaffolds available to guide partial or total reconstruction of hard, soft, periodontal, and bone tissues. Some scaffoldless techniques used in TE are also presented. Then actual and future roles of nanotechnologies about TE in dentistry are presented.

  15. Airway tissue engineering for congenital laryngotracheal disease.

    Science.gov (United States)

    Maughan, Elizabeth; Lesage, Flore; Butler, Colin R; Hynds, Robert E; Hewitt, Richard; Janes, Sam M; Deprest, Jan A; Coppi, Paolo De

    2016-06-01

    Regenerative medicine offers hope of a sustainable solution for severe airway disease by the creation of functional, immunocompatible organ replacements. When considering fetuses and newborns, there is a specific spectrum of airway pathologies that could benefit from cell therapy and tissue engineering applications. While hypoplastic lungs associated with congenital diaphragmatic hernia (CDH) could benefit from cellular based treatments aimed at ameliorating lung function, patients with upper airway obstruction could take advantage from a de novo tissue engineering approach. Moreover, the international acceptance of the EXIT procedure as a means of securing the precarious neonatal airway, together with the advent of fetal surgery as a method of heading off postnatal co-morbidities, offers the revolutionary possibility of extending the clinical indication for tissue-engineered airway transplantation to infants affected by diverse severe congenital laryngotracheal malformations. This article outlines the necessary basic components for regenerative medicine solutions in this potential clinical niche. Copyright © 2016. Published by Elsevier Inc.

  16. Nanostructured scaffolds for bone tissue engineering.

    Science.gov (United States)

    Li, Xiaoming; Wang, Lu; Fan, Yubo; Feng, Qingling; Cui, Fu-Zhai; Watari, Fumio

    2013-08-01

    It has been demonstrated that nanostructured materials, compared with conventional materials, may promote greater amounts of specific protein interactions, thereby more efficiently stimulating new bone formation. It has also been indicated that, when features or ingredients of scaffolds are nanoscaled, a variety of interactions can be stimulated at the cellular level. Some of those interactions induce favorable cellular functions while others may leads to toxicity. This review presents the mechanism of interactions between nanoscaled materials and cells and focuses on the current research status of nanostructured scaffolds for bone tissue engineering. Firstly, the main requirements for bone tissue engineering scaffolds were discussed. Then, the mechanism by which nanoscaled materials promote new bone formation was explained, following which the current research status of main types of nanostructured scaffolds for bone tissue engineering was reviewed and discussed. Copyright © 2013 Wiley Periodicals, Inc.

  17. Composite Scaffolds for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Min Wang

    2006-01-01

    Full Text Available Biomaterial and scaffold development underpins the advancement of tissue engineering. Traditional scaffolds based on biodegradable polymers such as poly(lactic acid and poly(lactic acid-co-glycolic acid are weak and non-osteoconductive. For bone tissue engineering, polymer-based composite scaffolds containing bioceramics such as hydroxyapatite can be produced and used. The bioceramics can be either incorporated in the scaffolds as a dispersed secondary phase or form a thin coating on the pore surface of polymer scaffolds. This bioceramic phase renders the scaffolds bioactive and also strengthens the scaffolds. There are a number of methods that can be used to produce bioceramic-polymer composite scaffolds. This paper gives an overview of our efforts in developing composite scaffolds for bone tissue engineering.

  18. Developing 3D microstructures for tissue engineering

    DEFF Research Database (Denmark)

    Mohanty, Soumyaranjan

    casting process to generate various large scale tissue engineering constructs with single pore geometry with the desired mechanical stiffness and porosity. In addition, a new technique was developed to fa bricate dual-pore scaffolds for various tissue-engineering applications where 3D printing...... materials have been developed and tested for enhancing the differentiation of hiPSC-derived hepatocytes and fabricating biodegradable scaffolds for in-vivo tissue engineering applications. Along with various scaffolds fabrication methods we finally presented an optimized study of hepatic differentiation...... doxycycline was loaded into the hydrogel of the IPN materials, and the biological activity of released doxycycline was tested using a doxycycline regulated green fluorescent reporter gene expression assay in HeLa cells. Additionally, decellularized liver extracellular matrix (ECM) and natural silk protein...

  19. Bone tissue engineering using 3D printing

    Directory of Open Access Journals (Sweden)

    Susmita Bose

    2013-12-01

    Full Text Available With the advent of additive manufacturing technologies in the mid 1980s, many applications benefited from the faster processing of products without the need for specific tooling or dies. However, the application of such techniques in the area of biomedical devices has been slow due to the stringent performance criteria and concerns related to reproducibility and part quality, when new technologies are in their infancy. However, the use of additive manufacturing technologies in bone tissue engineering has been growing in recent years. Among the different technology options, three dimensional printing (3DP is becoming popular due to the ability to directly print porous scaffolds with designed shape, controlled chemistry and interconnected porosity. Some of these inorganic scaffolds are biodegradable and have proven ideal for bone tissue engineering, sometimes even with site specific growth factor/drug delivery abilities. This review article focuses on recent advances in 3D printed bone tissue engineering scaffolds along with current challenges and future directions.

  20. Stem Cell-Based Dental Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Petar Zivkovic

    2010-01-01

    Full Text Available The development of biological and biomaterial sciences profiled tissue engineering as a new and powerful tool for biological replacement of organs. The combination of stem cells and suitable scaffolds is widely used in experiments today, in order to achieve partial or whole organ regeneration. This review focuses on the use of tissue engineering strategies in tooth regeneration, using stem cells and stem cells/scaffold constructs. Although whole tooth regeneration is still not possible, there are promising results. However, to achieve this goal, it is important to understand and further explore the mechanisms underlying tooth development. Only then will we be able to mimic the natural processes with the use of stem cells and tissue engineering techniques.

  1. Advances in Skin Regeneration Using Tissue Engineering

    Science.gov (United States)

    Vig, Komal; Chaudhari, Atul; Tripathi, Shweta; Dixit, Saurabh; Sahu, Rajnish; Pillai, Shreekumar; Dennis, Vida A.; Singh, Shree R.

    2017-01-01

    Tissue engineered skin substitutes for wound healing have evolved tremendously over the last couple of years. New advances have been made toward developing skin substitutes made up of artificial and natural materials. Engineered skin substitutes are developed from acellular materials or can be synthesized from autologous, allograft, xenogenic, or synthetic sources. Each of these engineered skin substitutes has their advantages and disadvantages. However, to this date, a complete functional skin substitute is not available, and research is continuing to develop a competent full thickness skin substitute product that can vascularize rapidly. There is also a need to redesign the currently available substitutes to make them user friendly, commercially affordable, and viable with longer shelf life. The present review focuses on providing an overview of advances in the field of tissue engineered skin substitute development, the availability of various types, and their application. PMID:28387714

  2. Strategies for cell engineering in tissue repair.

    Science.gov (United States)

    Brown, R A; Smith, K D; Angus McGrouther, D

    1997-01-01

    Cellular and tissue engineering are new areas of research, currently attracting considerable interest because of the remarkable potential they have for clinical application. Some claims have indeed been dramatic, including the possibility of growing complete, artificial organs, such as the liver. However, amid such long-term aspirations there is the very real possibility that small tissues (artificial grafts) may be fabricated in the near future for use in reconstructive surgery. Logically, we should focus on how it is possible to produce modest, engineered tissues for tissue repair. It is evident that strategies to date either depend on innate information within implanted cells, to reform the target tissue or aim to provide appropriate environmental cues or guidance to direct cell behavior. It is argued here that present knowledge of tissue repair biology points us toward the latter approach, providing external cues which will direct how cells should organize the new tissue. This will be particularly true where we need to reproduce microscopic and ultrastructural features of the original tissue architecture. A number of such cues have been identified, and methods are already available, including substrate chemistry, substrate contact guidance, mechanical loading, and biochemical mediators to provide these cues. Examples of these are already being used with some success to control the formation of tissue structures.

  3. Tissue engineering of ligaments for reconstructive surgery.

    Science.gov (United States)

    Hogan, MaCalus V; Kawakami, Yohei; Murawski, Christopher D; Fu, Freddie H

    2015-05-01

    The use of musculoskeletal bioengineering and regenerative medicine applications in orthopaedic surgery has continued to evolve. The aim of this systematic review was to address tissue-engineering strategies for knee ligament reconstruction. A systematic review of PubMed/Medline using the terms "knee AND ligament" AND "tissue engineering" OR "regenerative medicine" was performed. Two authors performed the search, independently assessed the studies for inclusion, and extracted the data for inclusion in the review. Both preclinical and clinical studies were reviewed, and the articles deemed most relevant were included in this article to provide relevant basic science and recent clinical translational knowledge concerning "tissue-engineering" strategies currently used in knee ligament reconstruction. A total of 224 articles were reviewed in our initial PubMed search. Non-English-language studies were excluded. Clinical and preclinical studies were identified, and those with a focus on knee ligament tissue-engineering strategies including stem cell-based therapies, growth factor administration, hybrid biomaterial, and scaffold development, as well as mechanical stimulation modalities, were reviewed. The body of knowledge surrounding tissue-engineering strategies for ligament reconstruction continues to expand. Presently, various tissue-engineering techniques have some potential advantages, including faster recovery, better ligamentization, and possibly, a reduction of recurrence. Preclinical research of these novel therapies continues to provide promising results. There remains a need for well-designed, high-powered comparative clinical studies to serve as a foundation for successful translation into the clinical setting going forward. Level IV, systematic review of Level IV studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  4. Stem Cells and Tissue Engineering

    CERN Document Server

    Pavlovic, Mirjana

    2013-01-01

    Stem cells are the building blocks for all other cells in an organism. The human body has about 200 different types of cells and any of those cells can be produced by a stem cell. This fact emphasizes the significance of stem cells in transplantational medicine, regenerative therapy and bioengineering. Whether embryonic or adult, these cells can be used for the successful treatment of a wide range of diseases that were not treatable before, such as osteogenesis imperfecta in children, different forms of leukemias, acute myocardial infarction, some neural damages and diseases, etc. Bioengineering, e.g. successful manipulation of these cells with multipotential capacity of differentiation toward appropriate patterns and precise quantity, are the prerequisites for successful outcome and treatment. By combining in vivo and in vitro techniques, it is now possible to manage the wide spectrum of tissue damages and organ diseases. Although the stem-cell therapy is not a response to all the questions, it provides more...

  5. Oriented Collagen Scaffolds for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Shohta Kodama

    2012-03-01

    Full Text Available Oriented collagen scaffolds were developed in the form of sheet, mesh and tube by arraying flow-oriented collagen string gels and dehydrating the arrayed gels. The developed collagen scaffolds can be any practical size with any direction of orientation for tissue engineering applications. The birefringence of the collagen scaffolds was quantitatively analyzed by parallel Nicols method. Since native collagen in the human body has orientations such as bone, cartilage, tendon and cornea, and the orientation has a special role for the function of human organs, the developed various types of three-dimensional oriented collagen scaffolds are expected to be useful biomaterials for tissue engineering and regenerative medicines.

  6. Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction

    Directory of Open Access Journals (Sweden)

    Bressan Eriberto

    2012-01-01

    Full Text Available Bone tissue engineering strategies are emerging as attractive alternatives to autografts and allografts in bone tissue reconstruction, in particular thanks to their association with nanotechnologies. Nanostructured biomaterials, indeed, mimic the extracellular matrix (ECM of the natural bone, creating an artificial microenvironment that promotes cell adhesion, proliferation and differentiation. At the same time, the possibility to easily isolate mesenchymal stem cells (MSCs from different adult tissues together with their multi-lineage differentiation potential makes them an interesting tool in the field of bone tissue engineering. This review gives an overview of the most promising nanostructured biomaterials, used alone or in combination with MSCs, which could in future be employed as bone substitutes. Recent works indicate that composite scaffolds made of ceramics/metals or ceramics/polymers are undoubtedly more effective than the single counterparts in terms of osteoconductivity, osteogenicity and osteoinductivity. A better understanding of the interactions between MSCs and nanostructured biomaterials will surely contribute to the progress of bone tissue engineering.

  7. Current Status of Tissue Engineering Heart Valve.

    Science.gov (United States)

    Shinoka, Toshiharu; Miyachi, Hideki

    2016-11-01

    The development of surgically implantable heart valve prostheses has contributed to improved outcomes in patients with cardiovascular disease. However, there are drawbacks, such as risk of infection and lack of growth potential. Tissue-engineered heart valve (TEHV) holds great promise to address these drawbacks as the ideal TEHV is easily implanted, biocompatible, non-thrombogenic, durable, degradable, and ultimately remodels into native-like tissue. In general, three main components used in creating a tissue-engineered construct are (1) a scaffold material, (2) a cell type for seeding the scaffold, and (3) a subsequent remodeling process driven by cell accumulation and proliferation, and/or biochemical and mechanical signaling. Despite rapid progress in the field over the past decade, TEHVs have not been translated into clinical applications successfully. To successfully utilize TEHVs clinically, further elucidation of the mechanisms for TEHV remodeling and further translational research outcome evaluations will be required. Tissue engineering is a major breakthrough in cardiovascular medicine that holds amazing promise for the future of reconstructive surgical procedures. In this article, we review the history of regenerative medicine, advances in the field, and state-of-the-art in valvular tissue engineering. © The Author(s) 2016.

  8. Electrical stimulation systems for cardiac tissue engineering.

    Science.gov (United States)

    Tandon, Nina; Cannizzaro, Christopher; Chao, Pen-Hsiu Grace; Maidhof, Robert; Marsano, Anna; Au, Hoi Ting Heidi; Radisic, Milica; Vunjak-Novakovic, Gordana

    2009-01-01

    We describe a protocol for tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cells with the application of pulsatile electrical fields designed to mimic those present in the native heart. Tissue culture is conducted in a customized chamber built to allow for cultivation of (i) engineered three-dimensional (3D) cardiac tissue constructs, (ii) cell monolayers on flat substrates or (iii) cells on patterned substrates. This also allows for analysis of the individual and interactive effects of pulsatile electrical field stimulation and substrate topography on cell differentiation and assembly. The protocol is designed to allow for delivery of predictable electrical field stimuli to cells, monitoring environmental parameters, and assessment of cell and tissue responses. The duration of the protocol is 5 d for two-dimensional cultures and 10 d for 3D cultures.

  9. Bioactive polymeric scaffolds for tissue engineering

    Directory of Open Access Journals (Sweden)

    Scott Stratton

    2016-12-01

    Full Text Available A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

  10. Peptide Amphiphiles in Corneal Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Martina Miotto

    2015-08-01

    Full Text Available The increasing interest in effort towards creating alternative therapies have led to exciting breakthroughs in the attempt to bio-fabricate and engineer live tissues. This has been particularly evident in the development of new approaches applied to reconstruct corneal tissue. The need for tissue-engineered corneas is largely a response to the shortage of donor tissue and the lack of suitable alternative biological scaffolds preventing the treatment of millions of blind people worldwide. This review is focused on recent developments in corneal tissue engineering, specifically on the use of self-assembling peptide amphiphiles for this purpose. Recently, peptide amphiphiles have generated great interest as therapeutic molecules, both in vitro and in vivo. Here we introduce this rapidly developing field, and examine innovative applications of peptide amphiphiles to create natural bio-prosthetic corneal tissue in vitro. The advantages of peptide amphiphiles over other biomaterials, namely their wide range of functions and applications, versatility, and transferability are also discussed to better understand how these fascinating molecules can help solve current challenges in corneal regeneration.

  11. Bioreactor Technology in Cardiovascular Tissue Engineering

    Science.gov (United States)

    Mertsching, H.; Hansmann, J.

    Cardiovascular tissue engineering is a fast evolving field of biomedical science and technology to manufacture viable blood vessels, heart valves, myocar-dial substitutes and vascularised complex tissues. In consideration of the specific role of the haemodynamics of human circulation, bioreactors are a fundamental of this field. The development of perfusion bioreactor technology is a consequence of successes in extracorporeal circulation techniques, to provide an in vitro environment mimicking in vivo conditions. The bioreactor system should enable an automatic hydrodynamic regime control. Furthermore, the systematic studies regarding the cellular responses to various mechanical and biochemical cues guarantee the viability, bio-monitoring, testing, storage and transportation of the growing tissue.

  12. Skeletal tissue engineering: opportunities and challenges.

    Science.gov (United States)

    Luyten, F P; Dell'Accio, F; De Bari, C

    2001-12-01

    Tissue engineering is a field of biomedicine that is growing rapidly and is critically driven by scientific advances in the areas of developmental and cell biology and biomaterial sciences. Regeneration of skeletal tissues is among the most promising areas of biological tissue repair and is providing a broad spectrum of potential clinical applications, including joint resurfacing. The availability of novel tools such as pluripotent stem cells, morphogens, smart biomaterials and gene transfer technologies, makes us dream of many exciting novel therapeutic approaches. Despite these opportunities in regenerative medicine, good clinical practice requires the clinician to question the consistency, reproducibility, validation and appropriate regulation of these new biological treatments.

  13. Tissue Engineering for Vertical Ridge Reconstruction.

    Science.gov (United States)

    Patel, Neel; Kim, Beomjune; Zaid, Waleed; Spagnoli, Daniel

    2017-02-01

    This article provides an overview of basic tissue engineering principles as they are applied to vertical ridge defects and reconstructive techniques for these types of deficiencies. Presented are multiple clinical cases ranging from office-based dentoalveolar procedures to the more complex reconstruction of postresection mandibular defects. Several different types of regenerative tissue constructs are presented; either used alone or in combination with traditional reconstructive techniques and procedures, such as maxillary sinus augmentation, Le Fort I osteotomy, and microvascular free tissue transfer. The goal is to also familiarize the reconstructive surgeon to potential future strategies in vertical alveolar ridge augmentation. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Cell–scaffold interaction within engineered tissue

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Haiping; Liu, Yuanyuan, E-mail: Yuanyuan_liu@shu.edu.cn; Jiang, Zhenglong; Chen, Weihua; Yu, Yongzhe; Hu, Qingxi

    2014-05-01

    The structure of a tissue engineering scaffold plays an important role in modulating tissue growth. A novel gelatin–chitosan (Gel–Cs) scaffold with a unique structure produced by three-dimensional printing (3DP) technology combining with vacuum freeze-drying has been developed for tissue-engineering applications. The scaffold composed of overall construction, micro-pore, surface morphology, and effective mechanical property. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell–matrix interaction supports the active biocompatibility of the structure. The structure is capable of supporting cell attachment and proliferation. Cells seeded into this structure tend to maintain phenotypic shape and secreted large amounts of extracellular matrix (ECM) and the cell growth decreased the mechanical properties of scaffold. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique structure, which acts to support cell growth. - Highlights: • The scaffold is not only for providing a surface for cell residence but also for determining cell phenotype and retaining structural integrity. • The mechanical property of scaffold can be affected by activities of cell. • The scaffold provides a microenvironment for cell attachment, growth, and migration.

  15. Biodegradable synthetic polymers for tissue engineering

    Directory of Open Access Journals (Sweden)

    Gunatillake P. A.

    2003-05-01

    Full Text Available This paper reviews biodegradable synthetic polymers focusing on their potential in tissue engineering applications. The major classes of polymers are briefly discussed with regard to synthesis, properties and biodegradability, and known degradation modes and products are indicated based on studies reported in the literature. A vast majority of biodegradable polymers studied belongs to the polyester family, which includes polyglycolides and polylactides. Some disadvantages of these polymers in tissue engineering applications are their poor biocompatibility, release of acidic degradation products, poor processability and loss of mechanical properties very early during degradation. Other degradable polymers such as polyorthoesters, polyanhydrides, polyphosphazenes, and polyurethanes are also discussed and their advantages and disadvantages summarised. With advancements in tissue engineering it has become necessary to develop polymers that meet more demanding requirements. Recent work has focused on developing injectable polymer compositions based on poly (propylene fumarate and poly (anhydrides to meet these requirements in orthopaedic tissue engineering. Polyurethanes have received recent attention for development of degradable polymers because of their great potential in tailoring polymer structure to achieve mechanical properties and biodegradability to suit a variety of applications.

  16. Co-culture in cartilage tissue engineering

    NARCIS (Netherlands)

    Hendriks, Jeanine; Riesle, Jens; Blitterswijk, van Clemens A.

    2007-01-01

    For biotechnological research in vitro in general and tissue engineering specifically, it is essential to mimic the natural conditions of the cellular environment as much as possible. In choosing a model system for in vitro experiments, the investigator always has to balance between being able to ob

  17. A decade of progress in tissue engineering.

    Science.gov (United States)

    Khademhosseini, Ali; Langer, Robert

    2016-10-01

    Tremendous progress has been achieved in the field of tissue engineering in the past decade. Several major challenges laid down 10 years ago, have been studied, including renewable cell sources, biomaterials with tunable properties, mitigation of host responses, and vascularization. Here we review advancements in these areas and envision directions of further development.

  18. Biodegradable elastomeric scaffolds for soft tissue engineering

    NARCIS (Netherlands)

    Pêgo, A.P.; Poot, Andreas A.; Grijpma, Dirk W.; Feijen, Jan

    2003-01-01

    Elastomeric copolymers of 1,3-trimethylene carbonate (TMC) and ε-caprolactone (CL) and copolymers of TMC and D,L-lactide (DLLA) have been evaluated as candidate materials for the preparation of biodegradable scaffolds for soft tissue engineering. TMC-DLLA copolymers are amorphous and degrade more

  19. Confocal Raman Microscopy; applications in tissue engineering

    NARCIS (Netherlands)

    van Apeldoorn, Aart A.

    2005-01-01

    This dissertation describes the use of confocal Raman microscopy and spectroscopy in the field of tissue engineering. Moreover, it describes the combination of two already existing technologies, namely scanning electron microscopy and confocal Raman spectroscopy in one apparatus for the enhancement

  20. Biodegradable elastomeric scaffolds for soft tissue engineering

    NARCIS (Netherlands)

    Pego, Ana Paula; Poot, André A.; Grijpma, Dirk W.; Feijen, Jan

    2003-01-01

    Elastomeric copolymers of 1,3-trimethylene carbonate (TMC) and ε-caprolactone (CL) and copolymers of TMC and D,L-lactide (DLLA) have been evaluated as candidate materials for the preparation of biodegradable scaffolds for soft tissue engineering. TMC-DLLA copolymers are amorphous and degrade more r

  1. [Stem cells and tissue engineering techniques].

    Science.gov (United States)

    Sica, Gigliola

    2013-01-01

    The therapeutic use of stem cells and tissue engineering techniques are emerging in urology. Here, stem cell types, their differentiating potential and fundamental characteristics are illustrated. The cancer stem cell hypothesis is reported with reference to the role played by stem cells in the origin, development and progression of neoplastic lesions. In addition, recent reports of results obtained with stem cells alone or seeded in scaffolds to overcome problems of damaged urinary tract tissue are summarized. Among others, the application of these biotechnologies in urinary bladder, and urethra are delineated. Nevertheless, apart from the ethical concerns raised from the use of embryonic stem cells, a lot of questions need to be solved concerning the biology of stem cells before their widespread use in clinical trials. Further investigation is also required in tissue engineering utilizing animal models.

  2. Angiogenesis in tissue-engineered small intestine.

    Science.gov (United States)

    Gardner-Thorpe, James; Grikscheit, Tracy C; Ito, Hiromichi; Perez, Alexander; Ashley, Stanley W; Vacanti, Joseph P; Whang, Edward E

    2003-12-01

    Tissue-engineered intestine offers promise as a potential novel therapy for short bowel syndrome. In this study we characterized the microvasculature and angiogenic growth factor profile of the engineered intestine. Twenty-three tissue-engineered small intestinal grafts were harvested from Lewis rat recipients 1 to 8 weeks after implantation. Architectural similarity to native bowel obtained from juvenile rats was assessed with hematoxylin and eosin-stained sections. Capillary density, measured after immunohistochemical staining for CD34, was expressed as number of capillaries per 1000 nuclei. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) tissue levels were measured by ELISA and normalized to total protein. Over the 8-week period cysts increased in volume (0.5 cm(3) at week 1 versus 12.6 cm(3) at week 8) and mass (1.30 +/- 0.29 versus 9.74 +/- 0.3 g; mean +/- SEM). Muscular and mucosal layers increased in thickness, but capillary density remained constant (82.95 +/- 4.81 capillaries per 1000 nuclei). The VEGF level was significantly higher in juvenile rat bowel than in engineered cyst (147.6 +/- 23.9 versus 42.3 +/- 3.4 pg/mg; p < 0.001). Tissue bFGF levels were also higher (315 +/- 65.48 versus 162.3 +/- 15.09 pg/mg; p < 0.05). The mechanism driving angiogenesis differs in engineered intestine and in normal bowel. VEGF and bFGF delivery may prove useful for bioengineering of intestine.

  3. Tumor Engineering: The Other Face of Tissue Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Ghajar, Cyrus M; Bissell, Mina J

    2010-03-09

    Advances in tissue engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function for a given tissue.We believe that the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of 'tumor engineering', that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physical scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment. In 1993, Vacanti and Langer cast a spotlight on the growing gap between patients in need of organ transplants and the amount of available donor organs; they reaffirmed that tissue engineering could eventually address this problem by 'applying principles of engineering and the life sciences toward the development of biological substitutes. Mortality figures and direct health care costs for cancer patients rival those of patients who experience organ failure. Cancer is the second leading cause of death in the United States (Source: American Cancer Society) and it is estimated that direct medical costs for cancer patients approach $100B yearly in the United States alone (Source: National Cancer Institute). In addition, any promising therapy that emerges from the laboratory costs roughly $1.7B to take from bench to bedside. Whereas we have indeed waged war on

  4. Electrospun polyurethane membranes for Tissue Engineering applications.

    Science.gov (United States)

    Gabriel, Laís P; Rodrigues, Ana Amélia; Macedo, Milton; Jardini, André L; Maciel Filho, Rubens

    2017-03-01

    Tissue Engineering proposes, among other things, tissue regeneration using scaffolds integrated with biological molecules, growth factors or cells for such regeneration. In this research, polyurethane membranes were prepared using the electrospinning technique in order to obtain membranes to be applied in Tissue Engineering, such as epithelial, drug delivery or cardiac applications. The influence of fibers on the structure and morphology of the membranes was studied using scanning electron microscopy (SEM), the structure was evaluated by Fourier transform infrared spectroscopy (FT-IR), and the thermal stability was analyzed by thermogravimetry analysis (TGA). In vitro cells attachment and proliferation was investigated by SEM, and in vitro cell viability was studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays and Live/Dead® assays. It was found that the membranes present an homogeneous morphology, high porosity, high surface area/volume ratio, it was also observed a random fiber network. The thermal analysis showed that the membrane degradation started at 254°C. In vitro evaluation of fibroblasts cells showed that fibroblasts spread over the membrane surface after 24, 48 and 72h of culture. This study supports the investigation of electrospun polyurethane membranes as biocompatible scaffolds for Tissue Engineering applications and provides some guidelines for improved biomaterials with desired properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Biomimetic material strategies for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakaran, Molamma P., E-mail: nnimpp@nus.edu.sg [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Venugopal, J. [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Kai, Dan [NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (Singapore); Ramakrishna, Seeram [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore)

    2011-04-08

    Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.

  6. Bone tissue engineering: from bench to bedside

    Directory of Open Access Journals (Sweden)

    Maria A. Woodruff

    2012-10-01

    Full Text Available The drive to develop bone grafts for the filling of major gaps in the skeletal structure has led to a major research thrust towards developing biomaterials for bone engineering. Unfortunately, from a clinical perspective, the promise of bone tissue engineering which was so vibrant a decade ago has so far failed to deliver the anticipated results of becoming a routine therapeutic application in reconstructive surgery. Here we describe our bench to bedside concept, the first clinical results and a detailed analysis of long-term bone regeneration studies in preclinical animal models, exploiting methods of micro- and nano analysis of biodegradable composite scaffolds.

  7. 3D bioprinting for engineering complex tissues.

    Science.gov (United States)

    Mandrycky, Christian; Wang, Zongjie; Kim, Keekyoung; Kim, Deok-Ho

    2016-01-01

    Bioprinting is a 3D fabrication technology used to precisely dispense cell-laden biomaterials for the construction of complex 3D functional living tissues or artificial organs. While still in its early stages, bioprinting strategies have demonstrated their potential use in regenerative medicine to generate a variety of transplantable tissues, including skin, cartilage, and bone. However, current bioprinting approaches still have technical challenges in terms of high-resolution cell deposition, controlled cell distributions, vascularization, and innervation within complex 3D tissues. While no one-size-fits-all approach to bioprinting has emerged, it remains an on-demand, versatile fabrication technique that may address the growing organ shortage as well as provide a high-throughput method for cell patterning at the micrometer scale for broad biomedical engineering applications. In this review, we introduce the basic principles, materials, integration strategies and applications of bioprinting. We also discuss the recent developments, current challenges and future prospects of 3D bioprinting for engineering complex tissues. Combined with recent advances in human pluripotent stem cell technologies, 3D-bioprinted tissue models could serve as an enabling platform for high-throughput predictive drug screening and more effective regenerative therapies.

  8. 3D Printing and Biofabrication for Load Bearing Tissue Engineering.

    Science.gov (United States)

    Jeong, Claire G; Atala, Anthony

    2015-01-01

    Cell-based direct biofabrication and 3D bioprinting is becoming a dominant technological platform and is suggested as a new paradigm for twenty-first century tissue engineering. These techniques may be our next step in surpassing the hurdles and limitations of conventional scaffold-based tissue engineering, and may offer the industrial potential of tissue engineered products especially for load bearing tissues. Here we present a topically focused review regarding the fundamental concepts, state of the art, and perspectives of this new technology and field of biofabrication and 3D bioprinting, specifically focused on tissue engineering of load bearing tissues such as bone, cartilage, osteochondral and dental tissue engineering.

  9. Application of Stem Cells in Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Stem cells have become an important source of seed cells for tissue engineering because they are relatively easy to expand in vitro and can be induced to differentiate into various cell types in vitro or in vivo. In the current stage, most stem cell researches focus on in vitro studies, including in vitro induction and phenotype characterization. Our center has made a great deal of effort in the in vivo study by using stem cells as seed cells for tissue construction. We have used bone marrow stem cells (BMS...

  10. Tubular heart valves from decellularized engineered tissue.

    Science.gov (United States)

    Syedain, Zeeshan H; Meier, Lee A; Reimer, Jay M; Tranquillo, Robert T

    2013-12-01

    A novel tissue-engineered heart valve (TEHV) was fabricated from a decellularized tissue tube mounted on a frame with three struts, which upon back-pressure cause the tube to collapse into three coapting "leaflets." The tissue was completely biological, fabricated from ovine fibroblasts dispersed within a fibrin gel, compacted into a circumferentially aligned tube on a mandrel, and matured using a bioreactor system that applied cyclic distension. Following decellularization, the resulting tissue possessed tensile mechanical properties, mechanical anisotropy, and collagen content that were comparable to native pulmonary valve leaflets. When mounted on a custom frame and tested within a pulse duplicator system, the tubular TEHV displayed excellent function under both aortic and pulmonary conditions, with minimal regurgitant fractions and transvalvular pressure gradients at peak systole, as well as well as effective orifice areas exceeding those of current commercially available valve replacements. Short-term fatigue testing of one million cycles with pulmonary pressure gradients was conducted without significant change in mechanical properties and no observable macroscopic tissue deterioration. This study presents an attractive potential alternative to current tissue valve replacements due to its avoidance of chemical fixation and utilization of a tissue conducive to recellularization by host cell infiltration.

  11. Electrospun Nanofibrous Materials for Neural Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Yee-Shuan Lee

    2011-02-01

    Full Text Available The use of biomaterials processed by the electrospinning technique has gained considerable interest for neural tissue engineering applications. The tissue engineering strategy is to facilitate the regrowth of nerves by combining an appropriate cell type with the electrospun scaffold. Electrospinning can generate fibrous meshes having fiber diameter dimensions at the nanoscale and these fibers can be nonwoven or oriented to facilitate neurite extension via contact guidance. This article reviews studies evaluating the effect of the scaffold’s architectural features such as fiber diameter and orientation on neural cell function and neurite extension. Electrospun meshes made of natural polymers, proteins and compositions having electrical activity in order to enhance neural cell function are also discussed.

  12. Electrospun Nanofibers for Neural and Tissue Engineering

    Science.gov (United States)

    Xia, Younan

    2009-03-01

    Electrospinning has been exploited for almost one century to process polymers and other materials into nanofibers with controllable compositions, diameters, porosities, and porous structures for a variety of applications. Owing to its small size, high porosity, and large surface area, a nonwoven mat of electrospun nanofibers can serve as an ideal scaffold to mimic the extra cellular matrix for cell attachment and nutrient transportation. The nanofiber itself can also be functionalized through encapsulation or attachment of bioactive species such as extracellular matrix proteins, enzymes, and growth factors. In addition, the nanofibers can be further assembled into a variety of arrays or architectures by manipulating their alignment, stacking, or folding. All these attributes make electrospinning a powerful tool for generating nanostructured materials for a range of biomedical applications that include controlled release, drug delivery, and tissue engineering. This talk will focus on the use of electrospun nanofibers as scaffolds for neural and bone tissue engineering.

  13. Distilling complexity to advance cardiac tissue engineering

    OpenAIRE

    Ogle, Brenda M.; Bursac, Nenad; Domian, Ibrahim; Huang, Ngan F.; Menasché, Philippe; Murry, Charles; Pruitt, Beth; Radisic, Milica; Wu, Joseph C; Wu, Sean M.; Zhang, Jianyi; Zimmermann, Wolfram-Hubertus; Vunjak-Novakovic, Gordana

    2016-01-01

    The promise of cardiac tissue engineering is in the ability to recapitulate in vitro the functional aspects of healthy heart and disease pathology as well as to design replacement muscle for clinical therapy. Parts of this promise have been realized; others have not. In a meeting of scientists in this field, five central challenges or “big questions” were articulated that, if addressed, could substantially advance the current state-of-the-art in modeling heart disease and realizing heart repa...

  14. Airway tissue engineering for congenital laryngotracheal disease

    OpenAIRE

    Maughan, E.; Lesage, F; Butler, C. R.; Hynds, R.E. (Robert E.); Hewitt, R; Janes, S. M.; Deprest, J. A.; Coppi, P. D.

    2016-01-01

    Regenerative medicine offers hope of a sustainable solution for severe airway disease by the creation of functional, immunocompatible organ replacements. When considering fetuses and newborns, there is a specific spectrum of airway pathologies that could benefit from cell therapy and tissue engineering applications. While hypoplastic lungs associated with congenital diaphragmatic hernia (CDH) could benefit from cellular based treatments aimed at ameliorating lung function, patients with upper...

  15. Application of microdialysis in tissue engineering monitoring

    Institute of Scientific and Technical Information of China (English)

    Zhaohui Li; Zhanfeng Cui

    2008-01-01

    In this review article,the microdialysis for tissue engineering monitoring is discussed.Among various monitoring techniques,microdialysis is advantageous for its capacity of perfusion on-line,and off-line multiple parameter monitoring.Following a description on the general system and performance,the main challenges to apply this technique for reliable long term monitoring are outlined.Further opportunities are identified.

  16. Research progress in liver tissue engineering.

    Science.gov (United States)

    Zhang, Lei; Guan, Zheng; Ye, Jun-Song; Yin, Yan-Feng; Stoltz, Jean-François; de Isla, Natalia

    2017-01-01

    Liver transplantation is the definitive treatment for patients with end-stage liver diseases (ESLD). However, it is hampered by shortage of liver donor. Liver tissue engineering, aiming at fabricating new livers in vitro, provides a potential resolution for donor shortage. Three elements need to be considered in liver tissue engineering: seeding cell resources, scaffolds and bioreactors. Studies have shown potential cell sources as hepatocytes, hepatic cell line, mesenchymal stem cells and others. They need scaffolds with perfect biocompatiblity, suitable micro-structure and appropriate degradation rate, which are essential charateristics for cell attachment, proliferation and secretion in forming extracellular matrix. The most promising scaffolds in research include decellularized whole liver, collagens and biocompatible plastic. The development and function of cells in scaffold need a microenvironment which can provide them with oxygen, nutrition, growth factors, et al. Bioreactor is expected to fulfill these requirements by mimicking the living condition in vivo. Although there is great progress in these three domains, a large gap stays still between their researches and applications. Herein, we summarized the recent development in these three major fields which are indispensable in liver tissue engineering.

  17. Quantifying the motion of magnetic particles in excised tissue: Effect of particle properties and applied magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    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. Tissue Engineering Strategies in Ligament Regeneration

    Directory of Open Access Journals (Sweden)

    Caglar Yilgor

    2012-01-01

    Full Text Available Ligaments are dense fibrous connective tissues that connect bones to other bones and their injuries are frequently encountered in the clinic. The current clinical approaches in ligament repair and regeneration are limited to autografts, as the gold standard, and allografts. Both of these techniques have their own drawbacks that limit the success in clinical setting; therefore, new strategies are being developed in order to be able to solve the current problems of ligament grafting. Tissue engineering is a novel promising technique that aims to solve these problems, by producing viable artificial ligament substitutes in the laboratory conditions with the potential of transplantation to the patients with a high success rate. Direct cell and/or growth factor injection to the defect site is another current approach aiming to enhance the repair process of the native tissue. This review summarizes the current approaches in ligament tissue engineering strategies including the use of scaffolds, their modification techniques, as well as the use of bioreactors to achieve enhanced regeneration rates, while also discussing the advances in growth factor and cell therapy applications towards obtaining enhanced ligament regeneration.

  19. Engineering thick tissues - the vascularisation problem

    Directory of Open Access Journals (Sweden)

    H C H Ko

    2007-07-01

    Full Text Available The ability to create thick tissues is a major tissue engineering challenge, requiring the development of a suitable vascular supply. Current trends are seeing the utilization of cells seeded into hybrid matrix/scaffold systems to create in vitro vascular analogues. Approaches that aim to create vasculature in vitro include the use of biological extracellular matrices such as collagen hydrogels, porous biodegradable polymeric scaffolds with macro- and micro-lumens and micro-channels, co-culture of cells, incorporation of growth factors, culture in dynamic bioreactor environments, and combinations of these. Of particular interest are those approaches that aim to create bioengineered tissues in vitro that can be readily connected to the host's vasculature following implantation in order to maintain cell viability.

  20. Silk film biomaterials for cornea tissue engineering.

    Science.gov (United States)

    Lawrence, Brian D; Marchant, Jeffrey K; Pindrus, Mariya A; Omenetto, Fiorenzo G; Kaplan, David L

    2009-03-01

    Biomaterials for corneal tissue engineering must demonstrate several critical features for potential utility in vivo, including transparency, mechanical integrity, biocompatibility and slow biodegradation. Silk film biomaterials were designed and characterized to meet these functional requirements. Silk protein films were used in a biomimetic approach to replicate corneal stromal tissue architecture. The films were 2 microm thick to emulate corneal collagen lamellae dimensions, and were surface patterned to guide cell alignment. To enhance trans-lamellar diffusion of nutrients and to promote cell-cell interaction, pores with 0.5-5.0 microm diameters were introduced into the silk films. Human and rabbit corneal fibroblast proliferation, alignment and corneal extracellular matrix expression on these films in both 2D and 3D cultures were demonstrated. The mechanical properties, optical clarity and surface patterned features of these films, combined with their ability to support corneal cell functions suggest that this new biomaterial system offers important potential benefits for corneal tissue regeneration.

  1. Electrospinning of Nanofibers for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Haifeng Liu

    2013-01-01

    Full Text Available Electrospinning is a method in which materials in solution are formed into nano- and micro-sized continuous fibers. Recent interest in this technique stems from both the topical nature of nanoscale material fabrication and the considerable potential for use of these nanoscale fibres in a range of applications including, amongst others, a range of biomedical applications processes such as drug delivery and the use of scaffolds to provide a framework for tissue regeneration in both soft and hard tissue applications systems. The objectives of this review are to describe the theory behind the technique, examine the effect of changing the process parameters on fiber morphology, and discuss the application and impact of electrospinning on the fields of vascular, neural, bone, cartilage, and tendon/ligament tissue engineering.

  2. Construction of Tissue Engineering Artificial Cornea with Skin Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Yuan LIU; Yan JIN

    2005-01-01

    @@ 1 Introduction The clinical need for an alternative to donor corneal tissue has encouraged much interests in recent years. An artificial cornea must fulfill the functions of the cornea it replaces. More recently, the idea of a bio-engineered cornea has risen. Corneal equivalents have been reconstructed by tissue engineering method. Aim of this study is to construct an artificial rabbit cornea by employing tissue engineering method and to determine if skin stem cells have a role in tissue engineered cornea construction.

  3. Synthetic biodegradable functional polymers for tissue engineering: a brief review

    OpenAIRE

    BaoLin, GUO; Ma, Peter X

    2014-01-01

    Scaffolds play a crucial role in tissue engineering. Biodegradable polymers with great processing flexibility are the predominant scaffolding materials. Synthetic biodegradable polymers with well-defined structure and without immunological concerns associated with naturally derived polymers are widely used in tissue engineering. The synthetic biodegradable polymers that are widely used in tissue engineering, including polyesters, polyanhydrides, polyphosphazenes, polyurethane, and poly (glyce...

  4. Orthopaedic tissue engineering and bone regeneration.

    Science.gov (United States)

    Dickson, Glenn; Buchanan, Fraser; Marsh, David; Harkin-Jones, Eileen; Little, Uel; McCaigue, Mervyn

    2007-01-01

    Orthopaedic tissue engineering combines the application of scaffold materials, cells and the release of growth factors. It has been described as the science of persuading the body to reconstitute or repair tissues that have failed to regenerate or heal spontaneously. In the case of bone regeneration 3-D scaffolds are used as a framework to guide tissue regeneration. Mesenchymal cells obtained from the patient via biopsy are grown on biomaterials in vitro and then implanted at a desired site in the patient's body. Medical implants that encourage natural tissue regeneration are generally considered more desirable than metallic implants that may need to be removed by subsequent intervention. Numerous polymeric materials, from natural and artificial sources, are under investigation as substitutes for skeletal elements such as cartilage and bone. For bone regeneration, cells (obtained mainly from bone marrow aspirate or as primary cell outgrowths from bone biopsies) can be combined with biodegradable polymeric materials and/or ceramics and absorbed growth factors so that osteoinduction is facilitated together with osteoconduction; through the creation of bioactive rather than bioinert scaffold constructs. Relatively rapid biodegradation enables advantageous filling with natural tissue while loss of polymer strength before mass is disadvantageous. Innovative solutions are required to address this and other issues such as the biocompatibility of material surfaces and the use of appropriate scaffold topography and porosity to influence bone cell gene expression.

  5. Tumor Engineering: The Other Face of Tissue Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Ghajar, Cyrus M; Bissell, Mina J

    2010-03-09

    Advances in tissue engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function for a given tissue.We believe that the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of 'tumor engineering', that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physical scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment. In 1993, Vacanti and Langer cast a spotlight on the growing gap between patients in need of organ transplants and the amount of available donor organs; they reaffirmed that tissue engineering could eventually address this problem by 'applying principles of engineering and the life sciences toward the development of biological substitutes. Mortality figures and direct health care costs for cancer patients rival those of patients who experience organ failure. Cancer is the second leading cause of death in the United States (Source: American Cancer Society) and it is estimated that direct medical costs for cancer patients approach $100B yearly in the United States alone (Source: National Cancer Institute). In addition, any promising therapy that emerges from the laboratory costs roughly $1.7B to take from bench to bedside. Whereas we have indeed waged war on

  6. Heterogeneity of Scaffold Biomaterials in Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Lauren Edgar

    2016-05-01

    Full Text Available Tissue engineering (TE offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced. Ideally, biomaterials should closely mimic the characteristics of desired organ, their function and their in vivo environments. A review of biomaterials used in TE highlighted natural polymers, synthetic polymers, and decellularized organs as sources of scaffolding. Studies of discarded organs supported that decellularization offers a remedy to reducing waste of donor organs, but does not yet provide an effective solution to organ demand because it has shown varied success in vivo depending on organ complexity and physiological requirements. Review of polymer-based scaffolds revealed that a composite scaffold formed by copolymerization is more effective than single polymer scaffolds because it allows copolymers to offset disadvantages a single polymer may possess. Selection of biomaterials for use in TE is essential for transplant success. There is not, however, a singular biomaterial that is universally optimal.

  7. Shear stress facilitates tissue-engineered odontogenesis.

    Science.gov (United States)

    Honda, M J; Shinohara, Y; Sumita, Y; Tonomura, A; Kagami, H; Ueda, M

    2006-07-01

    Numerous studies have demonstrated the effect of shear stress on osteoblasts, but its effect on odontogenic cells has never been reported. In this study, we focused on the effect of shear stress on facilitating tissue-engineered odontogenesis by dissociated single cells. Cells were harvested from the porcine third molar tooth at the early stage of crown formation, and the isolated heterogeneous cells were seeded on a biodegradable polyglycolic acid fiber mesh. Then, cell-polymer constructs with and without exposure to shear stress were evaluated by in vitro and in vivo studies. In in vitro studies, the expression of both epithelial and mesenchymal odontogenic-related mRNAs was significantly enhanced by shear stress for 2 h. At 12 h after exposure to shear stress, the expression of amelogenin, bone sialoprotein and vimentin protein was significantly enhanced compared with that of control. Moreover, after 7 days, alkaline phosphatase activity exhibited a significant increase without any significant effect on cell proliferation in vitro. In vivo, enamel and dentin tissues formed after 15 weeks of in vivo implantation in constructs exposure to in vitro shear stress for 12 h. Such was not the case in controls. We concluded that shear stress facilitates odontogenic cell differentiation in vitro as well as the process of tooth tissue engineering in vivo.

  8. Design, fabrication and application of tissue engineering used cells scaffold

    Institute of Scientific and Technical Information of China (English)

    WANG Shenguo; BEI Jianzhong

    2001-01-01

    @@ FUNCTIONS OF CELLS SCAFFOLD IN THE TISSUE ENGINEERINGCell, cells scaffold and the construction of tissue and organ are three main factors for the Tissue Engineering. A main function of cells scaffold in tissue engineering is to provide an environment for cells propagation.

  9. Gene therapy for cartilage and bone tissue engineering

    CERN Document Server

    Hu, Yu-Chen

    2014-01-01

    "Gene Therapy for Cartilage and Bone Tissue Engineering" outlines the tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery, specifically for cartilage and bone engineering. It is intended for tissue engineers, cell therapists, regenerative medicine scientists and engineers, gene therapist and virologists. Dr. Yu-Chen Hu is a Distinguished Professor at the Department of Chemical Engineering, National Tsing Hua University and has received the Outstanding Research Award (National Science Council), Asia Research Award (Society of Chemical Engineers, Japan) and Professor Tsai-Teh Lai Award (Taiwan Institute of Chemical Engineers). He is also a fellow of the American Institute for Medical and Biological Engineering (AIMBE) and a member of the Tissue Engineering International & Regenerative Medicine Society (TERMIS)-Asia Pacific Council.

  10. Adipose tissue extract promotes adipose tissue regeneration in an adipose tissue engineering chamber model.

    Science.gov (United States)

    Lu, Zijing; Yuan, Yi; Gao, Jianhua; Lu, Feng

    2016-05-01

    An adipose tissue engineering chamber model of spontaneous adipose tissue generation from an existing fat flap has been described. However, the chamber does not completely fill with adipose tissue in this model. Here, the effect of adipose tissue extract (ATE) on adipose tissue regeneration was investigated. In vitro, the adipogenic and angiogenic capacities of ATE were evaluated using Oil Red O and tube formation assays on adipose-derived stem cells (ASCs) and rat aortic endothelial cells (RAECs), respectively. In vivo, saline or ATE was injected into the adipose tissue engineering chamber 1 week after its implantation. At different time points post-injection, the contents were morphometrically, histologically, and immunohistochemically evaluated, and the expression of growth factors and adipogenic genes was analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. With the exception of the baseline control group, in which fat flaps were not inserted into a chamber, the total volume of fat flap tissue increased significantly in all groups, especially in the ATE group. Better morphology and structure, a thinner capsule, and more vessels were observed in the ATE group than in the control group. Expression of angiogenic growth factors and adipogenic markers were significantly higher in the ATE group. ATE therefore significantly promoted adipose tissue regeneration and reduced capsule formation in an adipose tissue engineering chamber model. These data suggest that ATE provides a more angiogenic and adipogenic microenvironment for adipose tissue formation by releasing various cytokines and growth factors that also inhibit capsule formation.

  11. New dimensions in tissue engineering: possible models for human physiology.

    Science.gov (United States)

    Baar, Keith

    2005-11-01

    Tissue engineering is a discipline of great promise. In some areas, such as the cornea, tissues engineered in the laboratory are already in clinical use. In other areas, where the tissue architecture is more complex, there are a number of obstacles to manoeuvre before clinically relevant tissues can be produced. However, even in areas where clinically relevant tissues are decades away, the tissues being produced at the moment provide powerful new models to aid the understanding of complex physiological processes. This article provides a personal view of the role of tissue engineering in advancing our understanding of physiology, with specific attention being paid to musculoskeletal tissues.

  12. Biomaterials and tissue engineering in reconstructive surgery

    Indian Academy of Sciences (India)

    D F Williams

    2003-06-01

    This paper provides an account of the rationale for the development of implantable medical devices over the last half-century and explains the criteria that have controlled the selection of biomaterials for these critical applications. In spite of some good successes and excellent materials, there are still serious limitations to the performance of implants today, and the paper explains these limitations and develops this theme in order to describe the recent innovations in tissue engineering, which involves a different approach to reconstruction of the body.

  13. Tissue engineering of skin for wound coverage.

    Science.gov (United States)

    Biedermann, Thomas; Boettcher-Haberzeth, Sophie; Reichmann, Ernst

    2013-10-01

    Over the past few decades, important milestones have been reached in the field of skin tissue engineering, bringing the ultimate goal of fabricating an autologous dermoepidermal skin substitute with all its cellular components and skin appendages closer to reality. Yet, scientific progress alone is not enough, clinical demands must be addressed and commercial interests need to be fulfilled. This review gives an overview of commercially available skin substitutes for skin replacement therapies and an insight into the recent development of an autologous full-thickness skin substitute that can readily be transplanted in large quantities onto the patient. Georg Thieme Verlag KG Stuttgart · New York.

  14. Periodontics--tissue engineering and the future.

    Science.gov (United States)

    Douglass, Gordon L

    2005-03-01

    Periodontics has a long history of utilizing advances in science to expand and improve periodontal therapies. Recently the American Academy of Periodontology published the findings of the Contemporary Science Workshop, which conducted state-of-the-art evidence-based reviews of current and emerging areas in periodontics. The findings of this workshop provide the basis for an evidence-based approach to periodontal therapy. While the workshop evaluated all areas of periodontics, it is in the area of tissue engineering that the most exciting advances are becoming a reality.

  15. Tissue Engineering Considerations in Dental Pulp Regeneration

    Science.gov (United States)

    Nosrat, Ali; Kim, Jong Ryul; Verma, Prashant; S. Chand, Priya

    2014-01-01

    Regenerative endodontic procedure is introduced as a biologically based treatment for immature teeth with pulp necrosis. Successful clinical and radiographic outcomes following regenerative procedures have been reported in landmark case reports. Retrospective studies have shown that this conservative treatment allows for continued root development and increases success and survival rate of the treated teeth compared to other treatment options. Although the goal of treatment is regeneration of a functional pulp tissue, histological analyses show a different outcome. Developing predictable protocols would require the use of key elements for tissue engineering: stem cells, bioactive scaffolds, and growth factors. In this study we will review the evidence based steps and outcomes of regenerative endodontics. PMID:24396373

  16. Tissue Engineering Organs for Space Biology Research

    Science.gov (United States)

    Vandenburgh, H. H.; Shansky, J.; DelTatto, M.; Lee, P.; Meir, J.

    1999-01-01

    Long-term manned space flight requires a better understanding of skeletal muscle atrophy resulting from microgravity. Atrophy most likely results from changes at both the systemic level (e.g. decreased circulating growth hormone, increased circulating glucocorticoids) and locally (e.g. decreased myofiber resting tension). Differentiated skeletal myofibers in tissue culture have provided a model system over the last decade for gaining a better understanding of the interactions of exogenous growth factors, endogenous growth factors, and muscle fiber tension in regulating protein turnover rates and muscle cell growth. Tissue engineering these cells into three dimensional bioartificial muscle (BAM) constructs has allowed us to extend their use to Space flight studies for the potential future development of countermeasures.

  17. Combined additive manufacturing approaches in tissue engineering.

    Science.gov (United States)

    Giannitelli, S M; Mozetic, P; Trombetta, M; Rainer, A

    2015-09-01

    Advances introduced by additive manufacturing (AM) have significantly improved the control over the microarchitecture of scaffolds for tissue engineering. This has led to the flourishing of research works addressing the optimization of AM scaffolds microarchitecture to optimally trade-off between conflicting requirements (e.g. mechanical stiffness and porosity level). A fascinating trend concerns the integration of AM with other scaffold fabrication methods (i.e. "combined" AM), leading to hybrid architectures with complementary structural features. Although this innovative approach is still at its beginning, significant results have been achieved in terms of improved biological response to the scaffold, especially targeting the regeneration of complex tissues. This review paper reports the state of the art in the field of combined AM, posing the accent on recent trends, challenges, and future perspectives.

  18. Piezoelectric polymers as biomaterials for tissue engineering applications.

    Science.gov (United States)

    Ribeiro, Clarisse; Sencadas, Vítor; Correia, Daniela M; Lanceros-Méndez, Senentxu

    2015-12-01

    Tissue engineering often rely on scaffolds for supporting cell differentiation and growth. Novel paradigms for tissue engineering include the need of active or smart scaffolds in order to properly regenerate specific tissues. In particular, as electrical and electromechanical clues are among the most relevant ones in determining tissue functionality in tissues such as muscle and bone, among others, electroactive materials and, in particular, piezoelectric ones, show strong potential for novel tissue engineering strategies, in particular taking also into account the existence of these phenomena within some specific tissues, indicating their requirement also during tissue regeneration. This referee reports on piezoelectric materials used for tissue engineering applications. The most used materials for tissue engineering strategies are reported together with the main achievements, challenges and future needs for research and actual therapies. This review provides thus a compilation of the most relevant results and strategies and a start point for novel research pathways in the most relevant and challenging open questions.

  19. Tissue engineering skeletal muscle for orthopaedic applications

    Science.gov (United States)

    Payumo, Francis C.; Kim, Hyun D.; Sherling, Michael A.; Smith, Lee P.; Powell, Courtney; Wang, Xiao; Keeping, Hugh S.; Valentini, Robert F.; Vandenburgh, Herman H.

    2002-01-01

    With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.

  20. Photocrosslinkable Gelatin Hydrogel for Epidermal Tissue Engineering.

    Science.gov (United States)

    Zhao, Xin; Lang, Qi; Yildirimer, Lara; Lin, Zhi Yuan; Cui, Wenguo; Annabi, Nasim; Ng, Kee Woei; Dokmeci, Mehmet R; Ghaemmaghami, Amir M; Khademhosseini, Ali

    2016-01-01

    Natural hydrogels are promising scaffolds to engineer epidermis. Currently, natural hydrogels used to support epidermal regeneration are mainly collagen- or gelatin-based, which mimic the natural dermal extracellular matrix but often suffer from insufficient and uncontrollable mechanical and degradation properties. In this study, a photocrosslinkable gelatin (i.e., gelatin methacrylamide (GelMA)) with tunable mechanical, degradation, and biological properties is used to engineer the epidermis for skin tissue engineering applications. The results reveal that the mechanical and degradation properties of the developed hydrogels can be readily modified by varying the hydrogel concentration, with elastic and compressive moduli tuned from a few kPa to a few hundred kPa, and the degradation times varied from a few days to several months. Additionally, hydrogels of all concentrations displayed excellent cell viability (>90%) with increasing cell adhesion and proliferation corresponding to increases in hydrogel concentrations. Furthermore, the hydrogels are found to support keratinocyte growth, differentiation, and stratification into a reconstructed multilayered epidermis with adequate barrier functions. The robust and tunable properties of GelMA hydrogels suggest that the keratinocyte laden hydrogels can be used as epidermal substitutes, wound dressings, or substrates to construct various in vitro skin models.

  1. Textile Technologies and Tissue Engineering: A Path Toward Organ Weaving.

    Science.gov (United States)

    Akbari, Mohsen; Tamayol, Ali; Bagherifard, Sara; Serex, Ludovic; Mostafalu, Pooria; Faramarzi, Negar; Mohammadi, Mohammad Hossein; Khademhosseini, Ali

    2016-04-06

    Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fibrous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fibers, microarchitecture, and mechanical properties of the fabrics play important roles in the effective use of textile technologies in tissue engineering. This review summarizes the current advances in the manufacturing of biofunctional fibers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engineering are highlighted.

  2. 3D Nanoprinting Technologies for Tissue Engineering Applications

    OpenAIRE

    Jin Woo Lee

    2015-01-01

    Tissue engineering recovers an original function of tissue by replacing the damaged part with a new tissue or organ regenerated using various engineering technologies. This technology uses a scaffold to support three-dimensional (3D) tissue formation. Conventional scaffold fabrication methods do not control the architecture, pore shape, porosity, or interconnectivity of the scaffold, so it has limited ability to stimulate cell growth and to generate new tissue. 3D printing technologies may ov...

  3. A modular approach to cardiac tissue engineering.

    Science.gov (United States)

    Leung, Brendan M; Sefton, Michael V

    2010-10-01

    Functional cardiac tissue was prepared using a modular tissue engineering approach with the goal of creating vascularized tissue. Rat aortic endothelial cells (RAEC) were seeded onto submillimeter-sized modules made of type I bovine collagen supplemented with Matrigel™ (25% v/v) embedded with cardiomyocyte (CM)-enriched neonatal rat heart cells and assembled into a contractile, macroporous, sheet-like construct. Modules (without RAEC) cultured in 10% bovine serum (BS) were more contractile and responsive to external stimulus (lower excitation threshold, higher maximum capture rate, and greater en face fractional area changes) than modules cultured in 10% fetal BS. Incorporating 25% Matrigel in the matrix reduced the excitation threshold and increased the fractional area change relative to collagen only modules (without RAEC). A coculture medium, containing 10% BS, low Mg2+ (0.814mM), and normal glucose (5.5mM), was used to maintain RAEC junction morphology (VE-cadherin) and CM contractility, although the responsiveness of CM was attenuated with RAEC on the modules. Macroporous, sheet-like module constructs were assembled by partially immobilizing a layer of modules in alginate gel until day 8, with or without RAEC. RAEC/CM module sheets were electrically responsive; however, like modules with RAEC this responsiveness was attenuated relative to CM-only sheets. Muscle bundles coexpressing cardiac troponin I and connexin-43 were evident near the perimeter of modules and at intermodule junctions. These results suggest the potential of the modular approach as a platform for building vascularized cardiac tissue.

  4. Biodegradable Polymers in Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Leon E. Govaert

    2009-07-01

    Full Text Available The use ofdegradable polymers in medicine largely started around the mid 20th century with their initial use as in vivo resorbing sutures. Thorough knowledge on this topic as been gained since then and the potential applications for these polymers were, and still are, rapidly expanding. After improving the properties of lactic acid-based polymers, these were no longer studied only from a scientific point of view, but also for their use in bone surgery in the 1990s. Unfortunately, after implanting these polymers, different foreign body reactions ranging from the presence of white blood cells to sterile sinuses with resorption of the original tissue were observed. This led to the misconception that degradable polymers would, in all cases, lead to inflammation and/or osteolysis at the implantation site. Nowadays, we have accumulated substantial knowledge on the issue of biocompatibility of biodegradable polymers and are able to tailor these polymers for specific applications and thereby strongly reduce the occurrence of adverse tissue reactions. However, the major issue of biofunctionality, when mechanical adaptation is taken into account, has hitherto been largely unrecognized. A thorough understanding of how to improve the biofunctionality, comprising biomechanical stability, but also visualization and sterilization of the material, together with the avoidance of fibrotic tissue formation and foreign body reactions, may greatly enhance the applicability and safety of degradable polymers in a wide area of tissue engineering applications. This review will address our current understanding of these biofunctionality factors, and will subsequently discuss the pitfalls remaining and potential solutions to solve these problems.

  5. Growth factor releasing scaffolds for cartilage tissue engineering

    NARCIS (Netherlands)

    Sohier, Jerome

    2006-01-01

    Over the last century, life expectancy has increased at a rapid pace resulting in an increase of articular cartilage disorders. To solve this problem, extensive research is currently performed using tissue engineering approaches. Cartilage tissue engineering aims to reconstruct this tissue both stru

  6. Tissue Engineering-Current Challenges and Expanding Opportunities

    Science.gov (United States)

    Griffith, Linda G.; Naughton, Gail

    2002-02-01

    Tissue engineering can be used to restore, maintain, or enhance tissues and organs. The potential impact of this field, however, is far broader-in the future, engineered tissues could reduce the need for organ replacement, and could greatly accelerate the development of new drugs that may cure patients, eliminating the need for organ transplants altogether.

  7. Tissue engineering in endodontics: root canal revascularization.

    Science.gov (United States)

    Palit Madhu Chanda; Hegde, K Sundeep; Bhat, Sham S; Sargod, Sharan S; Mantha, Somasundar; Chattopadhyay, Sayan

    2014-01-01

    Root canal revascularization attempts to make necrotic tooth alive by the use of certain simple clinical protocols. Earlier apexification was the treatment of choice for treating and preserving immature permanent teeth that have lost pulp vitality. This procedure promoted the formation of apical barrier to seal the root canal of immature teeth and nonvital filling materials contained within root canal space. However with the success of root canal revascularization to regenerate the pulp dentin complex of necrotic immature tooth has made us to rethink if apexification is at the beginning of its end. The objective of this review is to discuss the new concepts of tissue engineering in endodontics and the clinical steps of root canal revascularization.

  8. Tissue engineering scaffolds electrospun from cotton cellulose.

    Science.gov (United States)

    He, Xu; Cheng, Long; Zhang, Ximu; Xiao, Qiang; Zhang, Wei; Lu, Canhui

    2015-01-22

    Nonwovens of cellulose nanofibers were fabricated by electrospinning of cotton cellulose in its LiCl/DMAc solution. The key factors associated with the electrospinning process, including the intrinsic properties of cellulose solutions, the rotating speed of collector and the applied voltage, were systematically investigated. XRD data indicated the electrospun nanofibers were almost amorphous. When increasing the rotating speed of the collector, preferential alignment of fibers along the drawing direction and improved molecular orientation were revealed by scanning electron microscope and polarized FTIR, respectively. Tensile tests indicated the strength of the nonwovens along the orientation direction could be largely improved when collected at a higher speed. In light of the excellent biocompatibility and biodegradability as well as their unique porous structure, the nonwovens were further assessed as potential tissue engineering scaffolds. Cell culture experiments demonstrated human dental follicle cells could proliferate rapidly not only on the surface but also in the entire scaffold. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Ethical aspects of tissue engineering: a review.

    Science.gov (United States)

    de Vries, Rob B M; Oerlemans, Anke; Trommelmans, Leen; Dierickx, Kris; Gordijn, Bert

    2008-12-01

    Tissue engineering (TE) is a promising new field of medical technology. However, like other new technologies, it is not free of ethical challenges. Identifying these ethical questions at an early stage is not only part of science's responsibility toward society, but also in the interest of the field itself. In this review, we map which ethical issues related to TE have already been documented in the scientific literature. The issues that turn out to dominate the debate are the use of human embryonic stem cells and therapeutic cloning. Nevertheless, a variety of other ethical aspects are mentioned, which relate to different phases in the development of the field. In addition, we discuss a number of ethical issues that have not yet been raised in the literature.

  10. Hydroxyapatite-titanium bulk composites for bone tissue engineering applications.

    Science.gov (United States)

    Kumar, Alok; Biswas, Krishanu; Basu, Bikramjit

    2015-02-01

    The research work on bulk hydroxyapatite (HA)-based composites are driven by the need to develop biomaterials with better mechanical properties without compromising its bioactivity and biocompatibility properties. Despite several years of research, the mechanical properties of the HA-based composites still need to be enhanced to match the properties of natural cortical bone. In this regard, the scope of this review on the HA-based bulk biomaterials is limited to the processing and the mechanical as well as biocompatibility properties for bone tissue engineering applications of a model system that is hydroxyapatite-titanium (HA-Ti) bulk composites. It will be discussed in this review how HA-Ti based bulk composites can be processed to have better fracture toughness and strength without compromising biocompatibility. The advantages of the functionally gradient materials to integrate the mechanical and biocompatibility properties is a promising approach in hard tissue engineering and has been emphasized here in reference to the limited literature reports. On the biomaterials fabrication aspect, the recent results are discussed to demonstrate that advanced manufacturing techniques, like spark plasma sintering can be adopted as a processing route to restrict the sintering reactions, while enhancing the mechanical properties. Various toughening mechanisms related to careful tailoring of microstructure are discussed. The in vitro cytocompatibilty, cell fate processes as well as in vivo biocompatibility results are also reviewed and the use of flow cytometry to quantify in vitro cell fate processes is being emphasized. © 2014 Wiley Periodicals, Inc.

  11. Electrospun nanofiber scaffolds: engineering soft tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kumbar, S G; Nukavarapu, S P; Laurencin, C T [Department of Orthopaedic Surgery, University of Virginia, VA 22908 (United States); James, R [Department of Biomedical Engineering, University of Virginia, VA 22908 (United States)], E-mail: laurencin@virginia.edu

    2008-09-01

    Electrospinning has emerged to be a simple, elegant and scalable technique to fabricate polymeric nanofibers. Pure polymers as well as blends and composites of both natural and synthetics have been successfully electrospun into nanofiber matrices. Physiochemical properties of nanofiber matrices can be controlled by manipulating electrospinning parameters to meet the requirements of a specific application. Such efforts include the fabrication of fiber matrices containing nanofibers, microfibers, combination of nano-microfibers and also different fiber orientation/alignments. Polymeric nanofiber matrices have been extensively investigated for diversified uses such as filtration, barrier fabrics, wipes, personal care, biomedical and pharmaceutical applications. Recently electrospun nanofiber matrices have gained a lot of attention, and are being explored as scaffolds in tissue engineering due to their properties that can modulate cellular behavior. Electrospun nanofiber matrices show morphological similarities to the natural extra-cellular matrix (ECM), characterized by ultrafine continuous fibers, high surface-to-volume ratio, high porosity and variable pore-size distribution. Efforts have been made to modify nanofiber surfaces with several bioactive molecules to provide cells with the necessary chemical cues and a more in vivo like environment. The current paper provides an overlook on such efforts in designing nanofiber matrices as scaffolds in the regeneration of various soft tissues including skin, blood vessel, tendon/ligament, cardiac patch, nerve and skeletal muscle.

  12. Optimization of electrical stimulation parameters for cardiac tissue engineering.

    Science.gov (United States)

    Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo; Park, Hyoungshin; Vunjak-Novakovic, Gordana

    2011-06-01

    In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile engineered cardiac tissues. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, were thus used in tissue engineering studies. Engineered cardiac tissues stimulated at 3 V/cm amplitude and 3 Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43 and the best-developed contractile behaviour. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering.

  13. Functional tissue engineering of ligament healing

    Directory of Open Access Journals (Sweden)

    Hsu Shan-Ling

    2010-05-01

    Full Text Available Abstract Ligaments and tendons are dense connective tissues that are important in transmitting forces and facilitate joint articulation in the musculoskeletal system. Their injury frequency is high especially for those that are functional important, like the anterior cruciate ligament (ACL and medial collateral ligament (MCL of the knee as well as the glenohumeral ligaments and the rotator cuff tendons of the shoulder. Because the healing responses are different in these ligaments and tendons after injury, the consequences and treatments are tissue- and site-specific. In this review, we will elaborate on the injuries of the knee ligaments as well as using functional tissue engineering (FTE approaches to improve their healing. Specifically, the ACL of knee has limited capability to heal, and results of non-surgical management of its midsubstance rupture have been poor. Consequently, surgical reconstruction of the ACL is regularly performed to gain knee stability. However, the long-term results are not satisfactory besides the numerous complications accompanied with the surgeries. With the rapid development of FTE, there is a renewed interest in revisiting ACL healing. Approaches such as using growth factors, stem cells and scaffolds have been widely investigated. In this article, the biology of normal and healing ligaments is first reviewed, followed by a discussion on the issues related to the treatment of ACL injuries. Afterwards, current promising FTE methods are presented for the treatment of ligament injuries, including the use of growth factors, gene delivery, and cell therapy with a particular emphasis on the use of ECM bioscaffolds. The challenging areas are listed in the future direction that suggests where collection of energy could be placed in order to restore the injured ligaments and tendons structurally and functionally.

  14. Applications of Tissue Engineering in Joint Arthroplasty: Current Concepts Update.

    Science.gov (United States)

    Zeineddine, Hussein A; Frush, Todd J; Saleh, Zeina M; El-Othmani, Mouhanad M; Saleh, Khaled J

    2017-07-01

    Research in tissue engineering has undoubtedly achieved significant milestones in recent years. Although it is being applied in several disciplines, tissue engineering's application is particularly advanced in orthopedic surgery and in degenerative joint diseases. The literature is full of remarkable findings and trials using tissue engineering in articular cartilage disease. With the vast and expanding knowledge, and with the variety of techniques available at hand, the authors aimed to review the current concepts and advances in the use of cell sources in articular cartilage tissue engineering. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Construction of Tissue Engineering Artificial Cornea with Skin Stem Cells

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionThe clinical need for an alternative to donor corneal tissue has encouraged much interests in recent years. An artificial cornea must fulfill the functions of the cornea it replaces. More recently, the idea of a bio-engineered cornea has risen. Corneal equivalents have been reconstructed by tissue engineering method. Aim of this study is to construct an artificial rabbit cornea by employing tissue engineering method and to determine if skin stem cells have a role in tissue engineered cornea co...

  16. Biodegradable Polymer-Based Scaffolds for Bone Tissue Engineering

    CERN Document Server

    Sultana, Naznin

    2013-01-01

    This book addresses the principles, methods and applications of biodegradable polymer based scaffolds for bone tissue engineering. The general principle of bone tissue engineering is reviewed and the traditional and novel scaffolding materials, their properties and scaffold fabrication techniques are explored. By acting as temporary synthetic extracellular matrices for cell accommodation, proliferation, and differentiation, scaffolds play a pivotal role in tissue engineering. This book does not only provide the comprehensive summary of the current trends in scaffolding design but also presents the new trends and directions for scaffold development for the ever expanding tissue engineering applications.

  17. Tissue engineering strategies to study cartilage development, degeneration and regeneration.

    Science.gov (United States)

    Bhattacharjee, Maumita; Coburn, Jeannine; Centola, Matteo; Murab, Sumit; Barbero, Andrea; Kaplan, David L; Martin, Ivan; Ghosh, Sourabh

    2015-04-01

    Cartilage tissue engineering has primarily focused on the generation of grafts to repair cartilage defects due to traumatic injury and disease. However engineered cartilage tissues have also a strong scientific value as advanced 3D culture models. Here we first describe key aspects of embryonic chondrogenesis and possible cell sources/culture systems for in vitro cartilage generation. We then review how a tissue engineering approach has been and could be further exploited to investigate different aspects of cartilage development and degeneration. The generated knowledge is expected to inform new cartilage regeneration strategies, beyond a classical tissue engineering paradigm.

  18. Engineering bone tissue substitutes from human induced pluripotent stem cells

    National Research Council Canada - National Science Library

    Giuseppe Maria de Peppo; Iván Marcos-Campos; David John Kahler; Dana Alsalman; Linshan Shang; Gordana Vunjak-Novakovic; Darja Marolt

    2013-01-01

    ...) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling...

  19. Micro- and nanotechnology in cardiovascular tissue engineering.

    Science.gov (United States)

    Zhang, Boyang; Xiao, Yun; Hsieh, Anne; Thavandiran, Nimalan; Radisic, Milica

    2011-12-09

    While in nature the formation of complex tissues is gradually shaped by the long journey of development, in tissue engineering constructing complex tissues relies heavily on our ability to directly manipulate and control the micro-cellular environment in vitro. Not surprisingly, advancements in both microfabrication and nanofabrication have powered the field of tissue engineering in many aspects. Focusing on cardiac tissue engineering, this paper highlights the applications of fabrication techniques in various aspects of tissue engineering research: (1) cell responses to micro- and nanopatterned topographical cues, (2) cell responses to patterned biochemical cues, (3) controlled 3D scaffolds, (4) patterned tissue vascularization and (5) electromechanical regulation of tissue assembly and function.

  20. Tissue engineering and biotechnology in general thoracic surgery.

    Science.gov (United States)

    Molnar, Tamas F; Pongracz, Judit E

    2010-06-01

    Public interest in the recent progress of tissue engineering, a special line of biotechnology, makes the current review on thoracic surgery highly relevant. In this article, techniques, materials and cellular processes are discussed alongside their potential applications in tissue repair. Different applications of tissue engineering in tracheo-bronchial replacement, lung tissue cultures and chest-wall reconstruction are also summarised in the article. Potential tissue engineering-based solutions for destructive, chronic lung-injury-related conditions and replacement of tubular structures in the central airways are also examined. Copyright 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

  1. Perivascular cells and tissue engineering: Current applications and untapped potential.

    Science.gov (United States)

    Avolio, Elisa; Alvino, Valeria V; Ghorbel, Mohamed T; Campagnolo, Paola

    2017-03-01

    The recent development of tissue engineering provides exciting new perspectives for the replacement of failing organs and the repair of damaged tissues. Perivascular cells, including vascular smooth muscle cells, pericytes and other tissue specific populations residing around blood vessels, have been isolated from many organs and are known to participate to the in situ repair process and angiogenesis. Their potential has been harnessed for cell therapy of numerous pathologies; however, in this Review we will discuss the potential of perivascular cells in the development of tissue engineering solutions for healthcare. We will examine their application in the engineering of vascular grafts, cardiac patches and bone substitutes as well as other tissue engineering applications and we will focus on their extensive use in the vascularization of engineered constructs. Additionally, we will discuss the emerging potential of human pericytes for the development of efficient, vascularized and non-immunogenic engineered constructs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Tissue Engineering Strategies for the Regeneration of Orthopaedic Interfaces

    Science.gov (United States)

    Lu, Helen H.; Subramony, Siddarth D.; Boushell, Margaret K.; Zhang, Xinzhi

    2013-01-01

    A major focus in the field of orthopaedic tissue engineering is the development of tissue engineered bone and soft tissue grafts with biomimetic functionality to allow for their translation to the clinical setting. One of the most significant challenges of this endeavor is promoting the biological fixation of these grafts with each other as well as the implant site. Such fixation requires strategic biomimicry to be incorporated into the scaffold design in order to re-establish the critical structure-function relationship of the native soft tissue-to-bone interface. The integration of distinct tissue types (e.g. bone and soft tissues such as cartilage, ligaments, or tendons), requires a multi-phased or stratified scaffold with distinct yet continuous tissue regions accompanied by a gradient of mechanical properties that mimics that of the multi-tissue transition between bone and soft tissues. This review discusses tissue engineering strategies for regenerating common tissue-to-tissue interfaces (ligament-to-bone, tendon-to-bone or cartilage-to-bone), and the strategic biomimicry implemented in stratified scaffold design for multi-tissue regeneration. Potential challenges and future directions in this emerging field will also be presented. It is anticipated that interface tissue engineering will enable integrative soft tissue repair, and will be instrumental for the development of complex musculoskeletal tissue systems with biomimetic complexity and functionality. PMID:20422291

  3. Straining mode-dependent collagen remodeling in engineered cardiovascular tissue

    NARCIS (Netherlands)

    Rubbens, M.P.; Mol, A.; Marion, M.H. van; Hanemaaijer, R.; Bank, R.A.; Baaijens, F.P.T.; Bouten, C.V.C.

    2009-01-01

    Similar to native cardiovascular tissues, the mechanical properties of engineered cardiovascular constructs depend on the composition and quality of the extracellular matrix, which is a net result of matrix remodeling processes within the tissue. To improve tissue remodeling, and hence tissue mechan

  4. Utilizing stem cells for three-dimensional neural tissue engineering.

    Science.gov (United States)

    Knowlton, Stephanie; Cho, Yongku; Li, Xue-Jun; Khademhosseini, Ali; Tasoglu, Savas

    2016-05-26

    Three-dimensional neural tissue engineering has made great strides in developing neural disease models and replacement tissues for patients. However, the need for biomimetic tissue models and effective patient therapies remains unmet. The recent push to expand 2D neural tissue engineering into the third dimension shows great potential to advance the field. Another area which has much to offer to neural tissue engineering is stem cell research. Stem cells are well known for their self-renewal and differentiation potential and have been shown to give rise to tissues with structural and functional properties mimicking natural organs. Application of these capabilities to 3D neural tissue engineering may be highly useful for basic research on neural tissue structure and function, engineering disease models, designing tissues for drug development, and generating replacement tissues with a patient's genetic makeup. Here, we discuss the vast potential, as well as the current challenges, unique to integration of 3D fabrication strategies and stem cells into neural tissue engineering. We also present some of the most significant recent achievements, including nerve guidance conduits to facilitate better healing of nerve injuries, functional 3D biomimetic neural tissue models, physiologically relevant disease models for research purposes, and rapid and effective screening of potential drugs.

  5. Injectable hydrogels for cartilage and bone tissue engineering

    Science.gov (United States)

    Liu, Mei; Zeng, Xin; Ma, Chao; Yi, Huan; Ali, Zeeshan; Mou, Xianbo; Li, Song; Deng, Yan; He, Nongyue

    2017-01-01

    Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue. Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects. In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering. In addition, the biology of cartilage and the bony ECM is also summarized. Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed. PMID:28584674

  6. Optimization of nanoparticles for cardiovascular tissue engineering

    Science.gov (United States)

    Izadifar, Mohammad; Kelly, Michael E.; Haddadi, Azita; Chen, Xiongbiao

    2015-06-01

    Nano-particulate delivery systems have increasingly been playing important roles in cardiovascular tissue engineering. Properties of nanoparticles (e.g. size, polydispersity, loading capacity, zeta potential, morphology) are essential to system functions. Notably, these characteristics are regulated by fabrication variables, but in a complicated manner. This raises a great need to optimize fabrication process variables to ensure the desired nanoparticle characteristics. This paper presents a comprehensive experimental study on this matter, along with a novel method, the so-called Geno-Neural approach, to analyze, predict and optimize fabrication variables for desired nanoparticle characteristics. Specifically, ovalbumin was used as a protein model of growth factors used in cardiovascular tissue regeneration, and six fabrication variables were examined with regard to their influence on the characteristics of nanoparticles made from high molecular weight poly(lactide-co-glycolide). The six-factor five-level central composite rotatable design was applied to the conduction of experiments, and based on the experimental results, a geno-neural model was developed to determine the optimum fabrication conditions. For desired particle sizes of 150, 200, 250 and 300 nm, respectively, the optimum conditions to achieve the low polydispersity index, higher negative zeta potential and higher loading capacity were identified based on the developed geno-neural model and then evaluated experimentally. The experimental results revealed that the polymer and the external aqueous phase concentrations and their interactions with other fabrication variables were the most significant variables to affect the size, polydispersity index, zeta potential, loading capacity and initial burst release of the nanoparticles, while the electron microscopy images of the nanoparticles showed their spherical geometries with no sign of large pores or cracks on their surfaces. The release study revealed

  7. Bioactive polymers for cardiac tissue engineering

    Science.gov (United States)

    Wall, Samuel Thomas

    2007-05-01

    Prevalent in the US and worldwide, acute myocardial infarctions (AMI) can cause ischemic injuries to the heart that persist and lead to progressive degradation of the organ. Tissue engineering techniques exploiting biomaterials present a hopeful means of treating these injuries, either by mechanically stabilizing the injured ventricle, or by fostering cell growth to replace myocytes lost to damage. This thesis describes the development and testing of a synthetic extracellular matrix for cardiac tissue engineering applications. The first stage of this process was using an advanced finite element model of an injured ovine left ventricle to evaluate the potential benefits of injecting synthetic materials into the heart. These simulations indicated that addition of small amounts non-contractile material (on the order of 1--5% total wall volume) to infarct border zone regions reduced pathological systolic fiber stress to levels near those found in normal remote regions. Simulations also determined that direct addition to the infarct itself caused increases in ventricle ejection fraction while the underlying performance of the pump, ascertained by the Starling relation, was not improved. From these theoretical results, biomaterials were developed specifically for injection into the injured myocardium, and were characterized and tested for their mechanical properties and ability to sustain the proliferation of a stem cell population suitable for transplantation. Thermoresponsive synthetic copolymer hydrogels consisting of N-isopropylacrylamide and acrylic acid, p(NIPAAm-co-AAc), crosslinked with protease degradable amino acid sequences and modified with integrin binding ligands were synthesized, characterized in vitro, and used for myocardial implantation. These injectable materials could maintain a population of bone marrow derived mesenchymal stem cells in both two dimensional and three dimensional culture, and when tested in vivo in a murine infarct model they

  8. Bioreactors Drive Advances in Tissue Engineering

    Science.gov (United States)

    2012-01-01

    It was an unlikely moment for inspiration. Engineers David Wolf and Ray Schwarz stopped by their lab around midday. Wolf, of Johnson Space Center, and Schwarz, with NASA contractor Krug Life Sciences (now Wyle Laboratories Inc.), were part of a team tasked with developing a unique technology with the potential to enhance medical research. But that wasn t the focus at the moment: The pair was rounding up colleagues interested in grabbing some lunch. One of the lab s other Krug engineers, Tinh Trinh, was doing something that made Wolf forget about food. Trinh was toying with an electric drill. He had stuck the barrel of a syringe on the bit; it spun with a high-pitched whirr when he squeezed the drill s trigger. At the time, a multidisciplinary team of engineers and biologists including Wolf, Schwarz, Trinh, and project manager Charles D. Anderson, who formerly led the recovery of the Apollo capsules after splashdown and now worked for Krug was pursuing the development of a technology called a bioreactor, a cylindrical device used to culture human cells. The team s immediate goal was to grow human kidney cells to produce erythropoietin, a hormone that regulates red blood cell production and can be used to treat anemia. But there was a major barrier to the technology s success: Moving the liquid growth media to keep it from stagnating resulted in turbulent conditions that damaged the delicate cells, causing them to quickly die. The team was looking forward to testing the bioreactor in space, hoping the device would perform more effectively in microgravity. But on January 28, 1986, the Space Shuttle Challenger broke apart shortly after launch, killing its seven crewmembers. The subsequent grounding of the shuttle fleet had left researchers with no access to space, and thus no way to study the effects of microgravity on human cells. As Wolf looked from Trinh s syringe-capped drill to where the bioreactor sat on a workbench, he suddenly saw a possible solution to both

  9. [Strategies to choose scaffold materials for tissue engineering].

    Science.gov (United States)

    Gao, Qingdong; Zhu, Xulong; Xiang, Junxi; Lü, Yi; Li, Jianhui

    2016-02-01

    Current therapies of organ failure or a wide range of tissue defect are often not ideal. Transplantation is the only effective way for long time survival. But it is hard to meet huge patients demands because of donor shortage, immune rejection and other problems. Tissue engineering could be a potential option. Choosing a suitable scaffold material is an essential part of it. According to different sources, tissue engineering scaffold materials could be divided into three types which are natural and its modified materials, artificial and composite ones. The purpose of tissue engineering scaffold is to repair the tissues or organs damage, so could reach the ideal recovery in its function and structure aspect. Therefore, tissue engineering scaffold should even be as close as much to the original tissue or organs in function and structure. We call it "organic scaffold" and this strategy might be the drastic perfect substitute for the tissues or organs in concern. Optimized organization with each kind scaffold materials could make up for biomimetic structure and function of the tissue or organs. Scaffold material surface modification, optimized preparation procedure and cytosine sustained-release microsphere addition should be considered together. This strategy is expected to open new perspectives for tissue engineering. Multidisciplinary approach including material science, molecular biology, and engineering might find the most ideal tissue engineering scaffold. Using the strategy of drawing on each other strength and optimized organization with each kind scaffold material to prepare a multifunctional biomimetic tissue engineering scaffold might be a good method for choosing tissue engineering scaffold materials. Our research group had differentiated bone marrow mesenchymal stem cells into bile canaliculi like cells. We prepared poly(L-lactic acid)/poly(ε-caprolactone) biliary stent. The scaffold's internal played a part in the long-term release of cytokines which

  10. Bioresorbable and nonresorbable polymers for bone tissue engineering.

    Science.gov (United States)

    Girones Molera, Jordi; Mendez, José Alberto; San Roman, Julio

    2012-01-01

    In recent years, bone tissue engineering has emerged as one of the main research areas in the field of regenerative biomedicine. Frequency and relevance age-related diseases, such as healing and regeneration of bone tissues, are rising due to increasing life expectancy. Even though bone tissue has excellent self-regeneration ability, when bone defects exceed a critical size, impaired bone formation can occur and surgical intervention becomes mandatory. Bone tissue engineering represents an alternative approach to conventional bone transplants. The main aim of tissue engineering is to repair, regenerate or reconstruct damaged or degenerative tissue. This review presents an overview on the main materials, techniques and strategies in the field of bone tissue engineering. Whilst presenting some reviews recently published that deepen on each of the sections of the paper, this review article aims to present some of the most relevant advances, both in terms of new materials and strategies, currently being developed for bone repair and regeneration.

  11. Scaffolding in tissue engineering: general approaches and tissue-specific considerations.

    Science.gov (United States)

    Chan, B P; Leong, K W

    2008-12-01

    Scaffolds represent important components for tissue engineering. However, researchers often encounter an enormous variety of choices when selecting scaffolds for tissue engineering. This paper aims to review the functions of scaffolds and the major scaffolding approaches as important guidelines for selecting scaffolds and discuss the tissue-specific considerations for scaffolding, using intervertebral disc as an example.

  12. Acellular organ scaffolds for tumor tissue engineering

    Science.gov (United States)

    Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

    2015-12-01

    Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Translational Approaches in Tissue Engineering and Regenerative Medicine

    CERN Document Server

    Mao, Jeremy J

    2007-01-01

    This landmark book identifies the current and forthcoming roadblocks to scientific research and technological development in stem cell research, tissue engineering, wound healing, and in-vivo animal models. The book is the first to focus on the translational aspect of tissue engineering and regenerative medicine and bridges the gap between laboratory discovery and clinical applications.

  15. Tissue engineering in periodontal regeneration: A brief review

    Directory of Open Access Journals (Sweden)

    Sarita Dabra

    2012-01-01

    Full Text Available Periodontal disease is a major public health issue and the development of effective therapies to treat the disease and regenerate periodontal tissue is an important goal of today′s medicine. Regeneration of periodontal tissue is perhaps one of the most complex process to occur in the body. Langer and colleagues proposed tissue engineering as a possible technique for regenerating the lost periodontal tissues. Tissue engineering is a multidisciplinary field, which involves the application of the principles and methods of engineering and life sciences to help in the development of biological substitutes to restore, maintain or improve the function of damaged tissues and organs. A Google/Medline search was conducted and relevant literature evaluating the potential role of the tissue engineering in periodontal regeneration, which included histological studies and controlled clinical trials, was reviewed. A comprehensive search was designed. The articles were independently screened for eligibility. Articles with authentic controls and proper randomization and pertaining specifically to their role in periodontal regeneration were included. The available literature was analyzed and compiled. The analysis indicate tissue engineering to be a promising, as well as an effective novel approach to reconstruct and engineer the periodontal apparatus. Here, we represent several articles, as well as recent texts that make up a special and an in-depth review on the subject. The purpose behind writing this brief review has been to integrate the evidence of research related to tissue engineering so as to implement them in our daily practice.

  16. Tissue engineering in periodontal regeneration: A brief review.

    Science.gov (United States)

    Dabra, Sarita; Chhina, Kamalpreet; Soni, Nitin; Bhatnagar, Rakhi

    2012-11-01

    Periodontal disease is a major public health issue and the development of effective therapies to treat the disease and regenerate periodontal tissue is an important goal of today's medicine. Regeneration of periodontal tissue is perhaps one of the most complex process to occur in the body. Langer and colleagues proposed tissue engineering as a possible technique for regenerating the lost periodontal tissues. Tissue engineering is a multidisciplinary field, which involves the application of the principles and methods of engineering and life sciences to help in the development of biological substitutes to restore, maintain or improve the function of damaged tissues and organs. A Google/Medline search was conducted and relevant literature evaluating the potential role of the tissue engineering in periodontal regeneration, which included histological studies and controlled clinical trials, was reviewed. A comprehensive search was designed. The articles were independently screened for eligibility. Articles with authentic controls and proper randomization and pertaining specifically to their role in periodontal regeneration were included. The available literature was analyzed and compiled. The analysis indicate tissue engineering to be a promising, as well as an effective novel approach to reconstruct and engineer the periodontal apparatus. Here, we represent several articles, as well as recent texts that make up a special and an in-depth review on the subject. The purpose behind writing this brief review has been to integrate the evidence of research related to tissue engineering so as to implement them in our daily practice.

  17. Application of microtechnologies for the vascularization of engineered tissues

    Directory of Open Access Journals (Sweden)

    Gauvin Robert

    2011-10-01

    Full Text Available Abstract Recent advances in medicine and healthcare allow people to live longer, increasing the need for the number of organ transplants. However, the number of organ donors has not been able to meet the demand, resulting in an organ shortage. The field of tissue engineering has emerged to produce organs to overcome this limitation. While tissue engineering of connective tissues such as skin and blood vessels have currently reached clinical studies, more complex organs are still far away from commercial availability due to pending challenges with in vitro engineering of 3D tissues. One of the major limitations of engineering large tissue structures is cell death resulting from the inability of nutrients to diffuse across large distances inside a scaffold. This task, carried out by the vasculature inside the body, has largely been described as one of the foremost important challenges in engineering 3D tissues since it remains one of the key steps for both in vitro production of tissue engineered construct and the in vivo integration of a transplanted tissue. This short review highlights the important challenges for vascularization and control of the microcirculatory system within engineered tissues, with particular emphasis on the use of microfabrication approaches.

  18. Stem Cells in Skeletal Tissue Engineering: Technologies and Models

    Science.gov (United States)

    Langhans, Mark T.; Yu, Shuting; Tuan, Rocky S.

    2017-01-01

    This review surveys the use of pluripotent and multipotent stem cells in skeletal tissue engineering. Specific emphasis is focused on evaluating the function and activities of these cells in the context of development in vivo, and how technologies and methods of stem cell-based tissue engineering for stem cells must draw inspiration from developmental biology. Information on the embryonic origin and in vivo differentiation of skeletal tissues is first reviewed, to shed light on the persistence and activities of adult stem cells that remain in skeletal tissues after embryogenesis. Next, the development and differentiation of pluripotent stem cells is discussed, and some of their advantages and disadvantages in the context of tissue engineering is presented. The final section highlights current use of multipotent adult mesenchymal stem cells, reviewing their origin, differentiation capacity, and potential applications to tissue engineering. PMID:26423296

  19. Hyaluronan Benzyl Ester as a Scaffold for Tissue Engineering

    OpenAIRE

    2009-01-01

    Tissue engineering is a multidisciplinary field focused on in vitro reconstruction of mammalian tissues. In order to allow a similar three-dimensional organization of in vitro cultured cells, biocompatible scaffolds are needed. This need has provided immense momentum for research on “smart scaffolds” for use in cell culture. One of the most promising materials for tissue engineering and regenerative medicine is a hyaluronan derivative: a benzyl ester of hyaluronan (HYAFF®). HYAFF® can be proc...

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

    NARCIS (Netherlands)

    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

  1. Molecular Tissue Engineering:Concepts,Status and Challenge

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Tissue engineering has confronted many difficulties mainly as follows:1)How to modulate the adherence,proliferation,and oriented differentiation of seed cells, especially that of stemcells. 2) Massive preparation and sustained controllable delivery of tissue inducing factors or plasmid DNA, such as growth factors, angiogenesis stimulators,and so on. 3) Development of "intelligent biomimetic materials" as extracellular matrix with a good superficial and structural compatibility as well as biological activity to stimulate predictable, controllable and desirable responses under defined conditions.Molecular biology is currently one of the most exciting fields of research across life sciences,and the advances in it also bring a bright future for tissue engineering to overcome these difficulties.In recent years,tissue engineering benefits a lot from molecular biology.Only a comprehensive understanding of the involved ingredients of tissue engineering (cells,tissue inducing factors,genes,biomaterials) and the subtle relationships between them at molecular level can lead to a successful manipulation of reparative processes and a better biological substitute.Molecular tissue engineering,the offspring of the tissue engineering and molecular biology,has gained an increasing importance in recent years.It offers the promise of not simply replacing tissue,but improving the restoration.The studies presented in this article put forward this new concept for the first time and provide an insight into the basic principles,status and challenges of this emerging technology.

  2. MECHANICAL DESIGN CRITERIA FOR INTERVERTEBRAL DISC TISSUE ENGINEERING

    Science.gov (United States)

    Nerurkar, Nandan L.; Elliott, Dawn M.; Mauck, Robert L.

    2009-01-01

    Due to the inability of current clinical practices to restore function to degenerated intervertebral discs, the arena of disc tissue engineering has received substantial attention in recent years. Despite tremendous growth and progress in this field, translation to clinical implementation has been hindered by a lack of well-defined functional benchmarks. Because successful replacement of the disc is contingent upon replication of some or all of its complex mechanical behaviour, it is critically important that disc mechanics be well characterized in order to establish discrete functional goals for tissue engineering. In this review, the key functional signatures of the intervertebral disc are discussed and used to propose a series of native tissue benchmarks to guide the development of engineered replacement tissues. These benchmarks include measures of mechanical function under tensile, compressive and shear deformations for the disc and its substructures. In some cases, important functional measures are identified that have yet to be measured in the native tissue. Ultimately, native tissue benchmark values are compared to measurements that have been made on engineered disc tissues, identifying measures where functional equivalence was achieved, and others where there remain opportunities for advancement. Several excellent reviews exist regarding disc composition and structure, as well as recent tissue engineering strategies; therefore this review will remain focused on the functional aspects of disc tissue engineering. PMID:20080239

  3. Bioreactors in tissue engineering - principles, applications and commercial constraints.

    Science.gov (United States)

    Hansmann, Jan; Groeber, Florian; Kahlig, Alexander; Kleinhans, Claudia; Walles, Heike

    2013-03-01

    Bioreactor technology is vital for tissue engineering. Usually, bioreactors are used to provide a tissue-specific physiological in vitro environment during tissue maturation. In addition to this most obvious application, bioreactors have the potential to improve the efficiency of the overall tissue-engineering concept. To date, a variety of bioreactor systems for tissue-specific applications have been developed. Of these, some systems are already commercially available. With bioreactor technology, various functional tissues of different types were generated and cultured in vitro. Nevertheless, these efforts and achievements alone have not yet led to many clinically successful tissue-engineered implants. We review possible applications for bioreactor systems within a tissue-engineering process and present basic principles and requirements for bioreactor development. Moreover, the use of bioreactor systems for the expansion of clinically relevant cell types is addressed. In contrast to cell expansion, for the generation of functional three-dimensional tissue equivalents, additional physical cues must be provided. Therefore, bioreactors for musculoskeletal tissue engineering are discussed. Finally, bioreactor technology is reviewed in the context of commercial constraints.

  4. Synthetic Versus Tissue-Engineered Implants for Joint Replacement

    Directory of Open Access Journals (Sweden)

    Duncan E. T. Shepherd

    2007-01-01

    Full Text Available Human synovial joints are remarkable as they can last for a lifetime. However, they can be affected by disease that may lead to destruction of the joint surface. The most common treatment in the advanced stages of joint disease is artificial joint replacement, where the diseased synovial joint is replaced with an artificial implant made from synthetic materials, such as metals and polymers. A new technique for repairing diseased synovial joints is tissue engineering where cells are used to grow replacement tissue. This paper explores the relative merits of synthetic and tissue-engineered implants, using joint replacement as an example. Synthetic joint replacement is a well-established procedure with the advantages of early mobilisation, pain relief and high patient satisfaction. However, synthetic implants are not natural tissues; they can cause adverse reactions to the body and there could be a mismatch in mechanical properties compared to natural tissues. Tissue-engineered implants offer great potential and have major advantages over synthetic implants as they are natural tissue, which should ensure that they are totally biocompatible, have the correct mechanical properties and integrate well with the existing tissue. However, there are still many limitations to be addressed in tissue engineering such as scaling up for production, bioreactor design, appropriate regulation and the potential for disease to attack the new tissue-engineered implant.

  5. Advanced tissue engineering in periodontal Regeneration

    OpenAIRE

    Seyed Ali Banihashemrad

    2014-01-01

    The old wishes of people were to regenerate lost tissues of periodontium that this fact is achieved by gen and cell therapy .Periodontal disease is a chronic inflammation around the tooth by microbes that causes destruction of supporting structure of tissue of tooth such as alveolar bone, cementum and periodontal ligament. For treatment of periodontal diseases we can use the biomaterials which help to regenerate the periodontal tissues like; autogenous bone grafts, allograft, guided tissue re...

  6. Evaluation of a Method for Quantifying Eugenol Concentrations in the Fillet Tissue from Freshwater Fish Species.

    Science.gov (United States)

    Meinertz, Jeffery R; Schreier, Theresa M; Porcher, Scott T; Smerud, Justin R

    2016-01-01

    AQUI-S 20E(®) (active ingredient, eugenol; AQUI-S New Zealand Ltd, Lower Hutt, New Zealand) is being pursued for approval as an immediate-release sedative in the United States. A validated method to quantify the primary residue (the marker residue) in fillet tissue from AQUI-S 20E-exposed fish was needed. A method was evaluated for determining concentrations of the AQUI-S 20E marker residue, eugenol, in freshwater fish fillet tissue. Method accuracies from fillet tissue fortified at nominal concentrations of 0.15, 1, and 60 μg/g from six fish species ranged from 88-102%. Within-day and between-day method precisions (% CV) from the fortified tissue were ≤8.4% CV. There were no coextracted compounds from the control fillet tissue of seven fish species that interfered with eugenol analyses. Six compounds used as aquaculture drugs did not interfere with eugenol analyses. The lower limit of quantitation (LLOQ) was 0.012 μg/g. The method was robust, i.e., in most cases, minor changes to the method did not impact method performance. Eugenol was stable in acetonitrile-water (3 + 7, v/v) for at least 14 days, in fillet tissue extracts for 4 days, and in fillet tissue stored at ~ -80°C for at least 84 days.

  7. Evaluation of a method for quantifying eugenol concentrations in the fillet tissue from freshwater fish species

    Science.gov (United States)

    Meinertz, Jeffery R.; Schreier, Theresa M.; Porcher, Scott T.; Smerud, Justin R.

    2016-01-01

    AQUI-S 20E® (active ingredient, eugenol; AQUI-S New Zealand Ltd, Lower Hutt, New Zealand) is being pursued for approval as an immediate-release sedative in the United States. A validated method to quantify the primary residue (the marker residue) in fillet tissue from AQUI-S 20E–exposed fish was needed. A method was evaluated for determining concentrations of the AQUI-S 20E marker residue, eugenol, in freshwater fish fillet tissue. Method accuracies from fillet tissue fortified at nominal concentrations of 0.15, 1, and 60 μg/g from six fish species ranged from 88–102%. Within-day and between-day method precisions (% CV) from the fortified tissue were ≤8.4% CV. There were no coextracted compounds from the control fillet tissue of seven fish species that interfered with eugenol analyses. Six compounds used as aquaculture drugs did not interfere with eugenol analyses. The lower limit of quantitation (LLOQ) was 0.012 μg/g. The method was robust, i.e., in most cases, minor changes to the method did not impact method performance. Eugenol was stable in acetonitrile–water (3 + 7, v/v) for at least 14 days, in fillet tissue extracts for 4 days, and in fillet tissue stored at ~ −80°C for at least 84 days.

  8. Comparison of different fabrication techniques for human adipose tissue engineering in severe combined immunodeficient mice.

    Science.gov (United States)

    Frerich, Bernhard; Winter, Karsten; Scheller, Konstanze; Braumann, Ulf-Dietrich

    2012-03-01

    Adipose tissue engineering has been advocated for soft-tissue augmentation and for the treatment of soft tissue defects. The efficacy in terms of persistence of the engineered fat is, however, not yet understood and could depend on the nature of fabrication and application. The high metabolic demand of adipose tissue also points to the problem of vascularization. Endothelial cell (EC) cotransplantation could be a solution. Human adipose tissue-derived stromal cells were seeded on collagen microcarriers and submitted to adipogenic differentiation ("microparticles"). In a first run of experiments, these microparticles were implanted under the skin of severe combined immunodeficient (SCID) mice (n = 45) with and without the addition of human umbilical vein ECs (HUVECs). A group of carriers without any cells served as control. In a second run, adipose tissue constructs were fabricated by embedding microparticles in fibrin matrix with and without the addition of HUVEC, and were also implanted in SCID mice (n = 30). The mice were sacrificed after 12 days, 4 weeks, and 4 months. Mature adipose tissue, fibrous tissue, and acellular regions were quantified on whole-specimen histological sections. The implantation of microparticles showed a better sustainment of tissue volume and a higher degree of mature adipose tissue compared with adipose tissue constructs. Immunohistology proved obviously perfused human tissue-engineered vessels. There was a limited but not significant advantage in EC cotransplantation after 4 weeks in terms of tissue volume. In groups with EC cotransplantation, there were significantly fewer acellular/necrotic areas after 4 weeks and 4 months. In conclusion, the size of the implanted tissue equivalents is a crucial parameter, affecting volume maintenance and the gain of mature adipose tissue. EC cotransplantation leads to functional stable vascular networks connecting in part to the host vasculature and contributing to tissue perfusion; however

  9. Nano scaffolds and stem cell therapy in liver tissue engineering

    Science.gov (United States)

    Montaser, Laila M.; Fawzy, Sherin M.

    2015-08-01

    Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

  10. Ethical considerations in tissue engineering research: Case studies in translation.

    Science.gov (United States)

    Baker, Hannah B; McQuilling, John P; King, Nancy M P

    2016-04-15

    Tissue engineering research is a complex process that requires investigators to focus on the relationship between their research and anticipated gains in both knowledge and treatment improvements. The ethical considerations arising from tissue engineering research are similarly complex when addressing the translational progression from bench to bedside, and investigators in the field of tissue engineering act as moral agents at each step of their research along the translational pathway, from early benchwork and preclinical studies to clinical research. This review highlights the ethical considerations and challenges at each stage of research, by comparing issues surrounding two translational tissue engineering technologies: the bioartificial pancreas and a tissue engineered skeletal muscle construct. We present relevant ethical issues and questions to consider at each step along the translational pathway, from the basic science bench to preclinical research to first-in-human clinical trials. Topics at the bench level include maintaining data integrity, appropriate reporting and dissemination of results, and ensuring that studies are designed to yield results suitable for advancing research. Topics in preclinical research include the principle of "modest translational distance" and appropriate animal models. Topics in clinical research include key issues that arise in early-stage clinical trials, including selection of patient-subjects, disclosure of uncertainty, and defining success. The comparison of these two technologies and their ethical issues brings to light many challenges for translational tissue engineering research and provides guidance for investigators engaged in development of any tissue engineering technology.

  11. Cell-Based Strategies for Meniscus Tissue Engineering

    Science.gov (United States)

    Niu, Wei; Guo, Weimin; Han, Shufeng; Zhu, Yun; Liu, Shuyun; Guo, Quanyi

    2016-01-01

    Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering. PMID:27274735

  12. Cell-Based Strategies for Meniscus Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Wei Niu

    2016-01-01

    Full Text Available Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering.

  13. Coupled analysis of in vitro and histology tissue samples to quantify structure-function relationship.

    Directory of Open Access Journals (Sweden)

    Evrim Acar

    Full Text Available The structure/function relationship is fundamental to our understanding of biological systems at all levels, and drives most, if not all, techniques for detecting, diagnosing, and treating disease. However, at the tissue level of biological complexity we encounter a gap in the structure/function relationship: having accumulated an extraordinary amount of detailed information about biological tissues at the cellular and subcellular level, we cannot assemble it in a way that explains the correspondingly complex biological functions these structures perform. To help close this information gap we define here several quantitative temperospatial features that link tissue structure to its corresponding biological function. Both histological images of human tissue samples and fluorescence images of three-dimensional cultures of human cells are used to compare the accuracy of in vitro culture models with their corresponding human tissues. To the best of our knowledge, there is no prior work on a quantitative comparison of histology and in vitro samples. Features are calculated from graph theoretical representations of tissue structures and the data are analyzed in the form of matrices and higher-order tensors using matrix and tensor factorization methods, with a goal of differentiating between cancerous and healthy states of brain, breast, and bone tissues. We also show that our techniques can differentiate between the structural organization of native tissues and their corresponding in vitro engineered cell culture models.

  14. Exploring the Islamic Perspective on Tissue Engineering Principles and Practice

    Directory of Open Access Journals (Sweden)

    Munirah, S.

    2014-12-01

    Full Text Available Tissue engineering is related to the replacement, restoration, repair and/or regeneration of tissues/organs that are tailored to the needs of the individual patient. The potential applications of tissue engineering are being unveiled with much hype and expectations among the scientists and the public at large. The demand for engineered tissues may increase considerably, but the progress has been slow due to scientific and technical challenges that linked to moral, religious, philosophical, political and economic aspects. There are ongoing debates on certain aspects that seem to indicate that scientists maybe “playing God”. This article briefly analyses tissue engineering principles and the discourse surrounding it. Subsequently, the author briefly reflects on the Islamic perspectives, both for and against the technology. The discussions serve to provide a platform on how best to achieve a consensus that adequately deals with the scientific reality and the Islamic moral and legal jurisprudence that surrounds the technology.

  15. Quantification of Cardiomyocyte Alignment from Three-Dimensional (3D) Confocal Microscopy of Engineered Tissue.

    Science.gov (United States)

    Kowalski, William J; Yuan, Fangping; Nakane, Takeichiro; Masumoto, Hidetoshi; Dwenger, Marc; Ye, Fei; Tinney, Joseph P; Keller, Bradley B

    2017-08-01

    Biological tissues have complex, three-dimensional (3D) organizations of cells and matrix factors that provide the architecture necessary to meet morphogenic and functional demands. Disordered cell alignment is associated with congenital heart disease, cardiomyopathy, and neurodegenerative diseases and repairing or replacing these tissues using engineered constructs may improve regenerative capacity. However, optimizing cell alignment within engineered tissues requires quantitative 3D data on cell orientations and both efficient and validated processing algorithms. We developed an automated method to measure local 3D orientations based on structure tensor analysis and incorporated an adaptive subregion size to account for multiple scales. Our method calculates the statistical concentration parameter, κ, to quantify alignment, as well as the traditional orientational order parameter. We validated our method using synthetic images and accurately measured principal axis and concentration. We then applied our method to confocal stacks of cleared, whole-mount engineered cardiac tissues generated from human-induced pluripotent stem cells or embryonic chick cardiac cells and quantified cardiomyocyte alignment. We found significant differences in alignment based on cellular composition and tissue geometry. These results from our synthetic images and confocal data demonstrate the efficiency and accuracy of our method to measure alignment in 3D tissues.

  16. Noninvasive metabolic imaging of engineered 3D human adipose tissue in a perfusion bioreactor.

    Directory of Open Access Journals (Sweden)

    Andrew Ward

    Full Text Available The efficacy and economy of most in vitro human models used in research is limited by the lack of a physiologically-relevant three-dimensional perfused environment and the inability to noninvasively quantify the structural and biochemical characteristics of the tissue. The goal of this project was to develop a perfusion bioreactor system compatible with two-photon imaging to noninvasively assess tissue engineered human adipose tissue structure and function in vitro. Three-dimensional (3D vascularized human adipose tissues were engineered in vitro, before being introduced to a perfusion environment and tracked over time by automated quantification of endogenous markers of metabolism using two-photon excited fluorescence (TPEF. Depth-resolved image stacks were analyzed for redox ratio metabolic profiling and compared to prior analyses performed on 3D engineered adipose tissue in static culture. Traditional assessments with H&E staining were used to qualitatively measure extracellular matrix generation and cell density with respect to location within the tissue. The distribution of cells within the tissue and average cellular redox ratios were different between static and perfusion cultures, while the trends of decreased redox ratio and increased cellular proliferation with time in both static and perfusion cultures were similar. These results establish a basis for noninvasive optical tracking of tissue structure and function in vitro, which can be applied to future studies to assess tissue development or drug toxicity screening and disease progression.

  17. Noninvasive metabolic imaging of engineered 3D human adipose tissue in a perfusion bioreactor.

    Science.gov (United States)

    Ward, Andrew; Quinn, Kyle P; Bellas, Evangelia; Georgakoudi, Irene; Kaplan, David L

    2013-01-01

    The efficacy and economy of most in vitro human models used in research is limited by the lack of a physiologically-relevant three-dimensional perfused environment and the inability to noninvasively quantify the structural and biochemical characteristics of the tissue. The goal of this project was to develop a perfusion bioreactor system compatible with two-photon imaging to noninvasively assess tissue engineered human adipose tissue structure and function in vitro. Three-dimensional (3D) vascularized human adipose tissues were engineered in vitro, before being introduced to a perfusion environment and tracked over time by automated quantification of endogenous markers of metabolism using two-photon excited fluorescence (TPEF). Depth-resolved image stacks were analyzed for redox ratio metabolic profiling and compared to prior analyses performed on 3D engineered adipose tissue in static culture. Traditional assessments with H&E staining were used to qualitatively measure extracellular matrix generation and cell density with respect to location within the tissue. The distribution of cells within the tissue and average cellular redox ratios were different between static and perfusion cultures, while the trends of decreased redox ratio and increased cellular proliferation with time in both static and perfusion cultures were similar. These results establish a basis for noninvasive optical tracking of tissue structure and function in vitro, which can be applied to future studies to assess tissue development or drug toxicity screening and disease progression.

  18. Progress and opportunities for tissue-engineered skin

    Science.gov (United States)

    MacNeil, Sheila

    2007-02-01

    Tissue-engineered skin is now a reality. For patients with extensive full-thickness burns, laboratory expansion of skin cells to achieve barrier function can make the difference between life and death, and it was this acute need that drove the initiation of tissue engineering in the 1980s. A much larger group of patients have ulcers resistant to conventional healing, and treatments using cultured skin cells have been devised to restart the wound-healing process. In the laboratory, the use of tissue-engineered skin provides insight into the behaviour of skin cells in healthy skin and in diseases such as vitiligo, melanoma, psoriasis and blistering disorders.

  19. Review: Polymeric-Based 3D Printing for Tissue Engineering.

    Science.gov (United States)

    Wu, Geng-Hsi; Hsu, Shan-Hui

    Three-dimensional (3D) printing, also referred to as additive manufacturing, is a technology that allows for customized fabrication through computer-aided design. 3D printing has many advantages in the fabrication of tissue engineering scaffolds, including fast fabrication, high precision, and customized production. Suitable scaffolds can be designed and custom-made based on medical images such as those obtained from computed tomography. Many 3D printing methods have been employed for tissue engineering. There are advantages and limitations for each method. Future areas of interest and progress are the development of new 3D printing platforms, scaffold design software, and materials for tissue engineering applications.

  20. Scaffold Sheet Design Strategy for Soft Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Liping Tang

    2010-02-01

    Full Text Available Creating heterogeneous tissue constructs with an even cell distribution and robust mechanical strength remain important challenges to the success of in vivo tissue engineering. To address these issues, we are developing a scaffold sheet tissue engineering strategy consisting of thin (~200 μm, strong, elastic, and porous crosslinked urethane- doped polyester (CUPE scaffold sheets that are bonded together chemically or through cell culture. Suture retention of the tissue constructs (four sheets fabricated by the scaffold sheet tissue engineering strategy is close to the surgical requirement (1.8 N rendering their potential for immediate implantation without a need for long cell culture times. Cell culture results using 3T3 fibroblasts show that the scaffold sheets are bonded into a tissue construct via the extracellular matrix produced by the cells after 2 weeks of in vitro cell culture.

  1. A Review of Three-Dimensional Printing in Tissue Engineering.

    Science.gov (United States)

    Sears, Nick A; Seshadri, Dhruv R; Dhavalikar, Prachi S; Cosgriff-Hernandez, Elizabeth

    2016-08-01

    Recent advances in three-dimensional (3D) printing technologies have led to a rapid expansion of applications from the creation of anatomical training models for complex surgical procedures to the printing of tissue engineering constructs. In addition to achieving the macroscale geometry of organs and tissues, a print layer thickness as small as 20 μm allows for reproduction of the microarchitectures of bone and other tissues. Techniques with even higher precision are currently being investigated to enable reproduction of smaller tissue features such as hepatic lobules. Current research in tissue engineering focuses on the development of compatible methods (printers) and materials (bioinks) that are capable of producing biomimetic scaffolds. In this review, an overview of current 3D printing techniques used in tissue engineering is provided with an emphasis on the printing mechanism and the resultant scaffold characteristics. Current practical challenges and technical limitations are emphasized and future trends of bioprinting are discussed.

  2. Thermal infrared images to quantify thermal ablation effects of acid and base on target tissues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ran, E-mail: jliubme@tsinghua.edu.cn, E-mail: liuran@tsinghua.edu.cn; Liu, Jing, E-mail: jliubme@tsinghua.edu.cn, E-mail: liuran@tsinghua.edu.cn [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); Wang, Jia [Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218 (United States)

    2015-07-15

    Hyperthermia (42-46°C), treatment of tumor tissue through elevated temperature, offers several advantages including high cost-effectiveness, highly targeted ablation and fewer side effects and hence higher safety level over traditional therapies such as chemotherapy and radiotherapy. Recently, hyperthermia using heat release through exothermic acid-base neutralization comes into view owing to its relatively safe products of salt and water and highly confined ablation. However, lack of quantitative understanding of the spatial and temporal temperature profiles that are produced by simultaneous diffusion of liquid chemical and its chemical reaction within tumor tissue impedes the application of this method. This article is dedicated to quantify thermal ablation effects of acid and base both individually and as in neutralization via infrared captured thermal images. A theoretical model is used to approximate specific heat absorption rate (SAR) based on experimental measurements that contrast two types of tissue, normal pork and pig liver. According to the computation, both pork and liver tissue has a higher ability in absorbing hydrochloric acid (HCl) than sodium hydroxide, hence suggesting that a reduced dosage for HCl is appropriate in a surgery. The heating effect depends heavily on the properties of tissue types and amount of chemical reagents administered. Given thermal parameters such as SAR for different tissues, a computational model can be made in predicting temperature transitions which will be helpful in planning and optimizing surgical hyperthermia procedures.

  3. Thermal infrared images to quantify thermal ablation effects of acid and base on target tissues

    Directory of Open Access Journals (Sweden)

    Ran Liu

    2015-07-01

    Full Text Available Hyperthermia (42-46°C, treatment of tumor tissue through elevated temperature, offers several advantages including high cost-effectiveness, highly targeted ablation and fewer side effects and hence higher safety level over traditional therapies such as chemotherapy and radiotherapy. Recently, hyperthermia using heat release through exothermic acid-base neutralization comes into view owing to its relatively safe products of salt and water and highly confined ablation. However, lack of quantitative understanding of the spatial and temporal temperature profiles that are produced by simultaneous diffusion of liquid chemical and its chemical reaction within tumor tissue impedes the application of this method. This article is dedicated to quantify thermal ablation effects of acid and base both individually and as in neutralization via infrared captured thermal images. A theoretical model is used to approximate specific heat absorption rate (SAR based on experimental measurements that contrast two types of tissue, normal pork and pig liver. According to the computation, both pork and liver tissue has a higher ability in absorbing hydrochloric acid (HCl than sodium hydroxide, hence suggesting that a reduced dosage for HCl is appropriate in a surgery. The heating effect depends heavily on the properties of tissue types and amount of chemical reagents administered. Given thermal parameters such as SAR for different tissues, a computational model can be made in predicting temperature transitions which will be helpful in planning and optimizing surgical hyperthermia procedures.

  4. Toward quantifying the composition of soft tissues by spectral CT with Medipix3.

    Science.gov (United States)

    Ronaldson, J Paul; Zainon, Rafidah; Scott, Nicola Jean Agnes; Gieseg, Steven Paul; Butler, Anthony P; Butler, Philip H; Anderson, Nigel G

    2012-11-01

    To determine the potential of spectral computed tomography (CT) with Medipix3 for quantifying fat, calcium, and iron in soft tissues within small animal models and surgical specimens of diseases such as fatty liver (metabolic syndrome) and unstable atherosclerosis. The spectroscopic method was applied to tomographic data acquired using a micro-CT system incorporating a Medipix3 detector array with silicon sensor layer and microfocus x-ray tube operating at 50 kVp. A 10 mm diameter perspex phantom containing a fat surrogate (sunflower oil) and aqueous solutions of ferric nitrate, calcium chloride, and iodine was imaged with multiple energy bins. The authors used the spectroscopic characteristics of the CT number to establish a basis for the decomposition of soft tissue components. The potential of the method of constrained least squares for quantifying different sets of materials was evaluated in terms of information entropy and degrees of freedom, with and without the use of a volume conservation constraint. The measurement performance was evaluated quantitatively using atheroma and mouse equivalent phantoms. Finally the decomposition method was assessed qualitatively using a euthanized mouse and an excised human atherosclerotic plaque. Spectral CT measurements of a phantom containing tissue surrogates confirmed the ability to distinguish these materials by the spectroscopic characteristics of their CT number. The assessment of performance potential in terms of information entropy and degrees of freedom indicated that certain sets of up to three materials could be decomposed by the method of constrained least squares. However, there was insufficient information within the data set to distinguish calcium from iron within soft tissues. The quantification of calcium concentration and fat mass fraction within atheroma and mouse equivalent phantoms by spectral CT correlated well with the nominal values (R(2) = 0.990 and R(2) = 0.985, respectively). In the euthanized

  5. Tissue-engineering as an adjunct to pelvic reconstructive surgery

    DEFF Research Database (Denmark)

    Jangö, Hanna

    of pelvic organ prolapse (POP) are warranted. Traditional native tissue repair may be associated with poor long-term outcome and augmentation with permanent polypropylene meshes is associated with frequent and severe adverse effects. Tissue-engineering is a regenerative strategy that aims at creating...... functional tissue using stem cells, scaffolds and trophic factors. The aim of this thesis was to investigate the potential adjunctive use of a tissue-engineering technique for pelvic reconstructive surgery using two synthetic biodegradable materials; methoxypolyethyleneglycol-poly(lactic-co-glycolic acid...

  6. Perfusion systems that minimize vascular volume fraction in engineered tissues.

    Science.gov (United States)

    Truslow, James G; Tien, Joe

    2011-06-01

    This study determines the optimal vascular designs for perfusing engineered tissues. Here, "optimal" describes a geometry that minimizes vascular volume fraction (the fractional volume of a tissue that is occupied by vessels) while maintaining oxygen concentration above a set threshold throughout the tissue. Computational modeling showed that optimal geometries depended on parameters that affected vascular fluid transport and oxygen consumption. Approximate analytical expressions predicted optima that agreed well with the results of modeling. Our results suggest one basis for comparing the effectiveness of designs for microvascular tissue engineering.

  7. Biodegradable and biocompatible polymers for tissue engineering application: a review.

    Science.gov (United States)

    Asghari, Fatemeh; Samiei, Mohammad; Adibkia, Khosro; Akbarzadeh, Abolfazl; Davaran, Soodabeh

    2017-03-01

    Since so many years ago, tissue damages that are caused owing to various reasons attract scientists' attention to find a practical way to treat. In this regard, many studies were conducted. Nano scientists also suggested some ways and the newest one is called tissue engineering. They use biodegradable polymers in order to replace damaged structures in tissues to make it practical. Biodegradable polymers are dominant scaffolding materials in tissue engineering field. In this review, we explained about biodegradable polymers and their application as scaffolds.

  8. Bone Tissue Engineering Challenges in Oral & Maxillofacial Surgery.

    Science.gov (United States)

    Smith, Brandon T; Shum, Jonathan; Wong, Mark; Mikos, Antonios G; Young, Simon

    2015-01-01

    Over the past decades, there has been a substantial amount of innovation and research into tissue engineering and regenerative approaches for the craniofacial region. This highly complex area presents many unique challenges for tissue engineers. Recent research indicates that various forms of implantable biodegradable scaffolds may play a beneficial role in the clinical treatment of craniofacial pathological conditions. Additionally, the direct delivery of bioactive molecules may further increase de novo bone formation. While these strategies offer an exciting glimpse into potential future treatments, there are several challenges that still must be overcome. In this chapter, we will highlight both current surgical approaches for craniofacial reconstruction and recent advances within the field of bone tissue engineering. The clinical challenges and limitations of these strategies will help contextualize and inform future craniofacial tissue engineering strategies.

  9. Hollow fiber bioreactor technology for tissue engineering applications.

    Science.gov (United States)

    Eghbali, Hadis; Nava, Michele M; Mohebbi-Kalhori, Davod; Raimondi, Manuela T

    2016-01-01

    Hollow fiber bioreactors are the focus of scientific research aiming to mimic physiological vascular networks and engineer organs and tissues in vitro. The reason for this lies in the interesting features of this bioreactor type, including excellent mass transport properties. Indeed, hollow fiber bioreactors allow limitations to be overcome in nutrient transport by diffusion, which is often an obstacle to engineer sizable constructs in vitro. This work reviews the existing literature relevant to hollow fiber bioreactors in organ and tissue engineering applications. To this purpose, we first classify the hollow fiber bioreactors into 2 categories: cylindrical and rectangular. For each category, we summarize their main applications both at the tissue and at the organ level, focusing on experimental models and computational studies as predictive tools for designing innovative, dynamic culture systems. Finally, we discuss future perspectives on hollow fiber bioreactors as in vitro models for tissue and organ engineering applications.

  10. Production of extracellular matrix powder for tissue engineering

    Directory of Open Access Journals (Sweden)

    Sanambar Sadighi

    2014-09-01

    Conclusion: The results show that our decellularization method produced an adipose ECM scaffold rich of collagen fibers, suitable and effective substrate for use in soft tissue engineering and regenerative medicine.

  11. Polyacylurethanes as Novel Degradable Cell Carrier Materials for Tissue Engineering

    NARCIS (Netherlands)

    Jovanovic, Danijela; Roukes, Frans V.; Loeber, Andrea; Engels, Gerwin E.; van Oeveren, Willem; van Seijen, Xavier J. Gallego; van Luyn, Marja J. A.; Harmsen, Martin C.; Schouten, Arend Jan

    2011-01-01

    Polycaprolactone (PCL) polyester and segmented aliphatic polyester urethanes based on PCL soft segment have been thoroughly investigated as biodegradable scaffolds for tissue engineering. Although proven beneficial as long term implants, these materials degrade very slowly and are therefore not suit

  12. Cell Sheet-Based Tissue Engineering for Organizing Anisotropic Tissue Constructs Produced Using Microfabricated Thermoresponsive Substrates.

    Science.gov (United States)

    Takahashi, Hironobu; Okano, Teruo

    2015-11-18

    In some native tissues, appropriate microstructures, including orientation of the cell/extracellular matrix, provide specific mechanical and biological functions. For example, skeletal muscle is made of oriented myofibers that is responsible for the mechanical function. Native artery and myocardial tissues are organized three-dimensionally by stacking sheet-like tissues of aligned cells. Therefore, to construct any kind of complex tissue, the microstructures of cells such as myotubes, smooth muscle cells, and cardiomyocytes also need to be organized three-dimensionally just as in the native tissues of the body. Cell sheet-based tissue engineering allows the production of scaffold-free engineered tissues through a layer-by-layer construction technique. Recently, using microfabricated thermoresponsive substrates, aligned cells are being harvested as single continuous cell sheets. The cell sheets act as anisotropic tissue units to build three-dimensional tissue constructs with the appropriate anisotropy. This cell sheet-based technology is straightforward and has the potential to engineer a wide variety of complex tissues. In addition, due to the scaffold-free cell-dense environment, the physical and biological cell-cell interactions of these cell sheet constructs exhibit unique cell behaviors. These advantages will provide important clues to enable the production of well-organized tissues that closely mimic the structure and function of native tissues, required for the future of tissue engineering. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Self-synthesized extracellular matrix contributes to mature adipose tissue regeneration in a tissue engineering chamber.

    Science.gov (United States)

    Zhan, Weiqing; Chang, Qiang; Xiao, Xiaolian; Dong, Ziqing; Zeng, Zhaowei; Gao, Jianhua; Lu, Feng

    2015-01-01

    The development of an engineered adipose tissue substitute capable of supporting reliable, predictable, and complete fat tissue regeneration would be of value in plastic and reconstructive surgery. For adipogenesis, a tissue engineering chamber provides an optimized microenvironment that is both efficacious and reproducible; however, for reasons that remain unclear, tissues regenerated in a tissue engineering chamber consist mostly of connective rather than adipose tissue. Here, we describe a chamber-based system for improving the yield of mature adipose tissue and discuss the potential mechanism of adipogenesis in tissue-chamber models. Adipose tissue flaps with independent vascular pedicles placed in chambers were implanted into rabbits. Adipose volume increased significantly during the observation period (week 1, 2, 3, 4, 16). Histomorphometry revealed mature adipose tissue with signs of adipose tissue remolding. The induced engineered constructs showed high-level expression of adipogenic (peroxisome proliferator-activated receptor γ), chemotactic (stromal cell-derived factor 1a), and inflammatory (interleukin 1 and 6) genes. In our system, the extracellular matrix may have served as a scaffold for cell migration and proliferation, allowing mature adipose tissue to be obtained in a chamber microenvironment without the need for an exogenous scaffold. Our results provide new insights into key elements involved in the early development of adipose tissue regeneration.

  14. Biological augmentation and tissue engineering approaches in meniscus surgery.

    Science.gov (United States)

    Moran, Cathal J; Busilacchi, Alberto; Lee, Cassandra A; Athanasiou, Kyriacos A; Verdonk, Peter C

    2015-05-01

    The purpose of this review was to evaluate the role of biological augmentation and tissue engineering strategies in meniscus surgery. Although clinical (human), preclinical (animal), and in vitro tissue engineering studies are included here, we have placed additional focus on addressing preclinical and clinical studies reported during the 5-year period used in this review in a systematic fashion while also providing a summary review of some important in vitro tissue engineering findings in the field over the past decade. A search was performed on PubMed for original works published from 2009 to March 31, 2014 using the term "meniscus" with all the following terms: "scaffolds," "constructs," "cells," "growth factors," "implant," "tissue engineering," and "regenerative medicine." Inclusion criteria were the following: English-language articles and original clinical, preclinical (in vivo), and in vitro studies of tissue engineering and regenerative medicine application in knee meniscus lesions published from 2009 to March 31, 2014. Three clinical studies and 18 preclinical studies were identified along with 68 tissue engineering in vitro studies. These reports show the increasing promise of biological augmentation and tissue engineering strategies in meniscus surgery. The role of stem cell and growth factor therapy appears to be particularly useful. A review of in vitro tissue engineering studies found a large number of scaffold types to be of promise for meniscus replacement. Limitations include a relatively low number of clinical or preclinical in vivo studies, in addition to the fact there is as yet no report in the literature of a tissue-engineered meniscus construct used clinically. Neither does the literature provide clarity on the optimal meniscus scaffold type or biological augmentation with which meniscus repair or replacement would be best addressed in the future. There is increasing focus on the role of mechanobiology and biomechanical and

  15. Endochondral Priming: A Developmental Engineering Strategy for Bone Tissue Regeneration.

    Science.gov (United States)

    Freeman, Fiona E; McNamara, Laoise M

    2017-04-01

    Tissue engineering and regenerative medicine have significant potential to treat bone pathologies by exploiting the capacity for bone progenitors to grow and produce tissue constituents under specific biochemical and physical conditions. However, conventional tissue engineering approaches, which combine stem cells with biomaterial scaffolds, are limited as the constructs often degrade, due to a lack of vascularization, and lack the mechanical integrity to fulfill load bearing functions, and as such are not yet widely used for clinical treatment of large bone defects. Recent studies have proposed that in vitro tissue engineering approaches should strive to simulate in vivo bone developmental processes and, thereby, imitate natural factors governing cell differentiation and matrix production, following the paradigm recently defined as "developmental engineering." Although developmental engineering strategies have been recently developed that mimic specific aspects of the endochondral ossification bone formation process, these findings are not widely understood. Moreover, a critical comparison of these approaches to standard biomaterial-based bone tissue engineering has not yet been undertaken. For that reason, this article presents noteworthy experimental findings from researchers focusing on developing an endochondral-based developmental engineering strategy for bone tissue regeneration. These studies have established that in vitro approaches, which mimic certain aspects of the endochondral ossification process, namely the formation of the cartilage template and the vascularization of the cartilage template, can promote mineralization and vascularization to a certain extent both in vitro and in vivo. Finally, this article outlines specific experimental challenges that must be overcome to further exploit the biology of endochondral ossification and provide a tissue engineering construct for clinical treatment of large bone/nonunion defects and obviate the need for

  16. Tissue engineering: state of the art in oral rehabilitation

    OpenAIRE

    SCHELLER, E. L.; Krebsbach, P.H.; Kohn, D. H.

    2009-01-01

    More than 85% of the global population requires repair or replacement of a craniofacial structure. These defects range from simple tooth decay to radical oncologic craniofacial resection. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science and engineering technology. Identification of appropriate scaffolds, cell sources and spatial and temporal signals (the tissue engineering triad) is necessary to optimize d...

  17. Processing and characterization of piezoelectric polymers for tissue engineering applications

    OpenAIRE

    Ribeiro, Clarisse Marta Oliveira

    2012-01-01

    Tese de doutoramento em Ciências (ramo de conhecimento em Física) In the last decades, the biomaterials and tissue engineering interdisciplinary research fields have been two of the most dynamic ones and have attracted increasing attention by the scientific community. With the advancements in the tissue engineering field the necessity of study and develop a wide variety of biomaterials with different properties has emerged. Among the different types of materials, polymers hav...

  18. 3D Nanoprinting Technologies for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Jin Woo Lee

    2015-01-01

    Full Text Available Tissue engineering recovers an original function of tissue by replacing the damaged part with a new tissue or organ regenerated using various engineering technologies. This technology uses a scaffold to support three-dimensional (3D tissue formation. Conventional scaffold fabrication methods do not control the architecture, pore shape, porosity, or interconnectivity of the scaffold, so it has limited ability to stimulate cell growth and to generate new tissue. 3D printing technologies may overcome these disadvantages of traditional fabrication methods. These technologies use computers to assist in design and fabrication, so the 3D scaffolds can be fabricated as designed and standardized. Particularly, because nanofabrication technology based on two-photon absorption (2PA and on controlled electrospinning can generate structures with submicron resolution, these methods have been evaluated in various areas of tissue engineering. Recent combinations of 3D nanoprinting technologies with methods from molecular biology and cell dynamics have suggested new possibilities for improved tissue regeneration. If the interaction between cells and scaffold system with biomolecules can be understood and controlled and if an optimal 3D environment for tissue regeneration can be realized, 3D nanoprinting will become an important tool in tissue engineering.

  19. Tissue Engineering for the Neonatal and Pediatric Patients

    Directory of Open Access Journals (Sweden)

    Amulya K. Saxena

    2012-01-01

    Full Text Available Of all the surgical specialties, the remit of the pediatric surgeon encompasses the widest range of organ systems and includes disorders from the fetus to the adolescent. As such, the recent emergence of tissue engineering is of particular interest to the pediatric surgical community. The individual challenges of tissue engineering depend largely on the nature and function of the target tissue. In general, the main issues currently under investigation include the sourcing of an appropriate cell source, design of biomaterials for guided tissue growth, provision of a biomolecular stimulus to enhance cellular functions and the development of bioreactors to allow for prolonged periods of cell culture under specific physiological conditions. This review aims to provide a general overview of tissue engineering in the major organ systems, including the cardiovascular, digestive, urinary, respiratory, musculoskeletal, nervous, integumentary and lymphatic systems. Special attention is paid to pediatrics as well as recent clinical applications.

  20. 3D Bioprinting Technologies for Hard Tissue and Organ Engineering

    Directory of Open Access Journals (Sweden)

    Xiaohong Wang

    2016-09-01

    Full Text Available Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering.

  1. Soft Tissue Engineering with Micronized-Gingival Connective Tissues.

    Science.gov (United States)

    Noda, Sawako; Sumita, Yoshinori; Ohba, Seigo; Yamamoto, Hideyuki; Asahina, Izumi

    2017-02-24

    The free gingival graft (FGG) and connective tissue graft (CTG) are currently considered to be the gold standards for keratinized gingival tissue reconstruction and augmentation. However, these procedures have some disadvantages in harvesting large grafts, such as donor-site morbidity as well as insufficient gingival width and thickness at the recipient site post-treatment. To solve these problems, we focused on an alternative strategy using micronized tissue transplantation (micro-graft). In this study, we first investigated whether transplantation of micronized gingival connective tissues (MGCTs) promotes skin wound healing. MGCTs (≤100 µm) were obtained by mincing a small piece (8 mm(3) ) of porcine keratinized gingiva using the RIGENERA system. The MGCTs were then transplanted to a full skin defect (5 mm in diameter) on the dorsal surface of immunodeficient mice after seeding to an atelocollagen matrix. Transplantations of atelocollagen matrixes with and without micronized dermis were employed as experimental controls. The results indicated that MGCTs markedly promote the vascularization and epithelialization of the defect area 14 days after transplantation compared to the experimental controls. After 21 days, complete wound closure with low contraction was obtained only in the MGCT grafts. Tracking analysis of transplanted MGCTs revealed that some mesenchymal cells derived from MGCTs can survive during healing and may function to assist in wound healing. We propose here that micro-grafting with MGCTs represents an alternative strategy for keratinized tissue reconstruction that is characterized by low morbidity and ready availability. This article is protected by copyright. All rights reserved.

  2. Advances in polymeric systems for tissue engineering and biomedical applications.

    Science.gov (United States)

    Ravichandran, Rajeswari; Sundarrajan, Subramanian; Venugopal, Jayarama Reddy; Mukherjee, Shayanti; Ramakrishna, Seeram

    2012-03-01

    The characteristics of tissue engineered scaffolds are major concerns in the quest to fabricate ideal scaffolds for tissue engineering applications. The polymer scaffolds employed for tissue engineering applications should possess multifunctional properties such as biocompatibility, biodegradability and favorable mechanical properties as it comes in direct contact with the body fluids in vivo. Additionally, the polymer system should also possess biomimetic architecture and should support stem cell adhesion, proliferation and differentiation. As the progress in polymer technology continues, polymeric biomaterials have taken characteristics more closely related to that desired for tissue engineering and clinical needs. Stimuli responsive polymers also termed as smart biomaterials respond to stimuli such as pH, temperature, enzyme, antigen, glucose and electrical stimuli that are inherently present in living systems. This review highlights the exciting advancements in these polymeric systems that relate to biological and tissue engineering applications. Additionally, several aspects of technology namely scaffold fabrication methods and surface modifications to confer biological functionality to the polymers have also been discussed. The ultimate objective is to emphasize on these underutilized adaptive behaviors of the polymers so that novel applications and new generations of smart polymeric materials can be realized for biomedical and tissue engineering applications.

  3. Engineering parameters in bioreactor's design: a critical aspect in tissue engineering

    NARCIS (Netherlands)

    dds., N.; Amoabediny, G.; Pouran, B.; Tabesh, H.; Shokrgozar, M.A.; Haghighipour, N.; Khatibi, N.; Anisi, F.; Mottaghy, K.; Zandieh-Doulabi, B.

    2013-01-01

    Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transf

  4. 3D prostate histology image reconstruction: Quantifying the impact of tissue deformation and histology section location

    Directory of Open Access Journals (Sweden)

    Eli Gibson

    2013-01-01

    Full Text Available Background: Guidelines for localizing prostate cancer on imaging are ideally informed by registered post-prostatectomy histology. 3D histology reconstruction methods can support this by reintroducing 3D spatial information lost during histology processing. The need to register small, high-grade foci drives a need for high accuracy. Accurate 3D reconstruction method design is impacted by the answers to the following central questions of this work. (1 How does prostate tissue deform during histology processing? (2 What spatial misalignment of the tissue sections is induced by microtome cutting? (3 How does the choice of reconstruction model affect histology reconstruction accuracy? Materials and Methods: Histology, paraffin block face and magnetic resonance images were acquired for 18 whole mid-gland tissue slices from six prostates. 7-15 homologous landmarks were identified on each image. Tissue deformation due to histology processing was characterized using the target registration error (TRE after landmark-based registration under four deformation models (rigid, similarity, affine and thin-plate-spline [TPS]. The misalignment of histology sections from the front faces of tissue slices was quantified using manually identified landmarks. The impact of reconstruction models on the TRE after landmark-based reconstruction was measured under eight reconstruction models comprising one of four deformation models with and without constraining histology images to the tissue slice front faces. Results: Isotropic scaling improved the mean TRE by 0.8-1.0 mm (all results reported as 95% confidence intervals, while skew or TPS deformation improved the mean TRE by <0.1 mm. The mean misalignment was 1.1-1.9΀ (angle and 0.9-1.3 mm (depth. Using isotropic scaling, the front face constraint raised the mean TRE by 0.6-0.8 mm. Conclusions: For sub-millimeter accuracy, 3D reconstruction models should not constrain histology images to the tissue slice front faces and

  5. 3D prostate histology image reconstruction: Quantifying the impact of tissue deformation and histology section location

    Science.gov (United States)

    Gibson, Eli; Gaed, Mena; Gómez, José A.; Moussa, Madeleine; Pautler, Stephen; Chin, Joseph L.; Crukley, Cathie; Bauman, Glenn S.; Fenster, Aaron; Ward, Aaron D.

    2013-01-01

    Background: Guidelines for localizing prostate cancer on imaging are ideally informed by registered post-prostatectomy histology. 3D histology reconstruction methods can support this by reintroducing 3D spatial information lost during histology processing. The need to register small, high-grade foci drives a need for high accuracy. Accurate 3D reconstruction method design is impacted by the answers to the following central questions of this work. (1) How does prostate tissue deform during histology processing? (2) What spatial misalignment of the tissue sections is induced by microtome cutting? (3) How does the choice of reconstruction model affect histology reconstruction accuracy? Materials and Methods: Histology, paraffin block face and magnetic resonance images were acquired for 18 whole mid-gland tissue slices from six prostates. 7-15 homologous landmarks were identified on each image. Tissue deformation due to histology processing was characterized using the target registration error (TRE) after landmark-based registration under four deformation models (rigid, similarity, affine and thin-plate-spline [TPS]). The misalignment of histology sections from the front faces of tissue slices was quantified using manually identified landmarks. The impact of reconstruction models on the TRE after landmark-based reconstruction was measured under eight reconstruction models comprising one of four deformation models with and without constraining histology images to the tissue slice front faces. Results: Isotropic scaling improved the mean TRE by 0.8-1.0 mm (all results reported as 95% confidence intervals), while skew or TPS deformation improved the mean TRE by <0.1 mm. The mean misalignment was 1.1-1.9° (angle) and 0.9-1.3 mm (depth). Using isotropic scaling, the front face constraint raised the mean TRE by 0.6-0.8 mm. Conclusions: For sub-millimeter accuracy, 3D reconstruction models should not constrain histology images to the tissue slice front faces and should be

  6. Natural Polymer-Cell Bioconstructs for Bone Tissue Engineering.

    Science.gov (United States)

    Titorencu, Irina; Albu, Madalina Georgiana; Nemecz, Miruna; Jinga, Victor V

    2017-01-01

    The major goal of bone tissue engineering is to develop bioconstructs which substitute the functionality of damaged natural bone structures as much as possible if critical-sized defects occur. Scaffolds that mimic the structure and composition of bone tissue and cells play a pivotal role in bone tissue engineering applications. First, composition, properties and in vivo synthesis of bone tissue are presented for the understanding of bone formation. Second, potential sources of osteoprogenitor cells have been investigated for their capacity to induce bone repair and regeneration. Third, taking into account that the main property to qualify one scaffold as a future bioconstruct for bone tissue engineering is the biocompatibility, the assessments which prove it are reviewed in this paper. Forth, various types of natural polymer- based scaffolds consisting in proteins, polysaccharides, minerals, growth factors etc, are discussed, and interaction between scaffolds and cells which proved bone tissue engineering concept are highlighted. Finally, the future perspectives of natural polymer-based scaffolds for bone tissue engineering are considered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Stem Cell Sources for Vascular Tissue Engineering and Regeneration

    Science.gov (United States)

    Bajpai, Vivek K.

    2012-01-01

    This review focuses on the stem cell sources with the potential to be used in vascular tissue engineering and to promote vascular regeneration. The first clinical studies using tissue-engineered vascular grafts are already under way, supporting the potential of this technology in the treatment of cardiovascular and other diseases. Despite progress in engineering biomaterials with the appropriate mechanical properties and biological cues as well as bioreactors for generating the correct tissue microenvironment, the source of cells that make up the vascular tissues remains a major challenge for tissue engineers and physicians. Mature cells from the tissue of origin may be difficult to obtain and suffer from limited proliferative capacity, which may further decline as a function of donor age. On the other hand, multipotent and pluripotent stem cells have great potential to provide large numbers of autologous cells with a great differentiation capacity. Here, we discuss the adult multipotent as well as embryonic and induced pluripotent stem cells, their differentiation potential toward vascular lineages, and their use in engineering functional and implantable vascular tissues. We also discuss the associated challenges that need to be addressed in order to facilitate the transition of this technology from the bench to the bedside. PMID:22571595

  8. Polymeric Scaffolds in Tissue Engineering Application: A Review

    Directory of Open Access Journals (Sweden)

    Brahatheeswaran Dhandayuthapani

    2011-01-01

    Full Text Available Current strategies of regenerative medicine are focused on the restoration of pathologically altered tissue architectures by transplantation of cells in combination with supportive scaffolds and biomolecules. In recent years, considerable interest has been given to biologically active scaffolds which are based on similar analogs of the extracellular matrix that have induced synthesis of tissues and organs. To restore function or regenerate tissue, a scaffold is necessary that will act as a temporary matrix for cell proliferation and extracellular matrix deposition, with subsequent ingrowth until the tissues are totally restored or regenerated. Scaffolds have been used for tissue engineering such as bone, cartilage, ligament, skin, vascular tissues, neural tissues, and skeletal muscle and as vehicle for the controlled delivery of drugs, proteins, and DNA. Various technologies come together to construct porous scaffolds to regenerate the tissues/organs and also for controlled and targeted release of bioactive agents in tissue engineering applications. In this paper, an overview of the different types of scaffolds with their material properties is discussed. The fabrication technologies for tissue engineering scaffolds, including the basic and conventional techniques to the more recent ones, are tabulated.

  9. Interdigitated array of Pt electrodes for electrical stimulation and engineering of aligned muscle tissue.

    Science.gov (United States)

    Ahadian, Samad; Ramón-Azcón, Javier; Ostrovidov, Serge; Camci-Unal, Gulden; Hosseini, Vahid; Kaji, Hirokazu; Ino, Kosuke; Shiku, Hitoshi; Khademhosseini, Ali; Matsue, Tomokazu

    2012-09-21

    Engineered skeletal muscle tissues could be useful for applications in tissue engineering, drug screening, and bio-robotics. It is well-known that skeletal muscle cells are able to differentiate under electrical stimulation (ES), with an increase in myosin production, along with the formation of myofibers and contractile proteins. In this study, we describe the use of an interdigitated array of electrodes as a novel platform to electrically stimulate engineered muscle tissues. The resulting muscle myofibers were analyzed and quantified in terms of their myotube characteristics and gene expression. The engineered muscle tissues stimulated through the interdigitated array of electrodes demonstrated superior performance and maturation compared to the corresponding tissues stimulated through a conventional setup (i.e., through Pt wires in close proximity to the muscle tissue). In particular, the ES of muscle tissue (voltage 6 V, frequency 1 Hz and duration 10 ms for 1 day) through the interdigitated array of electrodes resulted in a higher degree of C2C12 myotube alignment (∼80%) as compared to ES using Pt wires (∼65%). In addition, higher amounts of C2C12 myotube coverage area, myotube length, muscle transcription factors and protein biomarkers were found for myotubes stimulated through the interdigitated array of electrodes compared to those stimulated using the Pt wires. Due to the wide array of potential applications of ES for two- and three-dimensional (2D and 3D) engineered tissues, the suggested platform could be employed for a variety of cell and tissue structures to more efficiently investigate their response to electrical fields.

  10. Stratified scaffold design for engineering composite tissues.

    Science.gov (United States)

    Mosher, Christopher Z; Spalazzi, Jeffrey P; Lu, Helen H

    2015-08-01

    A significant challenge to orthopaedic soft tissue repair is the biological fixation of autologous or allogeneic grafts with bone, whereby the lack of functional integration between such grafts and host bone has limited the clinical success of anterior cruciate ligament (ACL) and other common soft tissue-based reconstructive grafts. The inability of current surgical reconstruction to restore the native fibrocartilaginous insertion between the ACL and the femur or tibia, which minimizes stress concentration and facilitates load transfer between the soft and hard tissues, compromises the long-term clinical functionality of these grafts. To enable integration, a stratified scaffold design that mimics the multiple tissue regions of the ACL interface (ligament-fibrocartilage-bone) represents a promising strategy for composite tissue formation. Moreover, distinct cellular organization and phase-specific matrix heterogeneity achieved through co- or tri-culture within the scaffold system can promote biomimetic multi-tissue regeneration. Here, we describe the methods for fabricating a tri-phasic scaffold intended for ligament-bone integration, as well as the tri-culture of fibroblasts, chondrocytes, and osteoblasts on the stratified scaffold for the formation of structurally contiguous and compositionally distinct regions of ligament, fibrocartilage and bone. The primary advantage of the tri-phasic scaffold is the recapitulation of the multi-tissue organization across the native interface through the layered design. Moreover, in addition to ease of fabrication, each scaffold phase is similar in polymer composition and therefore can be joined together by sintering, enabling the seamless integration of each region and avoiding delamination between scaffold layers.

  11. Three-dimensional bioprinting in tissue engineering and regenerative medicine.

    Science.gov (United States)

    Gao, Guifang; Cui, Xiaofeng

    2016-02-01

    With the advances of stem cell research, development of intelligent biomaterials and three-dimensional biofabrication strategies, highly mimicked tissue or organs can be engineered. Among all the biofabrication approaches, bioprinting based on inkjet printing technology has the promises to deliver and create biomimicked tissue with high throughput, digital control, and the capacity of single cell manipulation. Therefore, this enabling technology has great potential in regenerative medicine and translational applications. The most current advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review, including vasculature, muscle, cartilage, and bone. In addition, the benign side effect of bioprinting to the printed mammalian cells can be utilized for gene or drug delivery, which can be achieved conveniently during precise cell placement for tissue construction. With layer-by-layer assembly, three-dimensional tissues with complex structures can be printed using converted medical images. Therefore, bioprinting based on thermal inkjet is so far the most optimal solution to engineer vascular system to the thick and complex tissues. Collectively, bioprinting has great potential and broad applications in tissue engineering and regenerative medicine. The future advances of bioprinting include the integration of different printing mechanisms to engineer biphasic or triphasic tissues with optimized scaffolds and further understanding of stem cell biology.

  12. Challenges and opportunities for tissue-engineering polarized epithelium.

    Science.gov (United States)

    Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

    2014-02-01

    The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

  13. Stem cell homing-based tissue engineering using bioactive materials

    Science.gov (United States)

    Yu, Yinxian; Sun, Binbin; Yi, Chengqing; Mo, Xiumei

    2017-06-01

    Tissue engineering focuses on repairing tissue and restoring tissue functions by employing three elements: scaffolds, cells and biochemical signals. In tissue engineering, bioactive material scaffolds have been used to cure tissue and organ defects with stem cell-based therapies being one of the best documented approaches. In the review, different biomaterials which are used in several methods to fabricate tissue engineering scaffolds were explained and show good properties (biocompatibility, biodegradability, and mechanical properties etc.) for cell migration and infiltration. Stem cell homing is a recruitment process for inducing the migration of the systemically transplanted cells, or host cells, to defect sites. The mechanisms and modes of stem cell homing-based tissue engineering can be divided into two types depending on the source of the stem cells: endogenous and exogenous. Exogenous stem cell-based bioactive scaffolds have the challenge of long-term culturing in vitro and for endogenous stem cells the biochemical signal homing recruitment mechanism is not clear yet. Although the stem cell homing-based bioactive scaffolds are attractive candidates for tissue defect therapies, based on in vitro studies and animal tests, there is still a long way before clinical application.

  14. Fabrication of nanofibrous scaffolds for tissue engineering applications

    NARCIS (Netherlands)

    Chen, H.; Truckenmuller, R.K.; Blitterswijk, van C.A.; Moroni, L.; Gaharwar, A.K.; Sant, S.; Hancock, M.J.; Hacking, A.A.

    2013-01-01

    Nanofibrous scaffolds which mimic the structural features of a natural extracellular matrix (ECM) can be appealing scaffold candidates for tissue engineering as they provide similar physical cues to the native environment of the targeted tissue to regenerate. This chapter discusses different strateg

  15. Training human mesenchymal stromal cells for bone tissue engineering applications

    NARCIS (Netherlands)

    Doorn, J.

    2012-01-01

    Human mesenchymal stromal cells (hMSCs) are an interesting source for cell therapies and tissue engineering applications, because these cells are able to differentiate into various target tissues, such as bone, cartilage, fat and endothelial cells. In addition, they secrete a wide array of growth fa

  16. A bioreactor system for clinically relevant bone tissue engineering

    NARCIS (Netherlands)

    Janssen, Franciscus Wilhelmus

    2010-01-01

    Tissue engineering of bone by combining mesenchymal stem cells (MSCs) with a suitable ceramic carrier provides a potential alternative for autologous bone grafts. However, for large scale-production, the current two dimensional (2D) multiplication process in tissue culture flasks has some serious dr

  17. Engineered Polymeric Hydrogels for 3D Tissue Models

    Directory of Open Access Journals (Sweden)

    Sujin Park

    2016-01-01

    Full Text Available Polymeric biomaterials are widely used in a wide range of biomedical applications due to their unique properties, such as biocompatibility, multi-tunability and easy fabrication. Specifically, polymeric hydrogel materials are extensively utilized as therapeutic implants and therapeutic vehicles for tissue regeneration and drug delivery systems. Recently, hydrogels have been developed as artificial cellular microenvironments because of the structural and physiological similarity to native extracellular matrices. With recent advances in hydrogel materials, many researchers are creating three-dimensional tissue models using engineered hydrogels and various cell sources, which is a promising platform for tissue regeneration, drug discovery, alternatives to animal models and the study of basic cell biology. In this review, we discuss how polymeric hydrogels are used to create engineered tissue constructs. Specifically, we focus on emerging technologies to generate advanced tissue models that precisely recapitulate complex native tissues in vivo.

  18. Spatial organization and correlation properties quantify structural changes on mesoscale of parenchymatous plant tissue

    Science.gov (United States)

    Valous, N. A.; Delgado, A.; Drakakis, K.; Sun, D.-W.

    2014-02-01

    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.

  19. Spatial organization and correlation properties quantify structural changes on mesoscale of parenchymatous plant tissue

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Diffuse Optical Spectroscopy and Imaging to Detect and Quantify Adipose Tissue Browning

    Science.gov (United States)

    Dinish, U. S; Wong, Chi Lok; Sriram, Sandhya; Ong, Wee Kiat; Balasundaram, Ghayathri; Sugii, Shigeki; Olivo, Malini

    2017-01-01

    Adipose (fat) tissue is a complex metabolic organ that is highly active and essential. In contrast to white adipose tissue (WAT), brown adipose tissue (BAT) is deemed metabolically beneficial because of its ability to burn calories through heat production. The conversion of WAT-resident adipocytes to “beige” or “brown-like” adipocytes has recently attracted attention. However, it typically takes a few days to analyze and confirm this browning of WAT through conventional molecular, biochemical, or histological methods. Moreover, accurate quantification of the overall browning process is not possible by any of these methods. In this context, we report the novel application of diffuse reflectance spectroscopy (DRS) and multispectral imaging (MSI) to detect and quantify the browning process in mice. We successfully demonstrated the time-dependent increase in browning of WAT, following its induction through β-adrenergic agonist injections. The results from these optical techniques were confirmed with those of standard molecular and biochemical assays, which measure gene and protein expression levels of UCP1 and PGC-1α, as well as with histological examinations. We envision that the reported optical methods can be developed into a fast, real time, cost effective and easy to implement imaging approach for quantification of the browning process in adipose tissue. PMID:28145475

  1. Cell Microenvironment Engineering and Monitoring for Tissue Engineering and Regenerative Medicine: The Recent Advances

    Science.gov (United States)

    Barthes, Julien; Özçelik, Hayriye; Hindié, Mathilde; Ndreu-Halili, Albana; Hasan, Anwarul

    2014-01-01

    In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future. PMID:25143954

  2. Blends and Nanocomposite Biomaterials for Articular Cartilage Tissue Engineering

    Science.gov (United States)

    Doulabi, Azadehsadat Hashemi; Mequanint, Kibret; Mohammadi, Hadi

    2014-01-01

    This review provides a comprehensive assessment on polymer blends and nanocomposite systems for articular cartilage tissue engineering applications. Classification of various types of blends including natural/natural, synthetic/synthetic systems, their combination and nanocomposite biomaterials are studied. Additionally, an inclusive study on their characteristics, cell responses ability to mimic tissue and regenerate damaged articular cartilage with respect to have functionality and composition needed for native tissue, are also provided. PMID:28788131

  3. BIOTECHNOLOGICAL CONDITIONS OF VALVE PROSTHESES CREATING BY TISSUE ENGINEERING METHOD

    OpenAIRE

    A. G. Popandopulo; M. V. Savchuk; D. L. Yudickiy

    2015-01-01

    Nowadays, definitive treatment for the end-stage organ failure is transplantation. Tissue engineering is an up to date solution to create the effective substitute of the defective organ. It involves the reconstitution of viable tissue with the use of autologous cells grown on connective tissue matrix, which has been acellularized before. Basis for the prothesis should be morphologically and physically nonmodified, so in case of making vessel-valvular biological prosthesises the decellularized...

  4. 3D Bioprinting Technologies for Hard Tissue and Organ Engineering

    OpenAIRE

    Xiaohong Wang; Qiang Ao; Xiaohong Tian; Jun Fan; Yujun Wei; Weijian Hou; Hao Tong; Shuling Bai

    2016-01-01

    Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especial...

  5. Reverse engineering development: crosstalk opportunities between developmental biology and tissue engineering.

    Science.gov (United States)

    Marcucio, Ralph S; Qin, Ling; Alsberg, Eben; Boerckel, Joel D

    2017-06-29

    The fields of developmental biology and tissue engineering have been revolutionized in recent years by technological advancements, expanded understanding, and biomaterials design, leading to the emerging paradigm of "developmental" or "biomimetic" tissue engineering. While developmental biology and tissue engineering have long overlapping histories, the fields have largely diverged in recent years at the same time that crosstalk opportunities for mutual benefit are more salient than ever. In this perspective article, we will use musculoskeletal development and tissue engineering as a platform on which to discuss these emerging crosstalk opportunities and will present our opinions on the bright future of these overlapping spheres of influence. The multicellular programs that control musculoskeletal development are rapidly becoming clarified, represented by shifting paradigms in our understanding of cellular function, identity, and lineage specification during development. Simultaneously, advancements in bioartificial matrices that replicate the biochemical, microstructural, and mechanical properties of developing tissues present new tools and approaches for recapitulating development in tissue engineering. Here, we introduce concepts and experimental approaches in musculoskeletal developmental biology and biomaterials design and discuss applications in tissue engineering as well as opportunities for tissue engineering approaches to inform our understanding of fundamental biology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Characterization of electrical stimulation electrodes for cardiac tissue engineering.

    Science.gov (United States)

    Tandon, Nina; Cannizzaro, Chris; Figallo, Elisa; Voldman, Joel; Vunjak-Novakovic, Gordana

    2006-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. The goal of this study was to assess the conditions of electrical stimulation with respect to the electrode geometry, material properties and charge-transfer characteristics at the electrode-electrolyte interface. We compared various biocompatible materials, including nanoporous carbon, stainless steel, titanium and titanium nitride, for use in cardiac tissue engineering bioreactors. The faradaic and non-faradaic charge transfer mechanisms were assessed by electrochemical impedance spectroscopy (EIS), studying current injection characteristics, and examining surface properties of electrodes with scanning electron microscopy. Carbon electrodes were found to have the best current injection characteristics. However, these electrodes require careful handling because of their limited mechanical strength. The efficacy of various electrodes for use in 2-D and 3-D cardiac tissue engineering systems with neonatal rat cardiomyocytes is being determined by assessing cell viability, amplitude of contractions, excitation thresholds, maximum capture rate, and tissue morphology.

  7. Powder-based 3D printing for bone tissue engineering.

    Science.gov (United States)

    Brunello, G; Sivolella, S; Meneghello, R; Ferroni, L; Gardin, C; Piattelli, A; Zavan, B; Bressan, E

    2016-01-01

    Bone tissue engineered 3-D constructs customized to patient-specific needs are emerging as attractive biomimetic scaffolds to enhance bone cell and tissue growth and differentiation. The article outlines the features of the most common additive manufacturing technologies (3D printing, stereolithography, fused deposition modeling, and selective laser sintering) used to fabricate bone tissue engineering scaffolds. It concentrates, in particular, on the current state of knowledge concerning powder-based 3D printing, including a description of the properties of powders and binder solutions, the critical phases of scaffold manufacturing, and its applications in bone tissue engineering. Clinical aspects and future applications are also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

    Directory of Open Access Journals (Sweden)

    Wan Nurlina Wan Yahya

    2014-07-01

    Full Text Available Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration.

  9. Cell Patterning for Liver Tissue Engineering via Dielectrophoretic Mechanisms

    Science.gov (United States)

    Yahya, Wan Nurlina Wan; Kadri, Nahrizul Adib; Ibrahim, Fatimah

    2014-01-01

    Liver transplantation is the most common treatment for patients with end-stage liver failure. However, liver transplantation is greatly limited by a shortage of donors. Liver tissue engineering may offer an alternative by providing an implantable engineered liver. Currently, diverse types of engineering approaches for in vitro liver cell culture are available, including scaffold-based methods, microfluidic platforms, and micropatterning techniques. Active cell patterning via dielectrophoretic (DEP) force showed some advantages over other methods, including high speed, ease of handling, high precision and being label-free. This article summarizes liver function and regenerative mechanisms for better understanding in developing engineered liver. We then review recent advances in liver tissue engineering techniques and focus on DEP-based cell patterning, including microelectrode design and patterning configuration. PMID:24991941

  10. Polycaprolactone thin films for retinal tissue engineering and drug delivery

    Science.gov (United States)

    Steedman, Mark Rory

    This dissertation focuses on the development of polycaprolactone thin films for retinal tissue engineering and drug delivery. We combined these thin films with techniques such as micro and nanofabrication to develop treatments for age-related macular degeneration (AMD), a disease that leads to the death of rod and cone photoreceptors. Current treatments are only able to slow or limit the progression of the disease, and photoreceptors cannot be regenerated or replaced by the body once lost. The first experiments presented focus on a potential treatment for AMD after photoreceptor death has occurred. We developed a polymer thin film scaffold technology to deliver retinal progenitor cells (RPCs) to the affected area of the eye. Earlier research showed that RPCs destined to become photoreceptors are capable of incorporating into a degenerated retina. In our experiments, we showed that RPC attachment to a micro-welled polycaprolactone (PCL) thin film surface enhanced the differentiation of these cells toward a photoreceptor fate. We then used our PCL thin films to develop a drug delivery device capable of sustained therapeutic release over a multi-month period that would maintain an effective concentration of the drug in the eye and eliminate the need for repeated intraocular injections. We first investigated the biocompatibility of PCL in the rabbit eye. We injected PCL thin films into the anterior chamber or vitreous cavity of rabbit eyes and monitored the animals for up to 6 months. We found that PCL thin films were well tolerated in the rabbit eye, showing no signs of chronic inflammation due to the implant. We then developed a multilayered thin film device containing a microporous membrane. We loaded these devices with lyophilized proteins and quantified drug elution for 10 weeks, finding that both bovine serum albumin and immunoglobulin G elute from these devices with zero order release kinetics. These experiments demonstrate that PCL is an extremely useful

  11. Electrical stimulation directs engineered cardiac tissue to an age-matched native phenotype

    Directory of Open Access Journals (Sweden)

    Richard A Lasher

    2012-12-01

    Full Text Available Quantifying structural features of native myocardium in engineered tissue is essential for creating functional tissue that can serve as a surrogate for in vitro testing or the eventual replacement of diseased or injured myocardium. We applied three-dimensional confocal imaging and image analysis to quantitatively describe the features of native and engineered cardiac tissue. Quantitative analysis methods were developed and applied to test the hypothesis that environmental cues direct engineered tissue toward a phenotype resembling that of age-matched native myocardium. The analytical approach was applied to engineered cardiac tissue with and without the application of electrical stimulation as well as to age-matched and adult native tissue. Individual myocytes were segmented from confocal image stacks and assigned a coordinate system from which measures of cell geometry and connexin-43 spatial distribution were calculated. The data were collected from 9 nonstimulated and 12 electrically stimulated engineered tissue constructs and 5 postnatal day 12 and 7 adult hearts. The myocyte volume fraction was nearly double in stimulated engineered tissue compared to nonstimulated engineered tissue (0.34 ± 0.14 vs 0.18 ± 0.06 but less than half of the native postnatal day 12 (0.90 ± 0.06 and adult (0.91 ± 0.04 myocardium. The myocytes under electrical stimulation were more elongated compared to nonstimulated myocytes and exhibited similar lengths, widths, and heights as in age-matched myocardium. Furthermore, the percentage of connexin-43-positive membrane staining was similar in the electrically stimulated, postnatal day 12, and adult myocytes, whereas it was significantly lower in the nonstimulated myocytes. Connexin-43 was found to be primarily located at cell ends for adult myocytes and irregularly but densely clustered over the membranes of nonstimulated, stimulated, and postnatal day 12 myocytes. These findings support our hypothesis and reveal

  12. Image-based metrology of porous tissue engineering scaffolds

    Science.gov (United States)

    Rajagopalan, Srinivasan; Robb, Richard A.

    2006-03-01

    Tissue engineering is an interdisciplinary effort aimed at the repair and regeneration of biological tissues through the application and control of cells, porous scaffolds and growth factors. The regeneration of specific tissues guided by tissue analogous substrates is dependent on diverse scaffold architectural indices that can be derived quantitatively from the microCT and microMR images of the scaffolds. However, the randomness of pore-solid distributions in conventional stochastic scaffolds presents unique computational challenges. As a result, image-based characterization of scaffolds has been predominantly qualitative. In this paper, we discuss quantitative image-based techniques that can be used to compute the metrological indices of porous tissue engineering scaffolds. While bulk averaged quantities such as porosity and surface are derived directly from the optimal pore-solid delineations, the spatially distributed geometric indices are derived from the medial axis representations of the pore network. The computational framework proposed (to the best of our knowledge for the first time in tissue engineering) in this paper might have profound implications towards unraveling the symbiotic structure-function relationship of porous tissue engineering scaffolds.

  13. Electrical stimulation: a novel tool for tissue engineering.

    Science.gov (United States)

    Balint, Richard; Cassidy, Nigel J; Cartmell, Sarah H

    2013-02-01

    New advances in tissue engineering are being made through the application of different types of electrical stimuli to influence cell proliferation and differentiation. Developments made in the last decade have allowed us to improve the structure and functionality of tissue-engineered products through the use of growth factors, hormones, drugs, physical stimuli, bioreactor use, and two-dimensional (2-D) and three-dimensional (3-D) artificial extracellular matrices (with various material properties and topography). Another potential type of stimulus is electricity, which is important in the physiology and development of the majority of all human tissues. Despite its great potential, its role in tissue regeneration and its ability to influence cell migration, orientation, proliferation, and differentiation has rarely been considered in tissue engineering. This review highlights the importance of endogenous electrical stimulation, gathering the current knowledge on its natural occurrence and role in vivo, discussing the novel methods of delivering this stimulus and examining its cellular and tissue level effects, while evaluating how the technique could benefit the tissue engineering discipline in the future.

  14. Surface modification of polyester biomaterials for tissue engineering.

    Science.gov (United States)

    Jiao, Yan-Peng; Cui, Fu-Zhai

    2007-12-01

    Surfaces play an important role in a biological system for most biological reactions occurring at surfaces and interfaces. The development of biomaterials for tissue engineering is to create perfect surfaces which can provoke specific cellular responses and direct new tissue regeneration. The improvement in biocompatibility of biomaterials for tissue engineering by directed surface modification is an important contribution to biomaterials development. Among many biomaterials used for tissue engineering, polyesters have been well documented for their excellent biodegradability, biocompatibility and nontoxicity. However, poor hydrophilicity and the lack of natural recognition sites on the surface of polyesters have greatly limited their further application in the tissue engineering field. Therefore, how to introduce functional groups or molecules to polyester surfaces, which ideally adjust cell/tissue biological functions, becomes more and more important. In this review, recent advances in polyester surface modification and their applications are reviewed. The development of new technologies or methods used to modify polyester surfaces for developing their biocompatibility is introduced. The results of polyester surface modifications by surface morphological modification, surface chemical group/charge modification, surface biomacromolecule modification and so on are reported in detail. Modified surface properties of polyesters directly related to in vitro/vivo biological performances are presented as well, such as protein adsorption, cell attachment and growth and tissue response. Lastly, the prospect of polyester surface modification is discussed, especially the current conception of biomimetic and molecular recognition.

  15. Stem and progenitor cells: advancing bone tissue engineering.

    Science.gov (United States)

    Tevlin, R; Walmsley, G G; Marecic, O; Hu, Michael S; Wan, D C; Longaker, M T

    2016-04-01

    Unlike many other postnatal tissues, bone can regenerate and repair itself; nevertheless, this capacity can be overcome. Traditionally, surgical reconstructive strategies have implemented autologous, allogeneic, and prosthetic materials. Autologous bone--the best option--is limited in supply and also mandates an additional surgical procedure. In regenerative tissue engineering, there are myriad issues to consider in the creation of a functional, implantable replacement tissue. Importantly, there must exist an easily accessible, abundant cell source with the capacity to express the phenotype of the desired tissue, and a biocompatible scaffold to deliver the cells to the damaged region. A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key advances in stem and progenitor cell contribution to the field of bone tissue engineering. In this review, we briefly introduce various adult stem cells implemented in bone tissue engineering such as mesenchymal stem cells (including bone marrow- and adipose-derived stem cells), endothelial progenitor cells, and induced pluripotent stem cells. We then discuss numerous advances associated with their application and subsequently focus on technological advances in the field, before addressing key regenerative strategies currently used in clinical practice. Stem and progenitor cell implementation in bone tissue engineering strategies have the ability to make a major impact on regenerative medicine and reduce patient morbidity. As the field of regenerative medicine endeavors to harness the body's own cells for treatment, scientific innovation has led to great advances in stem cell-based therapies in the past decade.

  16. Crossing kingdoms: Using decellularized plants as perfusable tissue engineering scaffolds.

    Science.gov (United States)

    Gershlak, Joshua R; Hernandez, Sarah; Fontana, Gianluca; Perreault, Luke R; Hansen, Katrina J; Larson, Sara A; Binder, Bernard Y K; Dolivo, David M; Yang, Tianhong; Dominko, Tanja; Rolle, Marsha W; Weathers, Pamela J; Medina-Bolivar, Fabricio; Cramer, Carole L; Murphy, William L; Gaudette, Glenn R

    2017-05-01

    Despite significant advances in the fabrication of bioengineered scaffolds for tissue engineering, delivery of nutrients in complex engineered human tissues remains a challenge. By taking advantage of the similarities in the vascular structure of plant and animal tissues, we developed decellularized plant tissue as a prevascularized scaffold for tissue engineering applications. Perfusion-based decellularization was modified for different plant species, providing different geometries of scaffolding. After decellularization, plant scaffolds remained patent and able to transport microparticles. Plant scaffolds were recellularized with human endothelial cells that colonized the inner surfaces of plant vasculature. Human mesenchymal stem cells and human pluripotent stem cell derived cardiomyocytes adhered to the outer surfaces of plant scaffolds. Cardiomyocytes demonstrated contractile function and calcium handling capabilities over the course of 21 days. These data demonstrate the potential of decellularized plants as scaffolds for tissue engineering, which could ultimately provide a cost-efficient, "green" technology for regenerating large volume vascularized tissue mass. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Nonlinear optical molecular imaging enables metabolic redox sensing in tissue-engineered constructs

    Science.gov (United States)

    Chen, Leng-Chun; Lloyd, William R.; Wilson, Robert H.; Kuo, Shiuhyang; Marcelo, Cynthia L.; Feinberg, Stephen E.; Mycek, Mary-Ann

    2011-07-01

    Tissue-engineered constructs require noninvasive monitoring of cellular viability prior to implantation. In a preclinical study on human Ex Vivo Produced Oral Mucosa Equivalent (EVPOME) constructs, nonlinear optical molecular imaging was employed to extract morphological and functional information from intact constructs. Multiphoton excitation fluorescence images were acquired using endogenous fluorescence from cellular nicotinamide adenine dinucleotide phosphate [NAD(P)H] and flavin adenine dinucleotide (FAD). The images were analyzed to report quantitatively on tissue structure and metabolism (redox ratio). Both thickness variations over time and cell distribution variations with depth were identified, while changes in redox were quantified. Our results show that nonlinear optical molecular imaging has the potential to visualize and quantitatively monitor the growth and viability of a tissue-engineered construct over time.

  18. Cnidarians biomineral in tissue engineering: a review.

    Science.gov (United States)

    Vago, Razi

    2008-01-01

    Biomineralization is the process by which organisms precipitate minerals. Crystals formed in this way are exploited by the organisms for a variety of purposes, including mechanical support and protection of soft tissue. Skeletal precipitation, via millions of years of evolution, has produced a wide variety of architectural configurations and material properties. It is exactly these properties that now attract the attention of researchers searching for new materials for a variety of biomedical applications.

  19. [Autologous tissue engineering by means of distraction osteogenesis: Biomechanical considerations].

    Science.gov (United States)

    Schouman, T; Raoul, G; Dubois, G

    2011-09-01

    Tissue engineering consists in producing functional replacement tissue. Distraction osteogenesis is a tissue engineering technique that uses the mechanical environment of cells to induce tissue regeneration, without need for exogenous biochemical factors. A better understanding of the optimal mechanical conditions of distraction callus stretching may reduce the duration, discomfort, and even social impact of distraction protocols, and complications and failures. We present the current state of knowledge in this field by addressing the fundamentals of elongating bone tissue biomechanics, the influence of rhythm and rate of distraction, and that of vectors and stability. Finally, we present the innovations currently studied, which may modify our clinical protocol in the short term. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  20. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

    Energy Technology Data Exchange (ETDEWEB)

    Lunsing, Roelineke J.; Strating, Kim [University Medical Centre Groningen, University of Groningen, Department of Child Neurology, Groningen (Netherlands); Koning, Tom J. de [University Medical Centre Groningen, University of Groningen, Department of Pediatric Metabolic Diseases, Groningen (Netherlands); Sijens, Paul E. [University Medical Centre Groningen, University of Groningen, Department of Radiology, Groningen (Netherlands)

    2017-03-15

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  1. Research progress on reconstruction of meniscus in tissue engineering.

    Science.gov (United States)

    Zhang, Yu; Li, Pengsong; Wang, Hai; Wang, Yiwei; Song, Kedong; Li, Tianqing

    2017-05-01

    Meniscus damages are most common in sports injuries and aged knees. One third of meniscus lesions are known as white-white zone or nonvascular zones, which are composed of chondrocyte and extracellular matrix composition only. Due to low vascularization the ability of regeneration in such zones is inherently limited, leading to impossible self-regeneration post damage. Meniscus tissue engineering is known for emerging techniques for treating meniscus damage, but there are questions that need to be answered, including an optimal and suitable cell source, the usability of growth factor, the selectivity of optimal biomaterial scaffolds as well as the technology for improving partial reconstruction of meniscus tears. This review focuses on current research on the in vitro reconstruction of the meniscus using tissue engineering methods with the expectation to develop a series of tissue engineering meniscus products for the benefit of sports injuries. With rapid growth of clinical demand, the key breakthrough of meniscus tissue engineering research foundation is enlarged to a great extent. This review discusses aspects of meniscus tissue engineering, which is relative to the clinical treatment of meniscus injuries for further support and establishment of fundamental and clinical studies.

  2. Tissue Engineering: Utopie oder Realität?

    Directory of Open Access Journals (Sweden)

    Reichmann E

    2005-01-01

    Full Text Available Eine neue Disziplin ist dabei, sich innerhalb der Biomedizin zu etablieren. Zellbiologen, Biochemiker, Ingenieure und Chirurgen arbeiten im Team an der Herstellung neuer Gewebe und Organe. Diese neue Disziplin nennt sich "Tissue Engineering". Im Tissue Engineering geht es darum, lebende, meist autologe Zellen aus einem Organismus zu isolieren, im Labor zu expandieren und ein funktionsfähiges Gewebe oder Organteil entstehen zu lassen. Das so hergestellte organtypische Konstrukt soll schließlich ein defektes oder fehlendes Gewebe bei einem Patienten ersetzen. Das Tissue Engineering hat bei einer Reihe von Laboratorien und Firmen Einzug gehalten und sorgt für eine erstaunliche Dynamik in der Forschung und im klinischen Anwendungsbereich. Wirtschaftsprognosen sagen voraus, daß das Tissue Engineering bereits in wenigen Jahrzehnten eine vergleichbare kommerzielle Bedeutung wie die heutige Gentechnologie erreichen wird. Neuere Studien kommen allerdings zu dem Ergebnis, daß nur sehr wenige der bisherigen Errungenschaften des Tissue Engineering besser oder billiger sind als etablierte Produkte. Kaum eines dieser Produkte bringt Gewinn.

  3. Clinical application of tissue-engineered transplants. Part I: mucosa.

    Science.gov (United States)

    Sauerbier, Sebastian; Gutwald, Ralf; Wiedmann-Al-Ahmad, Margit; Lauer, Günter; Schmelzeisen, Rainer

    2006-12-01

    The study series aims at testing the feasibility of the clinical application of tissue-engineered oral mucosa. The preliminary results were gathered over a period varying from 6 months to 12 years depending on the surgical method. Tissue-engineered oral mucosa was used to cover defects in various surgical procedures like vestibuloplasty (n=42), freeing of the tongue (n=10), prelaminating the radial flap (n=5) and reconstruction of the urethra (n=16). In all interventions small samples of oral mucosa were harvested, cut into small pieces, resuspended in culture medium and seeded into a culture flask. Cultured keratinocytes were transferred onto membranes which then were used to cover mucosal defects in the oral cavity. To gain a graft of 15 cm(2) size a mucosa biopsy of 4-8 mm(2) and 40 ml autologous patients serum is needed. Tissue-engineered oral mucosa was applied successfully in all four surgical methods. Six months after transplantation a regular epithelial layering with a histological delimitation of the stratum, epithelial crest and a strong basal membrane appeared. According to the reception site the tissue engineered oral mucosa differentiated in several ways. Tissue-engineered oral mucosa fulfils the requirements for clinical routine. With view to healing time and outcome it does not appear to be superior to regular harvested oral mucosa transplants. Because of a smaller harvesting defect and primary wound closure at the actual operation site the patients' convenience is increased. Thus this method reduces morbidity and advances the quality of life.

  4. An adipoinductive role of inflammation in adipose tissue engineering: key factors in the early development of engineered soft tissues.

    Science.gov (United States)

    Lilja, Heidi E; Morrison, Wayne A; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W; Abberton, Keren M

    2013-05-15

    Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

  5. Tissue-engineered heart valve: future of cardiac surgery.

    Science.gov (United States)

    Rippel, Radoslaw A; Ghanbari, Hossein; Seifalian, Alexander M

    2012-07-01

    Heart valve disease is currently a growing problem, and demand for heart valve replacement is predicted to increase significantly in the future. Existing "gold standard" mechanical and biological prosthesis offers survival at a cost of significantly increased risks of complications. Mechanical valves may cause hemorrhage and thromboembolism, whereas biologic valves are prone to fibrosis, calcification, degeneration, and immunogenic complications. A literature search was performed to identify all relevant studies relating to tissue-engineered heart valve in life sciences using the PubMed and ISI Web of Knowledge databases. Tissue engineering is a new, emerging alternative, which is reviewed in this paper. To produce a fully functional heart valve using tissue engineering, an appropriate scaffold needs to be seeded using carefully selected cells and proliferated under conditions that resemble the environment of a natural human heart valve. Bioscaffold, synthetic materials, and preseeded composites are three common approaches of scaffold formation. All available evidence suggests that synthetic scaffolds are the most suitable material for valve scaffold formation. Different cell sources of stem cells were used with variable results. Mesenchymal stem cells, fibroblasts, myofibroblasts, and umbilical blood stem cells are used in vitro tissue engineering of heart valve. Alternatively scaffold may be implanted and then autoseeded in vivo by circulating endothelial progenitor cells or primitive circulating cells from patient's blood. For that purpose, synthetic heart valves were developed. Tissue engineering is currently the only technology in the field with the potential for the creation of tissues analogous to a native human heart valve, with longer sustainability, and fever side effects. Although there is still a long way to go, tissue-engineered heart valves have the capability to revolutionize cardiac surgery of the future.

  6. Biocompatible magnetic core-shell nanocomposites for engineered magnetic tissues

    Science.gov (United States)

    Rodriguez-Arco, Laura; Rodriguez, Ismael A.; Carriel, Victor; Bonhome-Espinosa, Ana B.; Campos, Fernando; Kuzhir, Pavel; Duran, Juan D. G.; Lopez-Lopez, Modesto T.

    2016-04-01

    The inclusion of magnetic nanoparticles into biopolymer matrixes enables the preparation of magnetic field-responsive engineered tissues. Here we describe a synthetic route to prepare biocompatible core-shell nanostructures consisting of a polymeric core and a magnetic shell, which are used for this purpose. We show that using a core-shell architecture is doubly advantageous. First, gravitational settling for core-shell nanocomposites is slower because of the reduction of the composite average density connected to the light polymer core. Second, the magnetic response of core-shell nanocomposites can be tuned by changing the thickness of the magnetic layer. The incorporation of the composites into biopolymer hydrogels containing cells results in magnetic field-responsive engineered tissues whose mechanical properties can be controlled by external magnetic forces. Indeed, we obtain a significant increase of the viscoelastic moduli of the engineered tissues when exposed to an external magnetic field. Because the composites are functionalized with polyethylene glycol, the prepared bio-artificial tissue-like constructs also display excellent ex vivo cell viability and proliferation. When implanted in vivo, the engineered tissues show good biocompatibility and outstanding interaction with the host tissue. Actually, they only cause a localized transitory inflammatory reaction at the implantation site, without any effect on other organs. Altogether, our results suggest that the inclusion of magnetic core-shell nanocomposites into biomaterials would enable tissue engineering of artificial substitutes whose mechanical properties could be tuned to match those of the potential target tissue. In a wider perspective, the good biocompatibility and magnetic behavior of the composites could be beneficial for many other applications.The inclusion of magnetic nanoparticles into biopolymer matrixes enables the preparation of magnetic field-responsive engineered tissues. Here we

  7. Coaxial electrospun fibers: applications in drug delivery and tissue engineering.

    Science.gov (United States)

    Lu, Yang; Huang, Jiangnan; Yu, Guoqiang; Cardenas, Romel; Wei, Suying; Wujcik, Evan K; Guo, Zhanhu

    2016-09-01

    Coelectrospinning and emulsion electrospinning are two main methods for preparing core-sheath electrospun nanofibers in a cost-effective and efficient manner. Here, physical phenomena and the effects of solution and processing parameters on the coaxial fibers are introduced. Coaxial fibers with specific drugs encapsulated in the core can exhibit a sustained and controlled release. Their exhibited high surface area and three-dimensional nanofibrous network allows the electrospun fibers to resemble native extracellular matrices. These features of the nanofibers show that they have great potential in drug delivery and tissue engineering applications. Proteins, growth factors, antibiotics, and many other agents have been successfully encapsulated into coaxial fibers for drug delivery. A main advantage of the core-sheath design is that after the process of electrospinning and release, these drugs remain bioactive due to the protection of the sheath. Applications of coaxial fibers as scaffolds for tissue engineering include bone, cartilage, cardiac tissue, skin, blood vessels and nervous tissue, among others. A synopsis of novel coaxial electrospun fibers, discussing their applications in drug delivery and tissue engineering, is covered pertaining to proteins, growth factors, antibiotics, and other drugs and applications in the fields of bone, cartilage, cardiac, skin, blood vessel, and nervous tissue engineering, respectively. WIREs Nanomed Nanobiotechnol 2016, 8:654-677. doi: 10.1002/wnan.1391 For further resources related to this article, please visit the WIREs website.

  8. From stem to roots: Tissue engineering in endodontics

    Science.gov (United States)

    Kala, M.; Banthia, Priyank; Banthia, Ruchi

    2012-01-01

    The vitality of dentin-pulp complex is fundamental to the life of tooth and is a priority for targeting clinical management strategies. Loss of the tooth, jawbone or both, due to periodontal disease, dental caries, trauma or some genetic disorders, affects not only basic mouth functions but aesthetic appearance and quality of life. One novel approach to restore tooth structure is based on biology: regenerative endodontic procedure by application of tissue engineering. Regenerative endodontics is an exciting new concept that seeks to apply the advances in tissue engineering to the regeneration of the pulp-dentin complex. The basic logic behind this approach is that patient-specific tissue-derived cell populations can be used to functionally replace integral tooth tissues. The development of such ‘test tube teeth’ requires precise regulation of the regenerative events in order to achieve proper tooth size and shape, as well as the development of new technologies to facilitate these processes. This article provides an extensive review of literature on the concept of tissue engineering and its application in endodontics, providing an insight into the new developmental approaches on the horizon. Key words:Regenerative, tissue engineering, stem cells, scaffold. PMID:24558528

  9. Rapid prototyping technology and its application in bone tissue engineering.

    Science.gov (United States)

    Yuan, Bo; Zhou, Sheng-Yuan; Chen, Xiong-Sheng

    Bone defects arising from a variety of reasons cannot be treated effectively without bone tissue reconstruction. Autografts and allografts have been used in clinical application for some time, but they have disadvantages. With the inherent drawback in the precision and reproducibility of conventional scaffold fabrication techniques, the results of bone surgery may not be ideal. This is despite the introduction of bone tissue engineering which provides a powerful approach for bone repair. Rapid prototyping technologies have emerged as an alternative and have been widely used in bone tissue engineering, enhancing bone tissue regeneration in terms of mechanical strength, pore geometry, and bioactive factors, and overcoming some of the disadvantages of conventional technologies. This review focuses on the basic principles and characteristics of various fabrication technologies, such as stereolithography, selective laser sintering, and fused deposition modeling, and reviews the application of rapid prototyping techniques to scaffolds for bone tissue engineering. In the near future, the use of scaffolds for bone tissue engineering prepared by rapid prototyping technology might be an effective therapeutic strategy for bone defects.

  10. From stem to roots: Tissue engineering in endodontics.

    Science.gov (United States)

    Chandki, Rita; Kala, M; Banthia, Priyank; Banthia, Ruchi

    2012-02-01

    The vitality of dentin-pulp complex is fundamental to the life of tooth and is a priority for targeting clinical management strategies. Loss of the tooth, jawbone or both, due to periodontal disease, dental caries, trauma or some genetic disorders, affects not only basic mouth functions but aesthetic appearance and quality of life. One novel approach to restore tooth structure is based on biology: regenerative endodontic procedure by application of tissue engineering. Regenerative endodontics is an exciting new concept that seeks to apply the advances in tissue engineering to the regeneration of the pulp-dentin complex. The basic logic behind this approach is that patient-specific tissue-derived cell populations can be used to functionally replace integral tooth tissues. The development of such 'test tube teeth' requires precise regulation of the regenerative events in order to achieve proper tooth size and shape, as well as the development of new technologies to facilitate these processes. This article provides an extensive review of literature on the concept of tissue engineering and its application in endodontics, providing an insight into the new developmental approaches on the horizon. Key words:Regenerative, tissue engineering, stem cells, scaffold.

  11. Extracellular Matrix Scaffolds for Tissue Engineering and Regenerative Medicine.

    Science.gov (United States)

    Yi, Sheng; Ding, Fei; Gong, Leiiei; Gu, Xiaosong

    2017-01-01

    The extracellular matrix is produced by the resident cells in tissues and organs, and secreted into the surrounding medium to provide biophysical and biochemical support to the surrounding cells due to its content of diverse bioactive molecules. Recently, the extracellular matrix has been used as a promising approach for tissue engineering. Emerging studies demonstrate that extracellular matrix scaffolds are able to create a favorable regenerative microenvironment, promote tissue-specific remodeling, and act as an inductive template for the repair and functional reconstruction of skin, bone, nerve, heart, lung, liver, kidney, small intestine, and other organs. In the current review, we will provide a critical overview of the structure and function of various types of extracellular matrix, the construction of three-dimensional extracellular matrix scaffolds, and their tissue engineering applications, with a focus on translation of these novel tissue engineered products to the clinic. We will also present an outlook on future perspectives of the extracellular matrix in tissue engineering and regenerative medicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Superior Tissue Evolution in Slow-Degrading Scaffolds for Valvular Tissue Engineering.

    Science.gov (United States)

    Brugmans, Marieke M C P; Soekhradj-Soechit, R Sarita; van Geemen, Daphne; Cox, Martijn; Bouten, Carlijn V C; Baaijens, Frank P T; Driessen-Mol, Anita

    2016-01-01

    Synthetic polymers are widely used to fabricate porous scaffolds for the regeneration of cardiovascular tissues. To ensure mechanical integrity, a balance between the rate of scaffold absorption and tissue formation is of high importance. A higher rate of tissue formation is expected in fast-degrading materials than in slow-degrading materials. This could be a result of synthetic cells, which aim to compensate for the fast loss of mechanical integrity of the scaffold by deposition of collagen fibers. Here, we studied the effect of fast-degrading polyglycolic acid scaffolds coated with poly-4-hydroxybutyrate (PGA-P4HB) and slow-degrading poly-ɛ-caprolactone (PCL) scaffolds on amount of tissue, composition, and mechanical characteristics in time, and compared these engineered values with values for native human heart valves. Electrospun PGA-P4HB and PCL scaffolds were either kept unseeded in culture or were seeded with human vascular-derived cells. Tissue formation, extracellular matrix (ECM) composition, remaining scaffold weight, tissue-to-scaffold weight ratio, and mechanical properties were analyzed every week up to 6 weeks. Mass of unseeded PCL scaffolds remained stable during culture, whereas PGA-P4HB scaffolds degraded rapidly. When seeded with cells, both scaffold types demonstrated increasing amounts of tissue with time, which was more pronounced for PGA-P4HB-based tissues during the first 2 weeks; however, PCL-based tissues resulted in the highest amount of tissue after 6 weeks. This study is the first to provide insight into the tissue-to-scaffold weight ratio, therewith allowing for a fair comparison between engineered tissues cultured on scaffolds as well as between native heart valve tissues. Although the absolute amount of ECM components differed between the engineered tissues, the ratio between ECM components was similar after 6 weeks. PCL-based tissues maintained their shape, whereas the PGA-P4HB-based tissues deformed during culture. After 6 weeks

  13. Tissue-engineering strategies to repair joint tissue in osteoarthritis: nonviral gene-transfer approaches.

    Science.gov (United States)

    Madry, Henning; Cucchiarini, Magali

    2014-10-01

    Loss of articular cartilage is a common clinical consequence of osteoarthritis (OA). In the past decade, substantial progress in tissue engineering, nonviral gene transfer, and cell transplantation have provided the scientific foundation for generating cartilaginous constructs from genetically modified cells. Combining tissue engineering with overexpression of therapeutic genes enables immediate filling of a cartilage defect with an engineered construct that actively supports chondrogenesis. Several pioneering studies have proved that spatially defined nonviral overexpression of growth-factor genes in constructs of solid biomaterials or hydrogels is advantageous compared with gene transfer or scaffold alone, both in vitro and in vivo. Notably, these investigations were performed in models of focal cartilage defects, because advanced cartilage-repair strategies based on the principles of tissue engineering have not advanced sufficiently to enable resurfacing of extensively degraded cartilage as therapy for OA. These studies serve as prototypes for future technological developments, because they raise the possibility that cartilage constructs engineered from genetically modified chondrocytes providing autocrine and paracrine stimuli could similarly compensate for the loss of articular cartilage in OA. Because cartilage-tissue-engineering strategies are already used in the clinic, combining tissue engineering and nonviral gene transfer could prove a powerful approach to treat OA.

  14. Jellyfish collagen scaffolds for cartilage tissue engineering.

    Science.gov (United States)

    Hoyer, Birgit; Bernhardt, Anne; Lode, Anja; Heinemann, Sascha; Sewing, Judith; Klinger, Matthias; Notbohm, Holger; Gelinsky, Michael

    2014-02-01

    Porous scaffolds were engineered from refibrillized collagen of the jellyfish Rhopilema esculentum for potential application in cartilage regeneration. The influence of collagen concentration, salinity and temperature on fibril formation was evaluated by turbidity measurements and quantification of fibrillized collagen. The formation of collagen fibrils with a typical banding pattern was confirmed by atomic force microscopy and transmission electron microscopy analysis. Porous scaffolds from jellyfish collagen, refibrillized under optimized conditions, were fabricated by freeze-drying and subsequent chemical cross-linking. Scaffolds possessed an open porosity of 98.2%. The samples were stable under cyclic compression and displayed an elastic behavior. Cytotoxicity tests with human mesenchymal stem cells (hMSCs) did not reveal any cytotoxic effects of the material. Chondrogenic markers SOX9, collagen II and aggrecan were upregulated in direct cultures of hMSCs upon chondrogenic stimulation. The formation of typical extracellular matrix components was further confirmed by quantification of sulfated glycosaminoglycans.

  15. Alginate based scaffolds for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Valente, J.F.A.; Valente, T.A.M. [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal); Alves, P.; Ferreira, P. [CIEPQPF, Departamento de Engenharia Quimica, Universidade de Coimbra, Polo II, Pinhal de Marrocos, 3030-290 Coimbra (Portugal); Silva, A. [Centro de Ciencia e Tecnologia Aeroespaciais, Universidade da Beira Interior, Covilha (Portugal); Correia, I.J., E-mail: icorreia@ubi.pt [CICS-UBI - Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

    2012-12-01

    The design and production of scaffolds for bone tissue regeneration is yet unable to completely reproduce the native bone properties. In the present study new alginate microparticle and microfiber aggregated scaffolds were produced to be applied in this area of regenerative medicine. The scaffolds' mechanical properties were characterized by thermo mechanical assays. Their morphological characteristics were evaluated by isothermal nitrogen adsorption and scanning electron microscopy. The density of both types of scaffolds was determined by helium pycnometry and mercury intrusion porosimetry. Furthermore, scaffolds' cytotoxic profiles were evaluated in vitro by seeding human osteoblast cells in their presence. The results obtained showed that scaffolds have good mechanical and morphological properties compatible with their application as bone substitutes. Moreover, scaffold's biocompatibility was confirmed by the observation of cell adhesion and proliferation after 5 days of being seeded in their presence and by non-radioactive assays. - Highlights: Black-Right-Pointing-Pointer Design and production of scaffolds for bone tissue regeneration. Black-Right-Pointing-Pointer Microparticle and microfiber alginate scaffolds were produced through a particle aggregation technique; Black-Right-Pointing-Pointer Scaffolds' mechanically and biologically properties were characterized through in vitro studies;.

  16. Gelatin-Based Materials in Ocular Tissue Engineering

    Directory of Open Access Journals (Sweden)

    James B. Rose

    2014-04-01

    Full Text Available Gelatin has been used for many years in pharmaceutical formulation, cell culture and tissue engineering on account of its excellent biocompatibility, ease of processing and availability at low cost. Over the last decade gelatin has been extensively evaluated for numerous ocular applications serving as cell-sheet carriers, bio-adhesives and bio-artificial grafts. These different applications naturally have diverse physical, chemical and biological requirements and this has prompted research into the modification of gelatin and its derivatives. The crosslinking of gelatin alone or in combination with natural or synthetic biopolymers has produced a variety of scaffolds that could be suitable for ocular applications. This review focuses on methods to crosslink gelatin-based materials and how the resulting materials have been applied in ocular tissue engineering. Critical discussion of recent innovations in tissue engineering and regenerative medicine will highlight future opportunities for gelatin-based materials in ophthalmology.

  17. Synthetic biodegradable functional polymers for tissue engineering: a brief review.

    Science.gov (United States)

    BaoLin, Guo; Ma, Peter X

    2014-04-01

    Scaffolds play a crucial role in tissue engineering. Biodegradable polymers with great processing flexibility are the predominant scaffolding materials. Synthetic biodegradable polymers with well-defined structure and without immunological concerns associated with naturally derived polymers are widely used in tissue engineering. The synthetic biodegradable polymers that are widely used in tissue engineering, including polyesters, polyanhydrides, polyphosphazenes, polyurethane, and poly (glycerol sebacate) are summarized in this article. New developments in conducting polymers, photoresponsive polymers, amino-acid-based polymers, enzymatically degradable polymers, and peptide-activated polymers are also discussed. In addition to chemical functionalization, the scaffold designs that mimic the nano and micro features of the extracellular matrix (ECM) are presented as well, and composite and nanocomposite scaffolds are also reviewed.

  18. Fabrication of Biodegradable Polyester Nanocomposites by Electrospinning for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Zhi-Cai Xing

    2011-01-01

    Full Text Available Recently, nanocomposites have emerged as an efficient strategy to upgrade the structural and functional properties of synthetic polymers. Polyesters have attracted wide attention because of their biodegradability and biocompatibility. A logic consequence has been the introduction of natural extracellular matrix (ECM molecules, organic or inorganic nanostructures to biodegradable polymers to produce nanocomposites with enhanced properties. Consequently, the improvement of the interfacial adhesion between biodegradable polymers and natural ECM molecules or nanostructures has become the key technique in the fabrication of nanocomposites. Electrospinning has been employed extensively in the design and development of tissue engineering scaffolds to generate nanofibrous substrates of synthetic biodegradable polymers and to simulate the cellular microenvironment. In this paper, several types of biodegradable polyester nanocomposites were prepared by electrospinning, with the aim of being used as tissue engineering scaffolds. The combination of biodegradable nanofibrous polymers and natural ECM molecules or nanostructures opens new paradigms for tissue engineering applications.

  19. Quantifying collagen orientation in breast tissue biopsies using SLIM (Conference Presentation)

    Science.gov (United States)

    Majeed, Hassaan; Okoro, Chukwuemeka; Balla, Andre; Toussaint, Kimani C.; Popescu, Gabriel

    2017-02-01

    Breast cancer is a major public health problem worldwide, being the most common type of cancer among women according to the World Health Organization (WHO). The WHO has further stressed the importance of an early determination of the disease course through prognostic markers. Recent studies have shown that the alignment of collagen fibers in tumor adjacent stroma correlate with poorer health outcomes in patients. Such studies have typically been carried out using Second-Harmonic Generation (SHG) microscopy. SHG images are very useful for quantifying collagen fiber orientation due their specificity to non-centrosymmetric structures in tissue, leading to high contrast in collagen rich areas. However, the imaging throughput in SHG microscopy is limited by its point scanning geometry. In this work, we show that SLIM, a wide-field high-throughput QPI technique, can be used to obtain the same information on collagen fiber orientation as is obtainable through SHG microscopy. We imaged a tissue microarray containing both benign and malignant cores using both SHG microscopy and SLIM. The cellular (non-collagenous) structures in the SLIM images were next segmented out using an algorithm developed in-house. Using the previously published Fourier Transform Second Harmonic Generation (FT-SHG) tool, the fiber orientations in SHG and segmented SLIM images were then quantified. The resulting histograms of fiber orientation angles showed that both SHG and SLIM generate similar measurements of collagen fiber orientation. The SLIM modality, however, can generate these results at much higher throughput due to its wide-field, whole-slide scanning capabilities.

  20. Stem Cells and Scaffolds for Vascularizing Engineered Tissue Constructs

    Science.gov (United States)

    Luong, E.; Gerecht, S.

    The clinical impact of tissue engineering depends upon our ability to direct cells to form tissues with characteristic structural and mechanical properties from the molecular level up to organized tissue. Induction and creation of functional vascular networks has been one of the main goals of tissue engineering either in vitro, for the transplantation of prevascularized constructs, or in vivo, for cellular organization within the implantation site. In most cases, tissue engineering attempts to recapitulate certain aspects of normal development in order to stimulate cell differentiation and functional tissue assembly. The induction of tissue growth generally involves the use of biodegradable and bioactive materials designed, ideally, to provide a mechanical, physical, and biochemical template for tissue regeneration. Human embryonic stem cells (hESCs), derived from the inner cell mass of a developing blastocyst, are capable of differentiating into all cell types of the body. Specifically, hESCs have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. Human ESC-derived endothelial progenitor cells (EPCs) and endothelial cells have substantial potential for microvessel formation, in vitro and in vivo. Human adult EPCs are being isolated to understand the fundamental biology of how these cells are regulated as a population and to explore whether these cells can be differentiated and reimplanted as a cellular therapy in order to arrest or even reverse damaged vasculature. This chapter focuses on advances made toward the generation and engineering of functional vascular tissue, focusing on both the scaffolds - the synthetic and biopolymer materials - and the cell sources - hESCs and hEPCs.

  1. MR elastography monitoring of tissue-engineered constructs.

    Science.gov (United States)

    Othman, Shadi F; Curtis, Evan T; Plautz, Sarah A; Pannier, Angela K; Butler, Stephanie D; Xu, Huihui

    2012-03-01

    The objective of tissue engineering (TE) is to create functional replacements for various tissues; the mechanical properties of these engineered constructs are critical to their function. Several techniques have been developed for the measurement of the mechanical properties of tissues and organs; however, current methods are destructive. The field of TE will benefit immensely if biomechanical models developed by these techniques could be combined with existing imaging modalities to enable noninvasive, dynamic assessment of mechanical properties during tissue growth. Specifically, MR elastography (MRE), which is based on the synchronization of a mechanical actuator with a phase contrast imaging pulse sequence, has the capacity to measure tissue strain generated by sonic cyclic displacement. The captured displacement is presented in shear wave images from which the complex shear moduli can be extracted or simplified by a direct measure, termed the shear stiffness. MRE has been extended to the microscopic scale, combining clinical MRE with high-field magnets, stronger magnetic field gradients and smaller, more sensitive, radiofrequency coils, enabling the interrogation of smaller samples, such as tissue-engineered constructs. The following topics are presented in this article: (i) current mechanical measurement techniques and their limitations in TE; (ii) a description of the MRE system, MRE theory and how it can be applied for the measurement of mechanical properties of tissue-engineered constructs; (iii) a summary of in vitro MRE work for the monitoring of osteogenic and adipogenic tissues originating from human adult mesenchymal stem cells (MSCs); (iv) preliminary in vivo studies of MRE of tissues originating from mouse MSCs implanted subcutaneously in immunodeficient mice with an emphasis on in vivo MRE challenges; (v) future directions to resolve current issues with in vivo MRE in the context of how to improve the future role of MRE in TE.

  2. Application of adult stem cells in neural tissue engineering

    Institute of Scientific and Technical Information of China (English)

    Lihong Piao; Wei Wang

    2006-01-01

    OBJECTTIVE:To investigate the progress in finding,isolation and culture.proliferation and differentiation,and application in neural tissue engineering of adult stem cells(ASCs).DATA SOURCES:Using the terms"adult stem cells,nerve,tissue engineering".we searched the PubMed for adult stem ceils-related studies published in English from January 2001 to August 2006.Meanwhile,we also performed a China National Knowledge Infrastructure(CNKI)search for homochronous correlative literatures on the computer by inputting the terms"adult stem cells,nerve,tissue engineering"in Chinese.texts were searched for.Inclusive criteria:①Literatures about the sources,distribution,culture.proliferation and differentiation.and application in the repair of neural ASCs by tissue engineering.②Articles recommended either by randomized.blind or by other methods were not excluded.Exclusive criteria:①Embryonic stem cells.②Review,repetitive study,case report,Meta analysis. DATA EXTRACTION:Totally 1 278 articles related to ASCs were collected,32 were involved and the other 1 246 were excluded. DATA SYNTHESIS:Adult stem cell has the ability of self-renewal.unceasing proliferation and transdifferentiation.It has wide source,which does not involved in ethical problems.It has advantages over embryonic stem cell.Studies on the isolation and culture,induction and differentiation and application in neural ASCs by tissue engineering contribute to obtaining considerable ASCs,so as to provide experimental and theoretical bases for CONCLUSION:ASCs play a very important role in neural tissue engineering.

  3. Harnessing wound healing and regeneration for tissue engineering.

    Science.gov (United States)

    Metcalfe, A D; Ferguson, M W J

    2005-04-01

    Biomedical science has made major advances in understanding how cells grow into functioning tissue and the signalling mechanisms used to achieve this are slowly being dissected. Tissue engineering is the application of that knowledge to the building or repairing of organs, including skin, the largest organ in the body. Generally, engineered tissue is a combination of living cells and a supporting matrix. Besides serving as burn coverings, engineered skin substitutes can help patients with diabetic foot ulcers. Today, most of these ulcers are treated with an approach that includes antibiotics, glucose control, special shoes and frequent cleaning and bandaging. The results of such treatments are often disappointing and ineffectual, and scarring remains a major problem, mechanically, cosmetically and psychologically. Within our group we are attempting to address this by investigating novel approaches to skin tissue engineering. We are identifying novel therapeutic manipulations to improve the degree of integration between a tissue engineered dermal construct and the host by both molecular manipulation of growth factors but also by understanding and harnessing mechanisms of regenerative biology. For the purpose of this summary, we will concentrate primarily on the latter of these two approaches in that we have identified a novel mouse mutant that completely and perfectly regenerates skin and cartilaginous components following ear injury. This experimental animal will allow us to characterize not only novel genes involved in the regeneration process but also to utilize cells from such animals in artificial skin equivalents to assess their behaviour compared with normal cells. This approach should allow us to create a tissue-engineered substitute, which more closely resembles the normal regional microanatomy and physiology of the skin, allowing better integration to the host with minimal or no scarring.

  4. Fabrication and Application of Nanofibrous Scaffolds in Tissue Engineering

    OpenAIRE

    Li, Wan-Ju; Tuan, Rocky S

    2009-01-01

    Nanofibers fabricated by electrospinning are morphological mimics of fibrous components of the native extracellular matrix, making nanofibrous scaffolds ideal for three-dimensional cell culture and tissue engineering applications. Although electrospinning is not a conventional technique in cell biology, the experimental set-up may be constructed in a relatively straightforward manner and the procedure can be carried by individuals with limited engineering experience. We detail here a protocol...

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

    NARCIS (Netherlands)

    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 whic

  6. Pericyte-targeting drug delivery and tissue engineering

    Directory of Open Access Journals (Sweden)

    Kang E

    2016-05-01

    Full Text Available Eunah Kang,1 Jong Wook Shin2 1School of Chemical Engineering and Material Science, 2Division of Allergic and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, Chung-Ang University, Dongjak-Gu, Seoul, South Korea Abstract: Pericytes are contractile mural cells that wrap around the endothelial cells of capillaries and venules. Depending on the triggers by cellular signals, pericytes have specific functionality in tumor microenvironments, properties of potent stem cells, and plasticity in cellular pathology. These features of pericytes can be activated for the promotion or reduction of angiogenesis. Frontier studies have exploited pericyte-targeting drug delivery, using pericyte-specific peptides, small molecules, and DNA in tumor therapy. Moreover, the communication between pericytes and endothelial cells has been applied to the induction of vessel neoformation in tissue engineering. Pericytes may prove to be a novel target for tumor therapy and tissue engineering. The present paper specifically reviews pericyte-specific drug delivery and tissue engineering, allowing insight into the emerging research targeting pericytes. Keywords: pericytes, pericyte-targeting drug delivery, tissue engineering, platelet-derived growth factor, angiogenesis, vascular remodeling

  7. Plant-Derived Human Collagen Scaffolds for Skin Tissue Engineering

    Science.gov (United States)

    Willard, James J.; Drexler, Jason W.; Das, Amitava; Roy, Sashwati; Shilo, Shani; Shoseyov, Oded

    2013-01-01

    Tissue engineering scaffolds are commonly formed using proteins extracted from animal tissues, such as bovine hide. Risks associated with the use of these materials include hypersensitivity and pathogenic contamination. Human-derived proteins lower the risk of hypersensitivity, but possess the risk of disease transmission. Methods engineering recombinant human proteins using plant material provide an alternate source of these materials without the risk of disease transmission or concerns regarding variability. To investigate the utility of plant-derived human collagen (PDHC) in the development of engineered skin (ES), PDHC and bovine hide collagen were formed into tissue engineering scaffolds using electrospinning or freeze-drying. Both raw materials were easily formed into two common scaffold types, electrospun nonwoven scaffolds and lyophilized sponges, with similar architectures. The processing time, however, was significantly lower with PDHC. PDHC scaffolds supported primary human cell attachment and proliferation at an equivalent or higher level than the bovine material. Interleukin-1 beta production was significantly lower when activated THP-1 macrophages where exposed to PDHC electrospun scaffolds compared to bovine collagen. Both materials promoted proper maturation and differentiation of ES. These data suggest that PDHC may provide a novel source of raw material for tissue engineering with low risk of allergic response or disease transmission. PMID:23298216

  8. Physical non-viral gene delivery methods for tissue engineering.

    Science.gov (United States)

    Mellott, Adam J; Forrest, M Laird; Detamore, Michael S

    2013-03-01

    The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that "fits-all" cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications.

  9. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    Science.gov (United States)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  10. Design of electrical stimulation bioreactors for cardiac tissue engineering.

    Science.gov (United States)

    Tandon, N; Marsano, A; Cannizzaro, C; Voldman, J; Vunjak-Novakovic, G

    2008-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering.

  11. Towards a richer debate on tissue engineering: a consideration on the basis of NEST-ethics.

    Science.gov (United States)

    Oerlemans, A J M; van Hoek, M E C; van Leeuwen, E; van der Burg, S; Dekkers, W J M

    2013-09-01

    In their 2007 paper, Swierstra and Rip identify characteristic tropes and patterns of moral argumentation in the debate about the ethics of new and emerging science and technologies (or "NEST-ethics"). Taking their NEST-ethics structure as a starting point, we considered the debate about tissue engineering (TE), and argue what aspects we think ought to be a part of a rich and high-quality debate of TE. The debate surrounding TE seems to be predominantly a debate among experts. When considering the NEST-ethics arguments that deal directly with technology, we can generally conclude that consequentialist arguments are by far the most prominently featured in discussions of TE. In addition, many papers discuss principles, rights and duties relevant to aspects of TE, both in a positive and in a critical sense. Justice arguments are only sporadically made, some "good life" arguments are used, others less so (such as the explicit articulation of perceived limits, or the technology as a technological fix for a social problem). Missing topics in the discussion, at least from the perspective of NEST-ethics, are second "level" arguments-those referring to techno-moral change connected to tissue engineering. Currently, the discussion about tissue engineering mostly focuses on its so-called "hard impacts"-quantifiable risks and benefits of the technology. Its "soft impacts"-effects that cannot easily be quantified, such as changes to experience, habits and perceptions, should receive more attention.

  12. Musculoskeletal tissue engineering with human umbilical cord mesenchymal stromal cells

    Science.gov (United States)

    Wang, Limin; Ott, Lindsey; Seshareddy, Kiran; Weiss, Mark L; Detamore, Michael S

    2011-01-01

    Multipotent mesenchymal stromal cells (MSCs) hold tremendous promise for tissue engineering and regenerative medicine, yet with so many sources of MSCs, what are the primary criteria for selecting leading candidates? Ideally, the cells will be multipotent, inexpensive, lack donor site morbidity, donor materials should be readily available in large numbers, immunocompatible, politically benign and expandable in vitro for several passages. Bone marrow MSCs do not meet all of these criteria and neither do embryonic stem cells. However, a promising new cell source is emerging in tissue engineering that appears to meet these criteria: MSCs derived from Wharton’s jelly of umbilical cord MSCs. Exposed to appropriate conditions, umbilical cord MSCs can differentiate in vitro along several cell lineages such as the chondrocyte, osteoblast, adipocyte, myocyte, neuronal, pancreatic or hepatocyte lineages. In animal models, umbilical cord MSCs have demonstrated in vivo differentiation ability and promising immunocompatibility with host organs/tissues, even in xenotransplantation. In this article, we address their cellular characteristics, multipotent differentiation ability and potential for tissue engineering with an emphasis on musculoskeletal tissue engineering. PMID:21175290

  13. Evaluation of scaffold materials for tooth tissue engineering.

    Science.gov (United States)

    Ohara, Takayuki; Itaya, Toshimitsu; Usami, Kazutada; Ando, Yusuke; Sakurai, Hiroya; Honda, Masaki J; Ueda, Minoru; Kagami, Hideaki

    2010-09-01

    Recently, the possibility of tooth tissue engineering has been reported. Although there are a number of available materials, information about scaffolds for tooth tissue engineering is still limited. To improve the manageability of tooth tissue engineering, the effect of scaffolds on in vivo tooth regeneration was evaluated. Collagen and fibrin were selected for this study based on the biocompatibility to dental papilla-derived cells and the results were compared with those of polyglycolic acid (PGA) fiber and beta-tricalcium phosphate (beta-TCP) porous block, which are commonly used for tooth, dentin and bone tissue engineering. Isolated porcine tooth germ-derived cells were seeded onto one of those scaffolds and transplanted to the back of nude mice. Tooth bud-like structures were observed more frequently in collagen and fibrin gels than on PGA or beta-TCP, while the amount of hard tissue formation was less. The results showed that collagen and fibrin gel support the initial regeneration process of tooth buds possibly due to their ability to support the growth of epithelial and mesenchymal cells. On the other hand, maturation of tooth buds was difficult in fibrin and collagen gels, which may require other factors.

  14. Outlook for tissue engineering of the tympanic membrane

    Directory of Open Access Journals (Sweden)

    Maria A. Villar-Fernandez

    2015-01-01

    Full Text Available Tympanic membrane perforation is a common problem leading to hearing loss. Despite the autoregenerative activity of the eardrum, chronic perforations require surgery using different materials, from autologous tissue - fascia, cartilage, fat or perichondrium - to paper patch. However, both, surgical procedures (myringoplasty or tympanoplasty and the materials employed, have a number of limitations. Therefore, the advances in this field are incorporating the principles of tissue engineering, which includes the use of scaffolds, biomolecules and cells. This discipline allows the development of new biocompatible materials that reproduce the structure and mechanical properties of the native tympanic membrane, while it seeks to implement new therapeutic approaches that can be performed in an outpatient setting. Moreover, the creation of an artificial tympanic membrane commercially available would reduce the duration of the surgery and costs. The present review analyzes the current treatment of tympanic perforations and examines the techniques of tissue engineering, either to develop bioartificial constructs, or for tympanic regeneration by using different scaffold materials, bioactive molecules and cells. Finally, it considers the aspects regarding the design of scaffolds, release of biomolecules and use of cells that must be taken into account in the tissue engineering of the eardrum. The possibility of developing new biomaterials, as well as constructs commercially available, makes tissue engineering a discipline with great potential, capable of overcoming the drawbacks of current surgical procedures.

  15. Tissue Engineering the Cornea: The Evolution of RAFT.

    Science.gov (United States)

    Levis, Hannah J; Kureshi, Alvena K; Massie, Isobel; Morgan, Louise; Vernon, Amanda J; Daniels, Julie T

    2015-01-22

    Corneal blindness affects over 10 million people worldwide and current treatment strategies often involve replacement of the defective layer with healthy tissue. Due to a worldwide donor cornea shortage and the absence of suitable biological scaffolds, recent research has focused on the development of tissue engineering techniques to create alternative therapies. This review will detail how we have refined the simple engineering technique of plastic compression of collagen to a process we now call Real Architecture for 3D Tissues (RAFT). The RAFT production process has been standardised, and steps have been taken to consider Good Manufacturing Practice compliance. The evolution of this process has allowed us to create biomimetic epithelial and endothelial tissue equivalents suitable for transplantation and ideal for studying cell-cell interactions in vitro.

  16. Tissue Engineering the Cornea: The Evolution of RAFT

    Directory of Open Access Journals (Sweden)

    Hannah J. Levis

    2015-01-01

    Full Text Available Corneal blindness affects over 10 million people worldwide and current treatment strategies often involve replacement of the defective layer with healthy tissue. Due to a worldwide donor cornea shortage and the absence of suitable biological scaffolds, recent research has focused on the development of tissue engineering techniques to create alternative therapies. This review will detail how we have refined the simple engineering technique of plastic compression of collagen to a process we now call Real Architecture for 3D Tissues (RAFT. The RAFT production process has been standardised, and steps have been taken to consider Good Manufacturing Practice compliance. The evolution of this process has allowed us to create biomimetic epithelial and endothelial tissue equivalents suitable for transplantation and ideal for studying cell-cell interactions in vitro.

  17. Design and Validation of Equiaxial Mechanical Strain Platform, EQUicycler, for 3D Tissue Engineered Constructs.

    Science.gov (United States)

    Elsaadany, Mostafa; Harris, Matthew; Yildirim-Ayan, Eda

    2017-01-01

    It is crucial to replicate the micromechanical milieu of native tissues to achieve efficacious tissue engineering and regenerative therapy. In this study, we introduced an innovative loading platform, EQUicycler, that utilizes a simple, yet effective, and well-controlled mechanism to apply physiologically relevant homogenous mechanical equiaxial strain on three-dimensional cell-embedded tissue scaffolds. The design of EQUicycler ensured elimination of gripping effects through the use of biologically compatible silicone posts for direct transfer of the mechanical load to the scaffolds. Finite Element Modeling (FEM) was created to understand and to quantify how much applied global strain was transferred from the loading mechanism to the tissue constructs. In vitro studies were conducted on various cell lines associated with tissues exposed to equiaxial mechanical loading in their native environment. In vitro results demonstrated that EQUicycler was effective in maintaining and promoting the viability of different musculoskeletal cell lines and upregulating early differentiation of osteoprogenitor cells. By utilizing EQUicycler, collagen fibers of the constructs were actively remodeled. Residing cells within the collagen construct elongated and aligned with strain direction upon mechanical loading. EQUicycler can provide an efficient and cost-effective tool to conduct mechanistic studies for tissue engineered constructs designed for tissue systems under mechanical loading in vivo.

  18. The Use of Adipose Tissue-Derived Progenitors in Bone Tissue Engineering - a Review

    Science.gov (United States)

    Bhattacharya, Indranil; Ghayor, Chafik; Weber, Franz E.

    2016-01-01

    2500 years ago, Hippocrates realized that bone can heal without scaring. The natural healing potential of bone is, however, restricted to small defects. Extended bone defects caused by trauma or during tumor resections still pose a huge problem in orthopedics and cranio-maxillofacial surgery. Bone tissue engineering strategies using stem cells, growth factors, and scaffolds could overcome the problems with the treatment of extended bone defects. In this review, we give a short overview on bone tissue engineering with emphasis on the use of adipose tissue-derived stem cells and small molecules.

  19. Biomechanical Models and Experi ments in Bone Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    Christian; ODDOU; Julien; PIERRE; Karim; OUDINA; Hervé; PETITE

    2005-01-01

    1 IntroductionThe understanding of the interactions between convective and diffusive phenomena of fluid dynamics origin, on the one side, associate reactive effects of biochemical nature, on the other, is a fundamental challenge and key problem in the context of bone tissue engineering. From the mastering of the complex biological phenomena related to the substrate degradation and remodelling of the extra cellular matrix that take place during the in vitro tissue culturing processes using cell seeded implan...

  20. Stem Cell-based Tissue Engineering Approaches for Musculoskeletal Regeneration

    Science.gov (United States)

    Brown, Patrick T.; Handorf, Andrew M.; Jeon, Won Bae; Li, Wan-Ju

    2014-01-01

    The field of regenerative medicine and tissue engineering is an ever evolving field that holds promise in treating numerous musculoskeletal diseases and injuries. An important impetus in the development of the field was the discovery and implementation of stem cells. The utilization of mesenchymal stem cells, and later embryonic and induced pluripotent stem cells, opens new arenas for tissue engineering and presents the potential of developing stem cell-based therapies for disease treatment. Multipotent and pluripotent stem cells can produce various lineage tissues, and allow for derivation of a tissue that may be comprised of multiple cell types. As the field grows, the combination of biomaterial scaffolds and bioreactors provides methods to create an environment for stem cells that better represent their microenvironment for new tissue formation. As technologies for the fabrication of biomaterial scaffolds advance, the ability of scaffolds to modulate stem cell behavior advances as well. The composition of scaffolds could be of natural or synthetic materials and could be tailored to enhance cell self-renewal and/or direct cell fates. In addition to biomaterial scaffolds, studies of tissue development and cellular microenvironments have determined other factors, such as growth factors and oxygen tension, that are crucial to the regulation of stem cell activity. The overarching goal of stem cell-based tissue engineering research is to precisely control differentiation of stem cells in culture. In this article, we review current developments in tissue engineering, focusing on several stem cell sources, induction factors including growth factors, oxygen tension, biomaterials, and mechanical stimulation, and the internal and external regulatory mechanisms that govern proliferation and differentiation. PMID:23432679

  1. Anisotropic Porous Biodegradable Scaffolds for Musculoskeletal Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Eric L. W. de Mulder

    2009-10-01

    Full Text Available It has been generally accepted that tissue engineered constructs should closely resemble the in-vivo mechanical and structural properties of the tissues they are intended to replace. However, most scaffolds produced so far were isotropic porous scaffolds with non-characterized mechanical properties, different from those of the native healthy tissue. Tissues that are formed into these scaffolds are initially formed in the isotropic porous structure and since most tissues have significant anisotropic extracellular matrix components and concomitant mechanical properties, the formed tissues have no structural and functional relationships with the native tissues. The complete regeneration of tissues requires a second differentiation step after resorption of the isotropic scaffold. It is doubtful if the required plasticity for this remains present in already final differentiated tissue. It would be much more efficacious if the newly formed tissues in the scaffold could differentiate directly into the anisotropic organization of the native tissues. Therefore, anisotropic scaffolds that enable such a direct differentiation might be extremely helpful to realize this goal. Up to now, anisotropic scaffolds have been fabricated using modified conventional techniques, solid free-form fabrication techniques, and a few alternative methods. In this review we present the current status and discuss the procedures that are currently being used for anisotropic scaffold fabrication.

  2. Repair of osteochondral defects with allogeneic tissue engineered cartilage implants.

    Science.gov (United States)

    Schreiber, R E; Ilten-Kirby, B M; Dunkelman, N S; Symons, K T; Rekettye, L M; Willoughby, J; Ratcliffe, A

    1999-10-01

    The objective of this study was to evaluate the effect of allogeneic tissue engineered cartilage implants on healing of osteochondral defects. Rabbit chondrocytes were cultured in monolayer, then seeded onto biodegradable, three-dimensional polyglycolic acid meshes. Cartilage constructs were cultured hydrodynamically to yield tissue with relatively more (mature) or less (immature) hyalinelike cartilage, as compared with adult rabbit articular cartilage. Osteochondral defects in the patellar grooves of both stifle joints either were left untreated or implanted with allogeneic tissue engineered cartilage. Histologic samples from in and around the defect sites were examined 3, 6, 9, and 12, and 24 months after surgery. By 9 months after surgery, defects sites treated with cartilage implants contained significantly greater amounts of hyalinelike cartilage with high levels of proteoglycan, and had a smooth, nonfibrillated articular surface as compared to untreated defects. In contrast, the repair tissue formed in untreated defects had fibrillated articular surfaces, significant amounts of fibrocartilage, and negligible proteoglycan. These differences between treated and untreated defects persisted through 24 months after surgery. The results of this study suggest that the treatment of osteochondral lesions with allogenic tissue engineered cartilage implants may lead to superior repair tissue than that found in untreated osteochondral lesions.

  3. Adipose-derived stem cells and periodontal tissue engineering.

    Science.gov (United States)

    Tobita, Morikuni; Mizuno, Hiroshi

    2013-01-01

    Innovative developments in the multidisciplinary field of tissue engineering have yielded various implementation strategies and the possibility of functional tissue regeneration. Technologic advances in the combination of stem cells, biomaterials, and growth factors have created unique opportunities to fabricate tissues in vivo and in vitro. The therapeutic potential of human multipotent mesenchymal stem cells (MSCs), which are harvested from bone marrow and adipose tissue, has generated increasing interest in a wide variety of biomedical disciplines. These cells can differentiate into a variety of tissue types, including bone, cartilage, fat, and nerve tissue. Adipose-derived stem cells have some advantages compared with other sources of stem cells, most notably that a large number of cells can be easily and quickly isolated from adipose tissue. In current clinical therapy for periodontal tissue regeneration, several methods have been developed and applied either alone or in combination, such as enamel matrix proteins, guided tissue regeneration, autologous/allogeneic/xenogeneic bone grafts, and growth factors. However, there are various limitations and shortcomings for periodontal tissue regeneration using current methods. Recently, periodontal tissue regeneration using MSCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because the various secreted growth factors from MSCs might not only promote the regeneration of periodontal tissue but also encourage neovascularization of the damaged tissues. Adipose-derived stem cells are especially effective for neovascularization compared with other MSC sources. In this review, the possibility and potential of adipose-derived stem cells for regenerative medicine are introduced. Of particular interest, periodontal tissue regeneration with adipose-derived stem cells is discussed.

  4. X-ray Phase Contrast Imaging of Calcified Tissue and Biomaterial Structure in Bioreactor Engineered Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Appel, Alyssa A. [Illinois Inst. of Technology, Chicago, IL (United States); Edward Hines Jr. VA Hospital, IL (United States); Larson, Jeffery C. [Illinois Inst. of Technology, Chicago, IL (United States); Edward Hines Jr. VA Hospital, IL (United States); Garson, III, Alfred B. [George Washington Univ., Washington, DC (United States); Guan, Huifeng [George Washington Univ., Washington, DC (United States); Zhong, Zhong [Brookhaven National Lab. (BNL), Upton, NY (United States); Nguyen, Bao-Ngoc [Univ. of Maryland, College Park, MD (United States); Fisher, John P. [Univ. of Maryland, College Park, MD (United States); Anastasio, Mark A. [George Washington Univ., Washington, DC (United States); Brey, Eric M. [Illinois Inst. of Technology, Chicago, IL (United States); Edward Hines Jr. VA Hospital, IL (United States)

    2014-11-04

    Tissues engineered in bioreactor systems have been used clinically to replace damaged tissues and organs. In addition, these systems are under continued development for many tissue engineering applications. The ability to quantitatively assess material structure and tissue formation is critical for evaluating bioreactor efficacy and for preimplantation assessment of tissue quality. These techniques allow for the nondestructive and longitudinal monitoring of large engineered tissues within the bioreactor systems and will be essential for the translation of these strategies to viable clinical therapies. X-ray Phase Contrast (XPC) imaging techniques have shown tremendous promise for a number of biomedical applications owing to their ability to provide image contrast based on multiple X-ray properties, including absorption, refraction, and scatter. In this research, mesenchymal stem cell-seeded alginate hydrogels were prepared and cultured under osteogenic conditions in a perfusion bioreactor. The constructs were imaged at various time points using XPC microcomputed tomography (µCT). Imaging was performed with systems using both synchrotron- and tube-based X-ray sources. XPC µCT allowed for simultaneous three-dimensional (3D) quantification of hydrogel size and mineralization, as well as spatial information on hydrogel structure and mineralization. Samples were processed for histological evaluation and XPC showed similar features to histology and quantitative analysis consistent with the histomorphometry. Furthermore, these results provide evidence of the significant potential of techniques based on XPC for noninvasive 3D imaging engineered tissues grown in bioreactors.

  5. X-ray phase contrast imaging of calcified tissue and biomaterial structure in bioreactor engineered tissues.

    Science.gov (United States)

    Appel, Alyssa A; Larson, Jeffery C; Garson, Alfred B; Guan, Huifeng; Zhong, Zhong; Nguyen, Bao-Ngoc B; Fisher, John P; Anastasio, Mark A; Brey, Eric M

    2015-03-01

    Tissues engineered in bioreactor systems have been used clinically to replace damaged tissues and organs. In addition, these systems are under continued development for many tissue engineering applications. The ability to quantitatively assess material structure and tissue formation is critical for evaluating bioreactor efficacy and for preimplantation assessment of tissue quality. Techniques that allow for the nondestructive and longitudinal monitoring of large engineered tissues within the bioreactor systems will be essential for the translation of these strategies to viable clinical therapies. X-ray Phase Contrast (XPC) imaging techniques have shown tremendous promise for a number of biomedical applications owing to their ability to provide image contrast based on multiple X-ray properties, including absorption, refraction, and scatter. In this research, mesenchymal stem cell-seeded alginate hydrogels were prepared and cultured under osteogenic conditions in a perfusion bioreactor. The constructs were imaged at various time points using XPC microcomputed tomography (µCT). Imaging was performed with systems using both synchrotron- and tube-based X-ray sources. XPC µCT allowed for simultaneous three-dimensional (3D) quantification of hydrogel size and mineralization, as well as spatial information on hydrogel structure and mineralization. Samples were processed for histological evaluation and XPC showed similar features to histology and quantitative analysis consistent with the histomorphometry. These results provide evidence of the significant potential of techniques based on XPC for noninvasive 3D imaging engineered tissues grown in bioreactors.

  6. Nanotechnology, Cell Culture and Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Kazutoshi Haraguchi

    2011-01-01

    Full Text Available We have fabricated new types of polymer hydrogels and polymer nanocomposites, i.e., nanocomposite gels (NC gels and soft, polymer nanocomposites (M-NCs: solid, with novel organic/inorganic network structures. Both NC gels and M-NCs were synthesized by in-situ free-radical polymerization in the presence of exfoliated clay platelets in aqueous systems and were obtained in various forms such as film, sheet, tube, coating, etc. and sizes with a wide range of clay contents. Here, disk-like inorganic clay nanoparticles act as multi-functional crosslinkers to form new types of network systems. Both NC gels and M-NCs have extraordinary optical and mechanical properties including ultra-high reversible extensibility, as well as a number of new characteristics relating to optical anisotropy, polymer/clay morphology, biocompatibility, stimuli-sensitive surfaces, micro-patterning, etc. For examples, the biological testing of medical devices, comprised of a sensitization test, an irritation test, an intracutaneous test and an in vitro cytotoxicity test,was carried out for NC gels and M-NCs. The safety of NC gels and M-NCs was confirmed in all tests. Also, the interaction of living tissue with NC gel was investigated in vivo by implantation in live goats; neither inflammation nor concrescence occurred around the NC gels. Furthermore, it was found that both N-NC gels consisting of poly(N-isopropylacrylamide(PNIPA/clay network and M-NCs consisting of poly(2-methoxyethyacrylate(PMEA/clay network show characteristic cell culture and subsequent cell detachment on their surfaces, although it was almost impossible to culture cells on conventional, chemically-crosslinked PNIPA hydrogels and chemically crossslinked PMEA, regardless of their crosslinker concentration. Various kinds of cells, such ashumanhepatoma cells (HepG2, normal human dermal fibroblast (NHDF, and human umbilical vein endothelial cells (HUVEC, could be cultured to be confluent on the surfaces of N

  7. Assessing infection risk in implanted tissue-engineered devices

    NARCIS (Netherlands)

    Kuijer, Roel; Jansen, Edwin J. P.; Emans, Pieter J.; Bulstra, Sjoerd K.; Riesle, Jens; Pieper, Jeroen; Grainger, David W.; Busscher, Henk J.

    2007-01-01

    Peri-operative contamination is the major cause of biomaterial-associated infections, highly complicating surgical patient outcomes. While this risk in traditional implanted biomaterials is well-recognised, newer cell-seeded, biologically conducive tissue-engineered (TE) constructs now targeted for

  8. Ureteral tissue engineering: where are we and how to proceed?

    NARCIS (Netherlands)

    Simaioforidis, V.; Jonge, P. de; Sloff, M.; Oosterwijk, E.; Geutjes, P.; Feitz, W.F.J.

    2013-01-01

    In the field of regenerative medicine, various types of biodegradable and nonbiodegradable scaffolds have been developed for urinary tract tissue-engineering applications. Naturally derived or synthetic materials have been tested to determine their properties and their effectiveness. However, the ma

  9. Assessing infection risk in implanted tissue-engineered devices

    NARCIS (Netherlands)

    Kuijer, Roel; Jansen, Edwin J. P.; Emans, Pieter J.; Bulstra, Sjoerd K.; Riesle, Jens; Pieper, Jeroen; Grainger, David W.; Busscher, Henk J.

    2007-01-01

    Peri-operative contamination is the major cause of biomaterial-associated infections, highly complicating surgical patient outcomes. While this risk in traditional implanted biomaterials is well-recognised, newer cell-seeded, biologically conducive tissue-engineered (TE) constructs now targeted for

  10. 3D liver models in tissue engineering and toxicology

    NARCIS (Netherlands)

    Starokozhko, Viktoriia

    2016-01-01

    In her thesis, Viktoriia Starokozhko developed new and improved existing liver models for the use in tissue engineering and toxicology. One of the models she described and used are liver slices (PCLS), a mini-organ model for the liver. PCLS are used already for many years in various fields of pharma

  11. A high throughput mechanical screening device for cartilage tissue engineering.

    Science.gov (United States)

    Mohanraj, Bhavana; Hou, Chieh; Meloni, Gregory R; Cosgrove, Brian D; Dodge, George R; Mauck, Robert L

    2014-06-27

    Articular cartilage enables efficient and near-frictionless load transmission, but suffers from poor inherent healing capacity. As such, cartilage tissue engineering strategies have focused on mimicking both compositional and mechanical properties of native tissue in order to provide effective repair materials for the treatment of damaged or degenerated joint surfaces. However, given the large number design parameters available (e.g. cell sources, scaffold designs, and growth factors), it is difficult to conduct combinatorial experiments of engineered cartilage. This is particularly exacerbated when mechanical properties are a primary outcome, given the long time required for testing of individual samples. High throughput screening is utilized widely in the pharmaceutical industry to rapidly and cost-effectively assess the effects of thousands of compounds for therapeutic discovery. Here we adapted this approach to develop a high throughput mechanical screening (HTMS) system capable of measuring the mechanical properties of up to 48 materials simultaneously. The HTMS device was validated by testing various biomaterials and engineered cartilage constructs and by comparing the HTMS results to those derived from conventional single sample compression tests. Further evaluation showed that the HTMS system was capable of distinguishing and identifying 'hits', or factors that influence the degree of tissue maturation. Future iterations of this device will focus on reducing data variability, increasing force sensitivity and range, as well as scaling-up to even larger (96-well) formats. This HTMS device provides a novel tool for cartilage tissue engineering, freeing experimental design from the limitations of mechanical testing throughput.

  12. Current opportunities and challenges in skeletal muscle tissue engineering

    NARCIS (Netherlands)

    Koning, Merel; Harmsen, Martin C; van Luyn, Marja J A; Werker, Paul M N

    The purpose of this article is to give a concise review of the current state of the art in tissue engineering (TE) of skeletal muscle and the opportunities and challenges for future clinical applicability. The endogenous progenitor cells of skeletal muscle, i.e. satellite cells, show a high

  13. Tissue Engineered Medical Products (TEMPs): A prelude to risk management

    NARCIS (Netherlands)

    Wassenaar C; Geertsma RE; Kallewaard M; LGM

    2001-01-01

    In medical practice products containing cultured cells have emerged. These products could be labelled Tissue Engineered Medical Products (TEMPs). A literature review covering the past ten years was carried out to collect information useful for the assessment of risks associated with these products

  14. Non-viral gene therapy for bone tissue engineering

    NARCIS (Netherlands)

    Wegman, F.

    2013-01-01

    In bone tissue engineering bone morphogentic protein-2 (BMP-2) is one of the most commonly used growth factors. It induces stem cells to differentiate into the osteogenic lineage to form new bone. Clinically however, high dosages of protein are administered due to fast degradation, which is associat

  15. Mathematically defined tissue engineering scaffold architectures prepared by stereolithography

    NARCIS (Netherlands)

    Melchels, Ferry P. W.; Bertoldi, Katia; Gabbrielli, Ruggero; Velders, Aldrik H.; Feijen, Jan; Grijpma, Dirk W.

    2010-01-01

    The technologies employed for the preparation of conventional tissue engineering scaffolds restrict the materials choice and the extent to which the architecture can be designed. Here we show the versatility of stereolithography with respect to materials and freedom of design. Porous scaffolds are d

  16. Impedance-based monitoring for tissue engineering applications

    DEFF Research Database (Denmark)

    Canali, Chiara; Heiskanen, Arto; Martinsen, Ø.G.

    2015-01-01

    Impedance is a promising technique for sensing the overall process of tissue engineering. Different electrode configurations can be used to characterize the scaffold that supports cell organization in terms of hydrogel polymerization and degree of porosity, monitoring cell loading, cell prolifera...

  17. A review of rapid prototyping techniques for tissue engineering purposes

    NARCIS (Netherlands)

    Peltola, Sanna M.; Melchels, Ferry P. W.; Grijpma, Dirk W.; Kellomaki, Minna

    2008-01-01

    Rapid prototyping (RP) is a common name for several techniques, which read in data from computer-aided design (CAD) drawings and manufacture automatically three-dimensional objects layer-by-layer according to the virtual design. The utilization of RP in tissue engineering enables the production of t

  18. Mechanical cues in orofacial tissue engineering and regenerative medicine

    NARCIS (Netherlands)

    Brouwer, K.M.; Lundvig, D.M.S.; Middelkoop, E.; Wagener, F.A.D.T.G.; Hoff, J.W. Von den

    2015-01-01

    Cleft lip and palate patients suffer from functional, aesthetical, and psychosocial problems due to suboptimal regeneration of skin, mucosa, and skeletal muscle after restorative cleft surgery. The field of tissue engineering and regenerative medicine (TE/RM) aims to restore the normal physiology of

  19. Burn Injury: A Challenge for Tissue Engineers

    Directory of Open Access Journals (Sweden)

    Yerneni LK

    2009-01-01

    growth of human keratinocyte stem cells capable of producing epithelia for large-scale grafting in burns and maintain long-term functionality as a self-renewing tissue. The normal functioning of such an in vitro constructed graft under long-term artificial growth conditions is limited by the difficulties of maintaining the epidermal stem cell compartment. An apparent answer to this problem of stem cell depletion during autograft preparation would be to start with a pure population of progenitor stem cells and derive sustainable autograft from them. We have been aiming to this solution and currently attempting to isolate a pool of epidermal progenitor cells using Mebiol gel, which is a Thermo-Reversible Gelation polymer and was shown by others to support the growth of multi-potent skin-derived epithelial progenitor-1 cells. Additionally, the usefulness of Mebiol gel in maintaining epidermal stem cell compartment without FBS and/or animal origin feeder cells is being investigated by our group.

  20. Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    John G. Hardy

    2016-07-01

    Full Text Available Materials based on biodegradable polyesters, such as poly(butylene terephthalate (PBT or poly(butylene terephthalate-co-poly(alkylene glycol terephthalate (PBTAT, have potential application as pro-regenerative scaffolds for bone tissue engineering. Herein, the preparation of films composed of PBT or PBTAT and an engineered spider silk protein, (eADF4(C16, that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported. Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering.

  1. Bioceramics and scaffolds: a winning combination for tissue engineering

    Directory of Open Access Journals (Sweden)

    Francesco eBaino

    2015-12-01

    Full Text Available In the last few decades we have assisted to a general increase of elder population worldwide with associated age-related pathologies. Therefore, there is the need for new biomaterials that can substitute damaged tissues, stimulate the body’s own regenerative mechanisms and promote tissue healing. Porous templates referred to as scaffolds are thought to be required for three-dimensional tissue growth. Bioceramics, a special set of fully, partially or non-crystalline ceramics (e.g. calcium phosphates, bioactive glasses and glass-ceramics that are designed for the repair and reconstruction of diseased parts of the body, have high potential as scaffold materials. Traditionally, bioceramics have been used to fill and restore bone and dental defects (repair of hard tissues. More recently, this category of biomaterials has also revealed promising applications in the field of soft tissue engineering. Starting with an overview of the fundamental requirements for tissue engineering scaffolds, this article provides a detailed picture on recent developments of porous bioceramics and composites, including a summary of common fabrication technologies and a critical analysis of structure-property and structure-function relationships. Areas of future research are highlighted at the end of this review, with special attention to the development of multifunctional scaffolds exploiting therapeutic ion/drug release and emerging applications beyond hard tissue repair.

  2. Bioceramics and Scaffolds: A Winning Combination for Tissue Engineering.

    Science.gov (United States)

    Baino, Francesco; Novajra, Giorgia; Vitale-Brovarone, Chiara

    2015-01-01

    In the last few decades, we have assisted to a general increase of elder population worldwide associated with age-related pathologies. Therefore, there is the need for new biomaterials that can substitute damaged tissues, stimulate the body's own regenerative mechanisms, and promote tissue healing. Porous templates referred to as "scaffolds" are thought to be required for three-dimensional tissue growth. Bioceramics, a special set of fully, partially, or non-crystalline ceramics (e.g., calcium phosphates, bioactive glasses, and glass-ceramics) that are designed for the repair and reconstruction of diseased parts of the body, have high potential as scaffold materials. Traditionally, bioceramics have been used to fill and restore bone and dental defects (repair of hard tissues). More recently, this category of biomaterials has also revealed promising applications in the field of soft-tissue engineering. Starting with an overview of the fundamental requirements for tissue engineering scaffolds, this article provides a detailed picture on recent developments of porous bioceramics and composites, including a summary of common fabrication technologies and a critical analysis of structure-property and structure-function relationships. Areas of future research are highlighted at the end of this review, with special attention to the development of multifunctional scaffolds exploiting therapeutic ion/drug release and emerging applications beyond hard tissue repair.

  3. Role of tissue engineering in dental pulp regeneration

    Directory of Open Access Journals (Sweden)

    Shruti Sial

    2012-01-01

    Full Text Available Stem cells constitute the source of differentiated cells for the generation of tissues during development, and for regeneration of tissues that are diseased or injured postnatally. In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that span from Alzheimer′s disease to cardiac ischemia to bone or tooth loss. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental pulp is considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that dental pulp stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. The dental pulp stem cells are highly proliferative. Collectively, the multipotency, high proliferation rates, and accessibility make the dental pulp an attractive source of mesenchymal stem cells for tissue regeneration. This review discusses fundamental concepts of stem cell biology and tissue engineering within the context of regenerative dentistry.

  4. The interplay between tissue growth and scaffold degradation in engineered tissue constructs

    KAUST Repository

    O’Dea, R. D.

    2012-09-18

    In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation. In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (1) differential interactions between cells and the supporting scaffold and their associated ECM, (2) scaffold degradation, and (3) mechanotransduction-regulated cell proliferation and ECM deposition. Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from μCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of

  5. Hydrogel microfabrication technology toward three dimensional tissue engineering

    Directory of Open Access Journals (Sweden)

    Fumiki Yanagawa

    2016-03-01

    Full Text Available The development of biologically relevant three-dimensional (3D tissue constructs is essential for the alternative methods of organ transplantation in regenerative medicine, as well as the development of improved drug discovery assays. Recent technological advances in hydrogel microfabrication, such as micromolding, 3D bioprinting, photolithography, and stereolithography, have led to the production of 3D tissue constructs that exhibit biological functions with precise 3D microstructures. Furthermore, microfluidics technology has enabled the development of the perfusion culture of 3D tissue constructs with vascular networks. In this review, we present these hydrogel microfabrication technologies for the in vitro reconstruction and cultivation of 3D tissues. Additionally, we discuss current challenges and future perspectives of 3D tissue engineering.

  6. Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Kevin L., E-mail: kevinmoore@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Schmidt, Rachel [Department of Physics, Fort Hays State University, Hays, Kansas (United States); Moiseenko, Vitali [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Olsen, Lindsey A.; Tan, Jun [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States); Xiao, Ying; Galvin, James [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Pugh, Stephanie [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Seider, Michael J. [Akron City Hospital, Akron, Ohio (United States); Dicker, Adam P. [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Bosch, Walter; Michalski, Jeff; Mutic, Sasa [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States)

    2015-06-01

    Purpose: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. Methods and Materials: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH{sub 0126,top10%}). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed “high-quality,” “low-quality,” and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Results: Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH{sub 0126,top10%} to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the

  7. Spatiotemporal Characterization of Extracellular Matrix Microstructures in Engineered Tissue: A Whole-Field Spectroscopic Imaging Approach.

    Science.gov (United States)

    Xu, Zhengbin; Ozcelikkale, Altug; Kim, Young L; Han, Bumsoo

    2013-02-01

    Quality and functionality of engineered tissues are closely related to the microstructures and integrity of their extracellular matrix (ECM). However, currently available methods for characterizing ECM structures are often labor-intensive, destructive, and limited to a small fraction of the total area. These methods are also inappropriate for assessing temporal variations in ECM structures. In this study, to overcome these limitations and challenges, we propose an elastic light scattering approach to spatiotemporally assess ECM microstructures in a relatively large area in a nondestructive manner. To demonstrate its feasibility, we analyze spectroscopic imaging data obtained from acellular collagen scaffolds and dermal equivalents as model ECM structures. For spatial characterization, acellular scaffolds are examined after a freeze/thaw process mimicking a cryopreservation procedure to quantify freezing-induced structural changes in the collagen matrix. We further analyze spatial and temporal changes in ECM structures during cell-driven compaction in dermal equivalents. The results show that spectral dependence of light elastically backscattered from engineered tissue is sensitively associated with alterations in ECM microstructures. In particular, a spectral decay rate over the wavelength can serve as an indicator for the pore size changes in ECM structures, which are at nanometer scale. A decrease in the spectral decay rate suggests enlarged pore sizes of ECM structures. The combination of this approach with a whole-field imaging platform further allows visualization of spatial heterogeneity of EMC microstructures in engineered tissues. This demonstrates the feasibility of the proposed method that nano- and micrometer scale alteration of the ECM structure can be detected and visualized at a whole-field level. Thus, we envision that this spectroscopic imaging approach could potentially serve as an effective characterization tool to nondestructively, accurately

  8. SU-D-18A-04: Quantifying the Ability of Tumor Tracking to Spare Normal Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Burger, A; Buzurovic, I; Hurwitz, M; Williams, C; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical Sc, Boston, MA (United States); Mishra, P [Varian Medical Systems, Palo Alto, CA (United States); Seco, J [Mass General Hospital, Harvard Medical, Boston, MA (United States)

    2014-06-01

    Purpose: Tumor tracking allows for smaller tissue volumes to be treated, potentially reducing normal tissue damage. However, tumor tracking is a more complex treatment and has little benefit in some scenarios. Here we quantify the benefit of tumor tracking for a range of patients by estimating the dose of radiation to organs at risk and the normal tissue complication probability (NTCP) for both standard and tracking treatment plans. This comparison is performed using both patient 4DCT data and extended Cardiac-Torso (XCAT) digital phantoms. Methods: We use 4DCT data for 10 patients. Additionally, we generate digital phantoms with motion derived from measured patient long tumor trajectories to compare standard and tracking treatment plans. The standard treatment is based on the average intensity projection (AIP) of 4DCT images taken over a breath cycle. The tracking treatment is based on doses calculated on images representing the anatomy at each time point. It is assumed that there are no errors in tracking the target. The NTCP values are calculated based on RTOG guidelines. Results: The mean reduction in the mean dose delivered was 5.5% to the lungs (from 7.3 Gy to 6.9 Gy) and 4.0% to the heart (from 12.5 Gy to 12.0 Gy). The mean reduction in the max dose delivered was 13% to the spinal cord (from 27.6 Gy to 24.0 Gy), 2.5% to the carina (from 31.7 Gy to 30.9 Gy), and 15% to the esophagus (from 69.6 Gy to 58.9 Gy). The mean reduction in the probability of 2nd degree radiation pneumonitis (RP) was 8.7% (3.1% to 2.8%) and the mean reduction in the effective volume was 6.8% (10.8% to 10.2%). Conclusions: Tumor tracking has the potential to reduce irradiation of organs at risk, and consequentially reduce the normal tissue complication probability. The benefits vary based on the clinical scenario. This study is supported by Varian Medical Systems, Inc.

  9. SU-E-P-31: Quantifying the Amount of Missing Tissue in a Digital Breast Tomosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Goodenough, D [George Washington University, Washington, DC (United States); Olafsdottir, H; Olafsson, I; Fredriksson, J; Kristinsson, S; Oskarsdottir, G; Kristbjornsson, A [Raforninn Ehf., Reykjavik, Gullbringusysla (Iceland); Mallozzi, R; Healy, A; Levy, J [The Phantom Laboratory, Salem, NY (United States)

    2015-06-15

    Purpose: To automatically quantify the amount of missing tissue in a digital breast tomosynthesis system using four stair-stepped chest wall missing tissue gauges in the Tomophan™ from the Phantom Laboratory and image processing from Image Owl. Methods: The Tomophan™ phantom incorporates four stair-stepped missing tissue gauges by the chest wall, allowing measurement of missing chest wall in two different locations along the chest wall at two different heights. Each of the four gauges has 12 steps in 0.5 mm increments rising from the chest wall. An image processing algorithm was developed by Image Owl that first finds the two slices containing the steps then finds the signal through the highest step in all four gauges. Using the signal drop at the beginning of each gauge the distance to the end of the image gives the length of the missing tissue gauge in millimeters. Results: The Tomophan™ was imaged in digital breast tomosynthesis (DBT) systems from various vendors resulting in 46 cases used for testing. The results showed that on average 1.9 mm of 6 mm of the gauges are visible. A small focus group was asked to count the number of visible steps for each case which resulted in a good agreement between observer counts and computed data. Conclusion: First, the results indicate that the amount of missing chest wall can differ between vendors. Secondly it was shown that an automated method to estimate the amount of missing chest wall gauges agreed well with observer assessments. This finding indicates that consistency testing may be simplified using the Tomophan™ phantom and analysis by an automated image processing named Tomo QA. In general the reason for missing chest wall may be due to a function of the beam profile at the chest wall as DBT projects through the angular sampling. Research supported by Image Owl, Inc., The Phantom Laboratory, Inc. and Raforninn ehf; Mallozzi and Healy employed by The Phantom Laboratory, Inc.; Goodenough is a consultant to The

  10. Alginate composites for bone tissue engineering: a review.

    Science.gov (United States)

    Venkatesan, Jayachandran; Bhatnagar, Ira; Manivasagan, Panchanathan; Kang, Kyong-Hwa; Kim, Se-Kwon

    2015-01-01

    Bone is a complex and hierarchical tissue consisting of nano hydroxyapatite and collagen as major portion. Several attempts have been made to prepare the artificial bone so as to replace the autograft and allograft treatment. Tissue engineering is a promising approach to solve the several issues and is also useful in the construction of artificial bone with materials including polymer, ceramics, metals, cells and growth factors. Composites consisting of polymer-ceramics, best mimic the natural functions of bone. Alginate, an anionic polymer owing enormous biomedical applications, is gaining importance particularly in bone tissue engineering due to its biocompatibility and gel forming properties. Several composites such as alginate-polymer (PLGA, PEG and chitosan), alginate-protein (collagen and gelatin), alginate-ceramic, alginate-bioglass, alginate-biosilica, alginate-bone morphogenetic protein-2 and RGD peptides composite have been investigated till date. These alginate composites show enhanced biochemical significance in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, alkaline phosphatase increase, excellent mineralization and osteogenic differentiation. Hence, alginate based composite biomaterials will be promising for bone tissue regeneration. This review will provide a broad overview of alginate preparation and its applications towards bone tissue engineering.

  11. Bioceramics for Tissue Engineering Applications-A Review

    Directory of Open Access Journals (Sweden)

    Sunho Oh

    2006-01-01

    Full Text Available Three dimensional (3-D scaffolds have been explored in an attempt to persuade the body to heal or repair tissues that do not do so spontaneously. Considerable advances in tissue engineering and regeneration have been accomplished over the last decade. However, the material and 3-D scaffolds ideal for optimal regeneration of missing or lost tissues has not been identified. While current materials and techniques have met with varying successes, each exhibits limitations that must be addressed. In addition, despite the large amount of research in the area of 3-D scaffolds for bone tissue engineering that has been performed over the past decade, there is an overall lack of success in bringing this technology to the clinic, especially for porous scaffolds used to restore large bone defects. This review paper will focus on the use of calcium phosphate (CaP materials used for tissue engineering, the different known methods of scaffold synthesis, and some of the significant in vitro, in vivo, and clinical outcomes when these CaP scaffolds were used in patients.

  12. Chitosan: a versatile biopolymer for orthopaedic tissue-engineering.

    Science.gov (United States)

    Di Martino, Alberto; Sittinger, Michael; Risbud, Makarand V

    2005-10-01

    Current tissue engineering strategies are focused on the restoration of pathologically altered tissue architecture by transplantation of cells in combination with supportive scaffolds and biomolecules. In recent years, considerable attention has been given to chitosan (CS)-based materials and their applications in the field of orthopedic tissue engineering. Interesting characteristics that render chitosan suitable for this purpose are a minimal foreign body reaction, an intrinsic antibacterial nature, and the ability to be molded in various geometries and forms such as porous structures, suitable for cell ingrowth and osteoconduction. Due to its favorable gelling properties chitosan can deliver morphogenic factors and pharmaceutical agents in a controlled fashion. Its cationic nature allows it to complex DNA molecules making it an ideal candidate for gene delivery strategies. The ability to manipulate and reconstitute tissue structure and function using this material has tremendous clinical implications and is likely to play a key role in cell and gene therapies in coming years. In this paper we will review the current applications and future directions of CS in articular cartilage, intervertebral disk and bone tissue engineering.

  13. Additive manufacturing techniques for the production of tissue engineering constructs.

    Science.gov (United States)

    Mota, Carlos; Puppi, Dario; Chiellini, Federica; Chiellini, Emo

    2015-03-01

    'Additive manufacturing' (AM) refers to a class of manufacturing processes based on the building of a solid object from three-dimensional (3D) model data by joining materials, usually layer upon layer. Among the vast array of techniques developed for the production of tissue-engineering (TE) scaffolds, AM techniques are gaining great interest for their suitability in achieving complex shapes and microstructures with a high degree of automation, good accuracy and reproducibility. In addition, the possibility of rapidly producing tissue-engineered constructs meeting patient's specific requirements, in terms of tissue defect size and geometry as well as autologous biological features, makes them a powerful way of enhancing clinical routine procedures. This paper gives an extensive overview of different AM techniques classes (i.e. stereolithography, selective laser sintering, 3D printing, melt-extrusion-based techniques, solution/slurry extrusion-based techniques, and tissue and organ printing) employed for the development of tissue-engineered constructs made of different materials (i.e. polymeric, ceramic and composite, alone or in combination with bioactive agents), by highlighting their principles and technological solutions. Copyright © 2012 John Wiley & Sons, Ltd.

  14. A Novel Albumin-Based Tissue Scaffold for Autogenic Tissue Engineering Applications

    Science.gov (United States)

    Li, Pei-Shan; -Liang Lee, I.; Yu, Wei-Lin; Sun, Jui-Sheng; Jane, Wann-Neng; Shen, Hsin-Hsin

    2014-07-01

    Tissue scaffolds provide a framework for living tissue regeneration. However, traditional tissue scaffolds are exogenous, composed of metals, ceramics, polymers, and animal tissues, and have a defined biocompatibility and application. This study presents a new method for obtaining a tissue scaffold from blood albumin, the major protein in mammalian blood. Human, bovine, and porcine albumin was polymerised into albumin polymers by microbial transglutaminase and was then cast by freeze-drying-based moulding to form albumin tissue scaffolds. Scanning electron microscopy and material testing analyses revealed that the albumin tissue scaffold possesses an extremely porous structure, moderate mechanical strength, and resilience. Using a culture of human mesenchymal stem cells (MSCs) as a model, we showed that MSCs can be seeded and grown in the albumin tissue scaffold. Furthermore, the albumin tissue scaffold can support the long-term osteogenic differentiation of MSCs. These results show that the albumin tissue scaffold exhibits favourable material properties and good compatibility with cells. We propose that this novel tissue scaffold can satisfy essential needs in tissue engineering as a general-purpose substrate. The use of this scaffold could lead to the development of new methods of artificial fabrication of autogenic tissue substitutes.

  15. A new approach to heart valve tissue engineering

    DEFF Research Database (Denmark)

    Kaasi, Andreas; Cestari, Idágene A.; Stolf, Noedir A G.

    2011-01-01

    The 'biomimetic' approach to tissue engineering usually involves the use of a bioreactor mimicking physiological parameters whilst supplying nutrients to the developing tissue. Here we present a new heart valve bioreactor, having as its centrepiece a ventricular assist device (VAD), which exposes...... chamber. Subsequently, applied vacuum to the pneumatic chamber causes the blood chamber to fill. A mechanical heart valve was placed in the VAD's inflow position. The tissue engineered (TE) valve was placed in the outflow position. The VAD was coupled in series with a Windkessel compliance chamber......, variable throttle and reservoir, connected by silicone tubings. The reservoir sat on an elevated platform, allowing adjustment of ventricular preload between 0 and 11 mmHg. To allow for sterile gaseous exchange between the circuit interior and exterior, a 0.2 µm filter was placed at the reservoir. Pressure...

  16. Collagen-Based Biomaterials for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    François Berthod

    2010-03-01

    Full Text Available Collagen is the most widely distributed class of proteins in the human body. The use of collagen-based biomaterials in the field of tissue engineering applications has been intensively growing over the past decades. Multiple cross-linking methods were investigated and different combinations with other biopolymers were explored in order to improve tissue function. Collagen possesses a major advantage in being biodegradable, biocompatible, easily available and highly versatile. However, since collagen is a protein, it remains difficult to sterilize without alterations to its structure. This review presents a comprehensive overview of the various applications of collagen-based biomaterials developed for tissue engineering, aimed at providing a functional material for use in regenerative medicine from the laboratory bench to the patient bedside.

  17. Biofunctionalisation of polymeric scaffolds for neural tissue engineering.

    Science.gov (United States)

    Wang, T Y; Forsythe, J S; Parish, C L; Nisbet, D R

    2012-11-01

    Patients who experience injury to the central or peripheral nervous systems invariably suffer from a range of dysfunctions due to the limited ability for repair and reconstruction of damaged neural tissue. Whilst some treatment strategies can provide symptomatic improvement of motor and cognitive function, they fail to repair the injured circuits and rarely offer long-term disease modification. To this end, the biological molecules, used in combination with neural tissue engineering scaffolds, may provide feasible means to repair damaged neural pathways. This review will focus on three promising classes of neural tissue engineering scaffolds, namely hydrogels, electrospun nanofibres and self-assembling peptides. Additionally, the importance and methods for presenting biologically relevant molecules such as, neurotrophins, extracellular matrix proteins and protein-derived sequences that promote neuronal survival, proliferation and neurite outgrowth into the lesion will be discussed.

  18. Microstereolithography-based computer-aided manufacturing for tissue engineering.

    Science.gov (United States)

    Cho, Dong-Woo; Kang, Hyun-Wook

    2012-01-01

    Various solid freeform fabrication technologies have been introduced for constructing three-dimensional (3-D) freeform structures. Of these, microstereolithography (MSTL) technology performs the best in 3-D space because it not only has high resolution, but also fast fabrication speed. Using this technology, 3-D structures with mesoscale size and microscale resolution are achievable. Many researchers have been trying to apply this technology to tissue engineering to construct medically applicable scaffolds, which require a 3-D shape that fits a defect with a mesoscale size and microscale inner architecture for efficient regeneration of artificial tissue. This chapter introduces the principles of MSTL technology and representative systems. It includes fabrication and computer-aided design/computer-aided manufacturing (CAD/CAM) processes to show the automation process by which measurements from medical images are used to fabricate the required 3-D shape. Then, various tissue engineering applications based on MSTL are summarized.

  19. Nanotopography-guided tissue engineering and regenerative medicine☆

    Science.gov (United States)

    Kim, Hong Nam; Jiao, Alex; Hwang, Nathaniel S.; Kim, Min Sung; Kang, Do Hyun; Kim, Deok-Ho; Suh, Kahp-Yang

    2017-01-01

    Human tissues are intricate ensembles of multiple cell types embedded in complex and well-defined structures of the extracellular matrix (ECM). The organization of ECM is frequently hierarchical from nano to macro, with many proteins forming large scale structures with feature sizes up to several hundred microns. Inspired from these natural designs of ECM, nanotopography-guided approaches have been increasingly investigated for the last several decades. Results demonstrate that the nanotopography itself can activate tissue-specific function in vitro as well as promote tissue regeneration in vivo upon transplantation. In this review, we provide an extensive analysis of recent efforts to mimic functional nanostructures in vitro for improved tissue engineering and regeneration of injured and damaged tissues. We first characterize the role of various nanostructures in human tissues with respect to each tissue-specific function. Then, we describe various fabrication methods in terms of patterning principles and material characteristics. Finally, we summarize the applications of nanotopography to various tissues, which are classified into four types depending on their functions: protective, mechano-sensitive, electro-active, and shear stress-sensitive tissues. Some limitations and future challenges are briefly discussed at the end. PMID:22921841

  20. Multi-axial mechanical stimulation of tissue engineered cartilage: Review

    Directory of Open Access Journals (Sweden)

    S D Waldman

    2007-04-01

    Full Text Available The development of tissue engineered cartilage is a promising new approach for the repair of damaged or diseased tissue. Since it has proven difficult to generate cartilaginous tissue with properties similar to that of native articular cartilage, several studies have used mechanical stimuli as a means to improve the quantity and quality of the developed tissue. In this study, we have investigated the effect of multi-axial loading applied during in vitro tissue formation to better reflect the physiological forces that chondrocytes are subjected to in vivo. Dynamic combined compression-shear stimulation (5% compression and 5% shear strain amplitudes increased both collagen and proteoglycan synthesis (76 ± 8% and 73 ± 5%, respectively over the static (unstimulated controls. When this multi-axial loading condition was applied to the chondrocyte cultures over a four week period, there were significant improvements in both extracellular matrix (ECM accumulation and the mechanical properties of the in vitro-formed tissue (3-fold increase in compressive modulus and 1.75-fold increase in shear modulus. Stimulated tissues were also significantly thinner than the static controls (19% reduction suggesting that there was a degree of ECM consolidation as a result of long-term multi-axial loading. This study demonstrated that stimulation by multi-axial forces can improve the quality of the in vitro-formed tissue, but additional studies are required to further optimize the conditions to favour improved biochemical and mechanical properties of the developed tissue.

  1. Combination of biochemical and mechanical cues for tendon tissue engineering.

    Science.gov (United States)

    Testa, Stefano; Costantini, Marco; Fornetti, Ersilia; Bernardini, Sergio; Trombetta, Marcella; Seliktar, Dror; Cannata, Stefano; Rainer, Alberto; Gargioli, Cesare

    2017-05-04

    Tendinopathies negatively affect the life quality of millions of people in occupational and athletic settings, as well as the general population. Tendon healing is a slow process, often with insufficient results to restore complete endurance and functionality of the tissue. Tissue engineering, using tendon progenitors, artificial matrices and bioreactors for mechanical stimulation, could be an important approach for treating rips, fraying and tissue rupture. In our work, C3H10T1/2 murine fibroblast cell line was exposed to a combination of stimuli: a biochemical stimulus provided by Transforming Growth Factor Beta (TGF-β) and Ascorbic Acid (AA); a three-dimensional environment represented by PEGylated-Fibrinogen (PEG-Fibrinogen) biomimetic matrix; and a mechanical induction exploiting a custom bioreactor applying uniaxial stretching. In vitro analyses by immunofluorescence and mechanical testing revealed that the proposed combined approach favours the organization of a three-dimensional tissue-like structure promoting a remarkable arrangement of the cells and the neo-extracellular matrix, reflecting into enhanced mechanical strength. The proposed method represents a novel approach for tendon tissue engineering, demonstrating how the combined effect of biochemical and mechanical stimuli ameliorates biological and mechanical properties of the artificial tissue compared to those obtained with single inducement. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. Nuclear morphology and deformation in engineered cardiac myocytes and tissues.

    Science.gov (United States)

    Bray, Mark-Anthony P; Adams, William J; Geisse, Nicholas A; Feinberg, Adam W; Sheehy, Sean P; Parker, Kevin K

    2010-07-01

    Cardiac tissue engineering requires finely-tuned manipulation of the extracellular matrix (ECM) microenvironment to optimize internal myocardial organization. The myocyte nucleus is mechanically connected to the cell membrane via cytoskeletal elements, making it a target for the cellular response to perturbation of the ECM. However, the role of ECM spatial configuration and myocyte shape on nuclear location and morphology is unknown. In this study, printed ECM proteins were used to configure the geometry of cultured neonatal rat ventricular myocytes. Engineered one- and two-dimensional tissue constructs and single myocyte islands were assayed using live fluorescence imaging to examine nuclear position, morphology and motion as a function of the imposed ECM geometry during diastolic relaxation and systolic contraction. Image analysis showed that anisotropic tissue constructs cultured on microfabricated ECM lines possessed a high degree of nuclear alignment similar to that found in vivo; nuclei in isotropic tissues were polymorphic in shape with an apparently random orientation. Nuclear eccentricity was also increased for the anisotropic tissues, suggesting that intracellular forces deform the nucleus as the cell is spatially confined. During systole, nuclei experienced increasing spatial confinement in magnitude and direction of displacement as tissue anisotropy increased, yielding anisotropic deformation. Thus, the nature of nuclear displacement and deformation during systole appears to rely on a combination of the passive myofibril spatial organization and the active stress fields induced by contraction. Such findings have implications in understanding the genomic consequences and functional response of cardiac myocytes to their ECM surroundings under conditions of disease.

  3. Thermal inkjet printing in tissue engineering and regenerative medicine.

    Science.gov (United States)

    Cui, Xiaofeng; Boland, Thomas; D'Lima, Darryl D; Lotz, Martin K

    2012-08-01

    With the advantages of high throughput, digital control, and highly accurate placement of cells and biomaterial scaffold to the desired 2D and 3D locations, bioprinting has great potential to develop promising approaches in translational medicine and organ replacement. The most recent advances in organ and tissue bioprinting based on the thermal inkjet printing technology are described in this review. Bioprinting has no or little side effect to the printed mammalian cells and it can conveniently combine with gene transfection or drug delivery to the ejected living systems during the precise placement for tissue construction. With layer-by-layer assembly, 3D tissues with complex structures can be printed using scanned CT or MRI images. Vascular or nerve systems can be enabled simultaneously during the organ construction with digital control. Therefore, bioprinting is the only solution to solve this critical issue in thick and complex tissues fabrication with vascular system. Collectively, bioprinting based on thermal inkjet has great potential and broad applications in tissue engineering and regenerative medicine. This review article introduces some important patents related to bioprinting of living systems and the applications of bioprinting in tissue engineering field.

  4. Mapping of Mechanical Strains and Stresses around Quiescent Engineered Three-Dimensional Epithelial Tissues

    Science.gov (United States)

    Gjorevski, Nikolce; Nelson, Celeste M.

    2012-01-01

    Understanding how physical signals guide biological processes requires qualitative and quantitative knowledge of the mechanical forces generated and sensed by cells in a physiologically realistic three-dimensional (3D) context. Here, we used computational modeling and engineered epithelial tissues of precise geometry to define the experimental parameters that are required to measure directly the mechanical stress profile of 3D tissues embedded within native type I collagen. We found that to calculate the stresses accurately in these settings, we had to account for mechanical heterogeneities within the matrix, which we visualized and quantified using confocal reflectance and atomic force microscopy. Using this technique, we were able to obtain traction forces at the epithelium-matrix interface, and to resolve and quantify patterns of mechanical stress throughout the surrounding matrix. We discovered that whereas single cells generate tension by contracting and pulling on the matrix, the contraction of multicellular tissues can also push against the matrix, causing emergent compression. Furthermore, tissue geometry defines the spatial distribution of mechanical stress across the epithelium, which communicates mechanically over distances spanning hundreds of micrometers. Spatially resolved mechanical maps can provide insight into the types and magnitudes of physical parameters that are sensed and interpreted by multicellular tissues during normal and pathological processes. PMID:22828342

  5. Advancements in electrospinning of polymeric nanofibrous scaffolds for tissue engineering.

    Science.gov (United States)

    Ingavle, Ganesh C; Leach, J Kent

    2014-08-01

    Polymeric nanofibers have potential as tissue engineering scaffolds, as they mimic the nanoscale properties and structural characteristics of native extracellular matrix (ECM). Nanofibers composed of natural and synthetic polymers, biomimetic composites, ceramics, and metals have been fabricated by electrospinning for various tissue engineering applications. The inherent advantages of electrospinning nanofibers include the generation of substrata with high surface area-to-volume ratios, the capacity to precisely control material and mechanical properties, and a tendency for cellular in-growth due to interconnectivity within the pores. Furthermore, the electrospinning process affords the opportunity to engineer scaffolds with micro- to nanoscale topography similar to the natural ECM. This review describes the fundamental aspects of the electrospinning process when applied to spinnable natural and synthetic polymers; particularly, those parameters that influence fiber geometry, morphology, mesh porosity, and scaffold mechanical properties. We describe cellular responses to fiber morphology achieved by varying processing parameters and highlight successful applications of electrospun nanofibrous scaffolds when used to tissue engineer bone, skin, and vascular grafts.

  6. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  7. Mechanical stimulation improves tissue-engineered human skeletal muscle

    Science.gov (United States)

    Powell, Courtney A.; Smiley, Beth L.; Mills, John; Vandenburgh, Herman H.

    2002-01-01

    Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.

  8. Histological and immunohistochemical studies of tissue engineered odontogenesis.

    Science.gov (United States)

    Honda, Masaki J; Sumita, Yoshinori; Kagami, Hideaki; Ueda, Minoru

    2005-06-01

    The successful regeneration of complex tooth structures based on tissue-engineering principles was recently reported. The process of this regeneration, however, remains poorly characterized. In this study, we have used histochemistry to examine the regeneration process of tissue engineered teeth in order to determine the cell types that give rise to these engineered tooth structures. Porcine third molar tooth buds were dissociated into single-cell suspensions and seeded onto a biodegradable polyglycolic acid polymer scaffold. Following varying periods of growth in rat hosts, the specimens were evaluated by histology and immunohistochemistry. Aggregates of epithelial cells were first observed 4-6 weeks after implantation. These aggregates assumed three different shapes: a natural tooth germ-like shape, a circular shape, or a bilayer-bundle. Based on the structure of the stellate reticulum in the dental epithelium, the circular and bilayer-bundle aggregates could be clearly classified into two types: one with extensively developed stellate reticulum, and the other with negligible stellate reticulum. The epithelial cells in the circular aggregates differentiated into ameloblasts. The continuous bilayer bundles eventually formed the epithelial sheath, and dentin tissue was evident at the apex of these bundles. Finally, enamel-covered dentin and cementum-covered dentin formed, a process most likely mediated by epithelial-mesenchymal interaction. These results suggest that the development of these engineered teeth closely parallels that of natural odontogenesis derived from the immature epithelial and mesenchymal cells.

  9. Creating tissues from textiles: scalable nonwoven manufacturing techniques for fabrication of tissue engineering scaffolds.

    Science.gov (United States)

    Tuin, S A; Pourdeyhimi, B; Loboa, E G

    2016-02-23

    Electrospun nonwovens have been used extensively for tissue engineering applications due to their inherent similarities with respect to fibre size and morphology to that of native extracellular matrix (ECM). However, fabrication of large scaffold constructs is time consuming, may require harsh organic solvents, and often results in mechanical properties inferior to the tissue being treated. In order to translate nonwoven based tissue engineering scaffold strategies to clinical use, a high throughput, repeatable, scalable, and economic manufacturing process is needed. We suggest that nonwoven industry standard high throughput manufacturing techniques (meltblowing, spunbond, and carding) can meet this need. In this study, meltblown, spunbond and carded poly(lactic acid) (PLA) nonwovens were evaluated as tissue engineering scaffolds using human adipose derived stem cells (hASC) and compared to electrospun nonwovens. Scaffolds were seeded with hASC and viability, proliferation, and differentiation were evaluated over the course of 3 weeks. We found that nonwovens manufactured via these industry standard, commercially relevant manufacturing techniques were capable of supporting hASC attachment, proliferation, and both adipogenic and osteogenic differentiation of hASC, making them promising candidates for commercialization and translation of nonwoven scaffold based tissue engineering strategies.

  10. Nanocarbons in Electrospun Polymeric Nanomats for Tissue Engineering: A Review

    Directory of Open Access Journals (Sweden)

    Roberto Scaffaro

    2017-02-01

    Full Text Available Electrospinning is a versatile process technology, exploited for the production of fibers with varying diameters, ranging from nano- to micro-scale, particularly useful for a wide range of applications. Among these, tissue engineering is particularly relevant to this technology since electrospun fibers offer topological structure features similar to the native extracellular matrix, thus providing an excellent environment for the growth of cells and tissues. Recently, nanocarbons have been emerging as promising fillers for biopolymeric nanofibrous scaffolds. In fact, they offer interesting physicochemical properties due to their small size, large surface area, high electrical conductivity and ability to interface/interact with the cells/tissues. Nevertheless, their biocompatibility is currently under debate and strictly correlated to their surface characteristics, in terms of chemical composition, hydrophilicity and roughness. Among the several nanofibrous scaffolds prepared by electrospinning, biopolymer/nanocarbons systems exhibit huge potential applications, since they combine the features of the matrix with those determined by the nanocarbons, such as conductivity and improved bioactivity. Furthermore, combining nanocarbons and electrospinning allows designing structures with engineered patterns at both nano- and microscale level. This article presents a comprehensive review of various types of electrospun polymer-nanocarbon currently used for tissue engineering applications. Furthermore, the differences among graphene, carbon nanotubes, nanodiamonds and fullerenes and their effect on the ultimate properties of the polymer-based nanofibrous scaffolds is elucidated and critically reviewed.

  11. Polymeric scaffolds in tissue engineering: a literature review.

    Science.gov (United States)

    Jafari, Maissa; Paknejad, Zahrasadat; Rad, Maryam Rezai; Motamedian, Saeed Reza; Eghbal, Mohammad Jafar; Nadjmi, Nasser; Khojasteh, Arash

    2017-02-01

    The tissue engineering scaffold acts as an extracellular matrix that interacts to the cells prior to forming new tissues. The chemical and structural characteristics of scaffolds are major concerns in fabricating of ideal three-dimensional structure for tissue engineering applications. The polymer scaffolds used for tissue engineering should possess proper architecture and mechanical properties in addition to supporting cell adhesion, proliferation, and differentiation. Much research has been done on the topic of polymeric scaffold properties such as surface topographic features (roughness and hydrophilicity) and scaffold microstructures (pore size, porosity, pore interconnectivity, and pore and fiber architectures) that influence the cell-scaffold interactions. In this review, efforts were given to evaluate the effect of both chemical and structural characteristics of scaffolds on cell behaviors such as adhesion, proliferation, migration, and differentiation. This review would provide the fundamental information which would be beneficial for scaffold design in future. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 431-459, 2017.

  12. Osteochondral tissue engineering: scaffolds, stem cells and applications

    Science.gov (United States)

    Nooeaid, Patcharakamon; Salih, Vehid; Beier, Justus P; Boccaccini, Aldo R

    2012-01-01

    Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral tissue engineering, which are focused on the application of various materials forming bilayered composite scaffolds, including polymers and ceramics, discussing the variety of scaffold designs and fabrication methods being developed. Additionally, cell sources and biological protein incorporation methods are discussed, addressing their interaction with scaffolds and highlighting the potential for creating a new generation of bilayered composite scaffolds that can mimic the native interfacial tissue properties, and are able to adapt to the biological environment. PMID:22452848

  13. Conductive polymers: towards a smart biomaterial for tissue engineering.

    Science.gov (United States)

    Balint, Richard; Cassidy, Nigel J; Cartmell, Sarah H

    2014-06-01

    Developing stimulus-responsive biomaterials with easy-to-tailor properties is a highly desired goal of the tissue engineering community. A novel type of electroactive biomaterial, the conductive polymer, promises to become one such material. Conductive polymers are already used in fuel cells, computer displays and microsurgical tools, and are now finding applications in the field of biomaterials. These versatile polymers can be synthesised alone, as hydrogels, combined into composites or electrospun into microfibres. They can be created to be biocompatible and biodegradable. Their physical properties can easily be optimized for a specific application through binding biologically important molecules into the polymer using one of the many available methods for their functionalization. Their conductive nature allows cells or tissue cultured upon them to be stimulated, the polymers' own physical properties to be influenced post-synthesis and the drugs bound in them released, through the application of an electrical signal. It is thus little wonder that these polymers are becoming very important materials for biosensors, neural implants, drug delivery devices and tissue engineering scaffolds. Focusing mainly on polypyrrole, polyaniline and poly(3,4-ethylenedioxythiophene), we review conductive polymers from the perspective of tissue engineering. The basic properties of conductive polymers, their chemical and electrochemical synthesis, the phenomena underlying their conductivity and the ways to tailor their properties (functionalization, composites, etc.) are discussed.

  14. A Novel bioreactor with mechanical stimulation for skeletal tissue engineering

    Directory of Open Access Journals (Sweden)

    M. Petrović

    2009-01-01

    Full Text Available The provision of mechanical stimulation is believed to be necessary for the functional assembly of skeletal tissues, which are normally exposed to a variety of biomechanical signals in vivo. In this paper, we present a development and validation of a novel bioreactor aimed for skeletal tissue engineering that provides dynamic compression and perfusion of cultivated tissues. Dynamic compression can be applied at frequencies up to 67.5 Hz and displacements down to 5 m thus suitable for the simulation of physiological conditions in a native cartilage tissue (0.1-1 Hz, 5-10 % strain. The bioreactor also includes a load sensor that was calibrated so to measure average loads imposed on tissue samples. Regimes of the mechanical stimulation and acquisition of load sensor outputs are directed by an automatic control system using applications developed within the LabView platform. In addition, perfusion of tissue samples at physiological velocities (10–100 m/s provides efficient mass transfer, as well as the possibilities to expose the cells to hydrodynamic shear and simulate the conditions in a native bone tissue. Thus, the novel bioreactor is suited for studies of the effects of different biomechanical signals on in vitro regeneration of skeletal tissues, as well as for the studies of newly formulated biomaterials and cell biomaterial interactions under in vivo-like settings.

  15. Advancing biomaterials of human origin for tissue engineering.

    Science.gov (United States)

    Chen, Fa-Ming; Liu, Xiaohua

    2016-02-01

    Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for

  16. Collagen hydrogel as an immunomodulatory scaffold in cartilage tissue engineering.

    Science.gov (United States)

    Yuan, Tun; Zhang, Li; Li, Kuifeng; Fan, Hongsong; Fan, Yujiang; Liang, Jie; Zhang, Xingdong

    2014-02-01

    A collagen type I hydrogel was constructed and used as the scaffold for cartilage tissue engineering. Neonatal rabbit chondrocytes were seeded into the hydrogel, and the constructs were cultured in vitro for 7, 14, and 28 days. The immunomodulatory effect of the hydrogel on seeded chondrocytes was carefully investigated. The expressions of major histocompatibility complex classes I and II of seeded chondrocytes increased with the time, which indicated that the immunogenicity also increased with the time. Meanwhile, the properly designed collagen type I hydrogel could prompt the chondrogenesis of engineered cartilage. The extracellular matrix (ECM) synthesis ability of seeded chondrocytes and the accumulated ECM in the constructs continuously increased with the culture time. Both the isolation and protection, which come from formed ECM and hydrogel scaffold, can effectively control the adverse immunogenicity of seeded chondrocytes and even help to lessen the immunogenicity of the whole engineered cartilage. As the result, the levels of mixed lymphocyte chondrocyte reactions of seed cells and the constructs decreased gradually. The stimulation on allogeneic lymphocytes of the whole constructs was obviously lower than that of the retrieved cells from the constructs. Therefore, properly designed collagen type I hydrogel can give certain immunogenicity-reducing effects on engineered cartilage based on chondrocytes, and it may be a potential immunomodulatory biomaterial in tissue engineering.

  17. 3D printing of functional biomaterials for tissue engineering.

    Science.gov (United States)

    Zhu, Wei; Ma, Xuanyi; Gou, Maling; Mei, Deqing; Zhang, Kang; Chen, Shaochen

    2016-08-01

    3D printing is emerging as a powerful tool for tissue engineering by enabling 3D cell culture within complex 3D biomimetic architectures. This review discusses the prevailing 3D printing techniques and their most recent applications in building tissue constructs. The work associated with relatively well-known inkjet and extrusion-based bioprinting is presented with the latest advances in the fields. Emphasis is put on introducing two relatively new light-assisted bioprinting techniques, including digital light processing (DLP)-based bioprinting and laser based two photon polymerization (TPP) bioprinting. 3D bioprinting of vasculature network is particularly discussed for its foremost significance in maintaining tissue viability and promoting functional maturation. Limitations to current bioprinting approaches, as well as future directions of bioprinting functional tissues are also discussed.

  18. Today prospects for tissue engineering therapeutic approach in dentistry.

    Science.gov (United States)

    Bossù, Maurizio; Pacifici, Andrea; Carbone, Daniele; Tenore, Gianluca; Ierardo, Gaetano; Pacifici, Luciano; Polimeni, Antonella

    2014-01-01

    In dental practice there is an increasing need for predictable therapeutic protocols able to regenerate tissues that, due to inflammatory or traumatic events, may suffer from loss of their function. One of the topics arising major interest in the research applied to regenerative medicine is represented by tissue engineering and, in particular, by stem cells. The study of stem cells in dentistry over the years has shown an exponential increase in literature. Adult mesenchymal stem cells have recently been isolated and characterized from tooth-related tissues and they might represent, in the near future, a new gold standard in the regeneration of all oral tissues. The aim of our review is to provide an overview on the topic reporting the current knowledge for each class of dental stem cells and to identify their potential clinical applications as therapeutic tool in various branches of dentistry.

  19. BIOTECHNOLOGICAL CONDITIONS OF VALVE PROSTHESES CREATING BY TISSUE ENGINEERING METHOD

    Directory of Open Access Journals (Sweden)

    A. G. Popandopulo

    2015-02-01

    Full Text Available Nowadays, definitive treatment for the end-stage organ failure is transplantation. Tissue engineering is an up to date solution to create the effective substitute of the defective organ. It involves the reconstitution of viable tissue with the use of autologous cells grown on connective tissue matrix, which has been acellularized before. Basis for the prothesis should be morphologically and physically nonmodified, so in case of making vessel-valvular biological prosthesises the decellularized extracellular matrix is the best variant. The xenogeneic extracellular matrix is economically and ethically more useful. The possibility of preservation of the morphological and chemical properties of matrix structure initiates the process of programmed cell death. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis doesn’t cause the tissue damages. One of the ways of realizing the apoptosis is the usage of EDTA — chelate, which binds the Ca2+ ions.

  20. Tissue Engineering Using Transfected Growth-Factor Genes

    Science.gov (United States)

    Madry, Henning; Langer, Robert S.; Freed, Lisa E.; Trippel, Stephen; Vunjak-Novakovic, Gordana

    2005-01-01

    A method of growing bioengineered tissues includes, as a major component, the use of mammalian cells that have been transfected with genes for secretion of regulator and growth-factor substances. In a typical application, one either seeds the cells onto an artificial matrix made of a synthetic or natural biocompatible material, or else one cultures the cells until they secrete a desired amount of an extracellular matrix. If such a bioengineered tissue construct is to be used for surgical replacement of injured tissue, then the cells should preferably be the patient s own cells or, if not, at least cells matched to the patient s cells according to a human-leucocyteantigen (HLA) test. The bioengineered tissue construct is typically implanted in the patient's injured natural tissue, wherein the growth-factor genes enhance metabolic functions that promote the in vitro development of functional tissue constructs and their integration with native tissues. If the matrix is biodegradable, then one of the results of metabolism could be absorption of the matrix and replacement of the matrix with tissue formed at least partly by the transfected cells. The method was developed for articular chondrocytes but can (at least in principle) be extended to a variety of cell types and biocompatible matrix materials, including ones that have been exploited in prior tissue-engineering methods. Examples of cell types include chondrocytes, hepatocytes, islet cells, nerve cells, muscle cells, other organ cells, bone- and cartilage-forming cells, epithelial and endothelial cells, connective- tissue stem cells, mesodermal stem cells, and cells of the liver and the pancreas. Cells can be obtained from cell-line cultures, biopsies, and tissue banks. Genes, molecules, or nucleic acids that secrete factors that influence the growth of cells, the production of extracellular matrix material, and other cell functions can be inserted in cells by any of a variety of standard transfection techniques.

  1. Tissue engineering and regenerative medicine: history, progress, and challenges.

    Science.gov (United States)

    Berthiaume, François; Maguire, Timothy J; Yarmush, Martin L

    2011-01-01

    The past three decades have seen the emergence of an endeavor called tissue engineering and regenerative medicine in which scientists, engineers, and physicians apply tools from a variety of fields to construct biological substitutes that can mimic tissues for diagnostic and research purposes and can replace (or help regenerate) diseased and injured tissues. A significant portion of this effort has been translated to actual therapies, especially in the areas of skin replacement and, to a lesser extent, cartilage repair. A good amount of thoughtful work has also yielded prototypes of other tissue substitutes such as nerve conduits, blood vessels, liver, and even heart. Forward movement to clinical product, however, has been slow. Another offshoot of these efforts has been the incorporation of some new exciting technologies (e.g., microfabrication, 3D printing) that may enable future breakthroughs. In this review we highlight the modest beginnings of the field and then describe three application examples that are in various stages of development, ranging from relatively mature (skin) to ongoing proof-of-concept (cartilage) to early stage (liver). We then discuss some of the major issues that limit the development of complex tissues, some of which are fundamentals-based, whereas others stem from the needs of the end users.

  2. The influence of topography on tissue engineering perspective

    Energy Technology Data Exchange (ETDEWEB)

    Mansouri, Negar [Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, 50603 Kuala Lumpur (Malaysia); SamiraBagheri, E-mail: samira_bagheri@edu.um.my [Nanotechnology & Catalysis Research Centre (NANOCAT), IPS Building, University of Malaya, 50603 Kuala Lumpur (Malaysia)

    2016-04-01

    The actual in vivo tissue scaffold offers a three-dimensional (3D) structural support along with a nano-textured surfaces consist of a fibrous network in order to deliver cell adhesion and signaling. A scaffold is required, until the tissue is entirely regenerated or restored, to act as a temporary ingrowth template for cell proliferation and extracellular matrix (ECM) deposition. This review depicts some of the most significant three dimensional structure materials used as scaffolds in various tissue engineering application fields currently being employed to mimic in vivo features. Accordingly, some of the researchers' attempts have envisioned utilizing graphene for the fabrication of porous and flexible 3D scaffolds. The main focus of this paper is to evaluate the topographical and topological optimization of scaffolds for tissue engineering applications in order to improve scaffolds' mechanical performances. - Highlights: • The in vivo tissue scaffold offers a three-dimensional structural support. • Graphene can be used for fabrication of porous and flexible 3D scaffold. • Topological optimization improves scaffolds' mechanical performances.

  3. A versatile modular bioreactor platform for Tissue Engineering.

    Science.gov (United States)

    Schuerlein, Sebastian; Schwarz, Thomas; Krziminski, Steffan; Gätzner, Sabine; Hoppensack, Anke; Schwedhelm, Ivo; Schweinlin, Matthias; Walles, Heike; Hansmann, Jan

    2017-02-01

    Tissue Engineering (TE) bears potential to overcome the persistent shortage of donor organs in transplantation medicine. Additionally, TE products are applied as human test systems in pharmaceutical research to close the gap between animal testing and the administration of drugs to human subjects in clinical trials. However, generating a tissue requires complex culture conditions provided by bioreactors. Currently, the translation of TE technologies into clinical and industrial applications is limited due to a wide range of different tissue-specific, non-disposable bioreactor systems. To ensure a high level of standardization, a suitable cost-effectiveness, and a safe graft production, a generic modular bioreactor platform was developed. Functional modules provide robust control of culture processes, e.g. medium transport, gas exchange, heating, or trapping of floating air bubbles. Characterization revealed improved performance of the modules in comparison to traditional cell culture equipment such as incubators, or peristaltic pumps. By combining the modules, a broad range of culture conditions can be achieved. The novel bioreactor platform allows using disposable components and facilitates tissue culture in closed fluidic systems. By sustaining native carotid arteries, engineering a blood vessel, and generating intestinal tissue models according to a previously published protocol the feasibility and performance of the bioreactor platform was demonstrated. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Electroactive 3D materials for cardiac tissue engineering

    Science.gov (United States)

    Gelmi, Amy; Zhang, Jiabin; Cieslar-Pobuda, Artur; Ljunngren, Monika K.; Los, Marek Jan; Rafat, Mehrdad; Jager, Edwin W. H.

    2015-04-01

    By-pass surgery and heart transplantation are traditionally used to restore the heart's functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

  5. Practical aspects of cardiac tissue engineering with electrical stimulation.

    Science.gov (United States)

    Cannizzaro, Christopher; Tandon, Nina; Figallo, Elisa; Park, Hyoungshin; Gerecht, Sharon; Radisic, Milica; Elvassore, Nicola; Vunjak-Novakovic, Gordana

    2007-01-01

    Heart disease is a leading cause of death in western society. Despite the success of heart transplantation, a chronic shortage of donor organs, along with the associated immunological complications of this approach, demands that alternative treatments be found. One such option is to repair, rather than replace, the heart with engineered cardiac tissue. Multiple studies have shown that to attain functional tissue, assembly signaling cues must be recapitulated in vitro. In their native environment, cardiomyocytes are directed to beat in synchrony by propagation of pacing current through the tissue. Recently, we have shown that electrical stimulation directs neonatal cardiomyocytes to assemble into native-like tissue in vitro. This chapter provides detailed methods we have employed in taking this "biomimetic" approach. After an initial discussion on how electric field stimulation can influence cell behavior, we examine the practical aspects of cardiac tissue engineering with electrical stimulation, such as electrode selection and cell seeding protocols, and conclude with what we feel are the remaining challenges to be overcome.

  6. Optically Controlled Oscillators in an Engineered Bioelectric Tissue

    Science.gov (United States)

    McNamara, Harold M.; Zhang, Hongkang; Werley, Christopher A.; Cohen, Adam E.

    2016-07-01

    Complex electrical dynamics in excitable tissues occur throughout biology, but the roles of individual ion channels can be difficult to determine due to the complex nonlinear interactions in native tissue. Here, we ask whether we can engineer a tissue capable of basic information storage and processing, where all functional components are known and well understood. We develop a cell line with four transgenic components: two to enable collective propagation of electrical waves and two to enable optical perturbation and optical readout of membrane potential. We pattern the cell growth to define simple cellular ring oscillators that run stably for >2 h (˜104 cycles ) and that can store data encoded in the direction of electrical circulation. Using patterned optogenetic stimulation, we probe the biophysical attributes of this synthetic excitable tissue in detail, including dispersion relations, curvature-dependent wave front propagation, electrotonic coupling, and boundary effects. We then apply the biophysical characterization to develop an optically reconfigurable bioelectric oscillator. These results demonstrate the feasibility of engineering bioelectric tissues capable of complex information processing with optical input and output.

  7. Competent processing techniques for scaffolds in tissue engineering.

    Science.gov (United States)

    Dutta, Ranjna C; Dey, Madhuri; Dutta, Aroop K; Basu, Bikramjit

    Engineering a functional tissue ex vivo requires a synchronized effort towards developing technologies for ECM mimicking scaffold and cultivating tissue-specific cells in an integrated and controlled manner. Cell-interactive scaffolds in three dimensions (3D), designed and processed appropriately with an apt biomaterial to yield optimal porosity and mechanical strength is the key in tissue engineering (TE). In order to accomplish these facets in a 3D scaffold, multiple techniques and processes have been explored by researchers all over the world. New techniques offering reasonable flexibility to use blends of different materials for integrated tissue-specific mechanical strength and biocompatibility have an edge over conventional methods. They may allow a combinatorial approach with a mix of materials while incorporating multiple processing techniques for successful creation of tissue-specific ECM mimics. In this review, we analyze the material requirement from different TE perspectives, while discussing pros and cons of advanced fabrication techniques for scale-up manufacturing. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Biological aspects of application of nanomaterials in tissue engineering

    Directory of Open Access Journals (Sweden)

    Markovic Dejan

    2016-01-01

    Full Text Available Millions of patients worldwide need surgery to repair or replace tissue that has been damaged through trauma or disease. To solve the problem of lost tissue, a major emphasis of tissue engineering (TE is on tissue regeneration. Stem cells and highly porous biomaterials used as cell carriers (scaffolds have an essential role in the production of new tissue by TE. Cellular component is important for the generation and establishment of the extracellular matrix, while a scaffold is necessary to determine the shape of the newly formed tissue and facilitate migration of cells into the desired location, as well as their growth and differentiation. This review describes the types, characteristics and classification of stem cells. Furthermore, it includes functional features of cell carriers - biocompatibility, biodegradability and mechanical properties of biomaterials used in developing state-of-the-art scaffolds for TE applications, as well as suitability for different tissues. Moreover, it explains the importance of nanotechnology and defines the challenges and the purpose of future research in this rapidly advancing field. [Projekat Ministarstva nauke Republike Srbije, br. 41030 i br. 172026

  9. Patterning methods for polymers in cell and tissue engineering.

    Science.gov (United States)

    Kim, Hong Nam; Kang, Do-Hyun; Kim, Min Sung; Jiao, Alex; Kim, Deok-Ho; Suh, Kahp-Yang

    2012-06-01

    Polymers provide a versatile platform for mimicking various aspects of physiological extracellular matrix properties such as chemical composition, rigidity, and topography for use in cell and tissue engineering applications. In this review, we provide a brief overview of patterning methods of various polymers with a particular focus on biocompatibility and processability. The materials highlighted here are widely used polymers including thermally curable polydimethyl siloxane, ultraviolet-curable polyurethane acrylate and polyethylene glycol, thermo-sensitive poly(N-isopropylacrylamide) and thermoplastic and conductive polymers. We also discuss how micro- and nanofabricated polymeric substrates of tunable elastic modulus can be used to engineer cell and tissue structure and function. Such synergistic effect of topography and rigidity of polymers may be able to contribute to constructing more physiologically relevant microenvironment.

  10. 3D-Printed Biopolymers for Tissue Engineering Application

    Directory of Open Access Journals (Sweden)

    Xiaoming Li

    2014-01-01

    Full Text Available 3D printing technology has recently gained substantial interest for potential applications in tissue engineering due to the ability of making a three-dimensional object of virtually any shape from a digital model. 3D-printed biopolymers, which combine the 3D printing technology and biopolymers, have shown great potential in tissue engineering applications and are receiving significant attention, which has resulted in the development of numerous research programs regarding the material systems which are available for 3D printing. This review focuses on recent advances in the development of biopolymer materials, including natural biopolymer-based materials and synthetic biopolymer-based materials prepared using 3D printing technology, and some future challenges and applications of this technology are discussed.

  11. Towards autotrophic tissue engineering: Photosynthetic gene therapy for regeneration.

    Science.gov (United States)

    Chávez, Myra Noemi; Schenck, Thilo Ludwig; Hopfner, Ursula; Centeno-Cerdas, Carolina; Somlai-Schweiger, Ian; Schwarz, Christian; Machens, Hans-Günther; Heikenwalder, Mathias; Bono, María Rosa; Allende, Miguel L; Nickelsen, Jörg; Egaña, José Tomás

    2016-01-01

    The use of artificial tissues in regenerative medicine is limited due to hypoxia. As a strategy to overcome this drawback, we have shown that photosynthetic biomaterials can produce and provide oxygen independently of blood perfusion by generating chimeric animal-plant tissues during dermal regeneration. In this work, we demonstrate the safety and efficacy of photosynthetic biomaterials in vivo after engraftment in a fully immunocompetent mouse skin defect model. Further, we show that it is also possible to genetically engineer such photosynthetic scaffolds to deliver other key molecules in addition to oxygen. As a proof-of-concept, biomaterials were loaded with gene modified microalgae expressing the angiogenic recombinant protein VEGF. Survival of the algae, growth factor delivery and regenerative potential were evaluated in vitro and in vivo. This work proposes the use of photosynthetic gene therapy in regenerative medicine and provides scientific evidence for the use of engineered microalgae as an alternative to deliver recombinant molecules for gene therapy.

  12. Nano-apatite/Polymer Biocomposite for Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    A new kind of tissue engineering scaffold materials of nano-apatite ( NA ) and polyamide6( PA6) biocomposite was prepared by means of the co-solution method. The NA crystals uniformly distribute in the composite with a size of 10- 30 nm in diameter by 50- 90 nm in length. The NA/ PA6 composite has good homogeneity and high NA content, and excellent mechanical properties close to those of natural bone. The porous 3-D scaffold has not only macropores, but also micropores on the walls of macropores with porosity of about 80% and the size of pore diameter of about 300μm made by injection foam. The biocomposite can be used for bone repair and as scaffolds in tissue engineering.

  13. Novel blood protein based scaffolds for cardiovascular tissue engineering

    Directory of Open Access Journals (Sweden)

    Kuhn Antonia I.

    2016-09-01

    Full Text Available A major challenge in cardiovascular tissue engineering is the fabrication of scaffolds, which provide appropriate morphological and mechanical properties while avoiding undesirable immune reactions. In this study electrospinning was used to fabricate scaffolds out of blood proteins for cardiovascular tissue engineering. Lyophilised porcine plasma was dissolved in deionised water at a final concentration of 7.5% m/v and blended with 3.7% m/v PEO. Electrospinning resulted in homogeneous fibre morphologies with a mean fibre diameter of 151 nm, which could be adapted to create macroscopic shapes (mats, tubes. Cross-linking with glutaraldehyde vapour improved the long-term stability of protein based scaffolds in comparison to untreated scaffolds, resulting in a mass loss of 41% and 96% after 28 days of incubation in aqueous solution, respectively.

  14. Novel Scaffolds Fabricated Using Oleuropein for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Hui Fan

    2014-01-01

    Full Text Available We investigated the feasibility of oleuropein as a cross-linking agent for fabricating three-dimensional (3D porous composite scaffolds for bone tissue engineering. Human-like collagen (HLC and nanohydroxyapatite (n-HAp were used to fabricate the composite scaffold by way of cross-linking. The mechanical tests revealed superior properties for the cross-linked scaffolds compared to the uncross-linked scaffolds. The as-obtained composite scaffold had a 3D porous structure with pores ranging from 120 to 300 μm and a porosity of 73.6±2.3%. The cross-linked scaffolds were seeded with MC3T3-E1 Subclone 14 mouse osteoblasts. Fluorescence staining, the Cell Counting Kit-8 (CCK-8 assay, and scanning electron microscopy (SEM indicated that the scaffolds enhanced cell adhesion and proliferation. Our results indicate the potential of these scaffolds for bone tissue engineering.

  15. Polymer Composites Reinforced by Nanotubes as Scaffolds for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2014-01-01

    Full Text Available The interest in polymer based composites for tissue engineering applications has been increasing in recent years. Nanotubes materials, including carbon nanotubes (CNTs and noncarbonic nanotubes, with unique electrical, mechanical, and surface properties, such as high aspect ratio, have long been recognized as effective reinforced materials for enhancing the mechanical properties of polymer matrix. This review paper is an attempt to present a coherent yet concise review on the mechanical and biocompatibility properties of CNTs and noncarbonic nanotubes/polymer composites, such as Boron nitride nanotubes (BNNTs and Tungsten disulfide nanotubes (WSNTs reinforced polymer composites which are used as scaffolds for tissue engineering. We also introduced different preparation methods of CNTs/polymer composites, such as in situ polymerization, solution mixing, melt blending, and latex technology, each of them has its own advantages.

  16. To fabricate artificial nerves with tissue engineering methods

    Institute of Scientific and Technical Information of China (English)

    程飚; 陈峥嵘

    2002-01-01

    To fabricate artificial nerves with tissue engineering methods in vitro. Methods: Schwann cells (SCs) were cultured and seeded on polyglactin 910 fibers wrapped by biomembrane coated with rat tail glue and laminin for 2 weeks. The absorbability on the scaffolds, growth and migration of SCs were assessed with a light microscope, a scanning electron microscope and a transmission electron microscope. Results: SCs could migrate and proliferate on polyglactin 910 fibers. They were well distributed between scaffolds and absorbed on surface of scaffolds and formed a bungner band, on which SCs produced more matrices. SCs seeded on the biomembrane could also grow well. Axon regeneration in the distal nerve stump was observed at 8 weeks. Conclusions: Adult SCs can be expanded on coated fibers and biomembrane. Three-dimensional scaffold of SCs has the basic characteristics of artificial nerves. These findings offer a novel method to fabricate artificial nerves with tissue engineering methods for repairing defected long nerves.

  17. Genetically modified cells in regenerative medicine and tissue engineering.

    Science.gov (United States)

    Sheyn, Dima; Mizrahi, Olga; Benjamin, Shimon; Gazit, Zulma; Pelled, Gadi; Gazit, Dan

    2010-06-15

    Regenerative medicine appears to take as its patron, the Titan Prometheus, whose liver was able to regenerate daily, as the field attempts to restore lost, damaged, or aging cells and tissues. The tremendous technological progress achieved during the last decade in gene transfer methods and imaging techniques, as well as recent increases in our knowledge of cell biology, have opened new horizons in the field of regenerative medicine. Genetically engineered cells are a tool for tissue engineering and regenerative medicine, albeit a tool whose development is fraught with difficulties. Gene-and-cell therapy offers solutions to severe problems faced by modern medicine, but several impediments obstruct the path of such treatments as they move from the laboratory toward the clinical setting. In this review we provide an overview of recent advances in the gene-and-cell therapy approach and discuss the main hurdles and bottlenecks of this approach on its path to clinical trials and prospective clinical practice.

  18. Polymeric Materials for Tissue Engineering of Arterial Substitutes

    Science.gov (United States)

    Ravi, Swathi; Qu, Zheng; Chaikof, Elliot L.

    2009-01-01

    Cardiovascular disease is the leading cause of mortality in the United States. The limited availability of healthy autologous vessels for bypass grafting procedures has led to the fabrication of prosthetic vascular conduits. Synthetic polymeric materials, while providing the appropriate mechanical strength, lack the compliance and biocompatibility that bioresorbable and naturally occurring protein polymers offer. Vascular tissue engineering approaches have emerged in order to meet the challenges of designing a vascular graft with long-term patency. In vitro culture techniques that have been explored with vascular cell seeding of polymeric scaffolds and the use of bioactive polymers for in situ arterial regeneration have yielded promising results. This review describes the development of polymeric materials in various tissue engineering strategies for the improvement in the mechanical and biological performance of an arterial substitute. PMID:19426609

  19. Fabrication and application of nanofibrous scaffolds in tissue engineering.

    Science.gov (United States)

    Li, Wan-Ju; Tuan, Rocky S

    2009-03-01

    Nanofibers fabricated by electrospinning are morphological mimics of fibrous components of the native extracellular matrix, making nanofibrous scaffolds ideal for three-dimensional cell culture and tissue engineering applications. Although electrospinning is not a conventional technique in cell biology, the experimental setup may be constructed in a relatively straightforward manner, and the procedure can be carried out by individuals with limited engineering experience. Here, we detail a protocol for electrospinning of nanofibers and provide relevant specific details concerning the optimization of fiber formation (Basic Protocol 1). The protocol also includes conditions required for preparing biodegradable polymer solutions for the fabrication of nonwoven and aligned nanofibrous scaffolds suitable for various cell/tissue applications. In addition, information on effective cell loading into nanofibrous scaffolds and cellular constructs grown in a bioreactor is provided (Basic Protocol 2). Instructions for building the electrospinning apparatus are also included (see the Support Protocol).

  20. Tissue Engineering and the Future of Facial Volumization.

    Science.gov (United States)

    Reuther, Marsha; Watson, Deborah

    2016-10-01

    Volume loss due to facial aging can be restored by facial volumization using a variety of materials. Volumization can be performed in isolation or concurrent with other facial rejuvenation procedures to obtain an optimal aesthetic result. There is a myriad of manufactured products available for volumization. The use of autologous fat as facial filler has been adopted more recently and possesses certain advantages; however, the ideal filler is still lacking. Tissue engineering may offer a solution. This technology would provide autologous soft-tissue components for use in facial volumization. The use of stem cells may enable customization of the engineered product for the specific needs of each patient. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  1. Mathematically defined tissue engineering scaffold architectures prepared by stereolithography.

    Science.gov (United States)

    Melchels, Ferry P W; Bertoldi, Katia; Gabbrielli, Ruggero; Velders, Aldrik H; Feijen, Jan; Grijpma, Dirk W

    2010-09-01

    The technologies employed for the preparation of conventional tissue engineering scaffolds restrict the materials choice and the extent to which the architecture can be designed. Here we show the versatility of stereolithography with respect to materials and freedom of design. Porous scaffolds are designed with computer software and built with either a poly(D,L-lactide)-based resin or a poly(D,L-lactide-co-epsilon-caprolactone)-based resin. Characterisation of the scaffolds by micro-computed tomography shows excellent reproduction of the designs. The mechanical properties are evaluated in compression, and show good agreement with finite element predictions. The mechanical properties of scaffolds can be controlled by the combination of material and scaffold pore architecture. The presented technology and materials enable an accurate preparation of tissue engineering scaffolds with a large freedom of design, and properties ranging from rigid and strong to highly flexible and elastic.

  2. Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

    Science.gov (United States)

    Caddeo, Silvia; Boffito, Monica; Sartori, Susanna

    2017-01-01

    In the tissue engineering (TE) paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D) microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D) models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the “3Rs” guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues) to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart, pancreas, and

  3. Tissue Engineering Approaches in the Design of Healthy and Pathological In Vitro Tissue Models

    Directory of Open Access Journals (Sweden)

    Silvia Caddeo

    2017-07-01

    Full Text Available In the tissue engineering (TE paradigm, engineering and life sciences tools are combined to develop bioartificial substitutes for organs and tissues, which can in turn be applied in regenerative medicine, pharmaceutical, diagnostic, and basic research to elucidate fundamental aspects of cell functions in vivo or to identify mechanisms involved in aging processes and disease onset and progression. The complex three-dimensional (3D microenvironment in which cells are organized in vivo allows the interaction between different cell types and between cells and the extracellular matrix, the composition of which varies as a function of the tissue, the degree of maturation, and health conditions. In this context, 3D in vitro models can more realistically reproduce a tissue or organ than two-dimensional (2D models. Moreover, they can overcome the limitations of animal models and reduce the need for in vivo tests, according to the “3Rs” guiding principles for a more ethical research. The design of 3D engineered tissue models is currently in its development stage, showing high potential in overcoming the limitations of already available models. However, many issues are still opened, concerning the identification of the optimal scaffold-forming materials, cell source and biofabrication technology, and the best cell culture conditions (biochemical and physical cues to finely replicate the native tissue and the surrounding environment. In the near future, 3D tissue-engineered models are expected to become useful tools in the preliminary testing and screening of drugs and therapies and in the investigation of the molecular mechanisms underpinning disease onset and progression. In this review, the application of TE principles to the design of in vitro 3D models will be surveyed, with a focus on the strengths and weaknesses of this emerging approach. In addition, a brief overview on the development of in vitro models of healthy and pathological bone, heart

  4. Pointwise mutual information quantifies intratumor heterogeneity in tissue sections labeled with multiple fluorescent biomarkers

    Directory of Open Access Journals (Sweden)

    Daniel M Spagnolo

    2016-01-01

    Full Text Available Background: Measures of spatial intratumor heterogeneity are potentially important diagnostic biomarkers for cancer progression, proliferation, and response to therapy. Spatial relationships among cells including cancer and stromal cells in the tumor microenvironment (TME are key contributors to heterogeneity. Methods: We demonstrate how to quantify spatial heterogeneity from immunofluorescence pathology samples, using a set of 3 basic breast cancer biomarkers as a test case. We learn a set of dominant biomarker intensity patterns and map the spatial distribution of the biomarker patterns with a network. We then describe the pairwise association statistics for each pattern within the network using pointwise mutual information (PMI and visually represent heterogeneity with a two-dimensional map. Results: We found a salient set of 8 biomarker patterns to describe cellular phenotypes from a tissue microarray cohort containing 4 different breast cancer subtypes. After computing PMI for each pair of biomarker patterns in each patient and tumor replicate, we visualize the interactions that contribute to the resulting association statistics. Then, we demonstrate the potential for using PMI as a diagnostic biomarker, by comparing PMI maps and heterogeneity scores from patients across the 4 different cancer subtypes. Estrogen receptor positive invasive lobular carcinoma patient, AL13-6, exhibited the highest heterogeneity score among those tested, while estrogen receptor negative invasive ductal carcinoma patient, AL13-14, exhibited the lowest heterogeneity score. Conclusions: This paper presents an approach for describing intratumor heterogeneity, in a quantitative fashion (via PMI, which departs from the purely qualitative approaches currently used in the clinic. PMI is generalizable to highly multiplexed/hyperplexed immunofluorescence images, as well as spatial data from complementary in situ methods including FISSEQ and CyTOF, sampling many different

  5. Comparison of extraction methods for quantifying vitamin E from animal tissues.

    Science.gov (United States)

    Xu, Zhimin

    2008-12-01

    Four extraction methods: (1) solvent (SOL), (2) ultrasound assisted solvent (UA), (3) saponification and solvent (SP), and (4) saponification and ultrasound assisted solvent (SP-UA), were used in sample preparation for quantifying vitamin E (tocopherols) in chicken liver and plasma samples. The extraction yields of SOL, UA, SP, and SP-UA methods obtained by adding delta-tocopherol as internal reference were 95%, 104%, 65%, and 62% for liver and 98%, 103%, 97%, and 94% for plasma, respectively. The methods with saponification significantly affected the stabilities of tocopherols in liver samples. The measured values of alpha- and gamma-tocopherols using the solvent only extraction (SOL) method were much lower than that using any of the other extraction methods. This indicated that less of the tocopherols in those samples were in a form that could be extracted directly by solvent. The measured value of alpha-tocopherol in the liver sample using the ultrasound assisted solvent (UA) method was 1.5-2.5 times of that obtained from the saponification and solvent (SP) method. The differences in measured values of tocopherols in the plasma samples by using the two methods were not significant. However, the measured value of the saponification and ultrasound assisted solvent (SP-UA) method was lower than either the saponification and solvent (SP) or the ultrasound assisted solvent (UA) method. Also, the reproducibility of the ultrasound assisted solvent (UA) method was greater than any of the saponification methods. Compared with the traditional saponification method, the ultrasound assisted solvent method could effectively extract tocopherols from sample matrix without any chemical degradation reactions, especially for complex animal tissue such as liver.

  6. Nanostructured polymer scaffolds for tissue engineering and regenerative medicine.

    Science.gov (United States)

    Smith, I O; Liu, X H; Smith, L A; Ma, P X

    2009-01-01

    The structural features of tissue engineering scaffolds affect cell response and must be engineered to support cell adhesion, proliferation and differentiation. The scaffold acts as an interim synthetic extracellular matrix (ECM) that cells interact with prior to forming a new tissue. In this review, bone tissue engineering is used as the primary example for the sake of brevity. We focus on nanofibrous scaffolds and the incorporation of other components including other nanofeatures into the scaffold structure. Since the ECM is comprised in large part of collagen fibers, between 50 and 500 nm in diameter, well-designed nanofibrous scaffolds mimic this structure. Our group has developed a novel thermally induced phase separation (TIPS) process in which a solution of biodegradable polymer is cast into a porous scaffold, resulting in a nanofibrous pore-wall structure. These nanoscale fibers have a diameter (50-500 nm) comparable to those collagen fibers found in the ECM. This process can then be combined with a porogen leaching technique, also developed by our group, to engineer an interconnected pore structure that promotes cell migration and tissue ingrowth in three dimensions. To improve upon efforts to incorporate a ceramic component into polymer scaffolds by mixing, our group has also developed a technique where apatite crystals are grown onto biodegradable polymer scaffolds by soaking them in simulated body fluid (SBF). By changing the polymer used, the concentration of ions in the SBF and by varying the treatment time, the size and distribution of these crystals are varied. Work is currently being done to improve the distribution of these crystals throughout three-dimensional scaffolds and to create nanoscale apatite deposits that better mimic those found in the ECM. In both nanofibrous and composite scaffolds, cell adhesion, proliferation and differentiation improved when compared to control scaffolds. Additionally, composite scaffolds showed a decrease in

  7. Esophageal tissue engineering: A new approach for esophageal replacement

    Institute of Scientific and Technical Information of China (English)

    Giorgia Totonelli; Panagiotis Maghsoudlou; Jonathan M Fishman; Giuseppe Orlando; Tahera Ansari; Paul Sibbons; Martin A Birchall

    2012-01-01

    A number of congenital and acquired disorders require esophageal tissue replacement.Various surgical techniques,such as gastric and colonic interposition,are standards of treatment,but frequently complicated by stenosis and other problems.Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function.We review the literature of esophageal tissue engineering,discuss its implications,compare the methodologies that have been employed and suggest possible directions for the future.Medline,Embase,the Cochrane Library,National Research Register and ClinicalTrials.gov databases were searched with the following search terms:stem cell and esophagus,esophageal replacement,esophageal tissue engineering,esophageal substitution.Reference lists of papers identified were also examined and experts in this field contacted for further information.All full-text articles in English of all potentially relevant abstracts were reviewed.Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation.When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality.Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration,whilst omental wrapping to induce vascularization of the construct has an uncertain benefit.Decellularized matrices have been recently suggested as the optimal choice for scaffolds,but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution.Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a

  8. Sterilization techniques for biodegradable scaffolds in tissue engineering applications

    Science.gov (United States)

    Dai, Zheng; Ronholm, Jennifer; Tian, Yiping; Sethi, Benu; Cao, Xudong

    2016-01-01

    Biodegradable scaffolds have been extensively studied due to their wide applications in biomaterials and tissue engineering. However, infections associated with in vivo use of these scaffolds by different microbiological contaminants remain to be a significant challenge. This review focuses on different sterilization techniques including heat, chemical, irradiation, and other novel sterilization techniques for various biodegradable scaffolds. Comparisons of these techniques, including their sterilization mechanisms, post-sterilization effects, and sterilization efficiencies, are discussed. PMID:27247758

  9. Development of a Tissue Engineered Scaffold for Meniscus Replacement

    Science.gov (United States)

    2008-12-01

    Deliv Rev, 2003. 55(4): p. 447-66. Caruso, A.B., A Collagen Fiber Tissue Engineering Scaffold for Anterior Cruciate Ligament Reconstruction, in...scaffold was axially loaded in compression, it was extruded from the joint. The anterior and posterior anchor points resisted this extrusion...include loss of manpower, rehabilitation costs, waste of training time/money, cost to retrain members as replacements, hospitalization costs, disability

  10. Hypoxia and Stem Cell-Based Engineering of Mesenchymal Tissues

    OpenAIRE

    Ma, Teng; Grayson, Warren L.; Fröhlich, Mirjam; Vunjak-Novakovic, Gordana

    2009-01-01

    Stem cells have the ability for prolonged self-renewal and differentiation into mature cells of various lineages, which makes them important cell sources for tissue engineering applications. Their remarkable ability to replenish and differentiate in vivo is regulated by both intrinsic and extrinsic cellular mechanisms. The anatomical location where the stem cells reside, known as the “stem cell niche or microenvironment,” provides signals conducive to the maintenance of definitive stem cell p...

  11. From Stem to Roots: tissue engineering in Endodontics

    OpenAIRE

    Chandki, Rita; Kala, M; Banthia, Priyank; Banthia, Ruchi

    2012-01-01

    The vitality of dentin-pulp complex is fundamental to the life of tooth and is a priority for targeting clinical management strategies. Loss of the tooth, jawbone or both, due to periodontal disease, dental caries, trauma or some genetic disorders, affects not only basic mouth functions but aesthetic appearance and quality of life. One novel approach to restore tooth structure is based on biology: regenerative endodontic procedure by application of tissue engineering. Regenerative endodontics...

  12. Tissue Engineering Applications of Three-Dimensional Bioprinting.

    Science.gov (United States)

    Zhang, Xiaoying; Zhang, Yangde

    2015-07-01

    Recent advances in tissue engineering have adapted the additive manufacturing technology, also known as three-dimensional printing, which is used in several industrial applications, for the fabrication of bioscaffolds and viable tissue and/or organs to overcome the limitations of other in vitro conventional methods. 3D bioprinting technology has gained enormous attention as it enabled 3D printing of a multitude of biocompatible materials, different types of cells and other supporting growth factors into complex functional living tissues in a 3D format. A major advantage of this technology is its ability for simultaneously 3D printing various cell types in defined spatial locations, which makes this technology applicable to regenerative medicine to meet the need for suitable for transplantation suitable organs and tissues. 3D bioprinting is yet to successfully overcome the many challenges related to building 3D structures that closely resemble native organs and tissues, which are complex structures with defined microarchitecture and a variety of cell types in a confined area. An integrated approach with a combination of technologies from the fields of engineering, biomaterials science, cell biology, physics, and medicine is required to address these complexities. Meeting this challenge is being made possible by directing the 3D bioprinting to manufacture biomimetic-shaped 3D structures, using organ/tissue images, obtained from magnetic resonance imaging and computerized tomography, and employing computer-aided design and manufacturing technologies. Applications of 3D bioprinting include the generation of multilayered skin, bone, vascular grafts, heart valves, etc. The current 3D bioprinting technologies need to be improved with respect to the mechanical strength and integrity in the manufactured constructs as the presently used biomaterials are not of optimal viscosity. A better understanding of the tissue/organ microenvironment, which consists of multiple types of

  13. Recent Advances in Application of Biosensors in Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Anwarul Hasan

    2014-01-01

    Full Text Available Biosensors research is a fast growing field in which tens of thousands of papers have been published over the years, and the industry is now worth billions of dollars. The biosensor products have found their applications in numerous industries including food and beverages, agricultural, environmental, medical diagnostics, and pharmaceutical industries and many more. Even though numerous biosensors have been developed for detection of proteins, peptides, enzymes, and numerous other biomolecules for diverse applications, their applications in tissue engineering have remained limited. In recent years, there has been a growing interest in application of novel biosensors in cell culture and tissue engineering, for example, real-time detection of small molecules such as glucose, lactose, and H2O2 as well as serum proteins of large molecular size, such as albumin and alpha-fetoprotein, and inflammatory cytokines, such as IFN-g and TNF-α. In this review, we provide an overview of the recent advancements in biosensors for tissue engineering applications.

  14. Visualization of vascular ultrastructure during osteogenesis by tissue engineering technique

    Institute of Scientific and Technical Information of China (English)

    ZHANG Kaigang; ZENG Bingfang; ZHANG Changqing

    2007-01-01

    The aim of this Paper was to observe and visualize the changes in osteoblasts by electron microscopy during osteogenesis using tissue engineering technique.We also studied the feasibility of improving tissue vascularization of the engineered bone by using small intestine submucosa (SIS)as the scaffold.Bone mesenchyrnal stem cells (BMSCs)were isolated by gradient centrifugation method.Bone mesenchymal stem cells were seeded in the SIS,and the scaffold-cell constructs were cultured in vitro for 2 weeks.Small intestine submucosa without BMSCs served as control.Both SIS scaffolds were then implanted subcutaneously in the dorsa of athymic mice.The implants were harvested after in vivo incubation for 4,8 and 12 weeks.The changes in osteoblasts and vascularization were observed under a transmission electron microscope and a scanning electron microscope.The BMSCs grew quite well,differentiating on the surface of the SIS and secreting a great deal of extracellular matrices.The scaffold-cell constructs formed a lot of bone and blood vessels in vivo.The scaffold degraded after 12 weeks.No osteoblasts,but vascularization and fibroblasts were observed,in the control.The SIS can be used as a scaffold for constructing tissue-engineered bone as it can improve the formation of bone and vessels in vivo.

  15. Biodegradable Polyphosphazene Biomaterials for Tissue Engineering and Delivery of Therapeutics

    Science.gov (United States)

    Baillargeon, Amanda L.; Mequanint, Kibret

    2014-01-01

    Degradable biomaterials continue to play a major role in tissue engineering and regenerative medicine as well as for delivering therapeutic agents. Although the chemistry of polyphosphazenes has been studied extensively, a systematic review of their applications for a wide range of biomedical applications is lacking. Polyphosphazenes are synthesized through a relatively well-known two-step reaction scheme which involves the substitution of the initial linear precursor with a wide range of nucleophiles. The ease of substitution has led to the development of a broad class of materials that have been studied for numerous biomedical applications including as scaffold materials for tissue engineering and regenerative medicine. The objective of this review is to discuss the suitability of poly(amino acid ester)phosphazene biomaterials in regard to their unique stimuli responsive properties, tunable degradation rates and mechanical properties, as well as in vitro and in vivo biocompatibility. The application of these materials in areas such as tissue engineering and drug delivery is discussed systematically. Lastly, the utility of polyphosphazenes is further extended as they are being employed in blend materials for new applications and as another method of tailoring material properties. PMID:24883323

  16. Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery

    Directory of Open Access Journals (Sweden)

    Gabriele Ceccarelli

    2017-01-01

    Full Text Available Bone regeneration is currently one of the most important and challenging tissue engineering approaches in regenerative medicine. Bone regeneration is a promising approach in dentistry and is considered an ideal clinical strategy in treating diseases, injuries, and defects of the maxillofacial region. Advances in tissue engineering have resulted in the development of innovative scaffold designs, complemented by the progress made in cell-based therapies. In vitro bone regeneration can be achieved by the combination of stem cells, scaffolds, and bioactive factors. The biomimetic approach to create an ideal bone substitute provides strategies for developing combined scaffolds composed of adult stem cells with mesenchymal phenotype and different organic biomaterials (such as collagen and hyaluronic acid derivatives or inorganic biomaterials such as manufactured polymers (polyglycolic acid (PGA, polylactic acid (PLA, and polycaprolactone. This review focuses on different biomaterials currently used in dentistry as scaffolds for bone regeneration in treating bone defects or in surgical techniques, such as sinus lift, horizontal and vertical bone grafts, or socket preservation. Our review would be of particular interest to medical and surgical researchers at the interface of cell biology, materials science, and tissue engineering, as well as industry-related manufacturers and researchers in healthcare, prosthetics, and 3D printing, too.

  17. Biodegradable Polyphosphazene Biomaterials for Tissue Engineering and Delivery of Therapeutics

    Directory of Open Access Journals (Sweden)

    Amanda L. Baillargeon

    2014-01-01

    Full Text Available Degradable biomaterials continue to play a major role in tissue engineering and regenerative medicine as well as for delivering therapeutic agents. Although the chemistry of polyphosphazenes has been studied extensively, a systematic review of their applications for a wide range of biomedical applications is lacking. Polyphosphazenes are synthesized through a relatively well-known two-step reaction scheme which involves the substitution of the initial linear precursor with a wide range of nucleophiles. The ease of substitution has led to the development of a broad class of materials that have been studied for numerous biomedical applications including as scaffold materials for tissue engineering and regenerative medicine. The objective of this review is to discuss the suitability of poly(amino acid esterphosphazene biomaterials in regard to their unique stimuli responsive properties, tunable degradation rates and mechanical properties, as well as in vitro and in vivo biocompatibility. The application of these materials in areas such as tissue engineering and drug delivery is discussed systematically. Lastly, the utility of polyphosphazenes is further extended as they are being employed in blend materials for new applications and as another method of tailoring material properties.

  18. Engineering Parameters in Bioreactor's Design: A Critical Aspect in Tissue Engineering

    Science.gov (United States)

    Amoabediny, Ghassem; Pouran, Behdad; Tabesh, Hadi; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin; Khatibi, Nahid; Mottaghy, Khosrow; Zandieh-Doulabi, Behrouz

    2013-01-01

    Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors. PMID:24000327

  19. Engineering parameters in bioreactor's design: a critical aspect in tissue engineering.

    Science.gov (United States)

    Salehi-Nik, Nasim; Amoabediny, Ghassem; Pouran, Behdad; Tabesh, Hadi; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin; Khatibi, Nahid; Anisi, Fatemeh; Mottaghy, Khosrow; Zandieh-Doulabi, Behrouz

    2013-01-01

    Bioreactors are important inevitable part of any tissue engineering (TE) strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.

  20. Engineering Parameters in Bioreactor’s Design: A Critical Aspect in Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Nasim Salehi-Nik

    2013-01-01

    Full Text Available Bioreactors are important inevitable part of any tissue engineering (TE strategy as they aid the construction of three-dimensional functional tissues. Since the ultimate aim of a bioreactor is to create a biological product, the engineering parameters, for example, internal and external mass transfer, fluid velocity, shear stress, electrical current distribution, and so forth, are worth to be thoroughly investigated. The effects of such engineering parameters on biological cultures have been addressed in only a few preceding studies. Furthermore, it would be highly inefficient to determine the optimal engineering parameters by trial and error method. A solution is provided by emerging modeling and computational tools and by analyzing oxygen, carbon dioxide, and nutrient and metabolism waste material transports, which can simulate and predict the experimental results. Discovering the optimal engineering parameters is crucial not only to reduce the cost and time of experiments, but also to enhance efficacy and functionality of the tissue construct. This review intends to provide an inclusive package of the engineering parameters together with their calculation procedure in addition to the modeling techniques in TE bioreactors.

  1. Creation of a Large Adipose Tissue Construct in Humans Using a Tissue-engineering Chamber: A Step Forward in the Clinical Application of Soft Tissue Engineering.

    Science.gov (United States)

    Morrison, Wayne A; Marre, Diego; Grinsell, Damien; Batty, Andrew; Trost, Nicholas; O'Connor, Andrea J

    2016-04-01

    Tissue engineering is currently exploring new and exciting avenues for the repair of soft tissue and organ defects. Adipose tissue engineering using the tissue engineering chamber (TEC) model has yielded promising results in animals; however, to date, there have been no reports on the use of this device in humans. Five female post mastectomy patients ranging from 35 to 49years old were recruited and a pedicled thoracodorsal artery perforator fat flap ranging from 6 to 50ml was harvested, transposed onto the chest wall and covered by an acrylic perforated dome-shaped chamber ranging from 140 to 350cm(3). Magnetic resonance evaluation was performed at three and six months after chamber implantation. Chambers were removed at six months and samples were obtained for histological analysis. In one patient, newly formed tissue to a volume of 210ml was generated inside the chamber. One patient was unable to complete the trial and the other three failed to develop significant enlargement of the original fat flap, which, at the time of chamber explantation, was encased in a thick fibrous capsule. Our study provides evidence that generation of large well-vascularized tissue engineered constructs using the TEC is feasible in humans.

  2. Cardiac tissue engineering and regeneration using cell-based therapy

    Directory of Open Access Journals (Sweden)

    Alrefai MT

    2015-05-01

    Full Text Available Mohammad T Alrefai,1–3 Divya Murali,4 Arghya Paul,4 Khalid M Ridwan,1,2 John M Connell,1,2 Dominique Shum-Tim1,2 1Division of Cardiac Surgery, 2Division of Surgical Research, McGill University Health Center, Montreal, QC, Canada; 3King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, USA Abstract: Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. Keywords: stem cells, cardiomyocytes, cardiac surgery, heart failure, myocardial ischemia, heart, scaffolds, organoids, cell sheet and tissue engineering

  3. Cellular interactions with tissue-engineered microenvironments and nanoparticles

    Science.gov (United States)

    Pan, Zhi

    Tissue-engineered hydrogels composed of intermolecularlly crosslinked hyaluronan (HA-DTPH) and fibronectin functional domains (FNfds) were applied as a physiological relevant ECM mimic with controlled mechanical and biochemical properties. Cellular interactions with this tissue-engineered environment, especially physical interactions (cellular traction forces), were quantitatively measured by using the digital image speckle correlation (DISC) technique and finite element method (FEM). By correlating with other cell functions such as cell morphology and migration, a comprehensive structure-function relationship between cells and their environments was identified. Furthermore, spatiotemporal redistribution of cellular traction stresses was time-lapse measured during cell migration to better understand the dynamics of cell mobility. The results suggest that the reinforcement of the traction stresses around the nucleus, as well as the relaxation of nuclear deformation, are critical steps during cell migration, serving as a speed regulator, which must be considered in any dynamic molecular reconstruction model of tissue cell migration. Besides single cell migration, en masse cell migration was studied by using agarose droplet migration assay. Cell density was demonstrated to be another important parameter to influence cell behaviors besides substrate properties. Findings from these studies will provide fundamental design criteria to develop novel and effective tissue-engineered constructs. Cellular interactions with rutile and anatase TiO2 nanoparticles were also studied. These particles can penetrate easily through the cell membrane and impair cell function, with the latter being more damaging. The exposure to nanoparticles was found to decrease cell area, cell proliferation, motility, and contractility. To prevent this, a dense grafted polymer brush coating was applied onto the nanoparticle surface. These modified nanoparticles failed to adhere to and penetrate

  4. Silk fibroin porous scaffolds for nucleus pulposus tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Chao; Yang, Qiang [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Tianjin Medical University, Tianjin 300070 (China); Zhu, Meifeng [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China); Du, Lilong [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Tianjin Medical University, Tianjin 300070 (China); Zhang, Jiamin [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China); Ma, Xinlong [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Xu, Baoshan, E-mail: xubaoshan99@126.com [Department of Spine Surgery, Tianjin Hospital, Tianjin 300211 (China); Wang, Lianyong, E-mail: wly@nankai.edu.cn [The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2014-04-01

    Intervertebral discs (IVDs) are structurally complex tissue that hold the vertebrae together and provide mobility to spine. The nucleus pulposus (NP) degeneration often results in degenerative IVD disease that is one of the most common causes of back and neck pain. Tissue engineered nucleus pulposus offers an alternative approach to regain the function of the degenerative IVD. The aim of this study is to determine the feasibility of porous silk fibroin (SF) scaffolds fabricated by paraffin-sphere-leaching methods with freeze-drying in the application of nucleus pulposus regeneration. The prepared scaffold possessed high porosity of 92.38 ± 5.12% and pore size of 165.00 ± 8.25 μm as well as high pore interconnectivity and appropriate mechanical properties. Rabbit NP cells were seeded and cultured on the SF scaffolds. Scanning electron microscopy, histology, biochemical assays and mechanical tests revealed that the porous scaffolds could provide an appropriate microstructure and environment to support adhesion, proliferation and infiltration of NP cells in vitro as well as the generation of extracellular matrix. The NP cell–scaffold construction could be preliminarily formed after subcutaneously implanted in a nude mice model. In conclusion, The SF porous scaffold offers a potential candidate for tissue engineered NP tissue. - Highlights: • Paraffin microsphere-leaching method is used to fabricate silk fibroin scaffold. • The scaffold has appropriate mechanical property, porosity and pore size • The scaffold supports growth and infiltration of nucleus pulposus cells. • Nucleus pulposus cells can secrete extracellular matrix in the scaffolds. • The scaffold is a potential candidate for tissue engineered nucleus pulposus.

  5. A Novel Seeding and Conditioning Bioreactor for Vascular Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Julia Schulte

    2014-07-01

    Full Text Available Multiple efforts have been made to develop small-diameter tissue engineered vascular grafts using a great variety of bioreactor systems at different steps of processing. Nevertheless, there is still an extensive need for a compact all-in-one system providing multiple and simultaneous processing. The aim of this project was to develop a new device to fulfill the major requirements of an ideal system that allows simultaneous seeding, conditioning, and perfusion. The newly developed system can be actuated in a common incubator and consists of six components: a rotating cylinder, a pump, a pulse generator, a control unit, a mixer, and a reservoir. Components that are in direct contact with cell media, cells, and/or tissue allow sterile processing. Proof-of-concept experiments were performed with polyurethane tubes and collagen tubes. The scaffolds were seeded with fibroblasts and endothelial cells that were isolated from human saphenous vein segments. Scanning electron microscopy and immunohistochemistry showed better seeding success of polyurethane scaffolds in comparison to collagen. Conditioning of polyurethane tubes with 100 dyn/cm2 resulted in cell detachments, whereas a moderate conditioning program with stepwise increase of shear stress from 10 to 40 dyn/cm2 induced a stable and confluent cell layer. The new bioreactor is a powerful tool for quick and easy testing of various scaffold materials for the development of tissue engineered vascular grafts. The combination of this bioreactor with native tissue allows testing of medical devices and medicinal substances under physiological conditions that is a good step towards reduction of animal testing. In the long run, the bioreactor could turn out to produce tissue engineered vascular grafts for human applications “at the bedside”.

  6. Gene-enhanced tissue engineering for dental hard tissue regeneration: (1 overview and practical considerations

    Directory of Open Access Journals (Sweden)

    Mason James M

    2006-05-01

    Full Text Available Abstract Gene-based therapies for tissue regeneration involve delivering a specific gene to a target tissue with the goal of changing the phenotype or protein expression profile of the recipient cell; the ultimate goal being to form specific tissues required for regeneration. One of the principal advantages of this approach is that it provides for a sustained delivery of physiologic levels of the growth factor of interest. This manuscript will review the principals of gene-enhanced tissue engineering and the techniques of introducing DNA into cells. Part 2 will review recent advances in gene-based therapies for dental hard tissue regeneration, specifically as it pertains to dentin regeneration/pulp capping and periodontal regeneration.

  7. Decellularization of human and porcine lung tissues for pulmonary tissue engineering.

    Science.gov (United States)

    O'Neill, John D; Anfang, Rachel; Anandappa, Annabelle; Costa, Joseph; Javidfar, Jeffrey; Wobma, Holly M; Singh, Gopal; Freytes, Donald O; Bacchetta, Matthew D; Sonett, Joshua R; Vunjak-Novakovic, Gordana

    2013-09-01

    The only definitive treatment for end-stage organ failure is orthotopic transplantation. Lung extracellular matrix (LECM) holds great potential as a scaffold for lung tissue engineering because it retains the complex architecture, biomechanics, and topologic specificity of the lung. Decellularization of human lungs rejected from transplantation could provide "ideal" biologic scaffolds for lung tissue engineering, but the availability of such lungs remains limited. The present study was designed to determine whether porcine lung could serve as a suitable substitute for human lung to study tissue engineering therapies. Human and porcine lungs were procured, sliced into sheets, and decellularized by three different methods. Compositional, ultrastructural, and biomechanical changes to the LECM were characterized. The suitability of LECM for cellular repopulation was evaluated by assessing the viability, growth, and metabolic activity of human lung fibroblasts, human small airway epithelial cells, and human adipose-derived mesenchymal stem cells over a period of 7 days. Decellularization with 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) showed the best maintenance of both human and porcine LECM, with similar retention of LECM proteins except for elastin. Human and porcine LECM supported the cultivation of pulmonary cells in a similar way, except that the human LECM was stiffer and resulted in higher metabolic activity of the cells than porcine LECM. Porcine lungs can be decellularized with CHAPS to produce LECM scaffolds with properties resembling those of human lungs, for pulmonary tissue engineering. We propose that porcine LECM can be an excellent screening platform for the envisioned human tissue engineering applications of decellularized lungs. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  8. Bioreactor-free tissue engineering: directed tissue assembly by centrifugal casting.

    Science.gov (United States)

    Mironov, Vladimir; Kasyanov, Vladimir; Markwald, Roger R; Prestwich, Glenn D

    2008-02-01

    Casting is a process by which a material is introduced into a mold while it is liquid, allowed to solidify in a predefined shape inside the mold, and then removed to give a fabricated object, part or casing. Centrifugal casting could be defined as a process of molding using centrifugal forces. Although the centrifugal casting technology has a long history in metal manufacturing and in the plastics industry, only recently has this technology attracted the attention of tissue engineers. Initially, centrifugation was used to optimize cell seeding on a solid scaffold. More recently, centrifugal casting has been used to create tubular scaffolds and both tubular and flat multilayered, living tissue constructs. These newer applications were enabled by a new class of biocompatible in situ crosslinkable hydrogels that mimic the extracellular matrix. Herein the authors summarize the state of the art of centrifugal casting technology in tissue engineering, they outline associated technological challenges, and they discuss the potential future for clinical applications.

  9. Tissue engineering of the intestine in a murine model.

    Science.gov (United States)

    Barthel, Erik R; Speer, Allison L; Levin, Daniel E; Sala, Frédéric G; Hou, Xiaogang; Torashima, Yasuhiro; Wigfall, Clarence M; Grikscheit, Tracy C

    2012-12-01

    Tissue-engineered small intestine (TESI) has successfully been used to rescue Lewis rats after massive small bowel resection, resulting in return to preoperative weights within 40 days.(1) In humans, massive small bowel resection can result in short bowel syndrome, a functional malabsorptive state that confers significant morbidity, mortality, and healthcare costs including parenteral nutrition dependence, liver failure and cirrhosis, and the need for multivisceral organ transplantation.(2) In this paper, we describe and document our protocol for creating tissue-engineered intestine in a mouse model with a multicellular organoid units-on-scaffold approach. Organoid units are multicellular aggregates derived from the intestine that contain both mucosal and mesenchymal elements,(3) the relationship between which preserves the intestinal stem cell niche.(4) In ongoing and future research, the transition of our technique into the mouse will allow for investigation of the processes involved during TESI formation by utilizing the transgenic tools available in this species.(5)The availability of immunocompromised mouse strains will also permit us to apply the technique to human intestinal tissue and optimize the formation of human TESI as a mouse xenograft before its transition into humans. Our method employs good manufacturing practice (GMP) reagents and materials that have already been approved for use in human patients, and therefore offers a significant advantage over approaches that rely upon decellularized animal tissues. The ultimate goal of this method is its translation to humans as a regenerative medicine therapeutic strategy for short bowel syndrome.

  10. Concise Review : Engineering Myocardial Tissue: The Convergence of Stem Cells Biology and Tissue Engineering Technology

    NARCIS (Netherlands)

    Buikema, Jan Willem; Van der Meer, Peter; Sluijter, Joost P. G.; Domian, Ibrahim J.

    2013-01-01

    Advanced heart failure represents a leading public health problem in the developed world. The clinical syndrome results from the loss of viable and/or fully functional myocardial tissue. Designing new approaches to augment the number of functioning human cardiac muscle cells in the failing heart ser

  11. Gene delivery in tissue engineering and regenerative medicine.

    Science.gov (United States)

    Fang, Y L; Chen, X G; W T, Godbey

    2015-11-01

    As a promising strategy to aid or replace tissue/organ transplantation, gene delivery has been used for regenerative medicine applications to create or restore normal function at the cell and tissue levels. Gene delivery has been successfully performed ex vivo and in vivo in these applications. Excellent proliferation capabilities and differentiation potentials render certain cells as excellent candidates for ex vivo gene delivery for regenerative medicine applications, which is why multipotent and pluripotent cells have been intensely studied in this vein. In this review, gene delivery is discussed in detail, along with its applications to tissue engineering and regenerative medicine. A definition of a stem cell is compared to a definition of a stem property, and both provide the foundation for an in-depth look at gene delivery investigations from a germ lineage angle.

  12. Skin Tissue Engineering: Application of Adipose-Derived Stem Cells

    Science.gov (United States)

    Zimoch, Jakub; Biedermann, Thomas

    2017-01-01

    Perception of the adipose tissue has changed dramatically over the last few decades. Identification of adipose-derived stem cells (ASCs) ultimately transformed paradigm of this tissue from a passive energy depot into a promising stem cell source with properties of self-renewal and multipotential differentiation. As compared to bone marrow-derived stem cells (BMSCs), ASCs are more easily accessible and their isolation yields higher amount of stem cells. Therefore, the ASCs are of high interest for stem cell-based therapies and skin tissue engineering. Currently, freshly isolated stromal vascular fraction (SVF), which may be used directly without any expansion, was also assessed to be highly effective in treating skin radiation injuries, burns, or nonhealing wounds such as diabetic ulcers. In this paper, we review the characteristics of SVF and ASCs and the efficacy of their treatment for skin injuries and disorders.

  13. Regenerative surgery: tissue engineering in general surgical practice.

    Science.gov (United States)

    Wong, Victor W; Wan, Derrick C; Gurtner, Geoffrey C; Longaker, Michael T

    2012-10-01

    Tissue engineering is a broad interdisciplinary field that aims to develop complex tissue and organ constructs through a combination of cell-, biomaterial-, and molecular-based approaches. This approach has the potential to transform the surgical treatment for diseases including trauma, cancer, and congenital malformations. A fundamental knowledge of key concepts in regenerative medicine is imperative for surgeons to maintain a leading role in developing and implementing these technologies. Researchers have started to elucidate the biologic mechanisms that maintain organ homeostasis throughout life, indicating that humans may have the latent capacity to regenerate complex tissues. By exploiting this intrinsic potential of the body, we can move even closer to developing functional, autologous replacement parts for a wide range of surgical diseases.

  14. Adult stem cells applied to tissue engineering and regenerative medicine.

    Science.gov (United States)

    Cuenca-López, M D; Zamora-Navas, P; García-Herrera, J M; Godino, M; López-Puertas, J M; Guerado, E; Becerra, J; Andrades, J A

    2008-01-01

    Regeneration takes place in the body at a moment or another throughout life. Bone, cartilage, and tendons (the key components of the structure and articulation in the body) have a limited capacity for self-repair and, after traumatic injury or disease, the regenerative power of adult tissue is often insufficient. When organs or tissues are irreparably damaged, they may be replaced by an artificial device or by a donor organ. However, the number of available donor organs is considerably limited. Generation of tissue-engineered replacement organs by extracting stem cells from the patient, growing them and modifying them in clinical conditions after re-introduction in the body represents an ideal source for corrective treatment. Mesenchymal stem cells (MSCs) are the multipotential progenitors that give rise to skeletal cells, vascular smooth muscle cells, muscle (skeletal and cardiac muscle), adipocytes (fat tissue) and hematopoietic (blood)-supportive stromal cells. MSCs are found in multiple connective tissues, in adult bone marrow, skeletal muscles and fat pads. The wide representation in adult tissues may be related to the existence of a circulating blood pool or that MSCs are associated to the vascular system.

  15. Mechanical cues in orofacial tissue engineering and regenerative medicine.

    Science.gov (United States)

    Brouwer, Katrien M; Lundvig, Ditte M S; Middelkoop, Esther; Wagener, Frank A D T G; Von den Hoff, Johannes W

    2015-01-01

    Cleft lip and palate patients suffer from functional, aesthetical, and psychosocial problems due to suboptimal regeneration of skin, mucosa, and skeletal muscle after restorative cleft surgery. The field of tissue engineering and regenerative medicine (TE/RM) aims to restore the normal physiology of tissues and organs in conditions such as birth defects or after injury. A crucial factor in cell differentiation, tissue formation, and tissue function is mechanical strain. Regardless of this, mechanical cues are not yet widely used in TE/RM. The effects of mechanical stimulation on cells are not straight-forward in vitro as cellular responses may differ with cell type and loading regime, complicating the translation to a therapeutic protocol. We here give an overview of the different types of mechanical strain that act on cells and tissues and discuss the effects on muscle, and skin and mucosa. We conclude that presently, sufficient knowledge is lacking to reproducibly implement external mechanical loading in TE/RM approaches. Mechanical cues can be applied in TE/RM by fine-tuning the stiffness and architecture of the constructs to guide the differentiation of the seeded cells or the invading surrounding cells. This may already improve the treatment of orofacial clefts and other disorders affecting soft tissues.

  16. 3D conductive nanocomposite scaffold for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Shahini A

    2013-12-01

    Full Text Available Aref Shahini,1 Mostafa Yazdimamaghani,2 Kenneth J Walker,2 Margaret A Eastman,3 Hamed Hatami-Marbini,4 Brenda J Smith,5 John L Ricci,6 Sundar V Madihally,2 Daryoosh Vashaee,1 Lobat Tayebi2,7 1School of Electrical and Computer Engineering, Helmerich Advanced Technology Research Center, 2School of Chemical Engineering, 3Department of Chemistry, 4School of Mechanical and Aerospace Engineering, 5Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA; 6Department of Biomaterials and Biomimetics, New York University, New York, NY; 7School of Material Science and Engineering, Helmerich Advanced Technology Research Center, Oklahoma State University, Tulsa, OK, USA Abstract: Bone healing can be significantly expedited by applying electrical stimuli in the injured region. Therefore, a three-dimensional (3D ceramic conductive tissue engineering scaffold for large bone defects that can locally deliver the electrical stimuli is highly desired. In the present study, 3D conductive scaffolds were prepared by employing a biocompatible conductive polymer, ie, poly(3,4-ethylenedioxythiophene poly(4-styrene sulfonate (PEDOT:PSS, in the optimized nanocomposite of gelatin and bioactive glass. For in vitro analysis, adult human mesenchymal stem cells were seeded in the scaffolds. Material characterizations using hydrogen-1 nuclear magnetic resonance, in vitro degradation, as well as thermal and mechanical analysis showed that incorporation of PEDOT:PSS increased the physiochemical stability of the composite, resulting in improved mechanical properties and biodegradation resistance. The outcomes indicate that PEDOT:PSS and polypeptide chains have close interaction, most likely by forming salt bridges between arginine side chains and sulfonate groups. The morphology of the scaffolds and cultured human mesenchymal stem cells were observed and analyzed via scanning electron microscope, micro-computed tomography, and confocal fluorescent

  17. Cardiac tissue engineering: cell seeding, cultivation parameters, and tissue construct characterization.

    Science.gov (United States)

    Carrier, R L; Papadaki, M; Rupnick, M; Schoen, F J; Bursac, N; Langer, R; Freed, L E; Vunjak-Novakovic, G

    1999-09-01

    Cardiac tissue engineering has been motivated by the need to create functional tissue equivalents for scientific studies and cardiac tissue repair. We previously demonstrated that contractile cardiac cell-polymer constructs can be cultivated using isolated cells, 3-dimensional scaffolds, and bioreactors. In the present work, we examined the effects of (1) cell source (neonatal rat or embryonic chick), (2) initial cell seeding density, (3) cell seeding vessel, and (4) tissue culture vessel on the structure and composition of engineered cardiac muscle. Constructs seeded under well-mixed conditions with rat heart cells at a high initial density ((6-8) x 10(6) cells/polymer scaffold) maintained structural integrity and contained macroscopic contractile areas (approximately 20 mm(2)). Seeding in rotating vessels (laminar flow) rather than mixed flasks (turbulent flow) resulted in 23% higher seeding efficiency and 20% less cell damage as assessed by medium lactate dehydrogenase levels (p laminar and dynamic, yielded constructs with a more active, aerobic metabolism as compared to constructs cultured in mixed or static flasks. After 1-2 weeks of cultivation, tissue constructs expressed cardiac specific proteins and ultrastructural features and had approximately 2-6 times lower cellularity (p < 0.05) but similar metabolic activity per unit cell when compared to native cardiac tissue.

  18. Effects of Dexamethasone on Satellite Cells and Tissue Engineered Skeletal Muscle Units.

    Science.gov (United States)

    Syverud, Brian C; VanDusen, Keith W; Larkin, Lisa M

    2016-03-01

    Tissue engineered skeletal muscle has potential for application as a graft source for repairing soft tissue injuries, a model for testing pharmaceuticals, and a biomechanical actuator system for soft robots. However, engineered muscle to date has not produced forces comparable to native muscle, limiting its potential for repair and for use as an in vitro model for pharmaceutical testing. In this study, we examined the trophic effects of dexamethasone (DEX), a glucocorticoid that stimulates myoblast differentiation and fusion into myotubes, on our tissue engineered three-dimensional skeletal muscle units (SMUs). Using our established SMU fabrication protocol, muscle isolates were cultured with three experimental DEX concentrations (5, 10, and 25 nM) and compared to untreated controls. Following seeding onto a laminin-coated Sylgard substrate, the administration of DEX was initiated on day 0 or day 6 in growth medium or on day 9 after the switch to differentiation medium and was sustained until the completion of SMU fabrication. During this process, total cell proliferation was measured with a BrdU assay, and myogenesis and structural advancement of muscle cells were observed through immunostaining for MyoD, myogenin, desmin, and α-actinin. After SMU formation, isometric tetanic force production was measured to quantify function. The histological and functional assessment of the SMU showed that the administration of 10 nM DEX beginning on either day 0 or day 6 yielded optimal SMUs. These optimized SMUs exhibited formation of advanced sarcomeric structure and significant increases in myotube diameter and myotube fusion index, compared with untreated controls. Additionally, the optimized SMUs matured functionally, as indicated by a fivefold rise in force production. In conclusion, we have demonstrated that the addition of DEX to our process of engineering skeletal muscle tissue improves myogenesis, advances muscle structure, and increases force production in the

  19. The potential of tissue engineering for developing alternatives to animal experiments: a systematic review

    NARCIS (Netherlands)

    Vries, R.B.M. de; Leenaars, M.; Tra, J.; Huijbregtse, R.; Bongers, E.; Jansen, J.A.; Gordijn, B.; Ritskes-Hoitinga, M.

    2015-01-01

    An underexposed ethical issue raised by tissue engineering is the use of laboratory animals in tissue engineering research. Even though this research results in suffering and loss of life in animals, tissue engineering also has great potential for the development of alternatives to animal experiment

  20. Engineering prokaryotic channels for control of mammalian tissue excitability

    Science.gov (United States)

    Nguyen, Hung X.; Kirkton, Robert D.; Bursac, Nenad

    2016-01-01

    The ability to directly enhance electrical excitability of human cells is hampered by the lack of methods to efficiently overexpress large mammalian voltage-gated sodium channels (VGSC). Here we describe the use of small prokaryotic sodium channels (BacNav) to create de novo excitable human tissues and augment impaired action potential conduction in vitro. Lentiviral co-expression of specific BacNav orthologues, an inward-rectifying potassium channel, and connexin-43 in primary human fibroblasts from the heart, skin or brain yields actively conducting cells with customizable electrophysiological phenotypes. Engineered fibroblasts (‘E-Fibs') retain stable functional properties following extensive subculture or differentiation into myofibroblasts and rescue conduction slowing in an in vitro model of cardiac interstitial fibrosis. Co-expression of engineered BacNav with endogenous mammalian VGSCs enhances action potential conduction and prevents conduction failure during depolarization by elevated extracellular K+, decoupling or ischaemia. These studies establish the utility of engineered BacNav channels for induction, control and recovery of mammalian tissue excitability. PMID:27752065

  1. Scaffold-free vascular tissue engineering using bioprinting.

    Science.gov (United States)

    Norotte, Cyrille; Marga, Francois S; Niklason, Laura E; Forgacs, Gabor

    2009-10-01

    Current limitations of exogenous scaffolds or extracellular matrix based materials have underlined the need for alternative tissue-engineering solutions. Scaffolds may elicit adverse host responses and interfere with direct cell-cell interaction, as well as assembly and alignment of cell-produced ECM. Thus, fabrication techniques for production of scaffold-free engineered tissue constructs have recently emerged. Here we report on a fully biological self-assembly approach, which we implement through a rapid prototyping bioprinting method for scaffold-free small diameter vascular reconstruction. Various vascular cell types, including smooth muscle cells and fibroblasts, were aggregated into discrete units, either multicellular spheroids or cylinders of controllable diameter (300-500 microm). These were printed layer-by-layer concomitantly with agarose rods, used here as a molding template. The post-printing fusion of the discrete units resulted in single- and double-layered small diameter vascular tubes (OD ranging from 0.9 to 2.5mm). A unique aspect of the method is the ability to engineer vessels of distinct shapes and hierarchical trees that combine tubes of distinct diameters. The technique is quick and easily scalable.

  2. Tissue engineering and regenerative medicine: past, present, and future.

    Science.gov (United States)

    Salgado, António J; Oliveira, Joaquim M; Martins, Albino; Teixeira, Fábio G; Silva, Nuno A; Neves, Nuno M; Sousa, Nuno; Reis, Rui L

    2013-01-01

    Tissue and organ repair still represents a clinical challenge. Tissue engineering and regenerative medicine (TERM) is an emerging field focused on the development of alternative therapies for tissue/organ repair. This highly multidisciplinary field, in which bioengineering and medicine merge, is based on integrative approaches using scaffolds, cell populations from different sources, growth factors, nanomedicine, gene therapy, and other techniques to overcome the limitations that currently exist in the clinics. Indeed, its overall objective is to induce the formation of new functional tissues, rather than just implanting spare parts. This chapter aims at introducing the reader to the concepts and techniques of TERM. It begins by explaining how TERM have evolved and merged into TERM, followed by a short overview of some of its key aspects such as the combinations of scaffolds with cells and nanomedicine, scaffold processing, and new paradigms of the use of stem cells for tissue repair/regeneration, which ultimately could represent the future of new therapeutic approaches specifically aimed at clinical applications.

  3. Robotic Scaffolds for Tissue Engineering and Organ Growth

    Science.gov (United States)

    Stoica, Adrian

    2011-01-01

    The aim of tissue engineering (TE) is to restore tissue and organ functions with minimal host rejection. TE is seen as a future solution to solve the crisis of donor organs for transplant, which faces a shortage expected only to increase in the future. In this innovation, a flexible and configurable scaffold has been conceived that mechanically stresses cells that are seeded on it, stimulating them to increased growth. The influence of mechanical stress/ loading on cell growth has been observed on all forms of cells. For example, for cartilages, studies in animals, tissue explants, and engineered tissue scaffolds have all shown that cartilage cells (chondrocytes) modify their extracellular matrix in response to loading. The chondrocyte EMC production response to dynamics of the physical environment (in vivo cartilage development) illustrates a clear benefit (better growth) when stressed. It has been shown that static and dynamic compression regulates PRG4 biosynthesis by cartilage explants. Mechanical tissue stimulation is beneficial and (flexible) scaffolds with movable components, which are able to induce mechanical stimulation, offer advantages over the fixed, rigid scaffold design. In addition to improved cell growth from physical/mechanical stimulation, additional benefits include the ability to increase in size while preserving shape, or changing shape. By making scaffolds flexible, allowing relative movement between their components, adding sensing (e.g., for detecting response of cells to drug release and to mechanical actions), building controls for drug release and movement, and building even simple algorithms for mapping sensing to action, these structures can actually be made into biocompatible and biodegradable robots. Treating them as robots is a perspective shift that may offer advantages in the design and exploitation of these structures of the future.

  4. Bioreactors for tissue engineering--a new role for perfusionists?

    Science.gov (United States)

    Sistino, Joseph J

    2003-09-01

    Tissue engineering is an exciting new area of medicine with rapid growth and expansion over the last decade. It has the potential to have a profound impact on the practice of medicine and influence the economic development in the industry of biotechnology. In almost every specialty of medicine, the ability to generate replacement cells and develop tissues will change the focus from artificial organs and transplantation to growing replacement organs from the patient's own stem cells. Once these organs are at a size that requires perfusion to maintain oxygen and nutrient delivery, then automated perfusion systems termed "bioreactors" will be necessary to sustain the organ until harvesting. The design of these "bioreactors" will have a crucial role in the maintenance of cellular function throughout the growth period. The perfusion schemes necessary to determine the optimal conditions have not been well elucidated and will undergo extensive research over the next decade. The key to progress in this endeavor will development of long-term perfusion techniques and identifying the ideal pressures, flow rates, type of flow (pulsatile/nonpulsatile), and perfusate solution. Perfusionists are considered experts in the field of whole body perfusion, and it is possible that they can participate in the development and operation of these "bioreactors." Additional education of perfusionists in the area of tissue engineering is necessary in order for them to become integral parts of this exciting new area of medicine.

  5. Template-Mediated Biomineralization for Bone Tissue Engineering.

    Science.gov (United States)

    Leiendecker, Alexander; Witzleben, Steffen; Schulze, Margit; Tobiasch, Edda

    2017-01-01

    Template-mediated mineralization describes a research field of materials chemistry that deals with templates influencing product formation of foremost inorganic functional materials and composites. These templates are usually organic compounds - as far as molecules with natural origin are involved, the terminology "biomineralization" or "biomimetic mineralization: is used. The present review gives insight into recent developments in the research area of bone-tissue engineering with focus on chemical templates and cell-based approaches. The review is structured as follows: (1) a brief general overview about the principle of templating and recently used template materials, (2) important analytical methods, (3) examples of template-guided mineralization of various bone-related materials, (4) natural bone mineralization, (5) scaffolds for bone-tissue regeneration and (6) cell-based therapeutic approaches. For this purpose, a literature screening with emphasis on promising potential practical applications was performed. In particular, macromolecular structures and polymer composites with relation to naturally occurring compounds were favored. Priority was given to publications of the last five years. Although the present review does not cover the whole topic to full extent, it should provide information about current trends and the most promising approaches in the research area of bone-tissue engineering based on applications of organic templates/scaffolds as well as cell-based strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Uterine Tissue Engineering and the Future of Uterus Transplantation.

    Science.gov (United States)

    Hellström, Mats; Bandstein, Sara; Brännström, Mats

    2016-12-19

    The recent successful births following live donor uterus transplantation are proof-of-concept that absolute uterine factor infertility is a treatable condition which affects several hundred thousand infertile women world-wide due to a dysfunctional uterus. This strategy also provides an alternative to gestational surrogate motherhood which is not practiced in most countries due to ethical, religious or legal reasons. The live donor surgery involved in uterus transplantation takes more than 10 h and is then followed by years of immunosuppressive medication to prevent uterine rejection. Immunosuppression is associated with significant adverse side effects, including nephrotoxicity, increased risk of serious infections, and diabetes. Thus, the development of alternative approaches to treat absolute uterine factor infertility would be desirable. This review discusses tissue engineering principles in general, but also details strategies on how to create a bioengineered uterus that could be used for transplantation, without risky donor surgery and any need for immunosuppression. We discuss scaffolds derived from decellularized organs/tissues which may be recellularized using various types of autologous somatic/stem cells, in particular for uterine tissue engineering. It further highlights the hurdles that lay ahead in developing an alternative to an allogeneic source for uterus transplantation.

  7. Extracellular matrix, mechanotransduction and structural hierarchies in heart tissue engineering.

    Science.gov (United States)

    Parker, Kevin K; Ingber, Donald E

    2007-08-29

    The spatial and temporal scales of cardiac organogenesis and pathogenesis make engineering of artificial heart tissue a daunting challenge. The temporal scales range from nanosecond conformational changes responsible for ion channel opening to fibrillation which occurs over seconds and can lead to death. Spatial scales range from nanometre pore sizes in membrane channels and gap junctions to the metre length scale of the whole cardiovascular system in a living patient. Synchrony over these scales requires a hierarchy of control mechanisms that are governed by a single common principle: integration of structure and function. To ensure that the function of ion channels and contraction of muscle cells lead to changes in heart chamber volume, an elegant choreography of metabolic, electrical and mechanical events are executed by protein networks composed of extracellular matrix, transmembrane integrin receptors and cytoskeleton which are functionally connected across all size scales. These structural control networks are mechanoresponsive, and they process mechanical and chemical signals in a massively parallel fashion, while also serving as a bidirectional circuit for information flow. This review explores how these hierarchical structural networks regulate the form and function of living cells and tissues, as well as how microfabrication techniques can be used to probe this structural control mechanism that maintains metabolic supply, electrical activation and mechanical pumping of heart muscle. Through this process, we delineate various design principles that may be useful for engineering artificial heart tissue in the future.

  8. Tissue-engineered models of human tumors for cancer research

    Science.gov (United States)

    Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2015-01-01

    Introduction Drug toxicity often goes undetected until clinical trials, which are the most costly and dangerous phase of drug development. Both the cultures of human cells and animal studies have limitations that cannot be overcome by incremental improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. An area that could greatly benefit from these models is cancer research. Areas covered In this review, the authors first describe the engineered tumor systems, using Ewing's sarcoma as an example of human tumor that cannot be predictably studied in cell culture and animal models. Then, they discuss the importance of the tissue context for cancer progression and outline the biomimetic principles for engineering human tumors. Finally, they discuss the utility of bioengineered tumor models for cancer research and address the challenges in modeling human tumors for use in drug discovery and testing. Expert opinion While tissue models are just emerging as a new tool for cancer drug discovery, they are already demonstrating potential for recapitulating, in vitro, the native behavior of human tumors. Still, numerous challenges need to be addressed before we can have platforms with a predictive power appropriate for the pharmaceutical industry. Some of the key needs include the incorporation of the vascular compartment, immune system components, and mechanical signals that regulate tumor development and function. PMID:25662589

  9. Osteochondral tissue engineering with biphasic scaffold: current strategies and techniques.

    Science.gov (United States)

    Shimomura, Kazunori; Moriguchi, Yu; Murawski, Christopher D; Yoshikawa, Hideki; Nakamura, Norimasa

    2014-10-01

    The management of osteoarthritis (OA) remains challenging and controversial. Although several clinical options exist for the treatment of OA, regeneration of the damaged articular cartilage has proved difficult due to the limited healing capacity. With the advancements in tissue engineering and cell-based technologies over the past decade, new therapeutic options for patients with osteochondral lesions potentially exist. This review will focus on the feasibility of tissue-engineered biphasic scaffolds, which can mimic the native osteochondral complex, for osteochondral repair and highlight the recent development of these techniques toward tissue regeneration. Moreover, basic anatomy, strategy for osteochondral repair, the design and fabrication methods of scaffolds, as well as the choice of cells, growth factor, and materials will be discussed. Specifically, we focus on the latest preclinical animal studies using large animals and clinical trials with high clinical relevance. In turn, this will facilitate an understanding of the latest trends in osteochondral repair and contribute to the future application of such clinical therapies in patients with OA.

  10. Soy Protein Scaffold Biomaterials for Tissue Engineering and Regenerative Medicine

    Science.gov (United States)

    Chien, Karen B.

    Developing functional biomaterials using highly processable materials with tailorable physical and bioactive properties is an ongoing challenge in tissue engineering. Soy protein is an abundant, natural resource with potential use for regenerative medicine applications. Preliminary studies show that soy protein can be physically modified and fabricated into various biocompatible constructs. However, optimized soy protein structures for tissue regeneration (i.e. 3D porous scaffolds) have not yet been designed. Furthermore, little work has established the in vivo biocompatibility of implanted soy protein and the benefit of using soy over other proteins including FDA-approved bovine collagen. In this work, freeze-drying and 3D printing fabrication processes were developed using commercially available soy protein to create porous scaffolds that improve cell growth and infiltration compared to other soy biomaterials previously reported. Characterization of scaffold structure, porosity, and mechanical/degradation properties was performed. In addition, the behavior of human mesenchymal stem cells seeded on various designed soy scaffolds was analyzed. Biological characterization of the cell-seeded scaffolds was performed to assess feasibility for use in liver tissue regeneration. The acute and humoral response of soy scaffolds implanted in an in vivo mouse subcutaneous model was also investigated. All fabricated soy scaffolds were modified using thermal, chemical, and enzymatic crosslinking to change properties and cell growth behavior. 3D printing allowed for control of scaffold pore size and geometry. Scaffold structure, porosity, and degradation rate significantly altered the in vivo response. Freeze-dried soy scaffolds had similar biocompatibility as freeze-dried collagen scaffolds of the same protein content. However, the soy scaffolds degraded at a much faster rate, minimizing immunogenicity. Interestingly, subcutaneously implanted soy scaffolds affected blood

  11. Tissue engineering as a potential alternative or adjunct to surgical reconstruction in treating pelvic organ prolapse

    DEFF Research Database (Denmark)

    Boennelycke, M; Gräs, Søren; Lose, G

    2013-01-01

    Cell-based tissue engineering strategies could potentially provide attractive alternatives to surgical reconstruction of native tissue or the use of surgical implants in treating pelvic organ prolapse (POP).......Cell-based tissue engineering strategies could potentially provide attractive alternatives to surgical reconstruction of native tissue or the use of surgical implants in treating pelvic organ prolapse (POP)....

  12. Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons from the Common Sea Urchin Tissue

    Directory of Open Access Journals (Sweden)

    Kheng Lim Goh

    2017-04-01

    Full Text Available Scaffolds for tissue engineering application may be made from a collagenous extracellular matrix (ECM of connective tissues because the ECM can mimic the functions of the target tissue. The primary sources of collagenous ECM material are calf skin and bone. However, these sources are associated with the risk of having bovine spongiform encephalopathy or transmissible spongiform encephalopathy. Alternative sources for collagenous ECM materials may be derived from livestock, e.g., pigs, and from marine animals, e.g., sea urchins. Collagenous ECM of the sea urchin possesses structural features and mechanical properties that are similar to those of mammalian ones. However, even more intriguing is that some tissues such as the ligamentous catch apparatus can exhibit mutability, namely rapid reversible changes in the tissue mechanical properties. These tissues are known as mutable collagenous tissues (MCTs. The mutability of these tissues has been the subject of on-going investigations, covering the biochemistry, structural biology and mechanical properties of the collagenous components. Recent studies point to a nerve-control system for regulating the ECM macromolecules that are involved in the sliding action of collagen fibrils in the MCT. This review discusses the key attributes of the structure and function of the ECM of the sea urchin ligaments that are related to the fibril-fibril sliding action—the focus is on the respective components within the hierarchical architecture of the tissue. In this context, structure refers to size, shape and separation distance of the ECM components while function is associated with mechanical properties e.g., strength and stiffness. For simplicity, the components that address the different length scale from the largest to the smallest are as follows: collagen fibres, collagen fibrils, interfibrillar matrix and collagen molecules. Application of recent theories of stress transfer and fracture mechanisms in fibre

  13. Decellularized Tissue and Cell-Derived Extracellular Matrices as Scaffolds for Orthopaedic Tissue Engineering

    Science.gov (United States)

    Cheng, Christina W.; Solorio, Loran D.; Alsberg, Eben

    2014-01-01

    The reconstruction of musculoskeletal defects is a constant challenge for orthopaedic surgeons. Musculoskeletal injuries such as fractures, chondral lesions, infections and tumor debulking can often lead to large tissue voids requiring reconstruction with tissue grafts. Autografts are currently the gold standard in orthopaedic tissue reconstruction; however, there is a limit to the amount of tissue that can be harvested before compromising the donor site. Tissue engineering strategies using allogeneic or xenogeneic decellularized bone, cartilage, skeletal muscle, tendon and ligament have emerged as promising potential alternative treatment. The extracellular matrix provides a natural scaffold for cell attachment, proliferation and differentiation. Decellularization of in vitro cell-derived matrices can also enable the generation of autologous constructs from tissue specific cells or progenitor cells. Although decellularized bone tissue is widely used clinically in orthopaedic applications, the exciting potential of decellularized cartilage, skeletal muscle, tendon and ligament cell-derived matrices has only recently begun to be explored for ultimate translation to the orthopaedic clinic. PMID:24417915

  14. Preparation of laponite bioceramics for potential bone tissue engineering applications.

    Directory of Open Access Journals (Sweden)

    Chuanshun Wang

    Full Text Available We report a facile approach to preparing laponite (LAP bioceramics via sintering LAP powder compacts for bone tissue engineering applications. The sintering behavior and mechanical properties of LAP compacts under different temperatures, heating rates, and soaking times were investigated. We show that LAP bioceramic with a smooth and porous surface can be formed at 800°C with a heating rate of 5°C/h for 6 h under air. The formed LAP bioceramic was systematically characterized via different methods. Our results reveal that the LAP bioceramic possesses an excellent surface hydrophilicity and serum absorption capacity, and good cytocompatibility and hemocompatibility as demonstrated by resazurin reduction assay of rat mesenchymal stem cells (rMSCs and hemolytic assay of pig red blood cells, respectively. The potential bone tissue engineering applicability of LAP bioceramic was explored by studying the surface mineralization behavior via soaking in simulated body fluid (SBF, as well as the surface cellular response of rMSCs. Our results suggest that LAP bioceramic is able to induce hydroxyapatite deposition on its surface when soaked in SBF and rMSCs can proliferate well on the LAP bioceramic surface. Most strikingly, alkaline phosphatase activity together with alizarin red staining results reveal that the produced LAP bioceramic is able to induce osteoblast differentiation of rMSCs in growth medium without any inducing factors. Finally, in vivo animal implantation, acute systemic toxicity test and hematoxylin and eosin (H&E-staining data demonstrate that the prepared LAP bioceramic displays an excellent biosafety and is able to heal the bone defect. Findings from this study suggest that the developed LAP bioceramic holds a great promise for treating bone defects in bone tissue engineering.

  15. Preparation of laponite bioceramics for potential bone tissue engineering applications.

    Science.gov (United States)

    Wang, Chuanshun; Wang, Shige; Li, Kai; Ju, Yaping; Li, Jipeng; Zhang, Yongxing; Li, Jinhua; Liu, Xuanyong; Shi, Xiangyang; Zhao, Qinghua

    2014-01-01

    We report a facile approach to preparing laponite (LAP) bioceramics via sintering LAP powder compacts for bone tissue engineering applications. The sintering behavior and mechanical properties of LAP compacts under different temperatures, heating rates, and soaking times were investigated. We show that LAP bioceramic with a smooth and porous surface can be formed at 800°C with a heating rate of 5°C/h for 6 h under air. The formed LAP bioceramic was systematically characterized via different methods. Our results reveal that the LAP bioceramic possesses an excellent surface hydrophilicity and serum absorption capacity, and good cytocompatibility and hemocompatibility as demonstrated by resazurin reduction assay of rat mesenchymal stem cells (rMSCs) and hemolytic assay of pig red blood cells, respectively. The potential bone tissue engineering applicability of LAP bioceramic was explored by studying the surface mineralization behavior via soaking in simulated body fluid (SBF), as well as the surface cellular response of rMSCs. Our results suggest that LAP bioceramic is able to induce hydroxyapatite deposition on its surface when soaked in SBF and rMSCs can proliferate well on the LAP bioceramic surface. Most strikingly, alkaline phosphatase activity together with alizarin red staining results reveal that the produced LAP bioceramic is able to induce osteoblast differentiation of rMSCs in growth medium without any inducing factors. Finally, in vivo animal implantation, acute systemic toxicity test and hematoxylin and eosin (H&E)-staining data demonstrate that the prepared LAP bioceramic displays an excellent biosafety and is able to heal the bone defect. Findings from this study suggest that the developed LAP bioceramic holds a great promise for treating bone defects in bone tissue engineering.

  16. Chitosan for gene delivery and orthopedic tissue engineering applications.

    Science.gov (United States)

    Raftery, Rosanne; O'Brien, Fergal J; Cryan, Sally-Ann

    2013-05-15

    Gene therapy involves the introduction of foreign genetic material into cells in order exert a therapeutic effect. The application of gene therapy to the field of orthopaedic tissue engineering is extremely promising as the controlled release of therapeutic proteins such as bone morphogenetic proteins have been shown to stimulate bone repair. However, there are a number of drawbacks associated with viral and synthetic non-viral gene delivery approaches. One natural polymer which has generated interest as a gene delivery vector is chitosan. Chitosan is biodegradable, biocompatible and non-toxic. Much of the appeal of chitosan is due to the presence of primary amine groups in its repeating units which become protonated in acidic conditions. This property makes it a promising candidate for non-viral gene delivery. Chitosan-based vectors have been shown to transfect a number of cell types including human embryonic kidney cells (HEK293) and human cervical cancer cells (HeLa). Aside from its use in gene delivery, chitosan possesses a range of properties that show promise in tissue engineering applications; it is biodegradable, biocompatible, has anti-bacterial activity, and, its cationic nature allows for electrostatic interaction with glycosaminoglycans and other proteoglycans. It can be used to make nano- and microparticles, sponges, gels, membranes and porous scaffolds. Chitosan has also been shown to enhance mineral deposition during osteogenic differentiation of MSCs in vitro. The purpose of this review is to critically discuss the use of chitosan as a gene delivery vector with emphasis on its application in orthopedic tissue engineering.

  17. Regenerative endodontics and tissue engineering: what the future holds?

    Science.gov (United States)

    Goodis, Harold E; Kinaia, Bassam Michael; Kinaia, Atheel M; Chogle, Sami M A

    2012-07-01

    The work performed by researchers in regenerative endodontics and tissue engineering over the last decades has been superb; however, many questions remain to be answered. The basic biologic mechanisms must be elucidated that will allow the development of dental pulp and dentin in situ. Stress must be placed on the many questions that will lead to the design of effective, safe treatment options and therapies. This article discusses those questions, the answers to which may become the future of regenerative endodontics. The future remains bright, but proper support and patience are required.

  18. The stem cell and tissue engineering research in Chinese ophthalmology

    Institute of Scientific and Technical Information of China (English)

    GE Jian; LIU Jingbo

    2007-01-01

    Much has been considerably developed recently in the ophthalmic research of stem cell (SC) and tissue engineering (TE).They have become closer to the clinical practice,standardized and observable.Leading edge research of SC and TE on the ocular surface reconstruction,neuroregeneration and protection,and natural animal model has become increasingly available.However,challenges remain on the way,especially on the aspects of function reconstruction and specific differentiation.This paper reviews the new developments in this area with an intention of identifying research priorities for the future.

  19. Electrospinning polymer blends for biomimetic scaffolds for ACL tissue engineering

    Science.gov (United States)

    Garcia, Vanessa Lizeth

    The anterior cruciate ligament (ACL) rupture is one of the most common knee injuries. Current ACL reconstructive strategies consist of using an autograft or an allograft to replace the ligament. However, limitations have led researchers to create tissue engineered grafts, known as scaffolds, through electrospinning. Scaffolds made of natural and synthetic polymer blends have the potential to promote cell adhesion while having strong mechanical properties. However, enzymes found in the knee are known to degrade tissues and affect the healing of intra-articular injuries. Results suggest that the natural polymers used in this study modify the thermal properties and tensile strength of the synthetic polymers when blended. Scanning electron microscopy display bead-free and enzyme biodegradability of the fibers. Raman spectroscopy confirms the presence of the natural and synthetic polymers in the scaffolds while, amino acid analysis present the types of amino acids and their concentrations found in the natural polymers.

  20. Polymeric composites containing carbon nanotubes for bone tissue engineering.

    Science.gov (United States)

    Sahithi, Kolli; Swetha, Maddela; Ramasamy, Kumarasamy; Srinivasan, Narasimhan; Selvamurugan, Nagarajan

    2010-04-01

    Several natural and synthetic polymers are now available for bone tissue engineering applications but they may lack mechanical integrity. In recent years, there are reports emphasizing the importance of carbon nanotubes (CNTs) in supporting bone growth. CNTs possess exceptional mechanical, thermal, and electrical properties, facilitating their use as reinforcements or additives in various materials to improve the properties of the materials. Biomaterials containing polymers often are placed adjacent to bone. The use of CNTs is anticipated in these biomaterials applied to bone mainly to improve their overall mechanical properties and expected to act as scaffolds to promote and guide bone tissue regeneration. This review paper provides a current state of knowledge available examining the use of the polymeric composites containing CNTs for promoting bone growth.

  1. Photoinduced cell morphology alterations quantified within adipose tissues by spectral optical coherence tomography.

    Science.gov (United States)

    Yanina, Irina Yu; Trunina, Natalia A; Tuchin, Valery V

    2013-11-01

    Morphological changes of the adipose tissue at phototreatment are studied in vitro using optical coherence tomography. The 200 to 600 μm fat tissue slices are used in the experiments. The observed change in the tissue structure was associated with fat cell lipolysis and destruction caused by the photodynamic effect. It is found that overall heating of a sample from room to physiological temperature leads to deeper and faster morphology tissue changes if other processing conditions are kept constant. These data support the hypothesis that photodynamic/photothermal treatment induces fat cell lipolysis during some period after treatment.

  2. Epidermal stem cells and skin tissue engineering in hairfollicle regeneration

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The reconstitution of a fully organized and functionalhair follicle from dissociated cells propagated underdefined tissue culture conditions is a challenge stillpending in tissue engineering. The loss of hair folliclescaused by injuries or pathologies such as alopecia notonly affects the patients' psychological well-being, butalso endangers certain inherent functions of the skin. Itis then of great interest to find different strategies aimingto regenerate or neogenerate the hair follicle underconditions proper of an adult individual. Based uponcurrent knowledge on the epithelial and dermal cells andtheir interactions during the embryonic hair generationand adult hair cycling, many researchers have tried toobtain mature hair follicles using different strategies andapproaches depending on the causes of hair loss. Thisreview summarizes current advances in the differentexperimental strategies to regenerate or neogenerate hairfollicles, with emphasis on those involving neogenesisof hair follicles in adult individuals using isolated cellsand tissue engineering. Most of these experiments wereperformed using rodent cells, particularly from embryonicor newborn origin. However, no successful strategy togenerate human hair follicles from adult cells has yetbeen reported. This review identifies several issues thatshould be considered to achieve this objective. Perhapsthe most important challenge is to provide threedimensionalculture conditionsmimicking the structure ofliving tissue. Improving culture conditions that allow theexpansion of specific cells while protecting their inductiveproperties, as well as methods for selecting populationsof epithelial stem cells, should give us the necessary toolsto overcome the difficulties that constrain human hairfollicle neogenesis. An analysis of patent trends showsthat the number of patent applications aimed at hairfollicle regeneration and neogenesis has been increasingduring the last decade. This field is attractive not only

  3. Tissue-engineered microenvironment systems for modeling human vasculature.

    Science.gov (United States)

    Tourovskaia, Anna; Fauver, Mark; Kramer, Gregory; Simonson, Sara; Neumann, Thomas

    2014-09-01

    The high attrition rate of drug candidates late in the development process has led to an increasing demand for test assays that predict clinical outcome better than conventional 2D cell culture systems and animal models. Government agencies, the military, and the pharmaceutical industry have started initiatives for the development of novel in-vitro systems that recapitulate functional units of human tissues and organs. There is growing evidence that 3D cell arrangement, co-culture of different cell types, and physico-chemical cues lead to improved predictive power. A key element of all tissue microenvironments is the vasculature. Beyond transporting blood the microvasculature assumes important organ-specific functions. It is also involved in pathologic conditions, such as inflammation, tumor growth, metastasis, and degenerative diseases. To provide a tool for modeling this important feature of human tissue microenvironments, we developed a microfluidic chip for creating tissue-engineered microenvironment systems (TEMS) composed of tubular cell structures. Our chip design encompasses a small chamber that is filled with an extracellular matrix (ECM) surrounding one or more tubular channels. Endothelial cells (ECs) seeded into the channels adhere to the ECM walls and grow into perfusable tubular tissue structures that are fluidically connected to upstream and downstream fluid channels in the chip. Using these chips we created models of angiogenesis, the blood-brain barrier (BBB), and tumor-cell extravasation. Our angiogenesis model recapitulates true angiogenesis, in which sprouting occurs from a "parent" vessel in response to a gradient of growth factors. Our BBB model is composed of a microvessel generated from brain-specific ECs within an ECM populated with astrocytes and pericytes. Our tumor-cell extravasation model can be utilized to visualize and measure tumor-cell migration through vessel walls into the surrounding matrix. The described technology can be used

  4. Polycaprolactone Scaffolds Fabricated via Bioextrusion for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Marco Domingos

    2009-01-01

    Full Text Available The most promising approach in Tissue Engineering involves the seeding of porous, biocompatible/biodegradable scaffolds, with donor cells to promote tissue regeneration. Additive biomanufacturing processes are increasingly recognized as ideal techniques to produce 3D structures with optimal pore size and spatial distribution, providing an adequate mechanical support for tissue regeneration while shaping in-growing tissues. This paper presents a novel extrusion-based system to produce 3D scaffolds with controlled internal/external geometry for TE applications.The BioExtruder is a low-cost system that uses a proper fabrication code based on the ISO programming language enabling the fabrication of multimaterial scaffolds. Poly(ε-caprolactone was the material chosen to produce porous scaffolds, made by layers of directionally aligned microfilaments. Chemical, morphological, and in vitro biological evaluation performed on the polymeric constructs revealed a high potential of the BioExtruder to produce 3D scaffolds with regular and reproducible macropore architecture, without inducing relevant chemical and biocompatibility alterations of the material.

  5. Quantifying the refractive index dispersion of a pigmented biological tissue using Jamin-Lebedeff interference microscopy

    NARCIS (Netherlands)

    Stavenga, Doekele G.; Leertouwer, Hein L.; Wilts, Bodo D.

    Jamin-Lebedeff polarizing interference microscopy is a classical method for determining the refractive index and thickness of transparent tissues. Here, we extend the application of this method to pigmented, absorbing biological tissues, based on a theoretical derivation using Jones calculus. This

  6. Quantifying the refractive index dispersion of a pigmented biological tissue using Jamin-Lebedeff interference microscopy

    NARCIS (Netherlands)

    Stavenga, Doekele G.; Leertouwer, Hein L.; Wilts, Bodo D.

    2013-01-01

    Jamin-Lebedeff polarizing interference microscopy is a classical method for determining the refractive index and thickness of transparent tissues. Here, we extend the application of this method to pigmented, absorbing biological tissues, based on a theoretical derivation using Jones calculus. This n

  7. Decellularized Lymph Nodes as Scaffolds for Tissue Engineered Lymph Nodes

    Science.gov (United States)

    Cuzzone, Daniel A.; Albano, Nicholas J.; Aschen, Seth Z.; Ghanta, Swapna

    2015-01-01

    Abstract Background: The lymphatic system is commonly injured during cancer treatment. However, despite the morbidity of these injuries, there are currently no options for replacing damaged lymphatics. The purpose of this study was to optimize methods for decellularization of murine lymph nodes (LN) and to determine if these scaffolds can be used to tissue engineer lymph node-like structures. Methods and Results: LNs were harvested from adult mice and subjected to various decellularization protocols. The degree of decellularization and removal of nuclear material was analyzed histologically and quantitatively using DNA isolation. In addition, we analyzed histological architecture by staining for matrix proteins. After the optimal method of decellularization was identified, decellularized constructs were implanted in the renal capsule of syngeneic or allogeneic recipient mice and analyzed for antigenicity. Finally, to determine if decellularized constructs could deliver lymphocytes to recipient animals, the matrices were repopulated with splenocytes, implanted in submuscular pockets, and harvested 14 days later. Decellularization was best accomplished with the detergent sodium dodecyl sulfate (SDS), resulting in negligible residual cellular material but maintenance of LN architecture. Implantation of decellularized LNs into syngeneic or allogeneic mice did not elicit a significant antigenic response. In addition, repopulation of decellularized LNs with splenocytes resulted in successful in vivo cellular delivery. Conclusions: We show, for the first time, that LNs can be successfully decellularized and that these matrices have preserved extracellular matrix architecture and the potential to deliver leukocytes in vivo. Future studies are needed to determine if tissue engineered lymph nodes maintain immunologic function. PMID:25144673

  8. Assuring consumer safety without animals: Applications for tissue engineering.

    Science.gov (United States)

    Westmoreland, Carl; Holmes, Anthony M

    2009-04-01

    Humans are exposed to a variety of chemicals in their everyday lives through interactions with the environment and through the use of consumer products. It is a basic requirement that these products are tested to assure they are safe under normal and reasonably foreseeable conditions of use. Within the European Union, the majority of tests used for generating toxicological data rely on animals. However recent changes in legislation (e.g., 7(th) amendment of the Cosmetics Directive and REACH) are driving researchers to develop and adopt non-animal alternative methods with which to assure human safety. Great strides have been made to this effect, but what other opportunities/technologies exist that could expedite this? Tissue engineering has increasing scope to contribute to replacing animals with scientifically robust alternatives in basic research and safety testing, but is this application of the technology being fully exploited? This review highlights how the consumer products industry is applying tissue engineering to ensure chemicals are safe for human use without using animals, and identifies areas for future development and application of the technology.

  9. Study on Different Modification Methods of Collagen for Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    XU Xin-yu

    2008-01-01

    Because of the excellent biocompatibility and its specific amino sequences, collagen is an ideal biomedical material for tissue engineering applications. But collagen is usually lack of mechanical strength to form a rigid 3-D matrix and lack of ability to resist collagenase. In order to be a tissue engineering scaffold, collagen must strengthen its structures by modifying with chemical crosslinkers. Chemical crosslinkers used for modif-ying collagen fibers include glutaraldehyde (GA), epoxy compounds (PC) and carbodiim-ides (EDC). The aim of this study is to choose the best chemical crosslinker from the three reagents. In terms of the resistance to collagenase degradation, chemical cross-link-ing with PC provided the best protection; in terms of the mechanical characterization, chemical cross-linking with GA provided the best;and in terms of the biocompatibility, chemical cross-linking with EDC provided the best. There is not a reagent which has all merits for collagen crosslinking, so we should select the crosslinking reagent as the de-mands of use ask.

  10. Osteocalcin/fibronectin-functionalized collagen matrices for bone tissue engineering.

    Science.gov (United States)

    Kim, S G; Lee, D S; Lee, S; Jang, J-H

    2015-06-01

    Collagen is the most abundant protein found in the extracellular matrix and is widely used to build scaffolds for biomedical applications which are the result of its biocompatibility and biodegradability. In the present study, we constructed a rhOCN/FNIII9-10 fusion protein and rhOCN/FNIII9-10-functionalized collagen matrices and investigated the potential value for bone tissue engineering. In vitro studies carried out with preosteoblastic MC3T3-E1 cells showed that rhOCN/FNIII9-10 fusion protein promoted cell adhesion and the mRNA levels of osteogenic markers including osteocalcin, runt-related transcription factor 2, alkaline phosphatase (ALP), and collagen type I. In addition, rhOCN/FNIII9-10-functionalized collagen matrices showed significant induction of the ALP activity more than rhFNIII9-10-functionalized collagen matrices or collagen matrices alone. These results suggested that rhOCN/FNIII9-10-functionalized collagen matrices have potential for bone tissue engineering.

  11. Tissue engineering of a bioartificial kidney: a universal donor organ.

    Science.gov (United States)

    Humes, H D

    1996-08-01

    Cell therapy and tissue engineering may well likely dominate medical therapeutics in the next century. Growing a functional glomerular filter and tubule reabsorber from a combination of cells, biomaterials, and synthetic polymers to replace renal excretory and regulatory functions is a specific example of these evolving technologies. The kidney was the first organ whose function was substituted by an artificial device. The kidney was also the first organ to be successfully transplanted. The ability to replace renal function with these revolutionary technologies in the past was due to the fact that renal excretory function is based on natural physical forces which govern solute and fluid movement from the body compartment to the external environment. The need for coordinated mechanical or electrical activities got renal substitution was not required. Accordingly, the kidney may well be the first organ to be available as a tissue-engineered implantable device as a fully functional replacement part for the human body. The prospects of a "universal donor" bioartificial kidney for the treatment of end-stage renal disease are clearly achievable as we approach the next millennium.

  12. Porous Three-Dimensional Carbon Nanotube Scaffolds for Tissue Engineering

    Science.gov (United States)

    Lalwani, Gaurav; Gopalan, Anu; D’Agati, Michael; Sankaran, Jeyantt Srinivas; Judex, Stefan; Qin, Yi-Xian; Sitharaman, Balaji

    2015-01-01

    Assembly of carbon nanomaterials into three-dimensional (3D) architectures is necessary to harness their unique physiochemical properties for tissue engineering and regenerative medicine applications. Herein, we report the fabrication and comprehensive cytocompatibility assessment of 3D chemically crosslinked macro-sized (5–8 mm height and 4–6 mm diameter) porous carbon nanotube (CNT) scaffolds. Scaffolds prepared via radical initiated thermal crosslinking of single- or multi- walled CNTs (SWCNTs and MWCNTs) possess high porosity (>80%), and nano-, micro- and macro-scale interconnected pores. MC3T3 pre-osteoblast cells on MWCNT and SWCNT scaffolds showed good cell viability comparable to poly(lactic-co-glycolic) acid (PLGA) scaffolds after 5 days. Confocal live cell and immunofluorescence imaging showed that MC3T3 cells were metabolically active and could attach, proliferate and infiltrate MWCNT and SWCNT scaffolds. SEM imaging corroborated cell attachment and spreading and suggested that cell morphology is governed by scaffold surface roughness. MC3T3 cells were elongated on scaffolds with high surface roughness (MWCNTs) and rounded on scaffolds with low surface roughness (SWCNTs). The surface roughness of scaffolds may be exploited to control cellular morphology, and in turn govern cell fate. These results indicate that crosslinked MWCNTs and SWCNTs scaffolds are cytocompatible, and open avenues towards development of multifunctional all-carbon scaffolds for tissue engineering applications. PMID:25788440

  13. Sonication induced silk fibroin cryogels for tissue engineering applications

    Science.gov (United States)

    Kadakia, P. U.; Jain, E.; Hixon, K. R.; Eberlin, C. T.; Sell, S. A.

    2016-05-01

    In this study, we report a method to form macroporous silk fibroin (SF) scaffolds through a combination of ultrasonication followed by cryogelation at subzero temperatures. The resultant sonication induced SF cryogels encompassed larger pore sizes (151 ± 56 μm) and higher mechanical stability (127.15 ± 24.71 kPa) than their hydrogel counterparts made at room temperature. Furthermore, the addition of dopants like Manuka honey and bone char in SF cryogels did not affect cryogel synthesis but decreased the pore size in a concentration dependent manner. With no crack propagation at 50% strain and promising stability under cyclic loads, mineralization and cellular infiltration potential were analyzed for bone tissue engineering purposes. Although the scaffolds showed limited mineralization, encouraging cellular infiltration results yield promise for other tissue engineering applications. The use of mild processing conditions, a simplistic procedure, and the lack of organic solvents or chemical cross-linkers renders the combination of sonication and cryogelation as an attractive fabrication technique for 3D SF macroporous scaffolds.

  14. Evaluation of immunocompatibility of tissue-engineered periosteum

    Energy Technology Data Exchange (ETDEWEB)

    Zhao Lin; Wang Shuanke; Xia Yayi; Liu Jia; He Jing; Wang Xin [Orthopaedic Institute of the 2nd Hospital of Lanzhou University, 80 CuiYingMen, ChengGuan District, Lanzhou City, 730030 (China); Zhao Junli, E-mail: bonezl@qq.com [Department of Nephrology, the 2nd Hospital of Lanzhou University, 80 CuiYingMen, ChengGuan District, Lanzhou City, 730030 (China)

    2011-02-15

    Tissue-engineered periosteum (TEP) and 'intramembranous ossification' may be an alternative approach to bone tissue engineering. In the previous study we attained successful bone defect reparation with homemade TEP in an allogenic rabbit model. But its allogenic immunocompatibility remained unknown. In this study TEP was constructed by seeding osteogenically induced mesenchymal stem cells of rabbit onto porcine small intestinal submucosa (SIS). A mixed lymphocyte reaction (MLR) was applied to evaluate the in vitro immunogenicity. The ratio of CD4{sup +}/CD8{sup +} T-lymphocytes was tested kinetically to evaluate the systematic reaction of the TEP allograft, and a histological examination was performed to investigate local inflammation and ectopic osteogenesis. MLR indicated that TEP had a higher in vitro immunostimulation than SIS (p < 0.05). The ratios of CD4{sup +}/CD8{sup +} lymphocytes increased in both TEP and SIS implanted groups in 2 weeks, followed by a decrease to a normal level from 2 to 4 weeks. Histological examination revealed modest lymphocyte infiltration for no more than 2 weeks. Moreover, subcutaneous ectopic ossification was observed in TEP allograft animals (8/12). Our findings imply that TEP has a certain immune reaction for the allograft, but it is not severe enough to impact osteogenesis in the allogenic rabbit model.

  15. Second harmonic generation imaging in tissue engineering and cartilage pathologies

    Science.gov (United States)

    Lilledahl, Magnus; Olderøy, Magnus; Finnøy, Andreas; Olstad, Kristin; Brinchman, Jan E.

    2015-03-01

    The second harmonic generation from collagen is highly sensitive to what extent collagen molecules are ordered into fibrils as the SHG signal is approximately proportional to the square of the fibril thickness. This can be problematic when interpreting SHG images as thick fibers are much brighter than thinner fibers such that quantification of the amount of collagen present is difficult. On the other hand SHG is therefore also a very sensitive probe to determine whether collagen have assembled into fibrils or are still dissolved as individual collagen molecules. This information is not available from standard histology or immunohistochemical techniques. The degree for fibrillation is an essential component for proper tissue function. We will present the usefulness of SHG imaging in tissue engineering of cartilage as well as cartilage related pathologies. When engineering cartilage it is essential to have the appropriate culturing conditions which cause the collagen molecules to assemble into fibrils. By employing SHG imaging we have studied how cell seeding densities affect the fibrillation of collagen molecules. Furthermore we have used SHG to study pathologies in developing cartilage in a porcine model. In both cases SHG reveals information which is not visible in conventional histology or immunohistochemistry

  16. Quantification of extracellular matrix proteins from a rat lung scaffold to provide a molecular readout for tissue engineering.

    Science.gov (United States)

    Hill, Ryan C; Calle, Elizabeth A; Dzieciatkowska, Monika; Niklason, Laura E; Hansen, Kirk C

    2015-04-01

    The use of extracellular matrix (ECM) scaffolds, derived from decellularized tissues for engineered organ generation, holds enormous potential in the field of regenerative medicine. To support organ engineering efforts, we developed a targeted proteomics method to extract and quantify extracellular matrix components from tissues. Our method provides more complete and accurate protein characterization than traditional approaches. This is accomplished through the analysis of both the chaotrope-soluble and -insoluble protein fractions and using recombinantly generated stable isotope labeled peptides for endogenous protein quantification. Using this approach, we have generated 74 peptides, representing 56 proteins to quantify protein in native (nondecellularized) and decellularized lung matrices. We have focused on proteins of the ECM and additional intracellular proteins that are challenging to remove during the decellularization procedure. Results indicate that the acellular lung scaffold is predominantly composed of structural collagens, with the majority of these proteins found in the insoluble ECM, a fraction that is often discarded using widely accepted proteomic methods. The decellularization procedure removes over 98% of intracellular proteins evaluated and retains, to varying degrees, proteoglycans and glycoproteins of the ECM. Accurate characterization of ECM proteins from tissue samples will help advance organ engineering efforts by generating a molecular readout that can be correlated with functional outcome to drive the next generation of engineered organs.

  17. Characterization of human myoblast cultures for tissue engineering.

    Science.gov (United States)

    Stern-Straeter, Jens; Bran, Gregor; Riedel, Frank; Sauter, Alexander; Hörmann, Karl; Goessler, Ulrich Reinhart

    2008-01-01

    Skeletal muscle tissue engineering, a promising specialty, aims at the reconstruction of skeletal muscle loss. In vitro tissue engineering attempts to achieve this goal by creating differentiated, functional muscle tissue through a process in which stem cells are extracted from the patient, e.g. by muscle biopsies, expanded and differentiated in a controlled environment, and subsequently re-implanted. A prerequisite for this undertaking is the ability to cultivate and differentiate human skeletal muscle cell cultures. Evidently, optimal culture conditions must be investigated for later clinical utilization. We therefore analysed the proliferation of human cells in different environments and evaluated the differentiation potential of different culture media. It was shown that human myoblasts have a higher rate of proliferation in the alamarBlue assay when cultured on gelatin-coated culture flasks rather than polystyrene-coated flasks. We also demonstrated that myoblasts treated with a culture medium with a high concentration of growth factors [growth medium (GM)] showed a higher proliferation compared to cultures treated with a culture medium with lower amounts of growth factors [differentiation medium (DM)]. Differentiation of human myoblast cell cultures treated with GM and DM was analysed until day 16 and myogenesis was verified by expression of MyoD, myogenin, alpha-sarcomeric actin and myosin heavy chain by semi-quantitative RT-PCR. Immunohistochemical staining for desmin, Myf-5 and alpha-sarcomeric actin was performed to verify the myogenic phenotype of extracted satellite cells and to prove the maturation of cells. Cultures treated with DM showed positive staining for alpha-sarcomeric actin. Notably, markers of differentiation were also detected in cultures treated with GM, but there was no formation of myotubes. In the enzymatic assay of creatine phosphokinase, cultures treated with DM showed a higher activity, evidencing a higher degree of differentiation

  18. Postproduction processing of electrospun fibres for tissue engineering.

    Science.gov (United States)

    Bye, Frazer J; Wang, Linge; Bullock, Anthony J; Blackwood, Keith A; Ryan, Anthony J; MacNeil, Sheila

    2012-08-09

    Electrospinning is a commonly used and versatile method to produce scaffolds (often biodegradable) for 3D tissue engineering.(1, 2, 3) Many tissues in vivo undergo biaxial distension to varying extents such as skin, bladder, pelvic floor and even the hard palate as children grow. In producing scaffolds for these purposes there is a need to develop scaffolds of appropriate biomechanical properties (whether achieved without or with cells) and which are sterile for clinical use. The focus of this paper is not how to establish basic electrospinning parameters (as there is extensive literature on electrospinning) but on how to modify spun scaffolds post production to make them fit for tissue engineering purposes--here thickness, mechanical properties and sterilisation (required for clinical use) are considered and we also describe how cells can be cultured on scaffolds and subjected to biaxial strain to condition them for specific applications. Electrospinning tends to produce thin sheets; as the electrospinning collector becomes coated with insulating fibres it becomes a poor conductor such that fibres no longer deposit on it. Hence we describe approaches to produce thicker structures by heat or vapour annealing increasing the strength of scaffolds but not necessarily the elasticity. Sequential spinning of scaffolds of different polymers to achieve complex scaffolds is also described. Sterilisation methodologies can adversely affect strength and elasticity of scaffolds. We compare three methods for their effects on the biomechanical properties on electrospun scaffolds of poly lactic-co-glycolic acid (PLGA). Imaging of cells on scaffolds and assessment of production of extracellular matrix (ECM) proteins by cells on scaffolds is described. Culturing cells on scaffolds in vitro can improve scaffold strength and elasticity but the tissue engineering literature shows that cells often fail to produce appropriate ECM when cultured under static conditions. There are few

  19. Modularity in developmental biology and artificial organs: a missing concept in tissue engineering.

    Science.gov (United States)

    Lenas, Petros; Luyten, Frank P; Doblare, Manuel; Nicodemou-Lena, Eleni; Lanzara, Andreina Elena

    2011-06-01

    Tissue engineering is reviving itself, adopting the concept of biomimetics of in vivo tissue development. A basic concept of developmental biology is the modularity of the tissue architecture according to which intermediates in tissue development constitute semiautonomous entities. Both engineering and nature have chosen the modular architecture to optimize the product or organism development and evolution. Bioartificial tissues do not have a modular architecture. On the contrary, artificial organs of modular architecture have been already developed in the field of artificial organs. Therefore the conceptual support of tissue engineering by the field of artificial organs becomes critical in its new endeavor of recapitulating in vitro the in vivo tissue development.

  20. Collagen in Human Tissues: Structure, Function, and Biomedical Implications from a Tissue Engineering Perspective

    Science.gov (United States)

    Balasubramanian, Preethi; Prabhakaran, Molamma P.; Sireesha, Merum; Ramakrishna, Seeram

    The extracellular matrix is a complex biological structure encoded with various proteins, among which the collagen family is the most significant and abundant of all, contributing 30-35% of the whole-body protein. "Collagen" is a generic term for proteins that forms a triple-helical structure with three polypeptide chains, and around 29 types of collagen have been identified up to now. Although most of the members of the collagen family form such supramolecular structures, extensive diversity exists between each type of collagen. The diversity is not only based on the molecular assembly and supramolecular structures of collagen types but is also observed within its tissue distribution, function, and pathology. Collagens possess complex hierarchical structures and are present in various forms such as collagen fibrils (1.5-3.5 nm wide), collagen fibers (50-70 nm wide), and collagen bundles (150-250 nm wide), with distinct properties characteristic of each tissue providing elasticity to skin, softness of the cartilage, stiffness of the bone and tendon, transparency of the cornea, opaqueness of the sclera, etc. There exists an exclusive relation between the structural features of collagen in human tissues (such as the collagen composition, collagen fibril length and diameter, collagen distribution, and collagen fiber orientation) and its tissue-specific mechanical properties. In bone, a transverse collagen fiber orientation prevails in regions of higher compressive stress whereas longitudinally oriented collagen fibers correlate to higher tensile stress. The immense versatility of collagen compels a thorough understanding of the collagen types and this review discusses the major types of collagen found in different human tissues, highlighting their tissue-specific uniqueness based on their structure and mechanical function. The changes in collagen during a specific tissue damage or injury are discussed further, focusing on the many tissue engineering applications for

  1. Design of a biaxial mechanical loading bioreactor for tissue engineering.

    Science.gov (United States)

    Bilgen, Bahar; Chu, Danielle; Stefani, Robert; Aaron, Roy K

    2013-04-25

    We designed a loading device that is capable of applying uniaxial or biaxial mechanical strain to a tissue engineered biocomposites fabricated for transplantation. While the device primarily functions as a bioreactor that mimics the native mechanical strains, it is also outfitted with a load cell for providing force feedback or mechanical testing of the constructs. The device subjects engineered cartilage constructs to biaxial mechanical loading with great precision of loading dose (amplitude and frequency) and is compact enough to fit inside a standard tissue culture incubator. It loads samples directly in a tissue culture plate, and multiple plate sizes are compatible with the system. The device has been designed using components manufactured for precision-guided laser applications. Bi-axial loading is accomplished by two orthogonal stages. The stages have a 50 mm travel range and are driven independently by stepper motor actuators, controlled by a closed-loop stepper motor driver that features micro-stepping capabilities, enabling step sizes of less than 50 nm. A polysulfone loading platen is coupled to the bi-axial moving platform. Movements of the stages are controlled by Thor-labs Advanced Positioning Technology (APT) software. The stepper motor driver is used with the software to adjust load parameters of frequency and amplitude of both shear and compression independently and simultaneously. Positional feedback is provided by linear optical encoders that have a bidirectional repeatability of 0.1 μm and a resolution of 20 nm, translating to a positional accuracy of less than 3 μm over the full 50 mm of travel. These encoders provide the necessary position feedback to the drive electronics to ensure true nanopositioning capabilities. In order to provide the force feedback to detect contact and evaluate loading responses, a precision miniature load cell is positioned between the loading platen and the moving platform. The load cell has high accuracies of 0

  2. Design of a Biaxial Mechanical Loading Bioreactor for Tissue Engineering

    Science.gov (United States)

    Bilgen, Bahar; Chu, Danielle; Stefani, Robert; Aaron, Roy K.

    2013-01-01

    We designed a loading device that is capable of applying uniaxial or biaxial mechanical strain to a tissue engineered biocomposites fabricated for transplantation. While the device primarily functions as a bioreactor that mimics the native mechanical strains, it is also outfitted with a load cell for providing force feedback or mechanical testing of the constructs. The device subjects engineered cartilage constructs to biaxial mechanical loading with great precision of loading dose (amplitude and frequency) and is compact enough to fit inside a standard tissue culture incubator. It loads samples directly in a tissue culture plate, and multiple plate sizes are compatible with the system. The device has been designed using components manufactured for precision-guided laser applications. Bi-axial loading is accomplished by two orthogonal stages. The stages have a 50 mm travel range and are driven independently by stepper motor actuators, controlled by a closed-loop stepper motor driver that features micro-stepping capabilities, enabling step sizes of less than 50 nm. A polysulfone loading platen is coupled to the bi-axial moving platform. Movements of the stages are controlled by Thor-labs Advanced Positioning Technology (APT) software. The stepper motor driver is used with the software to adjust load parameters of frequency and amplitude of both shear and compression independently and simultaneously. Positional feedback is provided by linear optical encoders that have a bidirectional repeatability of 0.1 μm and a resolution of 20 nm, translating to a positional accuracy of less than 3 μm over the full 50 mm of travel. These encoders provide the necessary position feedback to the drive electronics to ensure true nanopositioning capabilities. In order to provide the force feedback to detect contact and evaluate loading responses, a precision miniature load cell is positioned between the loading platen and the moving platform. The load cell has high accuracies of 0

  3. Neural tissue engineering options for peripheral nerve regeneration.

    Science.gov (United States)

    Gu, Xiaosong; Ding, Fei; Williams, David F

    2014-08-01

    Tissue engineered nerve grafts (TENGs) have emerged as a potential alternative to autologous nerve grafts, the gold standard for peripheral nerve repair. Typically, TENGs are composed of a biomaterial-based template that incorporates biochemical cues. A number of TENGs have been used experimentally to bridge long peripheral nerve gaps in various animal models, where the desired outcome is nerve tissue regeneration and functional recovery. So far, the translation of TENGs to the clinic for use in humans has met with a certain degree of success. In order to optimize the TENG design and further approach the matching of TENGs with autologous nerve grafts, many new cues, beyond the traditional ones, will have to be integrated into TENGs. Furthermore, there is a strong requirement for monitoring the real-time dynamic information related to the construction of TENGs. The aim of this opinion paper is to specifically and critically describe the latest advances in the field of neural tissue engineering for peripheral nerve regeneration. Here we delineate new attempts in the design of template (or scaffold) materials, especially in the context of biocompatibility, the choice and handling of support cells, and growth factor release systems. We further discuss the significance of RNAi for peripheral nerve regeneration, anticipate the potential application of RNAi reagents for TENGs, and speculate on the possible contributions of additional elements, including angiogenesis, electrical stimulation, molecular inflammatory mediators, bioactive peptides, antioxidant reagents, and cultured biological constructs, to TENGs. Finally, we consider that a diverse array of physicochemical and biological cues must be orchestrated within a TENG to create a self-consistent coordinated system with a close proximity to the regenerative microenvironment of the peripheral nervous system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Elastic, permeability and swelling properties of human intervertebral disc tissues: A benchmark for tissue engineering.

    Science.gov (United States)

    Cortes, Daniel H; Jacobs, Nathan T; DeLucca, John F; Elliott, Dawn M

    2014-06-27

    The aim of functional tissue engineering is to repair and replace tissues that have a biomechanical function, i.e., connective orthopaedic tissues. To do this, it is necessary to have accurate benchmarks for the elastic, permeability, and swelling (i.e., biphasic-swelling) properties of native tissues. However, in the case of the intervertebral disc, the biphasic-swelling properties of individual tissues reported in the literature exhibit great variation and even span several orders of magnitude. This variation is probably caused by differences in the testing protocols and the constitutive models used to analyze the data. Therefore, the objective of this study was to measure the human lumbar disc annulus fibrosus (AF), nucleus pulposus (NP), and cartilaginous endplates (CEP) biphasic-swelling properties using a consistent experimental protocol and analyses. The testing protocol was composed of a swelling period followed by multiple confined compression ramps. To analyze the confined compression data, the tissues were modeled using a biphasic-swelling model, which augments the standard biphasic model through the addition of a deformation-dependent osmotic pressure term. This model allows considering the swe