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Sample records for stimulate tissue-engineered constructs

  1. A Novel Pulsatile Bioreactor for Mechanical Stimulation of Tissue Engineered Cardiac Constructs

    Directory of Open Access Journals (Sweden)

    Günther Eissner

    2011-07-01

    Full Text Available After myocardial infarction, the implantation of stem cell seeded scaffolds on the ischemic zone represents a promising strategy for restoration of heart function. However, mechanical integrity and functionality of tissue engineered constructs need to be determined prior to implantation. Therefore, in this study a novel pulsatile bioreactor mimicking the myocardial contraction was developed to analyze the behavior of mesenchymal stem cells derived from umbilical cord tissue (UCMSC colonized on titanium-coated polytetrafluorethylene scaffolds to friction stress. The design of the bioreactor enables a simple handling and defined mechanical forces on three seeded scaffolds at physiological conditions. The compact system made of acrylic glass, Teflon®, silicone, and stainless steel allows the comparison of different media, cells and scaffolds. The bioreactor can be gas sterilized and actuated in a standard incubator. Macroscopic observations and pressure-measurements showed a uniformly sinusoidal pulsation, indicating that the bioreactor performed well. Preliminary experiments to determine the adherence rate and morphology of UCMSC after mechanical loadings showed an almost confluent cellular coating without damage on the cell surface. In summary, the bioreactor is an adequate tool for the mechanical stress of seeded scaffolds and offers dynamic stimuli for pre-conditioning of cardiac tissue engineered constructs in vitro.

  2. The effect of mechanical stimulation on the maturation of TDSCs-poly(L-lactide-co-e-caprolactone)/collagen scaffold constructs for tendon tissue engineering.

    Science.gov (United States)

    Xu, Yuan; Dong, Shiwu; Zhou, Qiang; Mo, Xiumei; Song, Lei; Hou, Tianyong; Wu, Jinglei; Li, Songtao; Li, Yudong; Li, Pei; Gan, Yibo; Xu, Jianzhong

    2014-03-01

    Mechanical stimulation plays an important role in the development and remodeling of tendons. Tendon-derived stem cells (TDSCs) are an attractive cell source for tendon injury and tendon tissue engineering. However, these cells have not yet been fully explored for tendon tissue engineering application, and there is also lack of understanding to the effect of mechanical stimulation on the maturation of TDSCs-scaffold construct for tendon tissue engineering. In this study, we assessed the efficacy of TDSCs in a poly(L-lactide-co-ε-caprolactone)/collagen (P(LLA-CL)/Col) scaffold under mechanical stimulation for tendon tissue engineering both in vitro and in vivo, and evaluated the utility of the transplanted TDSCs-scaffold construct to promote rabbit patellar tendon defect regeneration. TDSCs displayed good proliferation and positive expressed tendon-related extracellular matrix (ECM) genes and proteins under mechanical stimulation in vitro. After implanting into the nude mice, the fluorescence imaging indicated that TDSCs had long-term survival, and the macroscopic evaluation, histology and immunohistochemistry examinations showed high-quality neo-tendon formation under mechanical stimulation in vivo. Furthermore, the histology, immunohistochemistry, collagen content assay and biomechanical testing data indicated that dynamically cultured TDSCs-scaffold construct could significantly contributed to tendon regeneration in a rabbit patellar tendon window defect model. TDSCs have significant potential to be used as seeded cells in the development of tissue-engineered tendons, which can be successfully fabricated through seeding of TDSCs in a P(LLA-CL)/Col scaffold followed by mechanical stimulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Cryopreservation of tissue engineered constructs for bone.

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    Kofron, Michelle D; Opsitnick, Natalie C; Attawia, Mohamed A; Laurencin, Cato T

    2003-11-01

    The large-scale clinical use of tissue engineered constructs will require provisions for its mass availability and accessibility. Therefore, it is imperative to understand the effects of low temperature (-196 degrees C) on the tissue engineered biological system. Initial studies used samples of the osteoblast-like cell line (SaOS-2) adhered to a two-dimensional poly(lactide-co-glycolide) thin film (2D-PLAGA) or a three-dimensional poly(lactide-co-glycolide) sintered microsphere matrix (3D-PLAGA) designed for bone tissue engineering. Experimental samples were tested for their ability to maintain cell viability, following low temperature banking for one week, in solutions of the penetrating cryoprotective agents, dimethylsulfoxide (DMSO), ethylene glycol, and glycerol. Results indicated the DMSO solution yielded the greatest percent cell survival for SaOS-2 cells adhered to both the 2D- and 3D-PLAGA scaffolds; therefore, DMSO was used to cryopreserve mineralizing primary rabbit osteoblasts cells adhered to 2D-PLAGA matrices for 35 days. Results indicated retention of the extracellular matrix architecture as no statistically significant difference in the pre- and post-thaw mineralized structures was measured. Percent cell viability of the mineralized constructs following low temperature storage was approximately 50%. These are the first studies to address the issue of preservation techniques for tissue engineered constructs. The ability to successfully cryopreserve mineralized tissue engineered matrices for bone may offer an unlimited and readily available source of bone-like materials for orthopaedic applications.

  4. 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.

    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

  5. Development of multilayer constructs for tissue engineering

    NARCIS (Netherlands)

    Bettahalli Narasimha, M.S.; Groen, N.; Steg, H.; Unadkat, H.V.; de Boer, Jan; van Blitterswijk, Clemens; Wessling, Matthias; Stamatialis, Dimitrios

    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

  6. Tissue engineered constructs: perspectives on clinical translation.

    Science.gov (United States)

    Lu, Lichun; Arbit, Harvey M; Herrick, James L; Segovis, Suzanne Glass; Maran, Avudaiappan; Yaszemski, Michael J

    2015-03-01

    In this article, a "bedside to bench and back" approach for developing tissue engineered medical products (TEMPs) for clinical applications is reviewed. The driving force behind this approach is unmet clinical needs. Preclinical research, both in vitro and in vivo using small and large animal models, will help find solutions to key research questions. In clinical research, ethical issues regarding the use of cells and tissues, their sources, donor consent, as well as clinical trials are important considerations. Regulatory issues, at both institutional and government levels, must be addressed prior to the translation of TEMPs to clinical practice. TEMPs are regulated as drugs, biologics, devices, or combination products by the U.S. Food and Drug Administration (FDA). Depending on the mode of regulation, applications for TEMP introduction must be filed with the FDA to demonstrate safety and effectiveness in premarket clinical studies, followed by 510(k) premarket clearance or premarket approval (for medical devices), biologics license application approval (for biologics), or new drug application approval (for drugs). A case study on nerve cuffs is presented to illustrate the regulatory process. Finally, perspectives on commercialization such as finding a company partner and funding issues, as well as physician culture change, are presented.

  7. Vascularization of soft tissue engineering constructs

    DEFF Research Database (Denmark)

    Pimentel Carletto, Rodrigo

    with mechanical properties in the range of soft tissues has not been fully achieved. My project focused on the fabrication and the active perfusion of hydrogel constructs with multi-dimensional vasculature and controlled mechanical properties targeting soft tissues. Specifically, the initial part of the research...... nanotechnology-based paradigm for engineering vascularised liver tissue for transplantation”) and the Danish National Research Foundation and Villum Foundation’s Center for Intelligent Drug delivery and sensing Using microcontainers and Nanomechanics (Danish National Research Foundation (DNRF122)....

  8. Vascularization of soft tissue engineering constructs

    DEFF Research Database (Denmark)

    Pimentel Carletto, Rodrigo

    nanotechnology-based paradigm for engineering vascularised liver tissue for transplantation”) and the Danish National Research Foundation and Villum Foundation’s Center for Intelligent Drug delivery and sensing Using microcontainers and Nanomechanics (Danish National Research Foundation (DNRF122).......Vascularization is recognized to be the biggest challenge for the fabrication of tissues and finally, organs in vitro. So far, several fabrication techniques have been proposed to create a perfusable vasculature within hydrogels, however, the vascularization and perfusion of hydrogels...... with mechanical properties in the range of soft tissues has not been fully achieved. My project focused on the fabrication and the active perfusion of hydrogel constructs with multi-dimensional vasculature and controlled mechanical properties targeting soft tissues. Specifically, the initial part of the research...

  9. Influence of extremely low frequency, low energy electromagnetic fields and combined mechanical stimulation on chondrocytes in 3-D constructs for cartilage tissue engineering.

    Science.gov (United States)

    Hilz, Florian M; Ahrens, Philipp; Grad, Sibylle; Stoddart, Martin J; Dahmani, Chiheb; Wilken, Frauke L; Sauerschnig, Martin; Niemeyer, Philipp; Zwingmann, Jörn; Burgkart, Rainer; von Eisenhart-Rothe, Rüdiger; Südkamp, Norbert P; Weyh, Thomas; Imhoff, Andreas B; Alini, Mauro; Salzmann, Gian M

    2014-02-01

    Articular cartilage, once damaged, has very low regenerative potential. Various experimental approaches have been conducted to enhance chondrogenesis and cartilage maturation. Among those, non-invasive electromagnetic fields have shown their beneficial influence for cartilage regeneration and are widely used for the treatment of non-unions, fractures, avascular necrosis and osteoarthritis. One very well accepted way to promote cartilage maturation is physical stimulation through bioreactors. The aim of this study was the investigation of combined mechanical and electromagnetic stress affecting cartilage cells in vitro. Primary articular chondrocytes from bovine fetlock joints were seeded into three-dimensional (3-D) polyurethane scaffolds and distributed into seven stimulated experimental groups. They either underwent mechanical or electromagnetic stimulation (sinusoidal electromagnetic field of 1 mT, 2 mT, or 3 mT; 60 Hz) or both within a joint-specific bioreactor and a coil system. The scaffold-cell constructs were analyzed for glycosaminoglycan (GAG) and DNA content, histology, and gene expression of collagen-1, collagen-2, aggrecan, cartilage oligomeric matrix protein (COMP), Sox9, proteoglycan-4 (PRG-4), and matrix metalloproteinases (MMP-3 and -13). There were statistically significant differences in GAG/DNA content between the stimulated versus the control group with highest levels in the combined stimulation group. Gene expression was significantly higher for combined stimulation groups versus static control for collagen 2/collagen 1 ratio and lower for MMP-13. Amongst other genes, a more chondrogenic phenotype was noticed in expression patterns for the stimulated groups. To conclude, there is an effect of electromagnetic and mechanical stimulation on chondrocytes seeded in a 3-D scaffold, resulting in improved extracellular matrix production. © 2013 Wiley Periodicals, Inc.

  10. Artificial urinary conduit construction using tissue engineering methods.

    Science.gov (United States)

    Kloskowski, Tomasz; Pokrywczyńska, Marta; Drewa, Tomasz

    2015-01-01

    Incontinent urinary diversion using an ileal conduit is the most popular method used by urologists after bladder cystectomy resulting from muscle invasive bladder cancer. The use of gastrointestinal tissue is related to a series of complications with the necessity of surgical procedure extension which increases the time of surgery. Regenerative medicine together with tissue engineering techniques gives hope for artificial urinary conduit construction de novo without affecting the ileum. In this review we analyzed history of urinary diversion together with current attempts in urinary conduit construction using tissue engineering methods. Based on literature and our own experience we presented future perspectives related to the artificial urinary conduit construction. A small number of papers in the field of tissue engineered urinary conduit construction indicates that this topic requires more attention. Three main factors can be distinguished to resolve this topic: proper scaffold construction along with proper regeneration of both the urothelium and smooth muscle layers. Artificial urinary conduit has a great chance to become the first commercially available product in urology constructed by regenerative medicine methods.

  11. 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.

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

    Science.gov (United States)

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

    2018-04-26

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

  13. 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.

  14. [Construction of injectable tissue engineered nucleus pulposus in vitro].

    Science.gov (United States)

    Tian, Huake; Wang, Jian; Chen, Chao; Liu, Jie; Zhou, Yue

    2009-02-01

    To investigate the feasibility of using thermo-sensitive chitosan hydrogen as a scaffold to construct tissue engineered injectable nucleus pulposus (NP). Three-month-old neonatal New Zealand rabbits (male or female) weighing 150-200 g were selected to isolate and culture NP cells. The thermo-sensitive chitosan hydrogel scaffold was made of chitosan, disodium beta-glycerophosphate and hydroxyethyl cellulose. Its physical properties and gross condition were observed. The tissue engineered NP was constructed by compounding the scaffold and rabbit NP cells. Then, the viability of NP cells in the chitosan hydrogel was observed 2 days after compound culture and the growth condition of NP cells on the scaffold was observed by SEM 7 days after compound culture. NP cells went through histology and immunohistochemistry detection and their secretion of aggrecan and expression of Col II mRNA were analyzed by RT-PCR 21 days after compound culture. The thermo-sensitive chitosan hydrogel was liquid at room temperature and solidified into gel at 37 degrees C (15 minutes) due to crosslinking reaction. Acridine orange-propidium iodide staining showed that the viability rate of NP cells in chitosan hydrogel was above 90%. Scanning electron microscope observation demonstrated that the NP cells were distributed in the reticulate scaffold, with ECM on their surfaces. The results of HE, toluidine blue, safranin O and histology and immunohistochemistry staining confirmed that the NP cells in chitosan hydrogel were capable of producing ECM. RT-PCR results showed that the secretion of Col II and aggrecan mRNA in NP cells cultured three-dimensionally by chitosan hydrogen scaffold were 0.631 +/- 0.064 and 0.832 +/- 0.052, respectively, showing more strengths of producing matrix than that of monolayer culture (0.528 +/- 0.039, 0.773 +/- 0.046) with a significant difference (P compound culture, and may be a potential NP cells carrier for tissue engineered NP.

  15. 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.

  16. 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.

  17. A dual flow bioreactor with controlled mechanical stimulation for cartilage tissue engineering

    NARCIS (Netherlands)

    Spitters, Tim; Leijten, Jeroen Christianus Hermanus; Deus, F.D.; Costa, I.B.F.; van Apeldoorn, Aart A.; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2013-01-01

    In cartilage tissue engineering bioreactors can create a controlled environment to study chondrocyte behavior under mechanical stimulation or produce chondrogenic grafts of clinically relevant size. Here we present a novel bioreactor, which combines mechanical stimulation with a two compartment

  18. Review on patents for mechanical stimulation of articular cartilage tissue engineering

    NARCIS (Netherlands)

    Donkelaar, van C.C.; Schulz, R.M.

    2008-01-01

    To repair articular cartilage defects in osteoarthritic patients with three-dimensional tissue engineered chondrocyte grafts, requires the formation of new cartilage with sufficient mechanical properties. The premise is that mechanical stimulation during the culturing process is necessary to reach

  19. Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering

    NARCIS (Netherlands)

    Silva, J.M.; Georgi, Nicole; Costa, R.; Sher, P.; Reis, R L; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes; Mano, J.F.

    2013-01-01

    Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and

  20. Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

    Science.gov (United States)

    Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

    2016-05-17

    Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

  1. Designing electrical stimulated bioreactors for nerve tissue engineering

    Science.gov (United States)

    Sagita, Ignasius Dwi; Whulanza, Yudan; Dhelika, Radon; Nurhadi, Ibrahim

    2018-02-01

    Bioreactor provides a biomimetic ecosystem that is able to culture cells in a physically controlled system. In general, the controlled-parameters are temperature, pH, fluid flow, nutrition flow, etc. In this study, we develop a bioreactor that specifically targeted to culture neural stem cells. This bioreactor could overcome some limitations of conventional culture technology, such as petri dish, by providing specific range of observation area and a uniform treatment. Moreover, the microfluidic bioreactor, which is a small-controlled environment, is able to observe as small number of cells as possible. A perfusion flow is applied to mimic the physiological environment in human body. Additionally, this bioreactor also provides an electrical stimulation which is needed by neural stem cells. In conclusion, we found the correlation between the induced shear stress with geometric parameters of the bioreactor. Ultimately, this system shall be used to observe the interaction between stimulation and cell growth.

  2. Indirect Low-Intensity Ultrasonic Stimulation for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Hyoungshin Park

    2010-01-01

    Full Text Available Low-intensity ultrasound (LIUS treatment has been shown to increase mass transport, which could benefit tissue grafts during the immediate postimplant period, when blood supply to the implanted tissue is suboptimal. In this in vitro study, we investigated effects of LIUS stimulation on dye diffusion, proliferation, metabolism, and tropomyosin expression of muscle cells (C2C12 and on tissue viability and gene expression of human adipose tissue organoids. We found that LIUS increased dye diffusion within adjacent tissue culture wells and caused anisotropic diffusion patterns. This effect was confirmed by a hydrophone measurement resulting in acoustic pressure 150–341 Pa in wells. Cellular studies showed that LIUS significantly increased proliferation, metabolic activity, and expression of tropomyosin. Adipose tissue treated with LIUS showed significantly increased metabolic activity and the cells had similar morphology to normal unilocular adipocytes. Gene analysis showed that tumor necrosis factor-alpha expression (a marker for tissue damage was significantly lower for stimulated organoids than for control groups. Our data suggests that LIUS could be a useful modality for improving graft survival in vivo.

  3. Mechanical Stimulation of Adipose-Derived Stem Cells for Functional Tissue Engineering of the Musculoskeletal System via Cyclic Hydrostatic Pressure, Simulated Microgravity, and Cyclic Tensile Strain.

    Science.gov (United States)

    Nordberg, Rachel C; Bodle, Josie C; Loboa, Elizabeth G

    2018-01-01

    It is critical that human adipose stem cell (hASC) tissue-engineering therapies possess appropriate mechanical properties in order to restore function of the load bearing tissues of the musculoskeletal system. In an effort to elucidate the hASC response to mechanical stimulation and develop mechanically robust tissue engineered constructs, recent research has utilized a variety of mechanical loading paradigms including cyclic tensile strain, cyclic hydrostatic pressure, and mechanical unloading in simulated microgravity. This chapter describes methods for applying these mechanical stimuli to hASC to direct differentiation for functional tissue engineering of the musculoskeletal system.

  4. [Research progress of co-culture system for constructing vascularized tissue engineered bone].

    Science.gov (United States)

    Fu, Weili; Xiang, Zhou

    2014-02-01

    To review the research progress of the co-culture system for constructing vascularized tissue engineered bone. The recent literature concerning the co-culture system for constructing vascularized tissue engineered bone was reviewed, including the selection of osteogenic and endothelial lineages, the design and surface modification of scaffolds, the models and dimensions of the co-culture system, the mechanism, the culture conditions, and their application progress. The construction of vascularized tissue engineered bone is the prerequisite for their survival and further clinical application in vivo. Mesenchymal stem cells (owning the excellent osteogenic potential) and endothelial progenitor cells (capable of directional differentiation into endothelial cell) are considered as attractive cell types for the co-culture system to construct vascularized tissue engineered bone. The culture conditions need to be further optimized. Furthermore, how to achieve the clinical goals of minimal invasion and autologous transplantation also need to be further studied. The strategy of the co-culture system for constructing vascularized tissue engineered bone would have a very broad prospects for clinical application in future.

  5. Oxygen gradients in tissue-engineered PEGT/PBT cartilaginous constructs: Measurement and modeling

    NARCIS (Netherlands)

    Malda, J.; Rouwkema, Jeroen; Martens, D.E.; le Comte, EP; Kooy, F.K.; Tramper, J.; van Blitterswijk, Clemens; Riesle, J.U.

    2004-01-01

    The supply of oxygen within three-dimensional tissue-engineered (TE) cartilage polymer constructs is mainly by diffusion. Oxygen consumption by cells results in gradients in the oxygen concentration. The aims of this study were, firstly, to identify the gradients within TE cartilage polymer

  6. Oxygen gradients in tissue-engineered PEGT/PBT cartilaginous constructs: measurement and modeling

    NARCIS (Netherlands)

    Malda, J.; Rouwkema, J.; Martens, D.E.; Paul le Comte, E.; Kooy, F.K.; Tramper, J.; Blitterswijk, van C.A.; Riesle, J.

    2004-01-01

    The supply of oxygen within three-dimensional tissue-engineered (TE) cartilage polymer constructs is mainly by diffusion. Oxygen consumption by cells results in gradients in the oxygen concentration. The aims of this study were, firstly, to identify the gradients within TE: cartilage polymer

  7. The effect of PEGT/PBT scaffold architecture on oxygen gradients in tissue engineered cartilaginous constructs

    NARCIS (Netherlands)

    Malda, J.; Woodfield, T.B.F.; van der Vloodt, F.; Kooy, F.K.; Martens, D.E.; Tramper, J.C.; van Blitterswijk, Clemens; Riesle, J.U.

    2004-01-01

    Repair of articular cartilage defects using tissue engineered constructs composed of a scaffold and cultured autologous cells holds promise for future treatments. However, nutrient limitation (e.g. oxygen) has been suggested as a cause of the onset of chondrogenesis solely within the peripheral

  8. Bone tissue engineering with human mesenchymal stem cell sheets constructed using magnetite nanoparticles and magnetic force.

    Science.gov (United States)

    Shimizu, Kazunori; Ito, Akira; Yoshida, Tatsuro; Yamada, Yoichi; Ueda, Minoru; Honda, Hiroyuki

    2007-08-01

    An in vitro reconstruction of three-dimensional (3D) tissues without the use of scaffolds may be an alternative strategy for tissue engineering. We have developed a novel tissue engineering strategy, termed magnetic force-based tissue engineering (Mag-TE), in which magnetite cationic liposomes (MCLs) with a positive charge at the liposomal surface, and magnetic force were used to construct 3D tissue without scaffolds. In this study, human mesenchymal stem cells (MSCs) magnetically labeled with MCLs were seeded onto an ultra-low attachment culture surface, and a magnet (4000 G) was placed on the reverse side. The MSCs formed multilayered sheet-like structures after a 24-h culture period. MSCs in the sheets constructed by Mag-TE maintained an in vitro ability to differentiate into osteoblasts, adipocytes, or chondrocytes after a 21-day culture period using each induction medium. Using an electromagnet, MSC sheets constructed by Mag-TE were harvested and transplanted into the bone defect in the crania of nude rats. Histological observation revealed that new bone surrounded by osteoblast-like cells was formed in the defect area 14 days after transplantation with MSC sheets, whereas no bone formation was observed in control rats without the transplant. These results indicated that Mag-TE could be used for the transplantation of MSC sheets using magnetite nanoparticles and magnetic force, providing novel methodology for bone tissue engineering.

  9. Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

    Science.gov (United States)

    Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

    2017-01-01

    Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Monitoring sinew contraction during formation of tissue-engineered fibrin-based ligament constructs.

    Science.gov (United States)

    Paxton, Jennifer Z; Wudebwe, Uchena N G; Wang, Anqi; Woods, Daniel; Grover, Liam M

    2012-08-01

    The ability to study the gross morphological changes occurring during tissue formation is vital to producing tissue-engineered structures of clinically relevant dimensions in vitro. Here, we have used nondestructive methods of digital imaging and optical coherence tomography to monitor the early-stage formation and subsequent maturation of fibrin-based tissue-engineered ligament constructs. In addition, the effect of supplementation with essential promoters of collagen synthesis, ascorbic acid (AA) and proline (P), has been assessed. Contraction of the cell-seeded fibrin gel occurs unevenly within the first 5 days of culture around two fixed anchor points before forming a longitudinal ligament-like construct. AA+P supplementation accelerates gel contraction in the maturation phase of development, producing ligament-like constructs with a higher collagen content and distinct morphology to that of unsupplemented constructs. These studies highlight the importance of being able to control the methods of tissue formation and maturation in vitro to enable the production of tissue-engineered constructs with suitable replacement tissue characteristics for repair of clinical soft-tissue injuries.

  11. Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

    Science.gov (United States)

    Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

    2015-02-01

    Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Towards the design of 3D multiscale instructive tissue engineering constructs: Current approaches and trends.

    Science.gov (United States)

    Oliveira, Sara M; Reis, Rui L; Mano, João F

    2015-11-01

    The design of 3D constructs with adequate properties to instruct and guide cells both in vitro and in vivo is one of the major focuses of tissue engineering. Successful tissue regeneration depends on the favorable crosstalk between the supporting structure, the cells and the host tissue so that a balanced matrix production and degradation are achieved. Herein, the major occurring events and players in normal and regenerative tissue are overviewed. These have been inspiring the selection or synthesis of instructive cues to include into the 3D constructs. We further highlight the importance of a multiscale perception of the range of features that can be included on the biomimetic structures. Lastly, we focus on the current and developing tissue-engineering approaches for the preparation of such 3D constructs: top-down, bottom-up and integrative. Bottom-up and integrative approaches present a higher potential for the design of tissue engineering devices with multiscale features and higher biochemical control than top-down strategies, and are the main focus of this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Morphological changes in paraurethral area after introduction of tissue engineering construct on the basis of adipose tissue stromal cells.

    Science.gov (United States)

    Makarov, A V; Arutyunyan, I V; Bol'shakova, G B; Volkov, A V; Gol'dshtein, D V

    2009-10-01

    We studied morphological changes in the paraurethral area of Wistar rats after introduction of tissue engineering constructs on the basis of multipotent mesenchymal stem cells and gelatin sponge. The tissue engineering construct containing autologous culture of the stromal fraction of the adipose tissue was most effective. After introduction of this construct we observed more rapid degradation of the construct matrix and more intensive formation of collagen fibers.

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

    Science.gov (United States)

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

    2010-01-21

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

  15. Magnetic resonance microscopy for monitoring osteogenesis in tissue-engineered construct in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xu Huihui [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Othman, Shadi F [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Hong Liu [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Peptan, Ioana A [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States); Magin, Richard L [Bioengineering Department (MC 063), University of Illinois at Chicago, 851 South Morgan Street, Chicago, IL 60607-7052 (United States)

    2006-02-07

    Magnetic resonance microscopy (MRM) is used to monitor osteogenesis in tissue-engineered constructs. Measurements of the developing tissue's MR relaxation times (T{sub 1} and T{sub 2}), apparent diffusion coefficient (ADC) and elastic shear modulus were conducted over a 4-week growth period using an 11.74 T Bruker spectrometer with an imaging probe adapted for MR elastography (MRE). Both the relaxation times and the ADC show a statistically significant decrease after only one week of tissue development while the tissue stiffness increases progressively during the first two weeks of in vitro growth. The measured MR parameters are correlated with histologically monitored osteogenic tissue development. This study shows that MRM can provide quantitative data with which to characterize the growth and development of tissue-engineered bone.

  16. Mechanical stretching for tissue engineering: two-dimensional and three-dimensional constructs.

    Science.gov (United States)

    Riehl, Brandon D; Park, Jae-Hong; Kwon, Il Keun; Lim, Jung Yul

    2012-08-01

    Mechanical cell stretching may be an attractive strategy for the tissue engineering of mechanically functional tissues. It has been demonstrated that cell growth and differentiation can be guided by cell stretch with minimal help from soluble factors and engineered tissues that are mechanically stretched in bioreactors may have superior organization, functionality, and strength compared with unstretched counterparts. This review explores recent studies on cell stretching in both two-dimensional (2D) and three-dimensional (3D) setups focusing on the applications of stretch stimulation as a tool for controlling cell orientation, growth, gene expression, lineage commitment, and differentiation and for achieving successful tissue engineering of mechanically functional tissues, including cardiac, muscle, vasculature, ligament, tendon, bone, and so on. Custom stretching devices and lab-specific mechanical bioreactors are described with a discussion on capabilities and limitations. While stretch mechanotransduction pathways have been examined using 2D stretch, studying such pathways in physiologically relevant 3D environments may be required to understand how cells direct tissue development under stretch. Cell stretch study using 3D milieus may also help to develop tissue-specific stretch regimens optimized with biochemical feedback, which once developed will provide optimal tissue engineering protocols.

  17. An antibody based approach for multi-coloring osteogenic and chondrogenic proteins in tissue engineered constructs.

    Science.gov (United States)

    Leferink, Anne M; Reis, Diogo Santos; van Blitterswijk, Clemens A; Moroni, Lorenzo

    2018-04-11

    When tissue engineering strategies rely on the combination of three-dimensional (3D) polymeric or ceramic scaffolds with cells to culture implantable tissue constructs in vitro, it is desirable to monitor tissue growth and cell fate to be able to more rationally predict the quality and success of the construct upon implantation. Such a 3D construct is often referred to as a 'black-box' since the properties of the scaffolds material limit the applicability of most imaging modalities to assess important construct parameters. These parameters include the number of cells, the amount and type of tissue formed and the distribution of cells and tissue throughout the construct. Immunolabeling enables the spatial and temporal identification of multiple tissue types within one scaffold without the need to sacrifice the construct. In this report, we concisely review the applicability of antibodies (Abs) and their conjugation chemistries in tissue engineered constructs. With some preliminary experiments, we show an efficient conjugation strategy to couple extracellular matrix Abs to fluorophores. The conjugated probes proved to be effective in determining the presence of collagen type I and type II on electrospun and additive manufactured 3D scaffolds seeded with adult human bone marrow derived mesenchymal stromal cells. The conjugation chemistry applied in our proof of concept study is expected to be applicable in the coupling of any other fluorophore or particle to the Abs. This could ultimately lead to a library of probes to permit high-contrast imaging by several imaging modalities.

  18. Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs.

    Science.gov (United States)

    Wang, Bo; Patnaik, Sourav S; Brazile, Bryn; Butler, J Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

    2015-01-01

    Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

  19. Crosstalk between Substrates and Rho-Associated Kinase Inhibitors in Cryopreservation of Tissue-Engineered Constructs

    Directory of Open Access Journals (Sweden)

    Arindam Bit

    2017-01-01

    Full Text Available It is documented that human mesenchymal stem cells (hMSCs can be differentiated into various types of cells to present a tool for tissue engineering and regenerative medicine. Thus, the preservation of stem cells is a crucial factor for their effective long-term storage that further facilitates their continuous supply and transportation for application in regenerative medicine. Cryopreservation is the most important, practicable, and the only established mechanism for long-term preservation of cells, tissues, and organs, and engineered tissues; thus, it is the key step for the improvement of tissue engineering. A significant portion of MSCs loses cellular viability while freeze-thawing, which represents an important technical limitation to achieving sufficient viable cell numbers for maximum efficacy. Several natural and synthetic materials are extensively used as substrates for tissue engineering constructs and cryopreservation because they promote cell attachment and proliferation. Rho-associated kinase (ROCK inhibitors can improve the physiological function and postthaw viability of cryopreserved MSCs. This review proposes a crosstalk between substrate topology and interaction of cells with ROCK inhibitors. It is shown that incorporation of ionic nanoparticles in the presence of an external electrical field improves the generation of ROCK inhibitors to safeguard cellular viability for the enhanced cryopreservation of engineered tissues.

  20. Supplementation of exogenous adenosine 5'-triphosphate enhances mechanical properties of 3D cell-agarose constructs for cartilage tissue engineering.

    Science.gov (United States)

    Gadjanski, Ivana; Yodmuang, Supansa; Spiller, Kara; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana

    2013-10-01

    Formation of tissue-engineered cartilage is greatly enhanced by mechanical stimulation. However, direct mechanical stimulation is not always a suitable method, and the utilization of mechanisms underlying mechanotransduction might allow for a highly effective and less aggressive alternate means of stimulation. In particular, the purinergic, adenosine 5'-triphosphate (ATP)-mediated signaling pathway is strongly implicated in mechanotransduction within the articular cartilage. We investigated the effects of transient and continuous exogenous ATP supplementation on mechanical properties of cartilaginous constructs engineered using bovine chondrocytes and human mesenchymal stem cells (hMSCs) encapsulated in an agarose hydrogel. For both cell types, we have observed significant increases in equilibrium and dynamic compressive moduli after transient ATP treatment applied in the fourth week of cultivation. Continuous ATP treatment over 4 weeks of culture only slightly improved the mechanical properties of the constructs, without major changes in the total glycosaminoglycan (GAG) and collagen content. Structure-function analyses showed that transiently ATP-treated constructs, and in particular those based on hMSCs, had the highest level of correlation between compositional and mechanical properties. Transiently treated groups showed intense staining of the territorial matrix for GAGs and collagen type II. These results indicate that transient ATP treatment can improve functional mechanical properties of cartilaginous constructs based on chondrogenic cells and agarose hydrogels, possibly by improving the structural organization of the bulk phase and territorial extracellular matrix (ECM), that is, by increasing correlation slopes between the content of the ECM components (GAG, collagen) and mechanical properties of the construct.

  1. CD34/CD133 enriched bone marrow progenitor cells promote neovascularization of tissue engineered constructs in vivo

    Directory of Open Access Journals (Sweden)

    Marietta Herrmann

    2014-11-01

    We demonstrate that this population of cells, isolated in a clinically relevant manner and cultured with autologous growth factors readily promoted neovascularization in tissue engineered constructs in vivo enabling a potential translation into the clinic.

  2. Chitosan-based scaffolds for the support of smooth muscle constructs in intestinal tissue engineering

    Science.gov (United States)

    Zakhem, Elie; Raghavan, Shreya; Gilmont, Robert R; Bitar, Khalil N

    2012-01-01

    Intestinal tissue engineering is an emerging field due to a growing demand for intestinal lengthening and replacement procedures secondary to massive resections of the bowel. Here, we demonstrate the potential use of a chitosan/collagen scaffold as a 3D matrix to support the bioengineered circular muscle constructs maintain their physiological functionality. We investigated the biocompatibility of chitosan by growing rabbit colonic circular smooth muscle cells (RCSMCs) on chitosan-coated plates. The cells maintained their spindle-like morphology and preserved their smooth muscle phenotypic markers. We manufactured tubular scaffolds with central openings composed of chitosan and collagen in a 1:1 ratio. Concentrically-aligned 3D circular muscle constructs were bioengineered using fibrin-based hydrogel seeded with RCSMCs. The constructs were placed around the scaffold for 2 weeks, after which they were taken off and tested for their physiological functionality. The muscle constructs contracted in response to Acetylcholine (Ach) and potassium chloride (KCl) and they relaxed in response to vasoactive intestinal peptide (VIP). These results demonstrate that chitosan is a biomaterial possibly suitable for intestinal tissue engineering applications. PMID:22483012

  3. [Construction of a capsular tissue-engineered ureteral stent seeded with autologous urothelial cells].

    Science.gov (United States)

    Tan, Haisong; Fu, Weijun; Li, Jianqiang; Wang, Zhongxin; Li, Gang; Ma, Xin; Dong, Jun; Gao, Jiangping; Wang, Xiaoxiong; Zhang, Xu

    2013-01-01

    To investigate the feasibility of constructing a capsular poly L-lactic acid (PLLA) ureteral stent seeded with autologous urothelial cells using tissue engineering methods. The capsular ureteral stent was constructed by subcutaneously embedding PLLA ureteral stent in the back of beagles for 3 weeks to induce the formation of connective tissue on the surfaces. After decellularization of the stent, the expanded autologous urothelial cells were seeded on the stent. The surface structure and cell adhesion of the stent were observed using HE staining, scanning electron microscope (SEM) and immunocytochemical staining. MTT assay was used to evaluate urothelial cell proliferation on the capsular PLLA ureteral stent and on circumferential small intestinal submucosa graft. HE staining and VIII factor immunohistochemistry revealed numerous capillaries in the connective tissue encapsulating the stent without obvious local inflammatory response. The results of SEM and immunocytochemical staining showed that the capsule contained rich collagenic fibers forming three-dimensional structures, and the seeded autologous urothelial cells could adhere and well aligned on the surface. MTT assay showed normal growth of the cells on the stent as compared with the cells grown on circumferential small intestinal submucosa graft. The capsular PLLA ureteral stent allows adhesion and proliferation of autologous urothelial cells and shows a potential in applications of constructing tissue-engineered ureter.

  4. Regeneration of skull bones in adult rabbits after implantation of commercial osteoinductive materials and transplantation of a tissue-engineering construct.

    Science.gov (United States)

    Volkov, A V; Alekseeva, I S; Kulakov, A A; Gol'dshtein, D V; Shustrov, S A; Shuraev, A I; Arutyunyan, I V; Bukharova, T B; Rzhaninova, A A; Bol'shakova, G B; Grigor'yan, A S

    2010-10-01

    We performed a comparative study of reparative osteogenesis in rabbits with experimental critical defects of the parietal bones after implantation of commercial osteoinductive materials "Biomatrix", "Osteomatrix", "BioOss" in combination with platelet-rich plasma and transplantation of a tissue-engineering construct on the basis of autogenic multipotent stromal cells from the adipose tissue predifferentiated in osteogenic direction. It was found that experimental reparative osteogenesis is insufficiently stimulated by implantation materials and full-thickness trepanation holes were not completely closed. After transplantation of the studied tissue-engineering construct, the defect was filled with full-length bone regenerate (in the center of the regenerate and from the maternal bone) in contrast to control and reference groups, where the bone tissue was formed only on the side of the maternal bone. On day 120 after transplantation of the tissue-engineering construct, the percent of newly-formed bone tissue in the regenerate was 24% (the total percent of bone tissue in the regenerate was 39%), which attested to active incomplete regenerative process in contrast to control and reference groups. Thus, the study demonstrated effective regeneration of the critical defects of the parietal bones in rabbits 120 days after transplantation of the tissue-engineering construct in contrast to commercial osteoplastic materials for directed bone regeneration.

  5. A novel bioprinting method and system for forming hybrid tissue engineering constructs.

    Science.gov (United States)

    Shanjani, Y; Pan, C C; Elomaa, L; Yang, Y

    2015-12-18

    Three dimensional (3D) bioprinting is a promising approach to form tissue engineering constructs (TECs) via positioning biomaterials, growth factors, and cells with controlled spatial distribution due to its layer-by-layer manufacturing nature. Hybrid TECs composed of relatively rigid porous scaffolds for structural and mechanical integrity and soft hydrogels for cell- and growth factor-loading have a tremendous potential to tissue regeneration under mechanical loading. However, despite excessive progress in the field, the current 3D bioprinting techniques and systems fall short in integration of such soft and rigid multifunctional components. Here we present a novel 3D hybrid bioprinting technology (Hybprinter) and its capability enabling integration of soft and rigid components for TECs. Hybprinter employs digital light processing-based stereolithography (DLP-SLA) and molten material extrusion techniques for soft and rigid materials, respectively. In this study, poly-ethylene glycol diacrylate (PEGDA) and poly-(ε-caprolactone) (PCL) were used as a model material for soft hydrogel and rigid scaffold, respectively. It was shown that geometrical accuracy, swelling ratio and mechanical properties of the hydrogel component can be tailored by DLP-SLA module. We have demonstrated the printability of variety of complex hybrid construct designs using Hybprinter technology and characterized the mechanical properties and functionality of such constructs. The compressive mechanical stiffness of a hybrid construct (90% hydrogel) was significantly higher than hydrogel itself (∼6 MPa versus 100 kPa). In addition, viability of cells incorporated within the bioprinted hybrid constructs was determined approximately 90%. Furthermore, a functionality of a hybrid construct composed of porous scaffold with an embedded hydrogel conduit was characterized for vascularized tissue engineering applications. High material diffusion and high cell viability in about 2.5 mm distance

  6. [Construction and evaluation of the tissue engineered nerve of bFGF-PLGA sustained release microspheres].

    Science.gov (United States)

    Wang, Guanglin; Lin, Wei; Gao, Weiqiang; Xiao, Yuhua; Dong, Changchao

    2008-12-01

    To study the outcomes of nerve defect repair with the tissue engineered nerve, which is composed of the complex of SCs, 30% ECM gel, bFGF-PLGA sustained release microspheres, PLGA microfilaments and permeable poly (D, L-lactic acid) (PDLLA) catheters. SCs were cultured and purified from the sciatic nerves of 1-day-old neonatal SD rats. The 1st passage cells were compounded with bFGF-PLGA sustained release microspheres and ECM gel, and then were injected into permeable PDLLA catheters with PLGA microfilaments inside. In this way, the tissue engineered nerve was constructed. Sixty SD rats were included. The model of 15-mm sciatic nerve defects was made, and then the rats were randomly divided into 5 groups, with 12 rats in each. In group A, autograft was adopted. In group B, the blank PDLLA catheters with PBS inside were used. In group C, PDLLA catheters, with PLGA microfilaments and 30% ECM gel inside, were used. In group D, PDLLA catheters, with PLGA microfilaments, SCs and 30% ECM gel inside, were used. In group E, the tissue engineered nerve was applied. After the operation, observation was made for general conditions of the rats. The sciatic function index (SFI) analysis was performed at 12, 16, 20 and 24 weeks after the operation, respectively. Electrophysiological detection and histological observation were performed at 12 and 24 weeks after the operation, respectively. All rats survived to the end of the experiment. At 12 and 16 weeks after the operation, group E was significantly different from group B in SFI (P fibers in group E were significantly differents from those in groups A, B and C (P fibers in group E were smaller than those in group A (P fibers in group E was significantly different from those in groups A, B, C (P fibers in group E were bigger than those in groups B and C (P < 0.05). The tissue engineered nerve with the complex of SCs, ECM gel, bFGF-PLGA sustained release microspheres, PLGA microfilaments and permeable PDLLA catheters promote

  7. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications

    International Nuclear Information System (INIS)

    Xu Tao; Binder, Kyle W; Albanna, Mohammad Z; Dice, Dennis; Zhao Weixin; Yoo, James J; Atala, Anthony

    2013-01-01

    Bioprinting is an emerging technique used to fabricate viable, 3D tissue constructs through the precise deposition of cells and hydrogels in a layer-by-layer fashion. Despite the ability to mimic the native properties of tissue, printed 3D constructs that are composed of naturally-derived biomaterials still lack structural integrity and adequate mechanical properties for use in vivo, thus limiting their development for use in load-bearing tissue engineering applications, such as cartilage. Fabrication of viable constructs using a novel multi-head deposition system provides the ability to combine synthetic polymers, which have higher mechanical strength than natural materials, with the favorable environment for cell growth provided by traditional naturally-derived hydrogels. However, the complexity and high cost associated with constructing the required robotic system hamper the widespread application of this approach. Moreover, the scaffolds fabricated by these robotic systems often lack flexibility, which further restrict their applications. To address these limitations, advanced fabrication techniques are necessary to generate complex constructs with controlled architectures and adequate mechanical properties. In this study, we describe the construction of a hybrid inkjet printing/electrospinning system that can be used to fabricate viable tissues for cartilage tissue engineering applications. Electrospinning of polycaprolactone fibers was alternated with inkjet printing of rabbit elastic chondrocytes suspended in a fibrin–collagen hydrogel in order to fabricate a five-layer tissue construct of 1 mm thickness. The chondrocytes survived within the printed hybrid construct with more than 80% viability one week after printing. In addition, the cells proliferated and maintained their basic biological properties within the printed layered constructs. Furthermore, the fabricated constructs formed cartilage-like tissues both in vitro and in vivo as evidenced by the

  8. Construction and evaluation of urinary bladder bioreactor for urologic tissue-engineering purposes.

    LENUS (Irish Health Repository)

    Davis, Niall F

    2012-01-31

    OBJECTIVE: To design and construct a urinary bladder bioreactor for urologic tissue-engineering purposes and to compare the viability and proliferative activity of cell-seeded extracellular matrix scaffolds cultured in the bioreactor with conventional static growth conditions. MATERIALS AND METHODS: A urinary bladder bioreactor was designed and constructed to replicate physiologic bladder dynamics. The bioreactor mimicked the filling pressures of the human bladder by way of a cyclical low-delivery pressure regulator. In addition, cell growth was evaluated by culturing human urothelial cells (UCs) on porcine extracellular matrix scaffolds in the bioreactor and in static growth conditions for 5 consecutive days. The attachment, viability, and proliferative potential were assessed and compared with quantitative viability indicators and by fluorescent markers for intracellular esterase activity and plasma membrane integrity. Scaffold integrity was characterized with scanning electron microscopy and 4\\

  9. Construction of tissue-engineered small-diameter vascular grafts in fibrin scaffolds in 30 days.

    Science.gov (United States)

    Gui, Liqiong; Boyle, Michael J; Kamin, Yishai M; Huang, Angela H; Starcher, Barry C; Miller, Cheryl A; Vishnevetsky, Michael J; Niklason, Laura E

    2014-05-01

    Tissue-engineered small-diameter vascular grafts have been developed as a promising alternative to native veins or arteries for replacement therapy. However, there is still a crucial need to improve the current approaches to render the tissue-engineered blood vessels more favorable for clinical applications. A completely biological blood vessel (3-mm inner diameter) was constructed by culturing a 50:50 mixture of bovine smooth muscle cells (SMCs) with neonatal human dermal fibroblasts in fibrin gels. After 30 days of culture under pulsatile stretching, the engineered blood vessels demonstrated an average burst pressure of 913.3±150.1 mmHg (n=6), a suture retention (53.3±15.4 g) that is suitable for implantation, and a compliance (3.1%±2.5% per 100 mmHg) that is comparable to native vessels. These engineered grafts contained circumferentially aligned collagen fibers, microfibrils and elastic fibers, and differentiated SMCs, mimicking a native artery. These promising mechanical and biochemical properties were achieved in a very short culture time of 30 days, suggesting the potential of co-culturing SMCs with fibroblasts in fibrin gels to generate functional small-diameter vascular grafts for vascular reconstruction surgery.

  10. A new construction technique for tissue-engineered heart valves using the self-assembly method.

    Science.gov (United States)

    Tremblay, Catherine; Ruel, Jean; Bourget, Jean-Michel; Laterreur, Véronique; Vallières, Karine; Tondreau, Maxime Y; Lacroix, Dan; Germain, Lucie; Auger, François A

    2014-11-01

    Tissue engineering appears as a promising option to create new heart valve substitutes able to overcome the serious drawbacks encountered with mechanical substitutes or tissue valves. The objective of this article is to present the construction method of a new entirely biological stentless aortic valve using the self-assembly method and also a first assessment of its behavior in a bioreactor when exposed to a pulsatile flow. A thick tissue was created by stacking several fibroblast sheets produced with the self-assembly technique. Different sets of custom-made templates were designed to confer to the thick tissue a three-dimensional (3D) shape similar to that of a native aortic valve. The construction of the valve was divided in two sequential steps. The first step was the installation of the thick tissue in a flat preshaping template followed by a 4-week maturation period. The second step was the actual cylindrical 3D forming of the valve. The microscopic tissue structure was assessed using histological cross sections stained with Masson's Trichrome and Picrosirius Red. The thick tissue remained uniformly populated with cells throughout the construction steps and the dense extracellular matrix presented corrugated fibers of collagen. This first prototype of tissue-engineered heart valve was installed in a bioreactor to assess its capacity to sustain a light pulsatile flow at a frequency of 0.5 Hz. Under the light pulsed flow, it was observed that the leaflets opened and closed according to the flow variations. This study demonstrates that the self-assembly method is a viable option for the construction of complex 3D shapes, such as heart valves, with an entirely biological material.

  11. PROSPECTS OF APPLICATION OF TISSUE-ENGINEERED PANCREATIC CONSTRUCTS IN THE TREATMENT OF TYPE 1 DIABETES

    Directory of Open Access Journals (Sweden)

    G. N. Skaletskaya

    2016-01-01

    Full Text Available Allotransplantation of pancreatic islets remains the most effective method of treatment of diabetes mellitus type 1 being capable under combination of favorable conditions (suffi cient number of isolated islets, effective combination of immunosuppressive drugs to reach the recipients’ insulin independence for several years. However, the overwhelming shortage of donor pancreas and limited post-transplantation islet survival do not allow increasing the number of such transplants and their effectiveness. This review presents a critical analysis of the work done by Russian and foreign authors onto creation of tissue-engineered pancreatic constructs that may lead to the resolution of the three main pancreatic islet transplantation issues: 1 lack of donor material; 2 necessity of immunosuppressive therapy; 3 limited survival and functional activity of the islet.

  12. Monitoring Bone Tissue Engineered (BTE) Constructs Based on the Shifting Metabolism of Differentiating Stem Cells.

    Science.gov (United States)

    Simmons, Aaron D; Sikavitsas, Vassilios I

    2018-01-01

    Ever-increasing demand for bone grafts necessitates the realization of clinical implementation of bone tissue engineered constructs. The predominant hurdle to implementation remains to be securing FDA approval, based on the lack of viable methods for the rigorous monitoring of said constructs. The study presented herein details a method for such monitoring based on the shifting metabolism of mesenchymal stem cells (MSCs) as they differentiate into osteoblasts. To that end, rat MSCs seeded on 85% porous spunbonded poly(L-lactic acid) scaffolds were cultured in flow perfusion bioreactors with baseline or osteoinductive media, and levels of key physio-metabolic markers (oxygen, glucose, osteoprotegerin, and osteocalcin) were monitored throughout culture. Comparison of these non-destructively obtained values and current standard destructive analyses demonstrated key trends useful for the concurrent real-time monitoring of construct cellularity and maturation. Principle among these is the elucidation of the ratio of the rates of oxygen uptake to glucose consumption as a powerful quality marker. This ratio, supported on a physiological basis, has been shown herein to be reliable in the determination of both construct maturation (defined as osteoblastic differentiation and accompanying mineralization) and construct cellularity. Supplementary monitoring of OPG and OCN are shown to provide further validation of such metrics.

  13. Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

    Science.gov (United States)

    Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

    2014-10-01

    Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

  14. Nanostructured 3D constructs based on chitosan and chondroitin sulphate multilayers for cartilage tissue engineering.

    Directory of Open Access Journals (Sweden)

    Joana M Silva

    Full Text Available Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT and chondroitin sulphate (CS on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH. The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs.

  15. Nanostructured 3D constructs based on chitosan and chondroitin sulphate multilayers for cartilage tissue engineering.

    Science.gov (United States)

    Silva, Joana M; Georgi, Nicole; Costa, Rui; Sher, Praveen; Reis, Rui L; Van Blitterswijk, Clemens A; Karperien, Marcel; Mano, João F

    2013-01-01

    Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH). The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA) showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs) up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM) formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs.

  16. Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs.

    Science.gov (United States)

    Eweida, Ahmad; Fathi, Ibrahim; Eltawila, Ahmed M; Elsherif, Ahmad M; Elkerm, Yasser; Harhaus, Leila; Kneser, Ulrich; Sakr, Mahmoud F

    2018-02-01

     Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.  The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.  The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Tissue engineering

    CERN Document Server

    Fisher, John P; Bronzino, Joseph D

    2007-01-01

    Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

  18. Hydrogels for lung tissue engineering: Biomechanical properties of thin collagen-elastin constructs.

    Science.gov (United States)

    Dunphy, Siobhán E; Bratt, Jessica A J; Akram, Khondoker M; Forsyth, Nicholas R; El Haj, Alicia J

    2014-10-01

    In this study, collagen-elastin constructs were prepared with the aim of producing a material capable of mimicking the mechanical properties of a single alveolar wall. Collagen has been used in a wide range of tissue engineering applications; however, due to its low mechanical properties its use is limited to non load-bearing applications without further manipulation using methods such as cross-linking or mechanical compression. Here, it was hypothesised that the addition of soluble elastin to a collagen hydrogel could improve its mechanical properties. Hydrogels made from collagen only and collagen plus varying amounts elastin were prepared. Young׳s modulus of each membrane was measured using the combination of a non-destructive indentation and a theoretical model previously described. An increase in Young׳s modulus was observed with increasing concentration of elastin. The use of non-destructive indentation allowed for online monitoring of the elastic moduli of cell-seeded constructs over 8 days. The addition of lung fibroblasts into the membrane increased the stiffness of the hydrogels further and cell-seeded collagen hydrogels were found to have a stiffness equal to the theoretical value for a single alveolar wall (≈5kPa). Through provision of some of the native extracellular matrix components of the lung parenchyma these scaffolds may be able to provide an initial building block toward the regeneration of new functional lung tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Proteomic profiling of tissue-engineered blood vessel walls constructed by adipose-derived stem cells.

    Science.gov (United States)

    Wang, Chen; Guo, Fangfang; Zhou, Heng; Zhang, Yun; Xiao, Zhigang; Cui, Lei

    2013-02-01

    Adipose-derived stem cells (ASCs) can differentiate into smooth muscle cells and have been engineered into elastic small diameter blood vessel walls in vitro. However, the mechanisms involved in the development of three-dimensional (3D) vascular tissue remain poorly understood. The present study analyzed protein expression profiles of engineered blood vessel walls constructed by human ASCs using methods of two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS). These results were compared to normal arterial walls. A total of 1701±15 and 1265±26 protein spots from normal and engineered blood vessel wall extractions were detected by 2DE, respectively. A total of 20 spots with at least 2.0-fold changes in expression were identified, and 38 differently expressed proteins were identified by 2D electrophoresis and ion trap MS. These proteins were classified into seven functional categories: cellular organization, energy, signaling pathway, enzyme, anchored protein, cell apoptosis/defense, and others. These results demonstrated that 2DE, followed by ion trap MS, could be successfully utilized to characterize the proteome of vascular tissue, including tissue-engineered vessels. The method could also be employed to achieve a better understanding of differentiated smooth muscle protein expression in vitro. These results provide a basis for comparative studies of protein expression in vascular smooth muscles of different origin and could provide a better understanding of the mechanisms of action needed for constructing blood vessels that exhibit properties consistent with normal blood vessels.

  20. Tissue-engineered bone constructed in a bioreactor for repairing critical-sized bone defects in sheep.

    Science.gov (United States)

    Li, Deqiang; Li, Ming; Liu, Peilai; Zhang, Yuankai; Lu, Jianxi; Li, Jianmin

    2014-11-01

    Repair of bone defects, particularly critical-sized bone defects, is a considerable challenge in orthopaedics. Tissue-engineered bones provide an effective approach. However, previous studies mainly focused on the repair of bone defects in small animals. For better clinical application, repairing critical-sized bone defects in large animals must be studied. This study investigated the effect of a tissue-engineered bone for repairing critical-sized bone defect in sheep. A tissue-engineered bone was constructed by culturing bone marrow mesenchymal-stem-cell-derived osteoblast cells seeded in a porous β-tricalcium phosphate ceramic (β-TCP) scaffold in a perfusion bioreactor. A critical-sized bone defect in sheep was repaired with the tissue-engineered bone. At the eighth and 16th week after the implantation of the tissue-engineered bone, X-ray examination and histological analysis were performed to evaluate the defect. The bone defect with only the β-TCP scaffold served as the control. X-ray showed that the bone defect was successfully repaired 16 weeks after implantation of the tissue-engineered bone; histological sections showed that a sufficient volume of new bones formed in β-TCP 16 weeks after implantation. Eight and 16 weeks after implantation, the volume of new bones that formed in the tissue-engineered bone group was more than that in the β-TCP scaffold group (P bone improved osteogenesis in vivo and enhanced the ability to repair critical-sized bone defects in large animals.

  1. Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations.

    Science.gov (United States)

    Wang, Bo; Wang, Guangjun; To, Filip; Butler, J Ryan; Claude, Andrew; McLaughlin, Ronald M; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

    2013-09-03

    Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that after 2 days of culturing with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed a cardiomyocyte-like phenotype by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2 days of bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2 day and 4 day tissue constructs were comparable to those of the tissue constructs produced by stirring reseeding followed by 2 weeks of static culturing, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.

  2. An impedance method for spatial sensing of 3D cell constructs – towards applications in tissue engineering

    DEFF Research Database (Denmark)

    Canali, Chiara; Mazzoni, Chiara; Larsen, Layla Bashir

    2015-01-01

    ) cells were encapsulated in gelatin to form artificial 3D cell constructs and detected when placed in different positions inside large gelatin scaffolds. Taken together, these results open new perspectives for impedance-based sensing technologies for non-invasive monitoring in tissue engineering...

  3. 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.

  4. Fibrin Gels Exhibit Improved Biological, Structural, and Mechanical Properties Compared with Collagen Gels in Cell-Based Tendon Tissue-Engineered Constructs

    Science.gov (United States)

    Dyment, Nathaniel A.; Lu, Yinhui; Rao, Marepalli; Shearn, Jason T.; Rowe, David W.; Kadler, Karl E.; Butler, David L.

    2015-01-01

    The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair. PMID:25266738

  5. Effects of a combined mechanical stimulation protocol: Value for skeletal muscle tissue engineering

    NARCIS (Netherlands)

    Boonen, K.J.M.; Langelaan, M.L.P.; Polak, R.B.; Schaft, van der D.W.J.; Baaijens, F.P.T.; Post, M.J.

    2010-01-01

    Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications for regenerative medicine, in vitro physiological model systems, and in vitro meat production. Besides conventional biochemical cues to promote muscle tissue maturation in vitro, biophysical stimuli

  6. Application of electrical stimulation for functional tissue engineering in vitro and in vivo

    Science.gov (United States)

    Park, Hyoungshin (Inventor); Freed, Lisa (Inventor); Vunjak-Novakovic, Gordana (Inventor); Langer, Robert (Inventor); Radisic, Milica (Inventor)

    2013-01-01

    The present invention provides new methods for the in vitro preparation of bioartificial tissue equivalents and their enhanced integration after implantation in vivo. These methods include submitting a tissue construct to a biomimetic electrical stimulation during cultivation in vitro to improve its structural and functional properties, and/or in vivo, after implantation of the construct, to enhance its integration with host tissue and increase cell survival and functionality. The inventive methods are particularly useful for the production of bioartificial equivalents and/or the repair and replacement of native tissues that contain electrically excitable cells and are subject to electrical stimulation in vivo, such as, for example, cardiac muscle tissue, striated skeletal muscle tissue, smooth muscle tissue, bone, vasculature, and nerve tissue.

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

    Science.gov (United States)

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

    2017-07-01

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

  8. CRYOPRESERVATION STRATEGY FOR TISSUE ENGINEERING CONSTRUCTS CONSISTING OF HUMAN MESENHYMAL STEM CELLS AND HYDROGEL BIOMATERIALS.

    Science.gov (United States)

    Wu, Y; Wen, F; Gouk, S S; Lee, E H; Kuleshova, L

    2015-01-01

    The development of vitrification strategy for cell-biomaterial constructs, particularly biologically inspired nanoscale materials and hydrogels mimicking the in vivo environment is an active area. A cryopreservation strategy mimicking the in vivo environment for cell-hydrogel constructs may enhance cell proliferation and biological function. To demonstrate the efficacy of vitrification as a platform technology involving tissue engineering and human mesenchymal stem cells (hMSCs). Microcarriers made from alginate coated with chitosan and collagen are used. Conventional freezing and vitrification were compared. The vitrification strategy includes 10 min step-wise exposure to a vitrification solution (40% v/v EG, 0.6M sucrose) and immersion into liquid nitrogen. Confocal imaging of live/dead staining of hMSCs cultured on the surface of microcarriers demonstrated that vitrified cells had excellent appearance and prolonged spindle shape morphology. The proliferation ability of post-vitrified cells arbitrated to protein Ki-67 gene expression was not significantly different in comparison to untreated control, while that of post-freezing cells was almost lost. The ability of hMSCs cultured on the surface of microcarriers to proliferate has been not affected by vitrification and it was significantly better after vitrification than after conventional freezing during continuous culture. Collagen II related mRNA expression by 4 weeks post-vitrification and post-freezing showed that ability to differentiate into cartilage was sustained during vitrification and reduced during conventional freezing. No significant difference was found between control and vitrification groups only. Vitrification strategy coupled with advances in hMSC-expansion platform that completely preserves the ability of stem cells to proliferate and subsequently differentiate allows not only to reach a critical cell number, but also demonstrate prospects for effective utilization and transportation of cells

  9. [Experimental study of tissue engineered cartilage construction using oriented scaffold combined with bone marrow mesenchymal stem cells in vivo].

    Science.gov (United States)

    Duan, Wei; Da, Hu; Wang, Wentao; Lü, Shangjun; Xiong, Zhuo; Liu, Jian

    2013-05-01

    To investigate the feasibility of fabricating an oriented scaffold combined with chondrogenic-induced bone marrow mesenchymal stem cells (BMSCs) for enhancement of the biomechanical property of tissue engineered cartilage in vivo. Temperature gradient-guided thermal-induced phase separation was used to fabricate an oriented cartilage extracellular matrix-derived scaffold composed of microtubules arranged in parallel in vertical section. No-oriented scaffold was fabricated by simple freeze-drying. Mechanical property of oriented and non-oriented scaffold was determined by measurement of compressive modulus. Oriented and non-oriented scaffolds were seeded with chondrogenic-induced BMSCs, which were obtained from the New Zealand white rabbits. Proliferation, morphological characteristics, and the distribution of the cells on the scaffolds were analyzed by MTT assay and scanning electron microscope. Then cell-scaffold composites were implanted subcutaneously in the dorsa of nude mice. At 2 and 4 weeks after implantation, the samples were harvested for evaluating biochemical, histological, and biomechanical properties. The compressive modulus of oriented scaffold was significantly higher than that of non-oriented scaffold (t=201.099, P=0.000). The cell proliferation on the oriented scaffold was significantly higher than that on the non-oriented scaffold from 3 to 9 days (P fibers with chondrocyte-like cells on the oriented-structure constructs. Total DNA, glycosaminoglycan (GAG), and collagen contents increased with time, and no significant difference was found between 2 groups (P > 0.05). The compressive modulus of the oriented tissue engineered cartilage was significantly higher than that of the non-oriented tissue engineered cartilage at 2 and 4 weeks after implantation (P < 0.05). Total DNA, GAG, collagen contents, and compressive modulus in the 2 tissue engineered cartilages were significantly lower than those in normal cartilage (P < 0.05). Oriented extracellular

  10. The design and construction of an electrohydrodynamic cartesian robot for the preparation of tissue engineering constructs.

    Directory of Open Access Journals (Sweden)

    Shaikh Hafeez Hashimdeen

    Full Text Available In this work we bring together replicating rapid prototyping technology with electrohydrodynamic phenomena to develop a device with the ability to build structures in three-dimensions while simultaneously affording the user a degree of designing versatility and ease that is not seen in conventional computer numerically controlled machines. An attempt at reproducing an actual human ear using polycaprolactone was pursued to validate the hardware. Five different polycaprolactone solution concentrations between 7-15 wt% were used and printing was performed at applied voltages that ranged from 1 to 6 kV and at flow rates from 5 µl/min to 60 µl/min. The corresponding geometrical and aesthetic features of the printed constructs were studied to determine the effectiveness of the device. The 15 wt% concentration at 60 µl/min under an applied electric field of 6 kV was identified as the best operating parameters to work with.

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

    NARCIS (Netherlands)

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

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

  12. The effect of mechanical extension stimulation combined with epithelial cell sorting on outcomes of implanted tissue-engineered muscular urethras.

    Science.gov (United States)

    Fu, Qiang; Deng, Chen-Liang; Zhao, Ren-Yan; Wang, Ying; Cao, Yilin

    2014-01-01

    Urethral defects are common and frequent disorders and are difficult to treat. Simple natural or synthetic materials do not provide a satisfactory curative solution for long urethral defects, and urethroplasty with large areas of autologous tissues is limited and might interfere with wound healing. In this study, adipose-derived stem cells were used. These cells can be derived from a wide range of sources, have extensive expansion capability, and were combined with oral mucosal epithelial cells to solve the problem of finding seeding cell sources for producing the tissue-engineered urethras. We also used the synthetic biodegradable polymer poly-glycolic acid (PGA) as a scaffold material to overcome issues such as potential pathogen infections derived from natural materials (such as de-vascular stents or animal-derived collagen) and differing diameters. Furthermore, we used a bioreactor to construct a tissue-engineered epithelial-muscular lumen with a double-layer structure (the epithelial lining and the muscle layer). Through these steps, we used an epithelial-muscular lumen built in vitro to repair defects in a canine urethral defect model (1 cm). Canine urethral reconstruction was successfully achieved based on image analysis and histological techniques at different time points. This study provides a basis for the clinical application of tissue engineering of an epithelial-muscular lumen. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve.

    Science.gov (United States)

    Huang, Lanfeng; Li, Rui; Liu, Wanguo; Dai, Jin; Du, Zhenwu; Wang, Xiaonan; Ma, Jianchao; Zhao, Jinsong

    2014-07-15

    Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, but cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhesion stage. Moreover, seeded cells were distributed throughout the material.

  14. Bioactive glass 13-93 as a subchondral substrate for tissue-engineered osteochondral constructs: a pilot study.

    Science.gov (United States)

    Jayabalan, Prakash; Tan, Andrea R; Rahaman, Mohammed N; Bal, B Sonny; Hung, Clark T; Cook, James L

    2011-10-01

    Replacement of diseased areas of the joint with tissue-engineered osteochondral grafts has shown potential in the treatment of osteoarthritis. Bioactive glasses are candidates for the osseous analog of these grafts. (1) Does Bioactive Glass 13-93 (BG 13-93) as a subchondral substrate improve collagen and glycosaminoglycan production in a tissue-engineered cartilage layer? (2) Does BG 13-93 as a culture medium supplement increase the collagen and glycosaminoglycan production and improve the mechanical properties in a tissue-engineered cartilage layer? In Study 1, bioactive glass samples (n = 4) were attached to a chondrocyte-seeded agarose layer to form an osteochondral construct, cultured for 6 weeks, and compared to controls. In Study 2, bioactive glass samples (n = 5) were cocultured with cell-seeded agarose for 6 weeks. The cell-seeded agarose layer was exposed to BG 13-93 either continuously or for the first or last 2 weeks in culture or had no exposure. Osteochondral constructs with a BG 13-93 base had improved glycosaminoglycan deposition but less collagen II content. Agarose scaffolds that had a temporal exposure to BG 13-93 within the culture medium had improved mechanical and biochemical properties compared to continuous or no exposure. When used as a subchondral substrate, BG 13-93 did not improve biochemical properties compared to controls. However, as a culture medium supplement, BG 13-93 improved the biochemical and mechanical properties of a tissue-engineered cartilage layer. BG 13-93 may not be suitable in osteochondral constructs but could have potential as a medium supplement for neocartilage formation.

  15. Mechanical stimulation to stimulate formation of a physiological collagen architecture in tissue-engineered cartilage; a numerical study

    NARCIS (Netherlands)

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

    2011-01-01

    The load-bearing capacity of today's tissue-engineered (TE) cartilage is insufficient. The arcade-like collagen network in native cartilage plays an important role in its load-bearing properties. Inducing the formation of such collagen architecture in engineered cartilage can, therefore, enhance

  16. The development of the collagen fibre network in tissue-engineered cartilage constructs in vivo. Engineered cartilage reorganises fibre network

    Directory of Open Access Journals (Sweden)

    H Paetzold

    2012-04-01

    Full Text Available For long term durability of tissue-engineered cartilage implanted in vivo, the development of the collagen fibre network orientation is essential as well as the distribution of collagen, since expanded chondrocytes are known to synthesise collagen type I. Typically, these properties differ strongly between native and tissue-engineered cartilage. Nonetheless, the clinical results of a pilot study with implanted tissue-engineered cartilage in pigs were surprisingly good. The purpose of this study was therefore to analyse if the structure and composition of the artificial cartilage tissue changes in the first 52 weeks after implantation. Thus, collagen network orientation and collagen type distribution in tissue-engineered cartilage-carrier-constructs implanted in the knee joints of Göttinger minipigs for 2, 26 or 52 weeks have been further investigated by processing digitised microscopy images of histological sections. The comparison to native cartilage demonstrated that fibre orientation over the cartilage depth has a clear tendency towards native cartilage with increasing time of implantation. After 2 weeks, the collagen fibres of the superficial zone were oriented parallel to the articular surface with little anisotropy present in the middle and deep zones. Overall, fibre orientation and collagen distribution within the implants were less homogenous than in native cartilage tissue. Despite a relatively low number of specimens, the consistent observation of a continuous approximation to native tissue is very promising and suggests that it may not be necessary to engineer the perfect tissue for implantation but rather to provide an intermediate solution to help the body to heal itself.

  17. Functional evaluation of artificial skeletal muscle tissue constructs fabricated by a magnetic force-based tissue engineering technique.

    Science.gov (United States)

    Yamamoto, Yasunori; Ito, Akira; Fujita, Hideaki; Nagamori, Eiji; Kawabe, Yoshinori; Kamihira, Masamichi

    2011-01-01

    Skeletal muscle tissue engineering is currently applied in a variety of research fields, including regenerative medicine, drug screening, and bioactuator development, all of which require the fabrication of biomimic and functional skeletal muscle tissues. In the present study, magnetite cationic liposomes were used to magnetically label C2C12 myoblast cells for the construction of three-dimensional artificial skeletal muscle tissues by an applied magnetic force. Skeletal muscle functions, such as biochemical and contractile properties, were evaluated for the artificial tissue constructs. Histological studies revealed that elongated and multinucleated myotubes were observed within the tissue. Expression of muscle-specific markers, such as myogenin, myosin heavy chain and tropomyosin, were detected in the tissue constructs by western blot analysis. Further, creatine kinase activity increased during differentiation. In response to electric pulses, the artificial tissue constructs contracted to generate a physical force (the maximum twitch force, 33.2 μN [1.06 mN/mm2]). Rheobase and chronaxie of the tissue were determined as 4.45 V and 0.72 ms, respectively. These results indicate that the artificial skeletal muscle tissue constructs fabricated in this study were physiologically functional and the data obtained for the evaluation of their functional properties may provide useful information for future skeletal muscle tissue engineering studies.

  18. Engraftment of Prevascularized, Tissue Engineered Constructs in a Novel Rabbit Segmental Bone Defect Model

    Directory of Open Access Journals (Sweden)

    Alexandre Kaempfen

    2015-06-01

    Full Text Available The gold standard treatment of large segmental bone defects is autologous bone transfer, which suffers from low availability and additional morbidity. Tissue engineered bone able to engraft orthotopically and a suitable animal model for pre-clinical testing are direly needed. This study aimed to evaluate engraftment of tissue-engineered bone with different prevascularization strategies in a novel segmental defect model in the rabbit humerus. Decellularized bone matrix (Tutobone seeded with bone marrow mesenchymal stromal cells was used directly orthotopically or combined with a vessel and inserted immediately (1-step or only after six weeks of subcutaneous “incubation” (2-step. After 12 weeks, histological and radiological assessment was performed. Variable callus formation was observed. No bone formation or remodeling of the graft through TRAP positive osteoclasts could be detected. Instead, a variable amount of necrotic tissue formed. Although necrotic area correlated significantly with amount of vessels and the 2-step strategy had significantly more vessels than the 1-step strategy, no significant reduction of necrotic area was found. In conclusion, the animal model developed here represents a highly challenging situation, for which a suitable engineered bone graft with better prevascularization, better resorbability and higher osteogenicity has yet to be developed.

  19. Skin equivalent tissue-engineered construct: co-cultured fibroblasts/ keratinocytes on 3D matrices of sericin hope cocoons.

    Directory of Open Access Journals (Sweden)

    Sunita Nayak

    Full Text Available The development of effective and alternative tissue-engineered skin replacements to autografts, allografts and xenografts has became a clinical requirement due to the problems related to source of donor tissue and the perceived risk of disease transmission. In the present study 3D tissue engineered construct of sericin is developed using co-culture of keratinocytes on the upper surface of the fabricated matrices and with fibroblasts on lower surface. Sericin is obtained from "Sericin Hope" silkworm of Bombyx mori mutant and is extracted from cocoons by autoclave. Porous sericin matrices are prepared by freeze dried method using genipin as crosslinker. The matrices are characterized biochemically and biophysically. The cell proliferation and viability of co-cultured fibroblasts and keratinocytes on matrices for at least 28 days are observed by live/dead assay, Alamar blue assay, and by dual fluorescent staining. The growth of the fibroblasts and keratinocytes in co-culture is correlated with the expression level of TGF-β, b-FGF and IL-8 in the cultured supernatants by enzyme-linked immunosorbent assay. The histological analysis further demonstrates a multi-layered stratified epidermal layer of uninhibited keratinocytes in co-cultured constructs. Presence of involucrin, collagen IV and the fibroblast surface protein in immuno-histochemical stained sections of co-cultured matrices indicates the significance of paracrine signaling between keratinocytes and fibroblasts in the expression of extracellular matrix protein for dermal repair. No significant amount of pro inflammatory cytokines (TNF-α, IL-1β and nitric oxide production are evidenced when macrophages grown on the sericin matrices. The results all together depict the potentiality of sericin 3D matrices as skin equivalent tissue engineered construct in wound repair.

  20. Tissue-engineered cartilaginous constructs for the treatment of caprine cartilage defects, including distribution of laminin and type IV collagen.

    Science.gov (United States)

    Jeng, Lily; Hsu, Hu-Ping; Spector, Myron

    2013-10-01

    The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration.

  1. Bladder tissue engineering using biocompatible nanofibrous electrospun constructs: feasibility and safety investigation.

    Science.gov (United States)

    Shakhssalim, Nasser; Dehghan, Mohammad Mehdi; Moghadasali, Reza; Soltani, Mohammad Hossein; Shabani, Iman; Soleimani, Masoud

    2012-01-01

    To investigate the feasibility and safety of using biocompatible, nanofibrous electrospun polycaprolactone (PCL) and combination of polylactic acid (PLLA) and PCL mats in a canine model. Plasma-treated electrospun unseeded mats were implanted in three dogs. The first dog was sacrificed after 3 months and the second and third ones after 4 months, and then, the graft was examined macroscopically with subsequent morphological and histochemical evaluation. Both films showed high levels of cell infiltration and tissue formation, but body response to PLLA/PCL mat in comparison to PCL mat was very low. All three implantation models showed the same light microscopic morphology, immunohistochemistry, and scanning electron microscopy results; nevertheless, only the PCL/PLLA model showed favorable clinical results. Based on these data, nanofibrous PLLA/PCL scaffolding could be a suitable material for the bladder tissue engineering; however, it deserves further investigations.

  2. Mechanical evaluation of a tissue-engineered zone of calcification in a bone–hydrogel osteochondral construct

    Science.gov (United States)

    Hollenstein, Jérôme; Terrier, Alexandre; Cory, Esther; Chen, Albert C.; Sah, Robert L.; Pioletti, Dominique P.

    2016-01-01

    The objective of this study was to test the hypothesis that mechanical properties of artificial osteochondral constructs can be improved by a tissue-engineered zone of calcification (teZCC) at the bone–hydrogel interface. Experimental push-off tests were performed on osteochondral constructs with or without a teZCC. In parallel, a numerical model of the osteochondral defect treatment was developed and validated against experimental results. Experimental results showed that the shear strength at the bone–hydrogel interface increased by 100% with the teZCC. Numerical predictions of the osteochondral defect treatment showed that the shear stress at the bone–hydrogel interface was reduced with the teZCC. We conclude that a teZCC in osteochondral constructs can provide two improvements. First, it increases the strength of the bone–hydrogel interface and second, it reduces the stress at this interface. PMID:23706035

  3. Mechanical stimulation of mesenchymal stem cells: Implications for cartilage tissue engineering.

    Science.gov (United States)

    Fahy, Niamh; Alini, Mauro; Stoddart, Martin J

    2018-01-01

    Articular cartilage is a load-bearing tissue playing a crucial mechanical role in diarthrodial joints, facilitating joint articulation, and minimizing wear. The significance of biomechanical stimuli in the development of cartilage and maintenance of chondrocyte phenotype in adult tissues has been well documented. Furthermore, dysregulated loading is associated with cartilage pathology highlighting the importance of mechanical cues in cartilage homeostasis. The repair of damaged articular cartilage resulting from trauma or degenerative joint disease poses a major challenge due to a low intrinsic capacity of cartilage for self-renewal, attributable to its avascular nature. Bone marrow-derived mesenchymal stem cells (MSCs) are considered a promising cell type for cartilage replacement strategies due to their chondrogenic differentiation potential. Chondrogenesis of MSCs is influenced not only by biological factors but also by the environment itself, and various efforts to date have focused on harnessing biomechanics to enhance chondrogenic differentiation of MSCs. Furthermore, recapitulating mechanical cues associated with cartilage development and homeostasis in vivo, may facilitate the development of a cellular phenotype resembling native articular cartilage. The goal of this review is to summarize current literature examining the effect of mechanical cues on cartilage homeostasis, disease, and MSC chondrogenesis. The role of biological factors produced by MSCs in response to mechanical loading will also be examined. An in-depth understanding of the impact of mechanical stimulation on the chondrogenic differentiation of MSCs in terms of endogenous bioactive factor production and signaling pathways involved, may identify therapeutic targets and facilitate the development of more robust strategies for cartilage replacement using MSCs. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:52-63, 2018. © 2017 Orthopaedic Research

  4. 3D Printing of Tissue Engineered Constructs for in vitro Modeling of Disease Progression and Drug Screening

    Science.gov (United States)

    Vanderburgh, Joseph; Sterling, Julie A.

    2016-01-01

    2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D versus 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design (CAD) file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs (TECs) that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs. PMID:27169894

  5. [Preliminary study of constructing tissue-engineered cartilage with the endoskeletal scaffold of HDPE by bone marrow stromal cells].

    Science.gov (United States)

    Zhu, Lie; Jiang, Hua; Zhou, Guang-Dong; Wu, Yu-Jia; Luo, Xu-Song

    2008-09-01

    To explore the feasibility of using a nonreactive, permanent endoskeletal scaffold to create the prothesis in special shape which is covered with tissue-engineered cartilage. Porcine BMSCs and articular chondrocytes were isolated and expanded respectively in vitro. Porcine BMSC of passage 1 in the concentration of 10 x 10(7)/ml were seeded onto a cylinder-shaped PGA (1 mm in thickness)/Medpor (3mm in diameter and 5mm in highness) scaffold as the experimental group. After the cell-scaffold constructs were cultured for 5 days, the primary medium, high-glucose DMEM medium with 10% fetal bovine serum (FBS), was replaced by chondrogenically inductive medium for 4 weeks. BMSCs and chondrocytes of the same concentration were seeded respectively onto the scaffold as the negative control group and the positive control group. After cultured in vitro for 4 weeks, the cell-scaffolds construct were implanted into subcutaneous pockets on the back of nude mice. Four and eight weeks later, the formed cartilage prosthesis were harvested and then evaluated by gross view, histology, immunohistochemistry and glycosamino-glycan (GAG) content. Cells in all groups had fine adhesion to the scaffold and could secrete extracellular matrix. All specimens in experimental group and positive control group formed mature cartilage with collagen II expression.The mature catrtilage wraped HDPE compactly and grown into the gap of HDPE. Mature lacuna structures and metachromatic matrices were also observed in these specimens. GAG contents in experimental group were (5.13 +/- 0.32) mg/g (4 weeks), (5.37 +/- 0.12) mg/g (8 weeks). In contrast, specimens in BMSC group showed mainly fibrous tissue. It indicates that it is feasible to create special shaped tissue-engineering cartilage with the permanent internal support using BMSCs as seed cell.

  6. Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs.

    Science.gov (United States)

    Lee, Whitaik David; Gawri, Rahul; Pilliar, Robert M; Stanford, William L; Kandel, Rita A

    2017-10-15

    Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) acts as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates. However, as CPP degrades, it releases inorganic polyphosphates (polyP) that can inhibit local mineralization, thereby preventing the formation of a ZCC at the interface. Thus, we hypothesize that coating CPP substrate with a layer of hydroxyapatite (HA) might prevent or limit this polyP release. To investigate this we tested both inorganic or organic sol-gel processing methods, asa barrier coating on CPP substrate to inhibit polyP release. Both types of coating supported the formation of ZCC in direct contact with the substrate, however the ZCC appeared more continuous in the tissue formed on the organic HA sol gel coated CPP. Tissues formed on coated substrates accumulated comparable quantities of extracellular matrix and mineral, but tissues formed on organic sol-gel (OSG)-coated substrates accumulated less polyP than tissues formed on inorganic sol-gel (ISG)-coated substrates. Constructs formed with OSG-coated CPP substrates had greater interfacial shear strength than those formed with ISG-coated and non-coated substrates. These results suggest that the OSG coating method can modify the location and distribution of ZCC and can be used to improve the mechanical integrity of tissue-engineered constructs formed on porous CPP substrates. Articular cartilage interfaces with bone through a zone of calcified cartilage. This study describes a method to generate an "osteochondral-like" implant that mimics this

  7. Fabrication of Trabecular Bone-Templated Tissue-Engineered Constructs by 3D Inkjet Printing.

    Science.gov (United States)

    Vanderburgh, Joseph P; Fernando, Shanik J; Merkel, Alyssa R; Sterling, Julie A; Guelcher, Scott A

    2017-11-01

    3D printing enables the creation of scaffolds with precisely controlled morphometric properties for multiple tissue types, including musculoskeletal tissues such as cartilage and bone. Computed tomography (CT) imaging has been combined with 3D printing to fabricate anatomically scaled patient-specific scaffolds for bone regeneration. However, anatomically scaled scaffolds typically lack sufficient resolution to recapitulate the 3D constructs are fabricated via a new micro-CT/3D inkjet printing process. It is shown that this process reproducibly fabricates bone-templated constructs that recapitulate the anatomic site-specific morphometric properties of trabecular bone. A significant correlation is observed between the structure model index (a morphometric parameter related to surface curvature) and the degree of mineralization of human mesenchymal stem cells, with more concave surfaces promoting more extensive osteoblast differentiation and mineralization compared to predominately convex surfaces. These findings highlight the significant effects of trabecular architecture on osteoblast function. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Treatment of Ligament Constructs with Exercise-conditioned Serum: A Translational Tissue Engineering Model.

    Science.gov (United States)

    Lee-Barthel, Ann; Baar, Keith; West, Daniel W D

    2017-06-11

    In vitro experiments are essential to understand biological mechanisms; however, the gap between monolayer tissue culture and human physiology is large, and translation of findings is often poor. Thus, there is ample opportunity for alternative experimental approaches. Here we present an approach in which human cells are isolated from human anterior cruciate ligament tissue remnants, expanded in culture, and used to form engineered ligaments. Exercise alters the biochemical milieu in the blood such that the function of many tissues, organs and bodily processes are improved. In this experiment, ligament construct culture media was supplemented with experimental human serum that has been 'conditioned' by exercise. Thus the intervention is more biologically relevant since an experimental tissue is exposed to the full endogenous biochemical milieu, including binding proteins and adjunct compounds that may be altered in tandem with the activity of an unknown agent of interest. After treatment, engineered ligaments can be analyzed for mechanical function, collagen content, morphology, and cellular biochemistry. Overall, there are four major advantages versus traditional monolayer culture and animal models, of the physiological model of ligament tissue that is presented here. First, ligament constructs are three-dimensional, allowing for mechanical properties (i.e., function) such as ultimate tensile stress, maximal tensile load, and modulus, to be quantified. Second, the enthesis, the interface between boney and sinew elements, can be examined in detail and within functional context. Third, preparing media with post-exercise serum allows for the effects of the exercise-induced biochemical milieu, which is responsible for the wide range of health benefits of exercise, to be investigated in an unbiased manner. Finally, this experimental model advances scientific research in a humane and ethical manner by replacing the use of animals, a core mandate of the National

  9. Preclinical study of mouse pluripotent parthenogenetic embryonic stem cell derivatives for the construction of tissue-engineered skin equivalent.

    Science.gov (United States)

    Rao, Yang; Cui, Jihong; Yin, Lu; Liu, Wei; Liu, Wenguang; Sun, Mei; Yan, Xingrong; Wang, Ling; Chen, Fulin

    2016-10-22

    Embryonic stem cell (ESC) derivatives hold great promise for the construction of tissue-engineered skin equivalents (TESE). However, harvesting of ESCs destroys viable embryos and may lead to political and ethical concerns over their application. In the current study, we directed mouse parthenogenetic embryonic stem cells (pESCs) to differentiate into fibroblasts, constructed TESE, and evaluated its function in vivo. The stemness marker expression and the pluripotent differentiation ability of pESCs were tested. After embryoid body (EB) formation and adherence culture, mesenchymal stem cells (MSCs) were enriched and directed to differentiate into fibroblastic lineage. Characteristics of derived fibroblasts were assessed by quantitative real-time PCR and ELISA. Functional ability of the constructed TESE was tested by a mouse skin defects repair model. Mouse pESCs expressed stemness marker and could form teratoma containing three germ layers. MSCs could be enriched from outgrowths of EBs and directed to differentiate into fibroblastic lineage. These cells express a high level of growth factors including FGF, EGF, VEGF, TGF, PDGF, and IGF1, similar to those of ESC-derived fibroblasts and mouse fibroblasts. Seeded into collagen gels, the fibroblasts derived from pESCs could form TESE. Mouse skin defects could be successfully repaired 15 days after transplantation of TESE constructed by fibroblasts derived from pESCs. pESCs could be induced to differentiate into fibroblastic lineage, which could be applied to the construction of TESE and skin defect repair. Particularly, pESC derivatives avoid the limitations of political and ethical concerns, and provide a promising source for regenerative medicine.

  10. Automatic quantitative micro-computed tomography evaluation of angiogenesis in an axially vascularized tissue-engineered bone construct.

    Science.gov (United States)

    Arkudas, Andreas; Beier, Justus Patrick; Pryymachuk, Galyna; Hoereth, Tobias; Bleiziffer, Oliver; Polykandriotis, Elias; Hess, Andreas; Gulle, Heinz; Horch, Raymund E; Kneser, Ulrich

    2010-12-01

    We invented an automatic observer-independent quantitative method to analyze vascularization using micro-computed tomography (CT) along with three-dimensional (3D) reconstruction in a tissue engineering model. An arteriovenous loop was created in the medial thigh of 30 rats and was placed in a particulated porous hydroxyapatite and beta-tricalcium phosphate matrix, filled with fibrin (10 mg/mL fibrinogen and 2 IU/mL thrombin) without (group A) or with (group B) application of fibrin-gel-immobilized angiogenetic growth factors vascular endothelial growth factor (VEGF¹⁶⁵) and basic fibroblast growth factor (bFGF). The explantation intervals were 2, 4, and 8 weeks. Specimens were investigated by means of micro-CT followed by an automatic 3D analysis, which was correlated to histomorphometrical findings. In both groups, the arteriovenous loop led to generation of dense vascularized connective tissue with differentiated and functional vessels inside the matrix. Quantitative analysis of vascularization using micro-CT showed to be superior to histological analysis. The micro-CT analysis also allows the assessment of different other, more complex vascularization parameters within 3D constructs, demonstrating an early improvement of vascularization by application of fibrin-gel-immobilized VEGF¹⁶⁵ and bFGF. In this study quantitative analysis of vascularization using micro-CT along with 3D reconstruction and automatic analysis exhibit to be a powerful method superior to histological evaluation of cross sections.

  11. 3D bioprinting mesenchymal stem cell-laden construct with core-shell nanospheres for cartilage tissue engineering

    Science.gov (United States)

    Zhu, Wei; Cui, Haitao; Boualam, Benchaa; Masood, Fahed; Flynn, Erin; Rao, Raj D.; Zhang, Zhi-Yong; Zhang, Lijie Grace

    2018-05-01

    Cartilage tissue is prone to degradation and has little capacity for self-healing due to its avascularity. Tissue engineering, which provides artificial scaffolds to repair injured tissues, is a novel and promising strategy for cartilage repair. 3D bioprinting offers even greater potential for repairing degenerative tissue by simultaneously integrating living cells, biomaterials, and biological cues to provide a customized scaffold. With regard to cell selection, mesenchymal stem cells (MSCs) hold great capacity for differentiating into a variety of cell types, including chondrocytes, and could therefore be utilized as a cartilage cell source in 3D bioprinting. In the present study, we utilize a tabletop stereolithography-based 3D bioprinter for a novel cell-laden cartilage tissue construct fabrication. Printable resin is composed of 10% gelatin methacrylate (GelMA) base, various concentrations of polyethylene glycol diacrylate (PEGDA), biocompatible photoinitiator, and transforming growth factor beta 1 (TGF-β1) embedded nanospheres fabricated via a core-shell electrospraying technique. We find that the addition of PEGDA into GelMA hydrogel greatly improves the printing resolution. Compressive testing shows that modulus of the bioprinted scaffolds proportionally increases with the concentrations of PEGDA, while swelling ratio decreases with the increase of PEGDA concentration. Confocal microscopy images illustrate that the cells and nanospheres are evenly distributed throughout the entire bioprinted construct. Cells grown on 5%/10% (PEGDA/GelMA) hydrogel present the highest cell viability and proliferation rate. The TGF-β1 embedded in nanospheres can keep a sustained release up to 21 d and improve chondrogenic differentiation of encapsulated MSCs. The cell-laden bioprinted cartilage constructs with TGF-β1-containing nanospheres is a promising strategy for cartilage regeneration.

  12. Detection of abnormalities in the superficial zone of cartilage repaired using a tissue engineered construct derived from synovial stem cells

    Directory of Open Access Journals (Sweden)

    W Ando

    2012-09-01

    Full Text Available The present study investigated the surface structure and mechanical properties of repair cartilage generated from a tissue engineered construct (TEC derived from synovial mesenchymal stem cells at six months post-implantation compared to those of uninjured cartilage. TEC-mediated repair tissue was cartilaginous with Safranin O staining, and had comparable macro-scale compressive properties with uninjured cartilage. However, morphological assessments revealed that the superficial zone of TEC-mediated tissue was more fibrocartilage-like, in contrast to the middle or deep zones that were more hyaline cartilage-like with Safranin O staining. Histological scoring of the TEC-mediated tissue was significantly lower in the superficial zone than in the middle and deep zones. Scanning electron microscopy showed a thick tangential bundle of collagen fibres at the most superficial layer of uninjured cartilage, while no corresponding structure was detected at the surface of TEC-mediated tissue. Immunohistochemical analysis revealed that PRG4 was localised in the superficial area of uninjured cartilage, as well as the TEC-mediated tissue. Friction testing showed that the lubrication properties of the two tissues was similar, however, micro-indentation analysis revealed that the surface stiffness of the TEC-repair tissue was significantly lower than that of uninjured cartilage. Permeability testing indicated that the TEC-mediated tissue exhibited lower water retaining capacity than did uninjured cartilage, specifically at the superficial zone. Thus, TEC-mediated tissue exhibited compromised mechanical properties at the superficial zone, properties which need improvement in the future for maintenance of long term repair cartilage integrity.

  13. Detection of abnormalities in the superficial zone of cartilage repaired using a tissue engineered construct derived from synovial stem cells.

    Science.gov (United States)

    Ando, Wataru; Fujie, Hiromichi; Moriguchi, Yu; Nansai, Ryosuke; Shimomura, Kazunori; Hart, David A; Yoshikawa, Hideki; Nakamura, Norimasa

    2012-09-28

    The present study investigated the surface structure and mechanical properties of repair cartilage generated from a tissue engineered construct (TEC) derived from synovial mesenchymal stem cells at six months post-implantation compared to those of uninjured cartilage. TEC-mediated repair tissue was cartilaginous with Safranin O staining, and had comparable macro-scale compressive properties with uninjured cartilage. However, morphological assessments revealed that the superficial zone of TEC-mediated tissue was more fibrocartilage-like, in contrast to the middle or deep zones that were more hyaline cartilage-like with Safranin O staining. Histological scoring of the TEC-mediated tissue was significantly lower in the superficial zone than in the middle and deep zones. Scanning electron microscopy showed a thick tangential bundle of collagen fibres at the most superficial layer of uninjured cartilage, while no corresponding structure was detected at the surface of TEC-mediated tissue. Immunohistochemical analysis revealed that PRG4 was localised in the superficial area of uninjured cartilage, as well as the TEC-mediated tissue. Friction testing showed that the lubrication properties of the two tissues was similar, however, micro-indentation analysis revealed that the surface stiffness of the TEC-repair tissue was significantly lower than that of uninjured cartilage. Permeability testing indicated that the TEC-mediated tissue exhibited lower water retaining capacity than did uninjured cartilage, specifically at the superficial zone. Thus, TEC-mediated tissue exhibited compromised mechanical properties at the superficial zone, properties which need improvement in the future for maintenance of long term repair cartilage integrity.

  14. Vascular and micro-environmental influences on MSC-coral hydroxyapatite construct-based bone tissue engineering.

    Science.gov (United States)

    Cai, Lei; Wang, Qian; Gu, Congmin; Wu, Jingguo; Wang, Jian; Kang, Ning; Hu, Jiewei; Xie, Fang; Yan, Li; Liu, Xia; Cao, Yilin; Xiao, Ran

    2011-11-01

    Bone tissue engineering (BTE) has been demonstrated an effective approach to generate bone tissue and repair bone defect in ectopic and orthotopic sites. The strategy of using a prevascularized tissue-engineered bone grafts (TEBG) fabricated ectopically to repair bone defects, which is called live bone graft surgery, has not been reported. And the quantitative advantages of vascularization and osteogenic environment in promoting engineered bone formation have not been defined yet. In the current study we generated a tissue engineered bone flap with a vascular pedicle of saphenous arteriovenous in which an organized vascular network was observed after 4 weeks implantation, and followed by a successful repaire of fibular defect in beagle dogs. Besides, after a 9 months long term observation of engineered bone formation in ectopic and orthotopic sites, four CHA (coral hydroxyapatite) scaffold groups were evaluated by CT (computed tomography) analysis. By the comparison of bone formation and scaffold degradation between different groups, the influences of vascularization and micro-environment on tissue engineered bone were quantitatively analyzed. The results showed that in the first 3 months vascularization improved engineered bone formation by 2 times of non-vascular group and bone defect micro-environment improved it by 3 times of ectopic group, and the CHA-scaffold degradation was accelerated as well. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Development and validation of a novel bioreactor system for load- and perfusion-controlled tissue engineering of chondrocyte-constructs

    NARCIS (Netherlands)

    Schulz, R.M.; Wüstneck, N.; Donkelaar, van C.C.; Shelton, J.C; Bader, A.

    2008-01-01

    Osteoarthritis is a severe socio-economical disease,for which a suitable treatment modality does not exist.Tissue engineering of cartilage transplants is the most promisingmethod to treat focal cartilage defects. However,current culturing procedures do not yet meet the requirementsfor clinical

  16. Mimicking the micro-environment. Construction and evaluation of complex collagen-based scaffolds for tissue engineering

    NARCIS (Netherlands)

    Nillesen, S.T.M.

    2012-01-01

    The ultimate goal in tissue engineering is to create biomaterials that mimic normal tissue or are able to encourage cells cells to generate new functional tissue. For these biomaterials, it is important to use highly purified components in order to moderate the tissue response and to control the

  17. [Tribological assessment of articular cartilage. A system for the analysis of the friction coefficient of cartilage, regenerates and tissue engineering constructs; initial results].

    Science.gov (United States)

    Schwarz, M L R; Schneider-Wald, B; Krase, A; Richter, W; Reisig, G; Kreinest, M; Heute, S; Pott, P P; Brade, J; Schütte, A

    2012-10-01

    Values for the friction coefficient of articular cartilage are given in ranges of percentage and lower and are calculated as a quotient of the friction force and the perpendicular loading force acting on it. Thus, a sophisticated system has to be provided for analysing the friction coefficient under different conditions in particular when cartilage should be coupled as friction partner. It is possible to deep-freeze articular cartilage before measuring the friction coefficient as the procedure has no influence on the results. The presented tribological system was able to distinguish between altered and native cartilage. Furthermore, tissue engineered constructs for cartilage repair were differentiated from native cartilage probes by their friction coefficient. In conclusion a tribological equipment is presented to analyze the friction coefficient of articular cartilage, in vivo generated cartilage regenerates and in vitro tissue engineered constructs regarding their biomechanical properties for quality assessment.

  18. The healing of bony defects by cell-free collagen-based scaffolds compared to stem cell-seeded tissue engineered constructs.

    LENUS (Irish Health Repository)

    Lyons, Frank G

    2010-12-01

    One of the key challenges in tissue engineering is to understand the host response to scaffolds and engineered constructs. We present a study in which two collagen-based scaffolds developed for bone repair: a collagen-glycosaminoglycan (CG) and biomimetic collagen-calcium phosphate (CCP) scaffold, are evaluated in rat cranial defects, both cell-free and when cultured with MSCs prior to implantation. The results demonstrate that both cell-free scaffolds showed excellent healing relative to the empty defect controls and somewhat surprisingly, to the tissue engineered (MSC-seeded) constructs. Immunological analysis of the healing response showed higher M1 macrophage activity in the cell-seeded scaffolds. However, when the M2 macrophage response was analysed, both groups (MSC-seeded and non-seeded scaffolds) showed significant activity of these cells which are associated with an immunomodulatory and tissue remodelling response. Interestingly, the location of this response was confined to the construct periphery, where a capsule had formed, in the MSC-seeded groups as opposed to areas of new bone formation in the non-seeded groups. This suggests that matrix deposited by MSCs during in vitro culture may adversely affect healing by acting as a barrier to macrophage-led remodelling when implanted in vivo. This study thus improves our understanding of host response in bone tissue engineering.

  19. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization.

    Science.gov (United States)

    Weigand, Annika; Beier, Justus P; Hess, Andreas; Gerber, Thomas; Arkudas, Andreas; Horch, Raymund E; Boos, Anja M

    2015-05-01

    During the last decades, a range of excellent and promising strategies in Bone Tissue Engineering have been developed. However, the remaining major problem is the lack of vascularization. In this study, extrinsic and intrinsic vascularization strategies were combined for acceleration of vascularization. For optimal biomechanical stability of the defect site and simplifying future transition into clinical application, a primary stable and approved nanostructured bone substitute in clinically relevant size was used. An arteriovenous (AV) loop was microsurgically created in sheep and implanted, together with the bone substitute, in either perforated titanium chambers (intrinsic/extrinsic) for different time intervals of up to 18 weeks or isolated Teflon(®) chambers (intrinsic) for 18 weeks. Over time, magnetic resonance imaging and micro-computed tomography (CT) analyses illustrate the dense vascularization arising from the AV loop. The bone substitute was completely interspersed with newly formed tissue after 12 weeks of intrinsic/extrinsic vascularization and after 18 weeks of intrinsic/extrinsic and intrinsic vascularization. Successful matrix change from an inorganic to an organic scaffold could be demonstrated in vascularized areas with scanning electron microscopy and energy dispersive X-ray spectroscopy. Using the intrinsic vascularization method only, the degradation of the scaffold and osteoclastic activity was significantly lower after 18 weeks, compared with 12 and 18 weeks in the combined intrinsic-extrinsic model. Immunohistochemical staining revealed an increase in bone tissue formation over time, without a difference between intrinsic/extrinsic and intrinsic vascularization after 18 weeks. This study presents the combination of extrinsic and intrinsic vascularization strategies for the generation of an axially vascularized bone substitute in clinically relevant size using a large animal model. The additional extrinsic vascularization promotes tissue

  20. Application of polarization OCT in tissue engineering

    Science.gov (United States)

    Yang, Ying; Ahearne, Mark; Bagnaninchi, Pierre O.; Hu, Bin; Hampson, Karen; El Haj, Alicia J.

    2008-02-01

    For tissue engineering of load-bearing tissues, such as bone, tendon, cartilage, and cornea, it is critical to generate a highly organized extracellular matrix. The major component of the matrix in these tissues is collagen, which usually forms a highly hierarchical structure with increasing scale from fibril to fiber bundles. These bundles are ordered into a 3D network to withstand forces such as tensile, compressive or shear. To induce the formation of organized matrix and create a mimic body environment for tissue engineering, in particular, tendon tissue engineering, we have fabricated scaffolds with features to support the formation of uniaxially orientated collagen bundles. In addition, mechanical stimuli were applied to stimulate tissue formation and matrix organization. In parallel, we seek a nondestructive tool to monitor the changes within the constructs in response to these external stimulations. Polarizationsensitive optical coherence tomography (PSOCT) is a non-destructive technique that provides functional imaging, and possesses the ability to assess in depth the organization of tissue. In this way, an engineered tissue construct can be monitored on-line, and correlated with the application of different stimuli by PSOCT. We have constructed a PSOCT using a superluminescent diode (FWHM 52nm) in this study and produced two types of tendon constructs. The matrix structural evolution under different mechanical stimulation has been evaluated by the PSOCT. The results in this study demonstrate that PSOCT was a powerful tool enabling us to monitor non-destructively and real time the progressive changes in matrix organization and assess the impact of various stimuli on tissue orientation and growth.

  1. Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

    Science.gov (United States)

    Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

    2014-06-18

    After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

  2. Evaluation of the growth environment of a hydrostatic force bioreactor for preconditioning of tissue-engineered constructs.

    Science.gov (United States)

    Reinwald, Yvonne; Leonard, Katherine H L; Henstock, James R; Whiteley, Jonathan P; Osborne, James M; Waters, Sarah L; Levesque, Philippe; El Haj, Alicia J

    2015-01-01

    Bioreactors have been widely acknowledged as valuable tools to provide a growth environment for engineering tissues and to investigate the effect of physical forces on cells and cell-scaffold constructs. However, evaluation of the bioreactor environment during culture is critical to defining outcomes. In this study, the performance of a hydrostatic force bioreactor was examined by experimental measurements of changes in dissolved oxygen (O2), carbon dioxide (CO2), and pH after mechanical stimulation and the determination of physical forces (pressure and stress) in the bioreactor through mathematical modeling and numerical simulation. To determine the effect of hydrostatic pressure on bone formation, chick femur skeletal cell-seeded hydrogels were subjected to cyclic hydrostatic pressure at 0-270 kPa and 1 Hz for 1 h daily (5 days per week) over a period of 14 days. At the start of mechanical stimulation, dissolved O2 and CO2 in the medium increased and the pH of the medium decreased, but remained within human physiological ranges. Changes in physiological parameters (O2, CO2, and pH) were reversible when medium samples were placed in a standard cell culture incubator. In addition, computational modeling showed that the distribution and magnitude of physical forces depends on the shape and position of the cell-hydrogel constructs in the tissue culture format. Finally, hydrostatic pressure was seen to enhance mineralization of chick femur skeletal cell-seeded hydrogels.

  3. Modified n-HA/PA66 scaffolds with chitosan coating for bone tissue engineering: cell stimulation and drug release.

    Science.gov (United States)

    Zou, Qin; Li, Junfeng; Niu, Lulu; Zuo, Yi; Li, Jidong; Li, Yubao

    2017-09-01

    The dipping-drying procedure and cross-linking method were used to make drug-loaded chitosan (CS) coating on nano-hydroxyapatite/polyamide66 (nHA/PA66) composite porous scaffold, endowing the scaffold controlled drug release functionality. The prefabricated scaffold was immersed into an aqueous drug/CS solution in a vacuum condition and then crosslinked by vanillin. The structure, porosity, composition, compressive strength, swelling ratio, drug release and cytocompatibility of the pristine and coating scaffolds were investigated. After coating, the scaffold porosity and pore interconnection were slightly decreased. Cytocompatibility performance was observed through an in vitro experiment based on cell attachment and the MTT assay by MG63 cells which revealed positive cell viability and increasing proliferation over the 11-day period in vitro. The drug could effectively release from the coated scaffold in a controlled fashion and the release rate was sustained for a long period and highly dependent on coating swelling, suggesting the possibility of a controlled drug release. Our results demonstrate that the scaffold with drug-loaded crosslinked CS coating can be used as a simple technique to render the surfaces of synthetic scaffolds active, thus enabling them to be a promising high performance biomaterial in bone tissue engineering.

  4. Micro- and nanotechnology in cardiovascular tissue engineering

    International Nuclear Information System (INIS)

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

    2011-01-01

    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.

  5. Construction and characterization of an electrospun tubular scaffold for small-diameter tissue-engineered vascular grafts: a scaffold membrane approach.

    Science.gov (United States)

    Hu, Jin-Jia; Chao, Wei-Chih; Lee, Pei-Yuan; Huang, Chih-Hao

    2012-09-01

    Based on a postulate that the microstructure of a scaffold can influence that of the resulting tissue and hence its mechanical behavior, we fabricated a small-diameter tubular scaffold (∼3 mm inner diameter) that has a microstructure similar to the arterial media using a scaffold membrane approach. Scaffold membranes that contain randomly oriented, moderately aligned, or highly aligned fibers were fabricated by collecting electrospun poly([epsilon]-caprolactone) fibers on a grounded rotating drum at three different drum rotation speeds (250, 1000, and 1500 rpm). Membranes of each type were wrapped around a small-diameter mandrel to form the tubular scaffolds. Particularly, the tubular scaffolds with three different off-axis fiber angles (30, 45, and 60 degree) were formed using membranes that contain aligned fibers. These scaffolds were subjected to biaxial mechanical testing to examine the effects of fiber directions as well as the distribution of fiber orientations on their mechanical properties. The circumferential elastic modulus of the tubular scaffold was closely related to the fiber directions; the larger the off-axis fiber angle the greater the circumferential elastic modulus. The distribution of fiber orientations, on the other hand, manifested itself in the mechanical behavior via the Poisson effect. Similar to cell sheet-based vascular tissue engineering, tubular cell-seeded constructs were prepared by wrapping cell-seeded scaffold membranes, alleviating the difficulty associated with cell seeding in electrospun scaffolds. Histology of the construct illustrated that cells were aligned to the fiber directions in the construct, demonstrating the potential to control the microstructure of tissue-engineered vascular grafts using the electrospun scaffold membrane. Copyright © 2012 Elsevier Ltd. All rights reserved.

  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. Fact versus artifact: Avoiding erroneous estimates of sulfated glycosaminoglycan content using the dimethylmethylene blue colorimetric assay for tissue-engineered constructs

    Directory of Open Access Journals (Sweden)

    CH Zheng

    2015-04-01

    Full Text Available The 1,9-dimethylmethylene blue (DMMB assay is widely used to quantify sulfated glycosaminoglycan (sGAG contents of engineered tissues, culture media, tissue samples and bodily fluids, but the assay is subject to interference from polyanions such as hyaluronic acid (HA, DNA and RNA. We examined whether specific combinations of dye pH and absorbance wavelength could minimize non-sGAG artifacts without compromising DMMB assay sensitivity. HA and DNA solutions generated substantial signal at pH 3 but not at pH 1.5. Reducing dye pH did not significantly alter sGAG measurements for normal cartilage and meniscus tissues, but eliminated anomalously high apparent sGAG contents for enzymatically isolated chondrocytes, adipose-derived stem cell (ADSC-agarose constructs and ADSC pellets. In a cartilage tissue-engineering case study, pH 3 dye indicated high apparent sGAG readings throughout culture in both basal and chondrogenic media, with a marked decline between day 14 and 21 for chondrogenic constructs. The pH 1.5 dye, however, indicated minimal sGAG accumulation in basal medium and stable sGAG content throughout culture in chondrogenic medium. As it is often difficult to know a priori whether all groups in a study will have sGAG contents high enough to overwhelm artifacts, we recommend modifying the standard DMMB assay to reduce the risk of spurious findings in tissue engineering and clinical research. Specifically, we recommend shifting to a pH 1.5 DMMB dye and basing quantification on the absorbance difference between 525 nm (µ peak and 595 nm (β peak to compensate for the moderate loss of sensitivity associated with reducing the dye pH.

  8. 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.

  9. 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 ...

  10. Nanoscale Resolution 3D Printing with Pin-Modified Electrified Inkjets for Tailorable Nano/Macrohybrid Constructs for Tissue Engineering.

    Science.gov (United States)

    Kim, Jeong In; Kim, Cheol Sang

    2018-04-18

    Cells respond to their microenvironment, which is of a size comparable to that of the cells. The macroscale features of three-dimensional (3D) printing struts typically result in whole cell contact guidance (CCG). In contrast, at the nanoscale, where features are of a size similar to that of receptors of cells, the response of cells is more complex. The cell-nanotopography interaction involves nanoscale adhesion localized structures, which include cell adhesion-related particles that change in response to the clustering of integrin. For this reason, it is necessary to develop a technique for manufacturing tailorable nano/macrohybrid constructs capable of freely controlling the cellular activity. In this study, a hierarchical 3D nano- to microscale hybrid structure was fabricated by combinational processing of 3D printing and electrified inkjet spinning via pin motions. This method overcomes the disadvantages of conventional 3D printing, providing a novel combinatory technique for the fabrication of 3D hybrid constructs with excellent cell proliferation. Through a pin-modified electrified inkjet spinning, we have successfully fabricated customizable nano-/microscale hybrid constructs in a fibrous or mesh form, which can control the cell fate. We have conducted this study of cell-topography interactions from the fabrication approach to accelerate the development of next-generation 3D scaffolds.

  11. Tissue engineered tumor models.

    Science.gov (United States)

    Ingram, M; Techy, G B; Ward, B R; Imam, S A; Atkinson, R; Ho, H; Taylor, C R

    2010-08-01

    Many research programs use well-characterized tumor cell lines as tumor models for in vitro studies. Because tumor cells grown as three-dimensional (3-D) structures have been shown to behave more like tumors in vivo than do cells growing in monolayer culture, a growing number of investigators now use tumor cell spheroids as models. Single cell type spheroids, however, do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. We describe here a method for generating, reproducibly, more realistic 3-D tumor models that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. Because they are so tissue-like we refer to them as tumor histoids. They can be generated reproducibly in substantial quantities. The bioreactor developed to generate histoid constructs is described and illustrated. It accommodates disposable culture chambers that have filled volumes of either 10 or 64 ml, each culture yielding on the order of 100 or 600 histoid particles, respectively. Each particle is a few tenths of a millimeter in diameter. Examples of histological sections of tumor histoids representing cancers of breast, prostate, colon, pancreas and urinary bladder are presented. Potential applications of tumor histoids include, but are not limited to, use as surrogate tumors for pre-screening anti-solid tumor pharmaceutical agents, as reference specimens for immunostaining in the surgical pathology laboratory and use in studies of invasive properties of cells or other aspects of tumor development and progression. Histoids containing nonmalignant cells also may have potential as "seeds" in tissue engineering. For drug testing, histoids probably will have to meet certain criteria of size and tumor cell content. Using a COPAS Plus flow cytometer, histoids containing fluorescent tumor cells were analyzed successfully and sorted using such criteria.

  12. Degradable polymers for tissue engineering

    NARCIS (Netherlands)

    van Dijkhuizen-Radersma, Riemke; Moroni, Lorenzo; van Apeldoorn, Aart A.; Zhang, Zheng; Grijpma, Dirk W.; van Blitterswijk, Clemens A.

    2008-01-01

    This chapter elaborates the degradable polymers for tissue engineering and their required scaffold material in tissue engineering. It recognizes the examples of degradable polymers broadly used in tissue engineering. Tissue engineering is the persuasion of the body to heal itself through the

  13. Construction of multifunctional proteins for tissue engineering: epidermal growth factor with collagen binding and cell adhesive activities.

    Science.gov (United States)

    Hannachi Imen, Elloumi; Nakamura, Makiko; Mie, Masayasu; Kobatake, Eiry

    2009-01-01

    The development of different techniques based on natural and polymeric scaffolds are useful for the design of different biomimetic materials. These approaches, however, require supplementary steps for the chemical or physical modification of the biomaterial. To avoid such steps, in the present study, we constructed a new multifunctional protein that can be easily immobilized onto hydrophobic surfaces, and at the same time helps enhance specific cell adhesion and proliferation onto collagen substrates. A collagen binding domain was fused to a previously constructed protein, which had an epidermal growth factor fused to a hydrophobic peptide that allows for cell adhesion. The new fusion protein, designated fnCBD-ERE-EGF is produced in Escherichia coli, and its abilities to bind to collagen and promote cell proliferation were investigated. fnCBD-ERE-EGF was shown to keep both collagen binding and cell growth-promoting activities comparable to those of the corresponding unfused proteins. The results obtained in this study also suggest the use of a fnCBD-ERE-EGF as an alternative for the design of multifunctional ECM-bound growth factor based materials.

  14. Three-dimensional assembly of tissue-engineered cartilage constructs results in cartilaginous tissue formation without retainment of zonal characteristics.

    Science.gov (United States)

    Schuurman, W; Harimulyo, E B; Gawlitta, D; Woodfield, T B F; Dhert, W J A; van Weeren, P R; Malda, J

    2016-04-01

    Articular cartilage has limited regenerative capabilities. Chondrocytes from different layers of cartilage have specific properties, and regenerative approaches using zonal chondrocytes may yield better replication of the architecture of native cartilage than when using a single cell population. To obtain high seeding efficiency while still mimicking zonal architecture, cell pellets of expanded deep zone and superficial zone equine chondrocytes were seeded and cultured in two layers on poly(ethylene glycol)-terephthalate-poly(butylene terephthalate) (PEGT-PBT) scaffolds. Scaffolds seeded with cell pellets consisting of a 1:1 mixture of both cell sources served as controls. Parallel to this, pellets of superficial or deep zone chondrocytes, and combinations of the two cell populations, were cultured without the scaffold. Pellet cultures of zonal chondrocytes in scaffolds resulted in a high seeding efficiency and abundant cartilaginous tissue formation, containing collagen type II and glycosaminoglycans (GAGs) in all groups, irrespective of the donor (n = 3), zonal population or stratified scaffold-seeding approach used. However, whereas total GAG production was similar, the constructs retained significantly more GAG compared to pellet cultures, in which a high percentage of the produced GAGs were secreted into the culture medium. Immunohistochemistry for zonal markers did not show any differences between the conditions. We conclude that spatially defined pellet culture in 3D scaffolds is associated with high seeding efficiency and supports cartilaginous tissue formation, but did not result in the maintenance or restoration of the original zonal phenotype. The use of pellet-assembled constructs leads to a better retainment of newly produced GAGs than the use of pellet cultures alone. Copyright © 2013 John Wiley & Sons, Ltd.

  15. 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

  16. Neoproteoglycans in tissue engineering

    Science.gov (United States)

    Weyers, Amanda; Linhardt, Robert J.

    2014-01-01

    Proteoglycans, comprised of a core protein to which glycosaminoglycan chains are covalently linked, are an important structural and functional family of macromolecules found in the extracellular matrix. Advances in our understanding of biological interactions have lead to a greater appreciation for the need to design tissue engineering scaffolds that incorporate mimetics of key extracellular matrix components. A variety of synthetic and semisynthetic molecules and polymers have been examined by tissue engineers that serve as structural, chemical and biological replacements for proteoglycans. These proteoglycan mimetics have been referred to as neoproteoglycans and serve as functional and therapeutic replacements for natural proteoglycans that are often unavailable for tissue engineering studies. Although neoproteoglycans have important limitations, such as limited signaling ability and biocompatibility, they have shown promise in replacing the natural activity of proteoglycans through cell and protein binding interactions. This review focuses on the recent in vivo and in vitro tissue engineering applications of three basic types of neoproteoglycan structures, protein–glycosaminoglycan conjugates, nano-glycosaminoglycan composites and polymer–glycosaminoglycan complexes. PMID:23399318

  17. Multifactorial Optimization of Contrast-Enhanced Nanofocus Computed Tomography for Quantitative Analysis of Neo-Tissue Formation in Tissue Engineering Constructs.

    Directory of Open Access Journals (Sweden)

    Maarten Sonnaert

    Full Text Available To progress the fields of tissue engineering (TE and regenerative medicine, development of quantitative methods for non-invasive three dimensional characterization of engineered constructs (i.e. cells/tissue combined with scaffolds becomes essential. In this study, we have defined the most optimal staining conditions for contrast-enhanced nanofocus computed tomography for three dimensional visualization and quantitative analysis of in vitro engineered neo-tissue (i.e. extracellular matrix containing cells in perfusion bioreactor-developed Ti6Al4V constructs. A fractional factorial 'design of experiments' approach was used to elucidate the influence of the staining time and concentration of two contrast agents (Hexabrix and phosphotungstic acid and the neo-tissue volume on the image contrast and dataset quality. Additionally, the neo-tissue shrinkage that was induced by phosphotungstic acid staining was quantified to determine the operating window within which this contrast agent can be accurately applied. For Hexabrix the staining concentration was the main parameter influencing image contrast and dataset quality. Using phosphotungstic acid the staining concentration had a significant influence on the image contrast while both staining concentration and neo-tissue volume had an influence on the dataset quality. The use of high concentrations of phosphotungstic acid did however introduce significant shrinkage of the neo-tissue indicating that, despite sub-optimal image contrast, low concentrations of this staining agent should be used to enable quantitative analysis. To conclude, design of experiments allowed us to define the most optimal staining conditions for contrast-enhanced nanofocus computed tomography to be used as a routine screening tool of neo-tissue formation in Ti6Al4V constructs, transforming it into a robust three dimensional quality control methodology.

  18. The influence of construct scale on the composition and functional properties of cartilaginous tissues engineered using bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Buckley, Conor T; Meyer, Eric G; Kelly, Daniel J

    2012-02-01

    Engineering cartilaginous tissue of a scale necessary to treat defects observed clinically is a well-documented challenge in the field of cartilage tissue engineering. The objective of this study was to determine how the composition and mechanical properties of cartilaginous tissues that are engineered by using bone marrow-derived mesenchymal stem cells (MSCs) depend on the scale of the construct. Porcine bone marrow-derived MSCs were encapsulated in agarose hydrogels, and constructs of different cylindrical geometries (Ø4×1.5 mm; Ø5×3 mm; Ø6×4.5 mm; Ø8×4.5 mm) were fabricated and maintained in a chemically defined serum-free medium supplemented with transforming growth factor-β3 for 42 days. Total sulfated glycosaminoglycan (sGAG) accumulation by day 42 increased from 0.14% w/w to 0.88% w/w as the construct geometry increased from Ø4×1.5 to Ø8×4.5 mm, with collagen accumulation increasing from 0.31% w/w to 1.62% w/w. This led to an increase in the dynamic modulus from 90.81 to 327.51 kPa as the engineered tissue increased in scale from Ø4×1.5 to Ø8×4.5 mm. By decreasing the external oxygen tension from 20% to 5%, it was possible to achieve these higher levels of mechanical functionality in the smaller engineered tissues. Constructs were then sectioned into smaller subregions to quantify the spatial accumulation of extracellular matrix components, and a model of oxygen diffusion and consumption was used to predict spatial gradients in oxygen concentration throughout the construct. sGAG accumulation was always highest in regions where oxygen concentration was predicted to be lowest. In addition, as the size of the engineered construct increased, different regions of the construct preferentially supported either sGAG or collagen accumulation, thus suggesting that gradients in regulatory factors other than oxygen were playing a role in determining levels of collagen synthesis. The identification of such factors and the means to control their

  19. Ligament Tissue Engineering

    OpenAIRE

    Khan, Wasim Sardar

    2016-01-01

    Ligaments are commonly injured in the knee joint, and have a poor capacity for healing due to their relative avascularity. Ligament reconstruction is well established for injuries such as anterior cruciate ligament rupture, however the use of autografts and allografts for ligament reconstruction are associated with complications, and outcomes are variable. Ligament tissue engineering using stem cells, growth factors and scaffolds is a novel technique that has the potential to provide an unlim...

  20. Biomaterials for Tissue Engineering

    Science.gov (United States)

    Lee, Esther J.; Kasper, F. Kurtis; Mikos, Antonios G.

    2013-01-01

    Biomaterials serve as an integral component of tissue engineering. They are designed to provide architectural framework reminiscent of native extracellular matrix in order to encourage cell growth and eventual tissue regeneration. Bone and cartilage represent two distinct tissues with varying compositional and mechanical properties. Despite these differences, both meet at the osteochondral interface. This article presents an overview of current biomaterials employed in bone and cartilage applications, discusses some design considerations, and alludes to future prospects within this field of research. PMID:23820768

  1. Construction of an Aptamer-SiRNA Chimera-Modified Tissue-Engineered Blood Vessel for Cell-Type-Specific Capture and Delivery.

    Science.gov (United States)

    Chen, Wen; Zeng, Wen; Sun, Jiansen; Yang, Mingcan; Li, Li; Zhou, Jingting; Wu, Yangxiao; Sun, Jun; Liu, Ge; Tang, Rui; Tan, Ju; Zhu, Chuhong

    2015-06-23

    The application of tissue-engineered blood vessels (TEBVs) is the main developmental direction of vascular replacement therapy. Due to few and/or dysfunctional endothelial progenitor cells (EPCs), it is difficult to successfully construct EPC capture TEBVs in diabetes. RNA has a potential application in cell protection and diabetes treatment, but poor specificity and low efficiency of RNA transfection in vivo limit the application of RNA. On the basis of an acellular vascular matrix, we propose an aptamer-siRNA chimera-modified TEBV that can maintain a satisfactory patency in diabetes. This TEBV consists of two parts, CD133-adenosine kinase (ADK) chimeras and a TEBV scaffold. Our results showed that CD133-ADK chimeras could selectively capture the CD133-positive cells in vivo, and then captured cells can internalize the bound chimeras to achieve RNA self-transfection. Subsequently, CD133-ADK chimeras were cut into ADK siRNA by a dicer, resulting in depletion of ADK. An ADK-deficient cell may act as a bioreactor that sustainably releases adenosine. To reduce nonspecific RNA transfection, we increased the proportion of HAuCl4 during the material preparation, through which the transfection capacity of polyethylenimine (PEI)/polyethylene glycol (PEG)-capped gold nanoparticles (PEI/PEG-AuNPs) was significantly decreased and the ability of TEBV to resist tensile and liquid shear stress was greatly enhanced. PEG and 2'-O-methyl modification was used to enhance the in vivo stability of RNA chimeras. At day 30 postgrafting, the patency rate of CD133-ADK chimera-modified TEBVs reached 90% in diabetic rats and good endothelialization was observed.

  2. Fresh and Frozen Tissue-Engineered Three-Dimensional Bone–Ligament–Bone Constructs for Sheep Anterior Cruciate Ligament Repair Following a 2-Year Implantation

    Directory of Open Access Journals (Sweden)

    Vasudevan Mahalingam

    2016-10-01

    Full Text Available njuries to the anterior cruciate ligament (ACL often require surgical reconstruction utilizing tendon grafts to restore knee function and stability. Some current graft options for ACL repair are associated with poor long-term outcomes. Our laboratory has fabricated tissue-engineered bone–ligament–bone (BLB constructs that demonstrate native ligament regeneration and advancement toward native ACL mechanical properties in a sheep ACL reconstruction model. Prior work has shown that freezing BLBs as a method of preservation resulted in similar outcomes compared with fresh BLBs after 6-month implantation. The purpose of this study was to evaluate the long-term efficacy of fresh and frozen BLBs. We hypothesized that both fresh and frozen BLBs would show continued regeneration of structural and functional properties toward those of native ACL after a 2-year implantation. Following removal of the native ACL, fresh (n = 2 and frozen (n = 2 BLBs were implanted arthroscopically. After 2 years of recovery, sheep were euthanized and both the experimental and contralateral hindlimbs were removed and radiographs were performed. Explanted knees were initially evaluated for joint laxity and were then further dissected for uniaxial tensile testing of the isolated ACL or BLB. Following mechanical testing, explanted contralateral ACL (C-ACL and BLBs were harvested for histology. Two years post-ACL reconstruction, fresh and frozen BLBs exhibited similar morphological and biomechanical properties as well as more advanced regeneration compared with our 6-month recovery study. These data indicate that an additional 1.5-year regeneration period allows the BLB to continue ligament regeneration in vivo. In addition, freezing the BLBs is a viable option for the preservation of the graft after fabrication.

  3. 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.

  4. 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.

  5. Nanomaterials for Craniofacial and Dental Tissue Engineering.

    Science.gov (United States)

    Li, G; Zhou, T; Lin, S; Shi, S; Lin, Y

    2017-07-01

    Tissue engineering shows great potential as a future treatment for the craniofacial and dental defects caused by trauma, tumor, and other diseases. Due to the biomimetic features and excellent physiochemical properties, nanomaterials are of vital importance in promoting cell growth and stimulating tissue regeneration in tissue engineering. For craniofacial and dental tissue engineering, the frequently used nanomaterials include nanoparticles, nanofibers, nanotubes, and nanosheets. Nanofibers are attractive for cell invasion and proliferation because of their resemblance to extracellular matrix and the presence of large pores, and they have been used as scaffolds in bone, cartilage, and tooth regeneration. Nanotubes and nanoparticles improve the mechanical and chemical properties of scaffold, increase cell attachment and migration, and facilitate tissue regeneration. In addition, nanofibers and nanoparticles are also used as a delivery system to carry the bioactive agent in bone and tooth regeneration, have better control of the release speed of agent upon degradation of the matrix, and promote tissue regeneration. Although applications of nanomaterials in tissue engineering remain in their infancy with numerous challenges to face, the current results indicate that nanomaterials have massive potential in craniofacial and dental tissue engineering.

  6. 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.

  7. Microgel Technology to Advance Modular Tissue Engineering

    NARCIS (Netherlands)

    Kamperman, Tom

    2018-01-01

    The field of tissue engineering aims to restore the function of damaged or missing tissues by combining cells and/or a supportive biomaterial scaffold into an engineered tissue construct. The construct’s design requirements are typically set by native tissues – the gold standard for tissue

  8. 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...... of hiPSC-derived DE cells cultured for 25 days in a 3D perfusion bioreactor system with an array of 16 small-scale tissue-bioreactors with integrated dual-pore pore scaffolds and flow rates. Hepatic differentiation and functionality of hiPSC-derived hepatocytes were successfully assessed and compared...

  9. 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.

  10. The essence of biophysical cues in skeletal muscle tissue engineering

    NARCIS (Netherlands)

    Langelaan, M.L.P.

    2010-01-01

    Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications. Evidently, tissue engineered skeletal muscle can be used in the field of regenerative medicine to repair muscular defects or dystrophies. Engineered skeletal muscle constructs can also be used as a

  11. Biomaterials for tissue engineering: summary

    Science.gov (United States)

    Christenson, L.; Mikos, A. G.; Gibbons, D. F.; Picciolo, G. L.; McIntire, L. V. (Principal Investigator)

    1997-01-01

    This article summarizes presentations and discussion at the workshop "Enabling Biomaterial Technology for Tissue Engineering," which was held during the Fifth World Biomaterials Congress in May 1996. Presentations covered the areas of material substrate architecture, barrier effects, and cellular response, including analysis of biomaterials challenges involved in producing specific tissue-engineered products.

  12. 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...

  13. Biochemical Stimulus-Based Strategies for Meniscus Tissue Engineering and Regeneration

    Science.gov (United States)

    Chen, Mingxue; Guo, Weimin; Gao, Shunag; Hao, Chunxiang; Shen, Shi; Zhang, Zengzeng; Wang, Zhenyong; Wang, Zehao; Li, Xu; Jing, Xiaoguang; Zhang, Xueliang; Yuan, Zhiguo; Wang, Mingjie; Zhang, Yu; Peng, Jiang; Wang, Aiyuan; Wang, Yu; Sui, Xiang

    2018-01-01

    Meniscus injuries are very common and still pose a challenge for the orthopedic surgeon. Meniscus injuries in the inner two-thirds of the meniscus remain incurable. Tissue-engineered meniscus strategies seem to offer a new approach for treating meniscus injuries with a combination of seed cells, scaffolds, and biochemical or biomechanical stimulation. Cell- or scaffold-based strategies play a pivotal role in meniscus regeneration. Similarly, biochemical and biomechanical stimulation are also important. Seed cells and scaffolds can be used to construct a tissue-engineered tissue; however, stimulation to enhance tissue maturation and remodeling is still needed. Such stimulation can be biomechanical or biochemical, but this review focuses only on biochemical stimulation. Growth factors (GFs) are one of the most important forms of biochemical stimulation. Frequently used GFs always play a critical role in normal limb development and growth. Further understanding of the functional mechanism of GFs will help scientists to design the best therapy strategies. In this review, we summarize some of the most important GFs in tissue-engineered menisci, as well as other types of biological stimulation. PMID:29581987

  14. 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.

  15. The growth of tissue engineering.

    Science.gov (United States)

    Lysaght, M J; Reyes, J

    2001-10-01

    This report draws upon data from a variety of sources to estimate the size, scope, and growth rate of the contemporary tissue engineering enterprise. At the beginning of 2001, tissue engineering research and development was being pursued by 3,300 scientists and support staff in more than 70 startup companies or business units with a combined annual expenditure of over $600 million. Spending by tissue engineering firms has been growing at a compound annual rate of 16%, and the aggregate investment since 1990 now exceeds $3.5 billion. At the beginning of 2001, the net capital value of the 16 publicly traded tissue engineering startups had reached $2.6 billion. Firms focusing on structural applications (skin, cartilage, bone, cardiac prosthesis, and the like) comprise the fastest growing segment. In contrast, efforts in biohybrid organs and other metabolic applications have contracted over the past few years. The number of companies involved in stem cells and regenerative medicine is rapidly increasing, and this area represents the most likely nidus of future growth for tissue engineering. A notable recent trend has been the emergence of a strong commercial activity in tissue engineering outside the United States, with at least 16 European or Australian companies (22% of total) now active.

  16. Efficient generation of smooth muscle cells from adipose-derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering.

    Science.gov (United States)

    Parvizi, Mojtaba; Bolhuis-Versteeg, Lydia A M; Poot, André A; Harmsen, Martin C

    2016-07-01

    Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep-free poly (1,3-trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue-derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF-β1 for 7d. Phenotype and function were assessed by qRT-PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non-differentiated and pre-differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT-PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF-β1-driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre-differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well-aligned ASC-derived SMC which deposited ECM. Under the same conditions, pre-differentiated ASC-derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF-β1 pre-stimulation to generate SMC from ASC and that pre-differentiated ASC keep their SMC phenotype with increased expression of SMC markers. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Braided nanofibrous scaffold for tendon and ligament tissue engineering.

    Science.gov (United States)

    Barber, John G; Handorf, Andrew M; Allee, Tyler J; Li, Wan-Ju

    2013-06-01

    Tendon and ligament (T/L) injuries present an important clinical challenge due to their intrinsically poor healing capacity. Natural healing typically leads to the formation of scar-like tissue possessing inferior mechanical properties. Therefore, tissue engineering has gained considerable attention as a promising alternative for T/L repair. In this study, we fabricated braided nanofibrous scaffolds (BNFSs) as a potential construct for T/L tissue engineering. Scaffolds were fabricated by braiding 3, 4, or 5 aligned bundles of electrospun poly(L-lactic acid) nanofibers, thus introducing an additional degree of flexibility to alter the mechanical properties of individual scaffolds. We observed that the Young's modulus, yield stress, and ultimate stress were all increased in the 3-bundle compared to the 4- and 5-bundle BNFSs. Interestingly, acellular BNFSs mimicked the normal tri-phasic mechanical behavior of native tendon and ligament (T/L) during loading. When cultured on the BNFSs, human mesenchymal stem cells (hMSCs) adhered, aligned parallel to the length of the nanofibers, and displayed a concomitant realignment of the actin cytoskeleton. In addition, the BNFSs supported hMSC proliferation and induced an upregulation in the expression of key pluripotency genes. When cultured on BNFSs in the presence of tenogenic growth factors and stimulated with cyclic tensile strain, hMSCs differentiated into the tenogenic lineage, evidenced most notably by the significant upregulation of Scleraxis gene expression. These results demonstrate that BNFSs provide a versatile scaffold capable of supporting both stem cell expansion and differentiation for T/L tissue engineering applications.

  18. Cardiac tissue engineering using perfusion bioreactor systems

    Science.gov (United States)

    Radisic, Milica; Marsano, Anna; Maidhof, Robert; Wang, Yadong; Vunjak-Novakovic, Gordana

    2009-01-01

    This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is ‘biomimetic’ in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and high-fidelity models for biological research. PMID:18388955

  19. 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.

  20. 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...

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

    Science.gov (United States)

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

    2016-01-01

    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, pore size and mechanical properties of the fabrics play important role 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. PMID:26924450

  2. Chitin Scaffolds in Tissue Engineering

    Science.gov (United States)

    Jayakumar, Rangasamy; Chennazhi, Krishna Prasad; Srinivasan, Sowmya; Nair, Shantikumar V.; Furuike, Tetsuya; Tamura, Hiroshi

    2011-01-01

    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. PMID:21673928

  3. 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.

  4. Construction of collagen II/hyaluronate/chondroitin-6-sulfate tri-copolymer scaffold for nucleus pulposus tissue engineering and preliminary analysis of its physico-chemical properties and biocompatibility.

    Science.gov (United States)

    Li, Chang-Qing; Huang, Bo; Luo, Gang; Zhang, Chuan-Zhi; Zhuang, Ying; Zhou, Yue

    2010-02-01

    To construct a novel scaffold for nucleus pulposus (NP) tissue engineering, The porous type II collagen (CII)/hyaluronate (HyA)-chondroitin-6-sulfate (6-CS) scaffold was prepared using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) cross-linking system. The physico-chemical properties and biocompatibility of CII/HyA-CS scaffolds were evaluated. The results suggested CII/HyA-CS scaffolds have a highly porous structure (porosity: 94.8 +/- 1.5%), high water-binding capacity (79.2 +/- 2.8%) and significantly improved mechanical stability by EDC/NHS crosslinking (denaturation temperature: 74.6 +/- 1.8 and 58.1 +/- 2.6 degrees C, respectively, for the crosslinked scaffolds and the non-crosslinked; collagenase degradation rate: 39.5 +/- 3.4 and 63.5 +/- 2.0%, respectively, for the crosslinked scaffolds and the non-crosslinked). The CII/HyA-CS scaffolds also showed satisfactory cytocompatibility and histocompatibility as well as low immunogenicity. These results indicate CII/HyA-CS scaffolds may be an alternative material for NP tissue engineering due to the similarity of its composition and physico-chemical properties to those of the extracellular matrices (ECM) of native NP.

  5. Biomaterials for tissue engineering applications.

    Science.gov (United States)

    Keane, Timothy J; Badylak, Stephen F

    2014-06-01

    With advancements in biological and engineering sciences, the definition of an ideal biomaterial has evolved over the past 50 years from a substance that is inert to one that has select bioinductive properties and integrates well with adjacent host tissue. Biomaterials are a fundamental component of tissue engineering, which aims to replace diseased, damaged, or missing tissue with reconstructed functional tissue. Most biomaterials are less than satisfactory for pediatric patients because the scaffold must adapt to the growth and development of the surrounding tissues and organs over time. The pediatric community, therefore, provides a distinct challenge for the tissue engineering community. Copyright © 2014. Published by Elsevier Inc.

  6. Silk: a potential medium for tissue engineering.

    Science.gov (United States)

    Sobajo, Cassandra; Behzad, Farhad; Yuan, Xue-Feng; Bayat, Ardeshir

    2008-01-01

    Human skin is a complex bilayered organ that serves as a protective barrier against the environment. The loss of integrity of skin by traumatic experiences such as burns and ulcers may result in considerable disability or ultimately death. Therefore, in skin injuries, adequate dermal substitutes are among primary care targets, aimed at replacing the structural and functional properties of native skin. To date, there are very few single application tissue-engineered dermal constructs fulfilling this criterion. Silk produced by the domestic silkworm, Bombyx mori, has a long history of use in medicine. It has recently been increasingly investigated as a promising biomaterial for dermal constructs. Silk contains 2 fibrous proteins, sericin and fibroin. Each one exhibits unique mechanical and biological properties. Comprehensive review of randomized-controlled trials investigating current dermal constructs and the structures and properties of silk-based constructs on wound healing. This review revealed that silk-fibroin is regarded as the most promising biomaterial, providing options for the construction of tissue-engineered skin. The research available indicates that silk fibroin is a suitable biomaterial scaffold for the provision of adequate dermal constructs.

  7. Potential of Bioactive Glasses for Cardiac and Pulmonary Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Saeid Kargozar

    2017-12-01

    Full Text Available Repair and regeneration of disorders affecting cardiac and pulmonary tissues through tissue-engineering-based approaches is currently of particular interest. On this matter, different families of bioactive glasses (BGs have recently been given much consideration with respect to treating refractory diseases of these tissues, such as myocardial infarction. The inherent properties of BGs, including their ability to bond to hard and soft tissues, to stimulate angiogenesis, and to elicit antimicrobial effects, along with their excellent biocompatibility, support these newly proposed strategies. Moreover, BGs can also act as a bioactive reinforcing phase to finely tune the mechanical properties of polymer-based constructs used to repair the damaged cardiac and pulmonary tissues. In the present study, we evaluated the potential of different forms of BGs, alone or in combination with other materials (e.g., polymers, in regards to repair and regenerate injured tissues of cardiac and pulmonary systems.

  8. Esophageal tissue engineering: Current status and perspectives.

    Science.gov (United States)

    Poghosyan, T; Catry, J; Luong-Nguyen, M; Bruneval, P; Domet, T; Arakelian, L; Sfeir, R; Michaud, L; Vanneaux, V; Gottrand, F; Larghero, J; Cattan, P

    2016-02-01

    Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets. In the near future, esophageal substitutes could be constructed from acellular "intelligent matrices" that contain the molecules necessary for tissue regeneration; this should allow circumvention of the implantation step and still obtain standardized in vivo biological responses. At present, tissue engineering applications to esophageal replacement are limited to enlargement plasties with absorbable, non-cellular matrices. Nevertheless, the application of existing clinical techniques for replacement of other organs by tissue engineering in combination with a multiplication of translational research protocols for esophageal replacement in large animals should soon pave the way for health agencies to authorize clinical trials. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Proangiogenic scaffolds as functional templates for cardiac tissue engineering

    OpenAIRE

    Madden, Lauran R.; Mortisen, Derek J.; Sussman, Eric M.; Dupras, Sarah K.; Fugate, James A.; Cuy, Janet L.; Hauch, Kip D.; Laflamme, Michael A.; Murry, Charles E.; Ratner, Buddy D.

    2010-01-01

    We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-s...

  10. Microfluidic systems for stem cell-based neural tissue engineering.

    Science.gov (United States)

    Karimi, Mahdi; Bahrami, Sajad; Mirshekari, Hamed; Basri, Seyed Masoud Moosavi; Nik, Amirala Bakhshian; Aref, Amir R; Akbari, Mohsen; Hamblin, Michael R

    2016-07-05

    Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a "brain-on-a-chip". In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

  11. Biomimetic material strategies for cardiac tissue engineering

    International Nuclear Information System (INIS)

    Prabhakaran, Molamma P.; Venugopal, J.; Kai, Dan; Ramakrishna, Seeram

    2011-01-01

    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.

  12. 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.

  13. 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.

  14. Development of an angiogenesis-promoting microvesicle-alginate-polycaprolactone composite graft for bone tissue engineering applications

    Directory of Open Access Journals (Sweden)

    Hui Xie

    2016-05-01

    Full Text Available One of the major challenges of bone tissue engineering applications is to construct a fully vascularized implant that can adapt to hypoxic environments in vivo. The incorporation of proangiogenic factors into scaffolds is a widely accepted method of achieving this goal. Recently, the proangiogenic potential of mesenchymal stem cell-derived microvesicles (MSC-MVs has been confirmed in several studies. In the present study, we incorporated MSC-MVs into alginate-polycaprolactone (PCL constructs that had previously been developed for bone tissue engineering applications, with the aim of promoting angiogenesis and bone regeneration. MSC-MVs were first isolated from the supernatant of rat bone marrow-derived MSCs and characterized by scanning electron microscopic, confocal microscopic, and flow cytometric analyses. The proangiogenic potential of MSC-MVs was demonstrated by the stimulation of tube formation of human umbilical vein endothelial cells in vitro. MSC-MVs and osteodifferentiated MSCs were then encapsulated with alginate and seeded onto porous three-dimensional printed PCL scaffolds. When combined with osteodifferentiated MSCs, the MV-alginate-PCL constructs enhanced vessel formation and tissue-engineered bone regeneration in a nude mouse subcutaneous bone formation model, as demonstrated by micro-computed tomographic, histological, and immunohistochemical analyses. This MV-alginate-PCL construct may offer a novel, proangiogenic, and cost-effective option for bone tissue engineering.

  15. The potential of 3-dimensional construct engineered from poly(lactic-co-glycolic acid)/fibrin hybrid scaffold seeded with bone marrow mesenchymal stem cells for in vitro cartilage tissue engineering.

    Science.gov (United States)

    Abdul Rahman, Rozlin; Mohamad Sukri, Norhamiza; Md Nazir, Noorhidayah; Ahmad Radzi, Muhammad Aa'zamuddin; Zulkifly, Ahmad Hafiz; Che Ahmad, Aminudin; Hashi, Abdurezak Abdulahi; Abdul Rahman, Suzanah; Sha'ban, Munirah

    2015-08-01

    Articular cartilage is well known for its simple uniqueness of avascular and aneural structure that has limited capacity to heal itself when injured. The use of three dimensional construct in tissue engineering holds great potential in regenerating cartilage defects. This study evaluated the in vitro cartilaginous tissue formation using rabbit's bone marrow mesenchymal stem cells (BMSCs)-seeded onto poly(lactic-co-glycolic acid) PLGA/fibrin and PLGA scaffolds. The in vitro cartilaginous engineered constructs were evaluated by gross inspection, histology, cell proliferation, gene expression and sulphated glycosaminoglycan (sGAG) production at week 1, 2 and 3. After 3 weeks of culture, the PLGA/fibrin construct demonstrated gross features similar to the native tissue with smooth, firm and glistening appearance, superior histoarchitectural and better cartilaginous extracellular matrix compound in concert with the positive glycosaminoglycan accumulation on Alcian blue. Significantly higher cell proliferation in PLGA/fibrin construct was noted at day-7, day-14 and day-21 (ptissue engineered cartilage. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Bladder tissue engineering through nanotechnology.

    Science.gov (United States)

    Harrington, Daniel A; Sharma, Arun K; Erickson, Bradley A; Cheng, Earl Y

    2008-08-01

    The field of tissue engineering has developed in phases: initially researchers searched for "inert" biomaterials to act solely as replacement structures in the body. Then, they explored biodegradable scaffolds--both naturally derived and synthetic--for the temporary support of growing tissues. Now, a third phase of tissue engineering has developed, through the subcategory of "regenerative medicine." This renewed focus toward control over tissue morphology and cell phenotype requires proportional advances in scaffold design. Discoveries in nanotechnology have driven both our understanding of cell-substrate interactions, and our ability to influence them. By operating at the size regime of proteins themselves, nanotechnology gives us the opportunity to directly speak the language of cells, through reliable, repeatable creation of nanoscale features. Understanding the synthesis of nanoscale materials, via "top-down" and "bottom-up" strategies, allows researchers to assess the capabilities and limits inherent in both techniques. Urology research as a whole, and bladder regeneration in particular, are well-positioned to benefit from such advances, since our present technology has yet to reach the end goal of functional bladder restoration. In this article, we discuss the current applications of nanoscale materials to bladder tissue engineering, and encourage researchers to explore these interdisciplinary technologies now, or risk playing catch-up in the future.

  17. Porous titanium bases for osteochondral tissue engineering

    Science.gov (United States)

    Nover, Adam B.; Lee, Stephanie L.; Georgescu, Maria S.; Howard, Daniel R.; Saunders, Reuben A.; Yu, William T.; Klein, Robert W.; Napolitano, Anthony P.; Ateshian, Gerard A.

    2015-01-01

    Tissue engineering of osteochondral grafts may offer a cell-based alternative to native allografts, which are in short supply. Previous studies promote the fabrication of grafts consisting of a viable cell-seeded hydrogel integrated atop a porous, bone-like metal. Advantages of the manufacturing process have led to the evaluation of porous titanium as the bone-like base material. Here, porous titanium was shown to support the growth of cartilage to produce native levels of Young’s modulus, using a clinically relevant cell source. Mechanical and biochemical properties were similar or higher for the osteochondral constructs compared to chondral-only controls. Further investigation into the mechanical influence of the base on the composite material suggests that underlying pores may decrease interstitial fluid pressurization and applied strains, which may be overcome by alterations to the base structure. Future studies aim to optimize titanium-based tissue engineered osteochondral constructs to best match the structural architecture and strength of native grafts. Statement of Significance The studies described in this manuscript follow up on previous studies from our lab pertaining to the fabrication of osteochondral grafts that consist of a bone-like porous metal and a chondrocyte-seeded hydrogel. Here, tissue engineered osteochondral grafts were cultured to native stiffness using adult chondrocytes, a clinically relevant cell source, and a porous titanium base, a material currently used in clinical implants. This porous titanium is manufactured via selective laser melting, offering the advantages of precise control over shape, pore size, and orientation. Additionally, this manuscript describes the mechanical influence of the porous base, which may have applicability to porous bases derived from other materials. PMID:26320541

  18. 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

  19. The role of mechanical loading in ligament tissue engineering.

    Science.gov (United States)

    Benhardt, Hugh A; Cosgriff-Hernandez, Elizabeth M

    2009-12-01

    Tissue-engineered ligaments have received growing interest as a promising alternative for ligament reconstruction when traditional transplants are unavailable or fail. Mechanical stimulation was recently identified as a critical component in engineering load-bearing tissues. It is well established that living tissue responds to altered loads through endogenous changes in cellular behavior, tissue organization, and bulk mechanical properties. Without the appropriate biomechanical cues, new tissue formation lacks the necessary collagenous organization and alignment for sufficient load-bearing capacity. Therefore, tissue engineers utilize mechanical conditioning to guide tissue remodeling and improve the performance of ligament grafts. This review provides a comparative analysis of the response of ligament and tendon fibroblasts to mechanical loading in current bioreactor studies. The differential effect of mechanical stimulation on cellular processes such as protease production, matrix protein synthesis, and cell proliferation is examined in the context of tissue engineering design.

  20. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    International Nuclear Information System (INIS)

    Shim, Jin-Hyung; Lee, Jung-Seob; Cho, Dong-Woo; Kim, Jong Young

    2012-01-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed. (paper)

  1. Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system

    Science.gov (United States)

    Shim, Jin-Hyung; Lee, Jung-Seob; Kim, Jong Young; Cho, Dong-Woo

    2012-08-01

    The aim of this study was to build a mechanically enhanced three-dimensional (3D) bioprinted construct containing two different cell types for osteochondral tissue regeneration. Recently, the production of 3D cell-laden structures using various scaffold-free cell printing technologies has opened up new possibilities. However, ideal 3D complex tissues or organs have not yet been printed because gel-state hydrogels have been used as the principal material and are unable to maintain the desired 3D structure due to their poor mechanical strength. In this study, thermoplastic biomaterial polycaprolactone (PCL), which shows relatively high mechanical properties as compared with hydrogel, was used as a framework for enhancing the mechanical stability of the bioprinted construct. Two different alginate solutions were then infused into the previously prepared framework consisting of PCL to create the 3D construct for osteochondral printing. For this work, a multi-head tissue/organ building system (MtoBS), which was particularly designed to dispense thermoplastic biomaterial and hydrogel having completely different rheology properties, was newly developed and used to bioprint osteochondral tissue. It was confirmed that the line width, position and volume control of PCL and alginate solutions were adjustable in the MtoBS. Most importantly, dual cell-laden 3D constructs consisting of osteoblasts and chondrocytes were successfully fabricated. Further, the separately dispensed osteoblasts and chondrocytes not only retained their initial position and viability, but also proliferated up to 7 days after being dispensed.

  2. Fundamentals of bladder tissue engineering | Mahfouz | African ...

    African Journals Online (AJOL)

    Fundamentals of bladder tissue engineering. ... could affect the bladder and lead to eventual loss of its integrity, with the need for replacement or repair. ... Tissue engineering relies upon three essential pillars; the scaffold, the cells seeded on ...

  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. Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

    Science.gov (United States)

    Thavornyutikarn, Boonlom; Chantarapanich, Nattapon; Sitthiseripratip, Kriskrai; Thouas, George A; Chen, Qizhi

    Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

  5. Bioreactors for Tissue Engineering of Cartilage

    Science.gov (United States)

    Concaro, S.; Gustavson, F.; Gatenholm, P.

    The cartilage regenerative medicine field has evolved during the last decades. The first-generation technology, autologous chondrocyte transplantation (ACT) involved the transplantation of in vitro expanded chondrocytes to cartilage defects. The second generation involves the seeding of chondrocytes in a three-dimensional scaffold. The technique has several potential advantages such as the ability of arthroscopic implantation, in vitro pre-differentiation of cells and implant stability among others (Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L, N Engl J Med 331(14):889-895, 1994; Henderson I, Francisco R, Oakes B, Cameron J, Knee 12(3):209-216, 2005; Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A, Clin Orthop (374):212-234, 2000; Nagel-Heyer S, Goepfert C, Feyerabend F, Petersen JP, Adamietz P, Meenen NM, et al. Bioprocess Biosyst Eng 27(4):273-280, 2005; Portner R, Nagel-Heyer S, Goepfert C, Adamietz P, Meenen NM, J Biosci Bioeng 100(3):235-245, 2005; Nagel-Heyer S, Goepfert C, Adamietz P, Meenen NM, Portner R, J Biotechnol 121(4):486-497, 2006; Heyland J, Wiegandt K, Goepfert C, Nagel-Heyer S, Ilinich E, Schumacher U, et al. Biotechnol Lett 28(20):1641-1648, 2006). The nutritional requirements of cells that are synthesizing extra-cellular matrix increase along the differentiation process. The mass transfer must be increased according to the tissue properties. Bioreactors represent an attractive tool to accelerate the biochemical and mechanical properties of the engineered tissues providing adequate mass transfer and physical stimuli. Different reactor systems have been [5] developed during the last decades based on different physical stimulation concepts. Static and dynamic compression, confined and nonconfined compression-based reactors have been described in this review. Perfusion systems represent an attractive way of culturing constructs under dynamic conditions. Several groups showed increased matrix

  6. Scientific and industrial status of tissue engineering ...

    African Journals Online (AJOL)

    Tissue engineering is a newly emerging field targeting many unresolved health problems. So far, the achievements of this technology in the production of different tissue engineered substitutes were promising. This review is intended to describe, briefly and in a simple language, what tissue engineering is, what the ...

  7. Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor

    Science.gov (United States)

    Sikavitsas, Vassilios I.; Bancroft, Gregory N.; Mikos, Antonios G.; McIntire, L. V. (Principal Investigator)

    2002-01-01

    The aim of this study is to investigate the effect of the cell culture conditions of three-dimensional polymer scaffolds seeded with rat marrow stromal cells (MSCs) cultured in different bioreactors concerning the ability of these cells to proliferate, differentiate towards the osteoblastic lineage, and generate mineralized extracellular matrix. MSCs harvested from male Sprague-Dawley rats were culture expanded, seeded on three-dimensional porous 75:25 poly(D,L-lactic-co-glycolic acid) biodegradable scaffolds, and cultured for 21 days under static conditions or in two model bioreactors (a spinner flask and a rotating wall vessel) that enhance mixing of the media and provide better nutrient transport to the seeded cells. The spinner flask culture demonstrated a 60% enhanced proliferation at the end of the first week when compared to static culture. On day 14, all cell/polymer constructs exhibited their maximum alkaline phosphatase activity (AP). Cell/polymer constructs cultured in the spinner flask had 2.4 times higher AP activity than constructs cultured under static conditions on day 14. The total osteocalcin (OC) secretion in the spinner flask culture was 3.5 times higher than the static culture, with a peak OC secretion occurring on day 18. No considerable AP activity and OC secretion were detected in the rotating wall vessel culture throughout the 21-day culture period. The spinner flask culture had the highest calcium content at day 14. On day 21, the calcium deposition in the spinner flask culture was 6.6 times higher than the static cultured constructs and over 30 times higher than the rotating wall vessel culture. Histological sections showed concentration of cells and mineralization at the exterior of the foams at day 21. This phenomenon may arise from the potential existence of nutrient concentration gradients at the interior of the scaffolds. The better mixing provided in the spinner flask, external to the outer surface of the scaffolds, may explain the

  8. Diffusion chamber system for testing of collagen-based cell migration barriers for separation of ligament enthesis zones in tissue-engineered ACL constructs.

    Science.gov (United States)

    Hahner, J; Hoyer, M; Hillig, S; Schulze-Tanzil, G; Meyer, M; Schröpfer, M; Lohan, A; Garbe, L-A; Heinrich, G; Breier, A

    2015-01-01

    A temporary barrier separating scaffold zones seeded with different cell types prevents faster growing cells from overgrowing co-cultured cells within the same construct. This barrier should allow sufficient nutrient diffusion through the scaffold. The aim of this study was to test the effect of two variants of collagen-based barriers on macromolecule diffusion, viability, and the spreading efficiency of primary ligament cells on embroidered scaffolds. Two collagen barriers, a thread consisting of a twisted film tape and a sponge, were integrated into embroidered poly(lactic-co-caprolactone) and polypropylene scaffolds, which had the dimension of lapine anterior cruciate ligaments (ACL). A diffusion chamber system was designed and established to monitor nutrient diffusion using fluorescein isothiocyanate-labeled dextran of different molecular weights (20, 40, 150, 500 kDa). Vitality of primary lapine ACL cells was tested at days 7 and 14 after seeding using fluorescein diacetate and ethidium bromide staining. Cell spreading on the scaffold surface was measured using histomorphometry. Nuclei staining of the cross-sectioned scaffolds revealed the penetration of ligament cells through both barrier types. The diffusion chamber was suitable to characterize the diffusivity of dextran molecules through embroidered scaffolds with or without integrated collagen barriers. The diffusion coefficients were generally significantly lower in scaffolds with barriers compared to those without barriers. No significant differences between diffusion coefficients of both barrier types were detected. Both barriers were cyto-compatible and prevented most of the ACL cells from crossing the barrier, whereby the collagen thread was easier to handle and allowed a higher rate of cell spreading.

  9. Tissue engineering and surgery: from translational studies to human trials

    Directory of Open Access Journals (Sweden)

    Vranckx Jan Jeroen

    2017-06-01

    Full Text Available Tissue engineering was introduced as an innovative and promising field in the mid-1980s. The capacity of cells to migrate and proliferate in growth-inducing medium induced great expectancies on generating custom-shaped bioconstructs for tissue regeneration. Tissue engineering represents a unique multidisciplinary translational forum where the principles of biomaterial engineering, the molecular biology of cells and genes, and the clinical sciences of reconstruction would interact intensively through the combined efforts of scientists, engineers, and clinicians. The anticipated possibilities of cell engineering, matrix development, and growth factor therapies are extensive and would largely expand our clinical reconstructive armamentarium. Application of proangiogenic proteins may stimulate wound repair, restore avascular wound beds, or reverse hypoxia in flaps. Autologous cells procured from biopsies may generate an ‘autologous’ dermal and epidermal laminated cover on extensive burn wounds. Three-dimensional printing may generate ‘custom-made’ preshaped scaffolds – shaped as a nose, an ear, or a mandible – in which these cells can be seeded. The paucity of optimal donor tissues may be solved with off-the-shelf tissues using tissue engineering strategies. However, despite the expectations, the speed of translation of in vitro tissue engineering sciences into clinical reality is very slow due to the intrinsic complexity of human tissues. This review focuses on the transition from translational protocols towards current clinical applications of tissue engineering strategies in surgery.

  10. 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.

  11. The Application of Corals in Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Iraj Nabipour

    2017-05-01

    Full Text Available Natural coral exoskeleton and coralline hydroxyapatite have been used as bone replacement graft for repairing of bone defects in animal models and humans since two decades ago. These bone replacement grafts have an osteoconductive, biodegradable and biocompatible features. Currently, three lines of researches in bone tissue engineering are conducting on corals. Corals have been used for construction of bony composites, stem cells attachments, and the growth factors-scaffold-based approaches. This review have paid to the wide range of coral use in clinical experiments as a bone graft substitute and cell-scaffold-based approaches in bone tissue engineering.

  12. 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.

  13. 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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Fibre-reinforced hydrogels for tissue engineering

    Science.gov (United States)

    Waters, Sarah; Byrne, Helen; Chen, Mike; Dias Castilho, Miguel; Kimpton, Laura; Please, Colin; Whiteley, Jonathan

    2017-11-01

    Tissue engineers aim to grow replacement tissues in vitro to replace those in the body that have been damaged through age, trauma or disease. One approach is to seed cells within a scaffold consisting of an interconnected 3D-printed lattice of polymer fibres, cast in a hydrogel, and subject the construct (cell-seeded scaffold) to an applied load in a bioreactor. A key question is to understand how this applied load is distributed throughout the construct to the mechanosensitive cells. To address this, we exploit the disparate length scales (small inter-fibre spacing compared with construct dimensions). The fibres are treated as a linear elastic material and the hydrogel as a poroelastic material. We employ homogenisation theory to derive equations governing the material properties of a periodic, elastic-poroelastic composite. To validate the mobel, model solutions are compared to experimental data describing the unconfined compression of the fibre-reinforced hydrogels. The model is used to derive the bulk mechanical properties of a cylindrical construct of the composite material for a range of fibre spacings, and the local mechanical environment experienced by cells embedded within the construct is determined. Funded by the European Union Seventh Framework Programme (FP7/2007-2013).

  15. Biomaterials in myocardial tissue engineering

    Science.gov (United States)

    Reis, Lewis A.; Chiu, Loraine L. Y.; Feric, Nicole; Fu, Lara; Radisic, Milica

    2016-01-01

    Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternate sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end-stage heart failure is a heart transplant. In this review we focus on biomaterial approaches to augment injured or impaired myocardium with specific emphasis on: the design criteria for these biomaterials; the types of scaffolds—composed of natural or synthetic biomaterials, or decellularized extracellular matrix—that have been used to develop cardiac patches and tissue models; methods to vascularize scaffolds and engineered tissue, and finally injectable biomaterials (hydrogels)designed for endogenous repair, exogenous repair or as bulking agents to maintain ventricular geometry post-infarct. The challenges facing the field and obstacles that must be overcome to develop truly clinically viable cardiac therapies are also discussed. PMID:25066525

  16. Silk fibroin in tissue engineering.

    Science.gov (United States)

    Kasoju, Naresh; Bora, Utpal

    2012-07-01

    Tissue engineering (TE) is a multidisciplinary field that aims at the in vitro engineering of tissues and organs by integrating science and technology of cells, materials and biochemical factors. Mimicking the natural extracellular matrix is one of the critical and challenging technological barriers, for which scaffold engineering has become a prime focus of research within the field of TE. Amongst the variety of materials tested, silk fibroin (SF) is increasingly being recognized as a promising material for scaffold fabrication. Ease of processing, excellent biocompatibility, remarkable mechanical properties and tailorable degradability of SF has been explored for fabrication of various articles such as films, porous matrices, hydrogels, nonwoven mats, etc., and has been investigated for use in various TE applications, including bone, tendon, ligament, cartilage, skin, liver, trachea, nerve, cornea, eardrum, dental, bladder, etc. The current review extensively covers the progress made in the SF-based in vitro engineering and regeneration of various human tissues and identifies opportunities for further development of this field. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Nanoparticles for bone tissue engineering.

    Science.gov (United States)

    Vieira, Sílvia; Vial, Stephanie; Reis, Rui L; Oliveira, J Miguel

    2017-05-01

    Tissue engineering (TE) envisions the creation of functional substitutes for damaged tissues through integrated solutions, where medical, biological, and engineering principles are combined. Bone regeneration is one of the areas in which designing a model that mimics all tissue properties is still a challenge. The hierarchical structure and high vascularization of bone hampers a TE approach, especially in large bone defects. Nanotechnology can open up a new era for TE, allowing the creation of nanostructures that are comparable in size to those appearing in natural bone. Therefore, nanoengineered systems are now able to more closely mimic the structures observed in naturally occurring systems, and it is also possible to combine several approaches - such as drug delivery and cell labeling - within a single system. This review aims to cover the most recent developments on the use of different nanoparticles for bone TE, with emphasis on their application for scaffolds improvement; drug and gene delivery carriers, and labeling techniques. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:590-611, 2017. © 2017 American Institute of Chemical Engineers.

  18. Growth factor stimulation improves the structure and properties of scaffold-free engineered auricular cartilage constructs.

    Directory of Open Access Journals (Sweden)

    Renata G Rosa

    Full Text Available The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1 was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm. While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation.

  19. Membrane supported scaffold architectures for tissue engineering

    NARCIS (Netherlands)

    Bettahalli Narasimha, M.S.

    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 sufficient

  20. Extracellular matrix and tissue engineering applications

    NARCIS (Netherlands)

    Fernandes, H.A.M.; Moroni, Lorenzo; van Blitterswijk, Clemens; de Boer, 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

  1. Biological aspects of tissue-engineered cartilage.

    Science.gov (United States)

    Hoshi, Kazuto; Fujihara, Yuko; Yamawaki, Takanori; Harai, Motohiro; Asawa, Yukiyo; Hikita, Atsuhiko

    2018-04-01

    Cartilage regenerative medicine has been progressed well, and it reaches the stage of clinical application. Among various techniques, tissue engineering, which incorporates elements of materials science, is investigated earnestly, driven by high clinical needs. The cartilage tissue engineering using a poly lactide scaffold has been exploratorily used in the treatment of cleft lip-nose patients, disclosing good clinical results during 3-year observation. However, to increase the reliability of this treatment, not only accumulation of clinical evidence on safety and usefulness of the tissue-engineered products, but also establishment of scientific background on biological mechanisms, are regarded essential. In this paper, we reviewed recent trends of cartilage tissue engineering in clinical practice, summarized experimental findings on cellular and matrix changes during the cartilage regeneration, and discussed the importance of further studies on biological aspects of tissue-engineered cartilage, especially by the histological and the morphological methods.

  2. Piezoelectric smart biomaterials for bone and cartilage tissue engineering.

    Science.gov (United States)

    Jacob, Jaicy; More, Namdev; Kalia, Kiran; Kapusetti, Govinda

    2018-01-01

    Tissues like bone and cartilage are remodeled dynamically for their functional requirements by signaling pathways. The signals are controlled by the cells and extracellular matrix and transmitted through an electrical and chemical synapse. Scaffold-based tissue engineering therapies largely disturb the natural signaling pathways, due to their rigidity towards signal conduction, despite their therapeutic advantages. Thus, there is a high need of smart biomaterials, which can conveniently generate and transfer the bioelectric signals analogous to native tissues for appropriate physiological functions. Piezoelectric materials can generate electrical signals in response to the applied stress. Furthermore, they can stimulate the signaling pathways and thereby enhance the tissue regeneration at the impaired site. The piezoelectric scaffolds can act as sensitive mechanoelectrical transduction systems. Hence, it is applicable to the regions, where mechanical loads are predominant. The present review is mainly concentrated on the mechanism related to the electrical stimulation in a biological system and the different piezoelectric materials suitable for bone and cartilage tissue engineering.

  3. 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. © 2015 by the Wound Healing Society.

  4. Tissue-engineered trachea: History, problems and the future

    OpenAIRE

    Tan, Qiang; Steiner, Rudolf; Hoerstrup, Simon P.; Weder, Walter

    2017-01-01

    This review tries to summarize the efforts over the past 20 years to construct a tissue-engineered trachea. After illustrating the main technical bottlenecks faced nowadays, we discuss what might be the solutions to these bottlenecks. You may find out why the focus in this research field shifts dramatically from the construction of a tubular cartilage tissue to reepithelialization and revascularization of the prosthesis. In the end we propose a novel concept of ‘in vivo bioreactor', defined a...

  5. Biocompatibility of biodegradable semiconducting melanin films for nerve tissue engineering.

    Science.gov (United States)

    Bettinger, Christopher J; Bruggeman, Joost P; Misra, Asish; Borenstein, Jeffrey T; Langer, Robert

    2009-06-01

    The advancement of tissue engineering is contingent upon the development and implementation of advanced biomaterials. Conductive polymers have demonstrated potential for use as a medium for electrical stimulation, which has shown to be beneficial in many regenerative medicine strategies including neural and cardiac tissue engineering. Melanins are naturally occurring pigments that have previously been shown to exhibit unique electrical properties. This study evaluates the potential use of melanin films as a semiconducting material for tissue engineering applications. Melanin thin films were produced by solution processing and the physical properties were characterized. Films were molecularly smooth with a roughness (R(ms)) of 0.341 nm and a conductivity of 7.00+/-1.10 x 10(-5)S cm(-1) in the hydrated state. In vitro biocompatibility was evaluated by Schwann cell attachment and growth as well as neurite extension in PC12 cells. In vivo histology was evaluated by examining the biomaterial-tissue response of melanin implants placed in close proximity to peripheral nerve tissue. Melanin thin films enhanced Schwann cell growth and neurite extension compared to collagen films in vitro. Melanin films induced an inflammation response that was comparable to silicone implants in vivo. Furthermore, melanin implants were significantly resorbed after 8 weeks. These results suggest that solution-processed melanin thin films have the potential for use as a biodegradable semiconducting biomaterial for use in tissue engineering applications.

  6. Growth Factor Stimulation Improves the Structure and Properties of Scaffold-Free Engineered Auricular Cartilage Constructs

    Science.gov (United States)

    Rosa, Renata G.; Joazeiro, Paulo P.; Bianco, Juares; Kunz, Manuela; Weber, Joanna F.; Waldman, Stephen D.

    2014-01-01

    The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation. PMID:25126941

  7. Oligoaniline-based conductive biomaterials for tissue engineering.

    Science.gov (United States)

    Zarrintaj, Payam; Bakhshandeh, Behnaz; Saeb, Mohammad Reza; Sefat, Farshid; Rezaeian, Iraj; Ganjali, Mohammad Reza; Ramakrishna, Seeram; Mozafari, Masoud

    2018-05-01

    The science and engineering of biomaterials have improved the human life expectancy. Tissue engineering is one of the nascent strategies with an aim to fulfill this target. Tissue engineering scaffolds are one of the most significant aspects of the recent tissue repair strategies; hence, it is imperative to design biomimetic substrates with suitable features. Conductive substrates can ameliorate the cellular activity through enhancement of cellular signaling. Biocompatible polymers with conductivity can mimic the cells' niche in an appropriate manner. Bioconductive polymers based on aniline oligomers can potentially actualize this purpose because of their unique and tailoring properties. The aniline oligomers can be positioned within the molecular structure of other polymers, thus painter acting with the side groups of the main polymer or acting as a comonomer in their backbone. The conductivity of oligoaniline-based conductive biomaterials can be tailored to mimic the electrical and mechanical properties of targeted tissues/organs. These bioconductive substrates can be designed with high mechanical strength for hard tissues such as the bone and with high elasticity to be used for the cardiac tissue or can be synthesized in the form of injectable hydrogels, particles, and nanofibers for noninvasive implantation; these structures can be used for applications such as drug/gene delivery and extracellular biomimetic structures. It is expected that with progress in the fields of biomaterials and tissue engineering, more innovative constructs will be proposed in the near future. This review discusses the recent advancements in the use of oligoaniline-based conductive biomaterials for tissue engineering and regenerative medicine applications. The tissue engineering applications of aniline oligomers and their derivatives have recently attracted an increasing interest due to their electroactive and biodegradable properties. However, no reports have systematically reviewed

  8. 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.

  9. 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

  10. Bone tissue engineering using silica-based mesoporous nanobiomaterials:Recent progress.

    Science.gov (United States)

    Shadjou, Nasrin; Hasanzadeh, Mohammad

    2015-10-01

    Bone disorders are of significant concern due to increase in the median age of our population. It is in this context that tissue engineering has been emerging as a valid approach to the current therapies for bone regeneration/substitution. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Silica based mesostructured nanomaterials possessing pore sizes in the range 2-50 nm and surface reactive functionalities have elicited immense interest due to their exciting prospects in bone tissue engineering. In this review we describe application of silica-based mesoporous nanomaterials for bone tissue engineering. We summarize the preparation methods, the effect of mesopore templates and composition on the mesopore-structure characteristics, and different forms of these materials, including particles, fibers, spheres, scaffolds and composites. Also, the effect of structural and textural properties of mesoporous materials on development of new biomaterials for production of bone implants and bone cements was discussed. Also, application of different mesoporous materials on construction of manufacture 3-dimensional scaffolds for bone tissue engineering was discussed. It begins by giving the reader a brief background on tissue engineering, followed by a comprehensive description of all the relevant components of silica-based mesoporous biomaterials on bone tissue engineering, going from materials to scaffolds and from cells to tissue engineering strategies that will lead to "engineered" bone. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. 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.

  12. 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.

  13. 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.

  14. Tissue engineering in the treatment of cartilage lesions

    Directory of Open Access Journals (Sweden)

    Jakob Naranđa

    2013-11-01

    Full Text Available Background: Articular cartilage lesions with the inherent limited healing potential are difficult to treat and thus remain a challenging problem for orthopaedic surgeons. Regenerative treatment techniques, such as autologous chondrocyte implantation (ACI, are promising as a treatment option to restore hyaline-like cartilage tissue in damaged articular surfaces, as opposed to the traditional reparative procedures (e.g. bone marrow stimulation – microfracture, which promote a fibrocartilage formation with lower tissue biomechanical properties and poorer clinical results. ACI technique has undergone several advances and is constantly improving. The new concept of cartilage tissue preservation uses tissue-engineering technologies, combining new biomaterials as a scaffold, application of growth factors, use of stem cells, and mechanical stimulation. The recent development of new generations of ACI uses a cartilage-like tissue in a 3-dimensional culture system that is based on the use of biodegradable material which serves as a temporary scaffold for the in vitro growth and subsequent implantation into the cartilage defect. For clinical practice, single stage procedures appear attractive to reduce cost and patient morbidity. Finally, modern concept of tissue engineering facilitates hyaline-like cartilage formation and a permanent treatment of cartilage lesions.Conclusion: The review focuses on innovations in the treatment of cartilage lesions and covers modern concepts of tissue engineering with the use of biomaterials, growth factors, stem cells and bioreactors, and presents options for clinical use.

  15. Textile Technologies and Tissue Engineering: A Path Towards Organ Weaving

    OpenAIRE

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

    2016-01-01

    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, pore size and mechanical properties of the fabrics play important role in the effective use of textile technol...

  16. [Development of computer aided forming techniques in manufacturing scaffolds for bone tissue engineering].

    Science.gov (United States)

    Wei, Xuelei; Dong, Fuhui

    2011-12-01

    To review recent advance in the research and application of computer aided forming techniques for constructing bone tissue engineering scaffolds. The literature concerning computer aided forming techniques for constructing bone tissue engineering scaffolds in recent years was reviewed extensively and summarized. Several studies over last decade have focused on computer aided forming techniques for bone scaffold construction using various scaffold materials, which is based on computer aided design (CAD) and bone scaffold rapid prototyping (RP). CAD include medical CAD, STL, and reverse design. Reverse design can fully simulate normal bone tissue and could be very useful for the CAD. RP techniques include fused deposition modeling, three dimensional printing, selected laser sintering, three dimensional bioplotting, and low-temperature deposition manufacturing. These techniques provide a new way to construct bone tissue engineering scaffolds with complex internal structures. With rapid development of molding and forming techniques, computer aided forming techniques are expected to provide ideal bone tissue engineering scaffolds.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  18. Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

    Science.gov (United States)

    Henkel, Jan; Woodruff, Maria A.; Epari, Devakara R.; Steck, Roland; Glatt, Vaida; Dickinson, Ian C.; Choong, Peter F. M.; Schuetz, Michael A.; Hutmacher, Dietmar W.

    2013-01-01

    The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental “origin” require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts. PMID:26273505

  19. 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)

  20. 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.

  1. Stem cells in bone tissue engineering

    International Nuclear Information System (INIS)

    Seong, Jeong Min; Kim, Byung-Chul; Park, Jae-Hong; Kwon, Il Keun; Hwang, Yu-Shik; Mantalaris, Anathathios

    2010-01-01

    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)

  2. Esophageal tissue engineering: a new approach for esophageal replacement.

    Science.gov (United States)

    Totonelli, Giorgia; Maghsoudlou, Panagiotis; Fishman, Jonathan M; Orlando, Giuseppe; Ansari, Tahera; Sibbons, Paul; Birchall, Martin A; Pierro, Agostino; Eaton, Simon; De Coppi, Paolo

    2012-12-21

    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

  3. Cell-laden hydrogels for osteochondral and cartilage tissue engineering.

    Science.gov (United States)

    Yang, Jingzhou; Zhang, Yu Shrike; Yue, Kan; Khademhosseini, Ali

    2017-07-15

    Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered artificial matrices that can replace the damaged regions and promote tissue regeneration. Hydrogels are emerging as a promising class of biomaterials for both soft and hard tissue regeneration. Many critical properties of hydrogels, such as mechanical stiffness, elasticity, water content, bioactivity, and degradation, can be rationally designed and conveniently tuned by proper selection of the material and chemistry. Particularly, advances in the development of cell-laden hydrogels have opened up new possibilities for cell therapy. In this article, we describe the problems encountered in this field and review recent progress in designing cell-hydrogel hybrid constructs for promoting the reestablishment of osteochondral/cartilage tissues. Our focus centers on the effects of hydrogel type, cell type, and growth factor delivery on achieving efficient chondrogenesis and osteogenesis. We give our perspective on developing next-generation matrices with improved physical and biological properties for osteochondral/cartilage tissue engineering. We also highlight recent advances in biomanufacturing technologies (e.g. molding, bioprinting, and assembly) for fabrication of hydrogel-based osteochondral and cartilage constructs with complex compositions and microarchitectures to mimic their native counterparts. Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue-engineered biomaterials that replace the damaged regions and promote tissue regeneration. Cell-laden hydrogel systems have emerged as a promising tissue-engineering

  4. Controlled drug release for tissue engineering.

    Science.gov (United States)

    Rambhia, Kunal J; Ma, Peter X

    2015-12-10

    Tissue engineering is often referred to as a three-pronged discipline, with each prong corresponding to 1) a 3D material matrix (scaffold), 2) drugs that act on molecular signaling, and 3) regenerative living cells. Herein we focus on reviewing advances in controlled release of drugs from tissue engineering platforms. This review addresses advances in hydrogels and porous scaffolds that are synthesized from natural materials and synthetic polymers for the purposes of controlled release in tissue engineering. We pay special attention to efforts to reduce the burst release effect and to provide sustained and long-term release. Finally, novel approaches to controlled release are described, including devices that allow for pulsatile and sequential delivery. In addition to recent advances, limitations of current approaches and areas of further research are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. 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.

  6. Bioprinting for Neural Tissue Engineering.

    Science.gov (United States)

    Knowlton, Stephanie; Anand, Shivesh; Shah, Twisha; Tasoglu, Savas

    2018-01-01

    Bioprinting is a method by which a cell-encapsulating bioink is patterned to create complex tissue architectures. Given the potential impact of this technology on neural research, we review the current state-of-the-art approaches for bioprinting neural tissues. While 2D neural cultures are ubiquitous for studying neural cells, 3D cultures can more accurately replicate the microenvironment of neural tissues. By bioprinting neuronal constructs, one can precisely control the microenvironment by specifically formulating the bioink for neural tissues, and by spatially patterning cell types and scaffold properties in three dimensions. We review a range of bioprinted neural tissue models and discuss how they can be used to observe how neurons behave, understand disease processes, develop new therapies and, ultimately, design replacement tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Biomechanical regulation of in vitro cardiogenesis for tissue-engineered heart repair.

    Science.gov (United States)

    Zimmermann, Wolfram-Hubertus

    2013-01-01

    The heart is a continuously pumping organ with an average lifespan of eight decades. It develops from the onset of embryonic cardiogenesis under biomechanical load, performs optimally within a defined range of hemodynamic load, and fails if acutely or chronically overloaded. Unloading of the heart leads to defective cardiogenesis in utero, but can also lead to a desired therapeutic outcome (for example, in patients with heart failure under left ventricular assist device therapy). In light of the well-documented relevance of mechanical loading for cardiac physiology and pathology, it is plausible that tissue engineers have integrated mechanical stimulation regimens into protocols for heart muscle construction. To achieve optimal results, physiological principles of beat-to-beat myocardial loading and unloading should be simulated. In addition, heart muscle engineering, in particular if based on pluripotent stem cell-derived cardiomyocytes, may benefit from staggered tonic loading protocols to simulate viscoelastic properties of the prenatal and postnatal myocardial stroma. This review will provide an overview of heart muscle mechanics, summarize observations on the role of mechanical loading for heart development and postnatal performance, and discuss how physiological loading regimens can be exploited to advance myocardial tissue engineering towards a therapeutic application.

  8. Tissue bionics: examples in biomimetic tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Green, David W [Bone and Joint Research Group, Developmental Origins of Health and Disease, General Hospital, University of Southampton, SO16 6YD (United Kingdom)], E-mail: Hindoostuart@googlemail.com

    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.

  9. Tissue bionics: examples in biomimetic tissue engineering

    International Nuclear Information System (INIS)

    Green, David W

    2008-01-01

    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

  10. Proangiogenic scaffolds as functional templates for cardiac tissue engineering.

    Science.gov (United States)

    Madden, Lauran R; Mortisen, Derek J; Sussman, Eric M; Dupras, Sarah K; Fugate, James A; Cuy, Janet L; Hauch, Kip D; Laflamme, Michael A; Murry, Charles E; Ratner, Buddy D

    2010-08-24

    We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.

  11. The Crosstalk between Tissue Engineering and Pharmaceutical Biotechnology: Recent Advances and Future Directions.

    Science.gov (United States)

    Pacheco, Daniela P; Reis, Rui L; Correlo, Vítor M; Marques, Alexandra P

    2015-01-01

    Tissue-engineered constructs made of biotechnology-derived materials have been preferred due to their chemical and physical composition, which offers both high versatility and a support to enclose/ incorporate relevant signaling molecules and/or genes known to therapeutically induce tissue repair. Herein, a critical overview of the impact of different biotechnology-derived materials, scaffolds, and recombinant signaling molecules over the behavior of cells, another element of tissue engineered constructs, as well its regulatory role in tissue regeneration and disease progression is given. Additionally, these tissue-engineered constructs evolved to three-dimensional (3D) tissue-like models that, as an advancement of two-dimensional standard culture methods, are expected to be a valuable tool in the field of drug discovery and pharmaceutical research. Despite the improved design and conception of current proposed 3D tissue-like models, advanced control systems to enable and accelerate streamlining and automation of the numerous labor-intensive steps intrinsic to the development of tissue-engineered constructs are still to be achieved. In this sense, this review intends to present the biotechnology- derived materials that are being explored in the field of tissue engineering to generate 3D tissue-analogues and briefly highlight their foremost breakthroughs in tissue regeneration and drug discovery. It also aims to reinforce that the crosstalk between tissue engineering and pharmaceutical biotechnology has been fostering the outcomes of tissue engineering approaches through the use of biotechnology-derived signaling molecules. Gene delivery/therapy is also discussed as a forefront area that represents another cross point between tissue engineering and pharmaceutical biotechnology, in which nucleic acids can be considered a "super pharmaceutical" to drive biological responses, including tissue regeneration.

  12. New trends in spinal cord tissue engineering

    Czech Academy of Sciences Publication Activity Database

    Kubinová, Šárka

    2015-01-01

    Roč. 10, č. 2 (2015), s. 129-145 ISSN 1479-6708 R&D Projects: GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : biomaterial * cell therapy * regenerative medicine * spinal cord injury * stem cells scaffold * tissue engineering Subject RIV: FH - Neurology

  13. Degradable Adhesives for Surgery and Tissue Engineering.

    Science.gov (United States)

    Bhagat, Vrushali; Becker, Matthew L

    2017-10-09

    This review highlights the research on degradable polymeric tissue adhesives for surgery and tissue engineering. Included are a comprehensive listing of specific uses, advantages, and disadvantages of different adhesive groups. A critical evaluation of challenges affecting the development of next generation materials is also discussed, and insights into the outlook of the field are explored.

  14. Principles of Tissue Engineering for Food

    NARCIS (Netherlands)

    Post, M.; Weele, van der Cor

    2014-01-01

    The technology required for tissue-engineering food is the same as for medical applications, and in fact is derived from it. There are major differences in the implementation of those technologies, primarily related to the enormous scale required for food production and the different economical

  15. MicroRNAs in skin tissue engineering.

    Science.gov (United States)

    Miller, Kyle J; Brown, David A; Ibrahim, Mohamed M; Ramchal, Talisha D; Levinson, Howard

    2015-07-01

    35.2 million annual cases in the U.S. require clinical intervention for major skin loss. To meet this demand, the field of skin tissue engineering has grown rapidly over the past 40 years. Traditionally, skin tissue engineering relies on the "cell-scaffold-signal" approach, whereby isolated cells are formulated into a three-dimensional substrate matrix, or scaffold, and exposed to the proper molecular, physical, and/or electrical signals to encourage growth and differentiation. However, clinically available bioengineered skin equivalents (BSEs) suffer from a number of drawbacks, including time required to generate autologous BSEs, poor allogeneic BSE survival, and physical limitations such as mass transfer issues. Additionally, different types of skin wounds require different BSE designs. MicroRNA has recently emerged as a new and exciting field of RNA interference that can overcome the barriers of BSE design. MicroRNA can regulate cellular behavior, change the bioactive milieu of the skin, and be delivered to skin tissue in a number of ways. While it is still in its infancy, the use of microRNAs in skin tissue engineering offers the opportunity to both enhance and expand a field for which there is still a vast unmet clinical need. Here we give a review of skin tissue engineering, focusing on the important cellular processes, bioactive mediators, and scaffolds. We further discuss potential microRNA targets for each individual component, and we conclude with possible future applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Elastin as a biomaterial for tissue engineering.

    NARCIS (Netherlands)

    Daamen, W.F.; Veerkamp, J.H.; Hest, J.C.M. van; Kuppevelt, A.H.M.S.M. van

    2007-01-01

    Biomaterials based upon elastin and elastin-derived molecules are increasingly investigated for their application in tissue engineering. This interest is fuelled by the remarkable properties of this structural protein, such as elasticity, self-assembly, long-term stability, and biological activity.

  17. Biomaterials and tissue engineering in reconstructive surgery

    Indian Academy of Sciences (India)

    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.

  18. Biomechanics and mechanobiology in functional tissue engineering

    NARCIS (Netherlands)

    Guilak, F.; Butler, D.L.; Goldstein, S.A.; Baaijens, F.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

  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. Modeling the development of tissue engineered cartilage

    NARCIS (Netherlands)

    Sengers, B.G.

    2005-01-01

    The limited healing capacity of articular cartilage forms a major clinical problem. In general, current treatments of cartilage damage temporarily reliefs symptoms, but fail in the long term. Tissue engineering (TE) has been proposed as a more permanent repair strategy. Cartilage TE aims at

  1. 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

  2. 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

  3. Co-culture in cartilage tissue engineering.

    NARCIS (Netherlands)

    Hendriks, J.A.A.; Riesle, J.U.; van Blitterswijk, Clemens

    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

  4. 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.

  5. Chitosan based nanofibers in bone tissue engineering.

    Science.gov (United States)

    Balagangadharan, K; Dhivya, S; Selvamurugan, N

    2017-11-01

    Bone tissue engineering involves biomaterials, cells and regulatory factors to make biosynthetic bone grafts with efficient mineralization for regeneration of fractured or damaged bones. Out of all the techniques available for scaffold preparation, electrospinning is given priority as it can fabricate nanostructures. Also, electrospun nanofibers possess unique properties such as the high surface area to volume ratio, porosity, stability, permeability and morphological similarity to that of extra cellular matrix. Chitosan (CS) has a significant edge over other materials and as a graft material, CS can be used alone or in combination with other materials in the form of nanofibers to provide the structural and biochemical cues for acceleration of bone regeneration. Hence, this review was aimed to provide a detailed study available on CS and its composites prepared as nanofibers, and their associated properties found suitable for bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Tissue Engineering: Current Strategies and Future Directions

    OpenAIRE

    Olson, Jennifer L.; Atala, Anthony; Yoo, James J.

    2011-01-01

    Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, or other clinical issues. Currently, patients with diseased and injured organs are often treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and as the number of new cases of organ failure increases. Scientists in the field of regenerative medicine and tissue eng...

  7. Recombinant protein scaffolds for tissue engineering

    International Nuclear Information System (INIS)

    Werkmeister, Jerome A; Ramshaw, John A M

    2012-01-01

    New biological materials for tissue engineering are now being developed using common genetic engineering capabilities to clone and express a variety of genetic elements that allow cost-effective purification and scaffold fabrication from these recombinant proteins, peptides or from chimeric combinations of these. The field is limitless as long as the gene sequences are known. The utility is dependent on the ease, product yield and adaptability of these protein products to the biomedical field. The development of recombinant proteins as scaffolds, while still an emerging technology with respect to commercial products, is scientifically superior to current use of natural materials or synthetic polymer scaffolds, in terms of designing specific structures with desired degrees of biological complexities and motifs. In the field of tissue engineering, next generation scaffolds will be the key to directing appropriate tissue regeneration. The initial period of biodegradable synthetic scaffolds that provided shape and mechanical integrity, but no biological information, is phasing out. The era of protein scaffolds offers distinct advantages, particularly with the combination of powerful tools of molecular biology. These include, for example, the production of human proteins of uniform quality that are free of infectious agents and the ability to make suitable quantities of proteins that are found in low quantity or are hard to isolate from tissue. For the particular needs of tissue engineering scaffolds, fibrous proteins like collagens, elastin, silks and combinations of these offer further advantages of natural well-defined structural scaffolds as well as endless possibilities of controlling functionality by genetic manipulation. (topical review)

  8. Tissue engineering and regenerative medicine: manufacturing challenges.

    Science.gov (United States)

    Williams, D J; Sebastine, I M

    2005-12-01

    Tissue engineering and regenerative medicine are interdisciplinary fields that apply principles of engineering and life sciences to develop biological substitutes, typically composed of biological and synthetic components, that restore, maintain or improve tissue function. Many tissue engineering technologies are still at a laboratory or pre-commercial scale. The short review paper describes the most significant manufacturing and bio-process challenges inherent in the commercialisation and exploitation of the exciting results emerging from the biological and clinical laboratories exploring tissue engineering and regenerative medicine. A three-generation road map of the industry has been used to structure a view of these challenges and to define where the manufacturing community can contribute to the commercial success of the products from these emerging fields. The first-generation industry is characterised by its demonstrated clinical applications and products in the marketplace, the second is characterised by emerging clinical applications, and the third generation is characterised by aspirational clinical applications. The paper focuses on the cost reduction requirement of the first generation of the industry to allow more market penetration and consequent patient impact. It indicates the technological requirements, for instance the creation of three-dimensional tissue structures, and value chain issues in the second generation of the industry. The third-generation industry challenges lie in fundamental biological and clinical science. The paper sets out a road map of these generations to identify areas for research.

  9. Electrospun polyurethane membranes for Tissue Engineering applications

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Laís P., E-mail: lagabriel@gmail.com [National Institute of Biofabrication, Campinas (Brazil); Department of Chemical Engineering, University of Campinas, Campinas (Brazil); Rodrigues, Ana Amélia [National Institute of Biofabrication, Campinas (Brazil); Department of Medical Sciences, University of Campinas, Campinas (Brazil); Macedo, Milton; Jardini, André L.; Maciel Filho, Rubens [National Institute of Biofabrication, Campinas (Brazil); Department of Chemical Engineering, University of Campinas, Campinas (Brazil)

    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 72 h 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.

  10. Natural Origin Materials for Osteochondral Tissue Engineering.

    Science.gov (United States)

    Bonani, Walter; Singhatanadgige, Weerasak; Pornanong, Aramwit; Motta, Antonella

    2018-01-01

    Materials selection is a critical aspect for the production of scaffolds for osteochondral tissue engineering. Synthetic materials are the result of man-made operations and have been investigated for a variety of tissue engineering applications. Instead, the products of physiological processes and the metabolic activity of living organisms are identified as natural materials. Over the recent decades, a number of natural materials, namely, biopolymers and bioceramics, have been proposed as the main constituent of osteochondral scaffolds, but also as cell carriers and signaling molecules. Overall, natural materials have been investigated both in the bone and in the cartilage compartment, sometimes alone, but often in combination with other biopolymers or synthetic materials. Biopolymers and bioceramics possess unique advantages over their synthetic counterparts due similarity with natural extracellular matrix, the presence of cell recognition sites and tunable chemistry. However, the characteristics of natural origin materials can vary considerably depending on the specific source and extraction process. A deeper understanding of the relationship between material variability and biological activity and the definition of standardized manufacturing procedures will be crucial for the future of natural materials in tissue engineering.

  11. Injectable biomaterials for adipose tissue engineering

    International Nuclear Information System (INIS)

    Young, D A; Christman, K L

    2012-01-01

    Adipose tissue engineering has recently gained significant attention from materials scientists as a result of the exponential growth of soft tissue filler procedures being performed within the clinic. While several injectable materials are currently being marketed for filling subcutaneous voids, they often face limited longevity due to rapid resorption. Their inability to encourage natural adipose formation or ingrowth necessitates repeated injections for a prolonged effect and thus classifies them as temporary fillers. As a result, a significant need for injectable materials that not only act as fillers but also promote in vivo adipogenesis is beginning to be realized. This paper will discuss the advantages and disadvantages of commercially available soft tissue fillers. It will then summarize the current state of research using injectable synthetic materials, biopolymers and extracellular matrix-derived materials for adipose tissue engineering. Furthermore, the successful attributes observed across each of these materials will be outlined along with a discussion of the current difficulties and future directions for adipose tissue engineering. (paper)

  12. The design and development of a high-throughput magneto-mechanostimulation device for cartilage tissue engineering.

    Science.gov (United States)

    Brady, Mariea A; Vaze, Reva; Amin, Harsh D; Overby, Darryl R; Ethier, C Ross

    2014-02-01

    To recapitulate the in vivo environment and create neo-organoids that replace lost or damaged tissue requires the engineering of devices, which provide appropriate biophysical cues. To date, bioreactors for cartilage tissue engineering have focused primarily on biomechanical stimulation. There is a significant need for improved devices for articular cartilage tissue engineering capable of simultaneously applying multiple biophysical (electrokinetic and mechanical) stimuli. We have developed a novel high-throughput magneto-mechanostimulation bioreactor, capable of applying static and time-varying magnetic fields, as well as multiple and independently adjustable mechanical loading regimens. The device consists of an array of 18 individual stations, each of which uses contactless magnetic actuation and has an integrated Hall Effect sensing system, enabling the real-time measurements of applied field, force, and construct thickness, and hence, the indirect measurement of construct mechanical properties. Validation tests showed precise measurements of thickness, within 14 μm of gold standard calliper measurements; further, applied force was measured to be within 0.04 N of desired force over a half hour dynamic loading, which was repeatable over a 3-week test period. Finally, construct material properties measured using the bioreactor were not significantly different (p=0.97) from those measured using a standard materials testing machine. We present a new method for articular cartilage-specific bioreactor design, integrating combinatorial magneto-mechanostimulation, which is very attractive from functional and cost viewpoints.

  13. 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.

  14. Bioactive glass-based scaffolds for bone tissue engineering

    NARCIS (Netherlands)

    Will, J.; Gerhardt, L.C.; Boccaccini, A.R.

    2012-01-01

    Originally developed to fill and restore bone defects, bioactive glasses are currently also being intensively investigated for bone tissue engineering applications. In this chapter, we review and discuss current knowledge on porous bone tissue engineering scaffolds made from bioactive silicate

  15. 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.

  16. Growth factor effects on costal chondrocytes for tissue engineering fibrocartilage

    Science.gov (United States)

    Johns, D.E.; Athanasiou, K.A.

    2010-01-01

    Tissue engineered fibrocartilage could become a feasible option for replacing tissues like the knee meniscus or temporomandibular joint disc. This study employed five growth factors insulin-like growth factor-I, transforming growth factor-β1, epidermal growth factor, platelet-derived growth factor-BB, and basic fibroblast growth factor in a scaffoldless approach with costal chondrocytes, attempting to improve biochemical and mechanical properties of engineered constructs. Samples were quantitatively assessed for total collagen, glycosaminoglycans, collagen type I, collagen type II, cells, compressive properties, and tensile properties at two time points. Most treated constructs were worse than the no growth factor control, suggesting a detrimental effect, but the IGF treatment tended to improve the constructs. Additionally, the 6wk time point was consistently better than 3wks, with total collagen, glycosaminoglycans, and aggregate modulus doubling during this time. Further optimization of the time in culture and exogenous stimuli will be important in making a more functional replacement tissue. PMID:18597118

  17. 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

  18. The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

    Science.gov (United States)

    Ganguli, Suman; Hunt, C Anthony

    2004-01-01

    Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

  19. 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...

  20. 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

    2017-11-01

    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.

  1. Hydrogels for precision meniscus tissue engineering: a comprehensive review.

    Science.gov (United States)

    Rey-Rico, Ana; Cucchiarini, Magali; Madry, Henning

    The meniscus plays a pivotal role to preserve the knee joint homeostasis. Lesions to the meniscus are frequent, have a reduced ability to heal, and may induce tibiofemoral osteoarthritis. Current reconstructive therapeutic options mainly focus on the treatment of lesions in the peripheral vascularized region. In contrast, few approaches are capable of stimulating repair of damaged meniscal tissue in the central, avascular portion. Tissue engineering approaches are of high interest to repair or replace damaged meniscus tissue in this area. Hydrogel-based biomaterials are of special interest for meniscus repair as its inner part contains relatively high proportions of proteoglycans which are responsible for the viscoelastic compressive properties and hydration grade. Hydrogels exhibiting high water content and providing a specific three-dimensional (3D) microenvironment may be engineered to precisely resemble this topographical composition of the meniscal tissue. Different polymers of both natural and synthetic origins have been manipulated to produce hydrogels hosting relevant cell populations for meniscus regeneration and provide platforms for meniscus tissue replacement. So far, these compounds have been employed to design controlled delivery systems of bioactive molecules involved in meniscal reparative processes or to host genetically modified cells as a means to enhance meniscus repair. This review describes the most recent advances on the use of hydrogels as platforms for precision meniscus tissue engineering.

  2. Tissue engineering of heart valves: in vitro experiences.

    Science.gov (United States)

    Sodian, R; Hoerstrup, S P; Sperling, J S; Daebritz, S H; Martin, D P; Schoen, F J; Vacanti, J P; Mayer, J E

    2000-07-01

    Tissue engineering is a new approach, whereby techniques are being developed to transplant autologous cells onto biodegradable scaffolds to ultimately form new functional tissue in vitro and in vivo. Our laboratory has focused on the tissue engineering of heart valves, and we have fabricated a trileaflet heart valve scaffold from a biodegradable polymer, a polyhydroxyalkanoate. In this experiment we evaluated the suitability of this scaffold material as well as in vitro conditioning to create viable tissue for tissue engineering of a trileaflet heart valve. We constructed a biodegradable and biocompatible trileaflet heart valve scaffold from a porous polyhydroxyalkanoate (Meatabolix Inc, Cambridge, MA). The scaffold consisted of a cylindrical stent (1 x 15 x 20 mm inner diameter) and leaflets (0.3 mm thick), which were attached to the stent by thermal processing techniques. The porous heart valve scaffold (pore size 100 to 240 microm) was seeded with vascular cells grown and expanded from an ovine carotid artery and placed into a pulsatile flow bioreactor for 1, 4, and 8 days. Analysis of the engineered tissue included biochemical examination, enviromental scanning electron microscopy, and histology. It was possible to create a trileaflet heart valve scaffold from polyhydroxyalkanoate, which opened and closed synchronously in a pulsatile flow bioreactor. The cells grew into the pores and formed a confluent layer after incubation and pulsatile flow exposure. The cells were mostly viable and formed connective tissue between the inside and the outside of the porous heart valve scaffold. Additionally, we demonstrated cell proliferation (DNA assay) and the capacity to generate collagen as measured by hydroxyproline assay and movat-stained glycosaminoglycans under in vitro pulsatile flow conditions. Polyhydroxyalkanoates can be used to fabricate a porous, biodegradable heart valve scaffold. The cells appear to be viable and extracellular matrix formation was induced

  3. Silk fibroin porous scaffolds for nucleus pulposus tissue engineering

    International Nuclear Information System (INIS)

    Zeng, Chao; Yang, Qiang; Zhu, Meifeng; Du, Lilong; Zhang, Jiamin; Ma, Xinlong; Xu, Baoshan; Wang, Lianyong

    2014-01-01

    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

  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 Simplified Method for Tissue Engineering Skeletal Muscle Organoids in Vitro

    Science.gov (United States)

    Shansky, Janet; DelTatto, Michael; Chromiak, Joseph; Vandenburgh, Herman

    1996-01-01

    Tissue-engineered three dimensional skeletal muscle organ-like structures have been formed in vitro from primary myoblasts by several different techniques. This report describes a simplified method for generating large numbers of muscle organoids from either primary embryonic avian or neonatal rodent myoblasts, which avoids the requirements for stretching and other mechanical stimulation.

  6. 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.

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

    Science.gov (United States)

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

    2016-12-01

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

  8. Accordion-like honeycombs for tissue engineering of cardiac anisotropy

    Science.gov (United States)

    Engelmayr, George C.; Cheng, Mingyu; Bettinger, Christopher J.; Borenstein, Jeffrey T.; Langer, Robert; Freed, Lisa E.

    2008-12-01

    Tissue-engineered grafts may be useful in myocardial repair; however, previous scaffolds have been structurally incompatible with recapitulating cardiac anisotropy. Here, we use microfabrication techniques to create an accordion-like honeycomb microstructure in poly(glycerol sebacate), which yields porous, elastomeric three-dimensional (3D) scaffolds with controllable stiffness and anisotropy. Accordion-like honeycomb scaffolds with cultured neonatal rat heart cells demonstrated utility through: (1) closely matched mechanical properties compared to native adult rat right ventricular myocardium, with stiffnesses controlled by polymer curing time; (2) heart cell contractility inducible by electric field stimulation with directionally dependent electrical excitation thresholds (pthe formation of grafts with aligned heart cells and mechanical properties more closely resembling native myocardium.

  9. 3D bioprinting and the current applications in tissue engineering.

    Science.gov (United States)

    Huang, Ying; Zhang, Xiao-Fei; Gao, Guifang; Yonezawa, Tomo; Cui, Xiaofeng

    2017-08-01

    Bioprinting as an enabling technology for tissue engineering possesses the promises to fabricate highly mimicked tissue or organs with digital control. As one of the biofabrication approaches, bioprinting has the advantages of high throughput and precise control of both scaffold and cells. Therefore, this technology is not only ideal for translational medicine but also for basic research applications. Bioprinting has already been widely applied to construct functional tissues such as vasculature, muscle, cartilage, and bone. In this review, the authors introduce the most popular techniques currently applied in bioprinting, as well as the various bioprinting processes. In addition, the composition of bioink including scaffolds and cells are described. Furthermore, the most current applications in organ and tissue bioprinting are introduced. The authors also discuss the challenges we are currently facing and the great potential of bioprinting. This technology has the capacity not only in complex tissue structure fabrication based on the converted medical images, but also as an efficient tool for drug discovery and preclinical testing. One of the most promising future advances of bioprinting is to develop a standard medical device with the capacity of treating patients directly on the repairing site, which requires the development of automation and robotic technology, as well as our further understanding of biomaterials and stem cell biology to integrate various printing mechanisms for multi-phasic tissue engineering. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Bridging the divide between neuroprosthetic design, tissue engineering and neurobiology

    Directory of Open Access Journals (Sweden)

    Jennie Leach

    2010-02-01

    Full Text Available Neuroprosthetic devices have made a major impact in the treatment of a variety of disorders such as paralysis and stroke. However, a major impediment in the advancement of this technology is the challenge of maintaining device performance during chronic implantation (months to years due to complex intrinsic host responses such as gliosis or glial scarring. The objective of this review is to bring together research communities in neurobiology, tissue engineering, and neuroprosthetics to address the major obstacles encountered in the translation of neuroprosthetics technology into long-term clinical use. This article draws connections between specific challenges faced by current neuroprosthetics technology and recent advances in the areas of nerve tissue engineering and neurobiology. Within the context of the device-nervous system interface and central nervous system (CNS implants, areas of synergistic opportunity are discussed, including platforms to present cells with multiple cues, controlled delivery of bioactive factors, three-dimensional constructs and in vitro models of gliosis and brain injury, nerve regeneration strategies, and neural stem/progenitor cell (NPC biology. Finally, recent insights gained from the fields of developmental neurobiology and cancer biology are discussed as examples of exciting new biological knowledge that may provide fresh inspiration towards novel technologies to address the complexities associated with long-term neuroprosthetic device performance.

  11. Vascular tissue engineering by computer-aided laser micromachining.

    Science.gov (United States)

    Doraiswamy, Anand; Narayan, Roger J

    2010-04-28

    Many conventional technologies for fabricating tissue engineering scaffolds are not suitable for fabricating scaffolds with patient-specific attributes. For example, many conventional technologies for fabricating tissue engineering scaffolds do not provide control over overall scaffold geometry or over cell position within the scaffold. In this study, the use of computer-aided laser micromachining to create scaffolds for vascular tissue networks was investigated. Computer-aided laser micromachining was used to construct patterned surfaces in agarose or in silicon, which were used for differential adherence and growth of cells into vascular tissue networks. Concentric three-ring structures were fabricated on agarose hydrogel substrates, in which the inner ring contained human aortic endothelial cells, the middle ring contained HA587 human elastin and the outer ring contained human aortic vascular smooth muscle cells. Basement membrane matrix containing vascular endothelial growth factor and heparin was to promote proliferation of human aortic endothelial cells within the vascular tissue networks. Computer-aided laser micromachining provides a unique approach to fabricate small-diameter blood vessels for bypass surgery as well as other artificial tissues with complex geometries.

  12. 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.

  13. 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.

  14. Advances and perspectives in tooth tissue engineering.

    Science.gov (United States)

    Monteiro, Nelson; Yelick, Pamela C

    2017-09-01

    Bio-engineered teeth that can grow and remodel in a manner similar to that of natural teeth have the potential to serve as permanent replacements to the currently used prosthetic teeth, such as dental implants. A major challenge in designing functional bio-engineered teeth is to mimic both the structural and anisotropic mechanical characteristics of the native tooth. Therefore, the field of dental and whole tooth regeneration has advanced towards the molecular and nanoscale design of bio-active, biomimetic systems, using biomaterials, drug delivery systems and stem cells. The focus of this review is to discuss recent advances in tooth tissue engineering, using biomimetic scaffolds that provide proper architectural cues, exhibit the capacity to support dental stem cell proliferation and differentiation and sequester and release bio-active agents, such as growth factors and nucleic acids, in a spatiotemporal controlled manner. Although many in vitro and in vivo studies on tooth regeneration appear promising, before tooth tissue engineering becomes a reality for humans, additional research is needed to perfect methods that use adult human dental stem cells, as opposed to embryonic dental stem cells, and to devise the means to generate bio-engineered teeth of predetermined size and shape. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. 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.

  16. Biomimetic composite coating on rapid prototyped scaffolds for bone tissue engineering.

    Science.gov (United States)

    Arafat, M Tarik; Lam, Christopher X F; Ekaputra, Andrew K; Wong, Siew Yee; Li, Xu; Gibson, Ian

    2011-02-01

    The objective of this present study was to improve the functional performance of rapid prototyped scaffolds for bone tissue engineering through biomimetic composite coating. Rapid prototyped poly(ε-caprolactone)/tri-calcium phosphate (PCL/TCP) scaffolds were fabricated using the screw extrusion system (SES). The fabricated PCL/TCP scaffolds were coated with a carbonated hydroxyapatite (CHA)-gelatin composite via biomimetic co-precipitation. The structure of the prepared CHA-gelatin composite coating was studied by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Compressive mechanical testing revealed that the coating process did not have any detrimental effect on the mechanical properties of the scaffolds. The cell-scaffold interaction was studied by culturing porcine bone marrow stromal cells (BMSCs) on the scaffolds and assessing the proliferation and bone-related gene and protein expression capabilities of the cells. Confocal laser microscopy and SEM images of the cell-scaffold constructs showed a uniformly distributed cell sheet and accumulation of extracellular matrix in the interior of CHA-gelatin composite-coated PCL/TCP scaffolds. The proliferation rate of BMSCs on CHA-gelatin composite-coated PCL/TCP scaffolds was about 2.3 and 1.7 times higher than that on PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds, respectively, by day 10. Furthermore, reverse transcription polymerase chain reaction and Western blot analysis revealed that CHA-gelatin composite-coated PCL/TCP scaffolds stimulate osteogenic differentiation of BMSCs the most, compared with PCL/TCP scaffolds and CHA-coated PCL/TCP scaffolds. These results demonstrate that CHA-gelatin composite-coated rapid prototyped PCL/TCP scaffolds are promising for bone tissue engineering. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  17. 3D Photo-Fabrication for Tissue Engineering and Drug Delivery

    Directory of Open Access Journals (Sweden)

    Rúben F. Pereira

    2015-03-01

    Full Text Available The most promising strategies in tissue engineering involve the integration of a triad of biomaterials, living cells, and biologically active molecules to engineer synthetic environments that closely mimic the healing milieu present in human tissues, and that stimulate tissue repair and regeneration. To be clinically effective, these environments must replicate, as closely as possible, the main characteristics of the native extracellular matrix (ECM on a cellular and subcellular scale. Photo-fabrication techniques have already been used to generate 3D environments with precise architectures and heterogeneous composition, through a multi-layer procedure involving the selective photocrosslinking reaction of a light-sensitive prepolymer. Cells and therapeutic molecules can be included in the initial hydrogel precursor solution, and processed into 3D constructs. Recently, photo-fabrication has also been explored to dynamically modulate hydrogel features in real time, providing enhanced control of cell fate and delivery of bioactive compounds. This paper focuses on the use of 3D photo-fabrication techniques to produce advanced constructs for tissue regeneration and drug delivery applications. State-of-the-art photo-fabrication techniques are described, with emphasis on the operating principles and biofabrication strategies to create spatially controlled patterns of cells and bioactive factors. Considering its fast processing, spatiotemporal control, high resolution, and accuracy, photo-fabrication is assuming a critical role in the design of sophisticated 3D constructs. This technology is capable of providing appropriate environments for tissue regeneration, and regulating the spatiotemporal delivery of therapeutics.

  18. Controlled Bioactive Molecules Delivery Strategies for Tendon and Ligament Tissue Engineering using Polymeric Nanofibers.

    Science.gov (United States)

    Hiong Teh, Thomas Kok; Hong Goh, James Cho; Toh, Siew Lok

    2015-01-01

    The interest in polymeric nanofibers has escalated over the past decade given its promise as tissue engineering scaffolds that can mimic the nanoscale structure of the native extracellular matrix. With functionalization of the polymeric nanofibers using bioactive molecules, localized signaling moieties can be established for the attached cells, to stimulate desired biological effects and direct cellular or tissue response. The inherently high surface area per unit mass of polymeric nanofibers can enhance cell adhesion, bioactive molecules loading and release efficiencies, and mass transfer properties. In this review article, the application of polymeric nanofibers for controlled bioactive molecules delivery will be discussed, with a focus on tendon and ligament tissue engineering. Various polymeric materials of different mechanical and degradation properties will be presented along with the nanofiber fabrication techniques explored. The bioactive molecules of interest for tendon and ligament tissue engineering, including growth factors and small molecules, will also be reviewed and compared in terms of their nanofiber incorporation strategies and release profiles. This article will also highlight and compare various innovative strategies to control the release of bioactive molecules spatiotemporally and explore an emerging tissue engineering strategy involving controlled multiple bioactive molecules sequential release. Finally, the review article concludes with challenges and future trends in the innovation and development of bioactive molecules delivery using polymeric nanofibers for tendon and ligament tissue engineering.

  19. STIMULATION OF CONSTRUCTION OF AFFORDABLE HOUSING BY REFORMATION OF A CONSTRUCTION COMPLEX MANAGEMENT SYSTEM

    Directory of Open Access Journals (Sweden)

    BRONEVYTSKYI S. P.

    2015-10-01

    Full Text Available Purpose. Development of offers on stimulation of construction of affordable housing by reformation of a construction complex management system. Methodology. The revelation of the problems of planning of construction in large cities. The analysis of forming of structure of a build complex management in soviet times and in a transitional period. The revelation of the modern, actual, socio-economic problems of the construction activity management. Proposition on the improvement of methods of construction management in cities of Ukraine. Results. The methods of a construction complex management in countries with a market economy as for building of affordable housing are shown. Originality. In composition of a town-planning documentations, except for the norms of the common use of territories of city (density of population of micro region, the maximum parameters of a construction examining of land areas are proposed to determine: building percent and coefficient of maximum superficial area. Practical value. The principle of management and organization of construction is norms of a build use of territories for building of mass affordable housing for funds of population and investors while providing of the comfort of housing in accordance with state construction norms.

  20. Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice.

    Science.gov (United States)

    Al-Himdani, Sarah; Jessop, Zita M; Al-Sabah, Ayesha; Combellack, Emman; Ibrahim, Amel; Doak, Shareen H; Hart, Andrew M; Archer, Charles W; Thornton, Catherine A; Whitaker, Iain S

    2017-01-01

    Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering "holds the promise of revolutionizing patient care in the twenty-first century." The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20-30 years from the start of basic science research to clinical utility

  1. Do cell based tissue engineering products for meniscus regeneration influence vascularization?

    Science.gov (United States)

    Koch, Matthias; Ehrenreich, Tobias; Koehl, Gudrun; Pattappa, Girish; Pfeifer, Christian; Loibl, Markus; Müller, Michael; Nerlich, Michael; Angele, Peter; Zellner, Johannes

    2017-01-01

    Meniscus regeneration is observed within the peripheral, vascularized zone but decreases in the inner two thirds alongside the vascularization. Within this avascular area, cell-based tissue-engineering-approaches appear to be a promising strategy for the treatment of meniscal defects. Evaluation of the angiogenic potential of cell-based tissue-engineering-products for meniscus healing. Evaluation of angiogenesis induced by rabbit meniscus-pellets, meniscus-cells (MC) or mesenchymal stem-cells (MSC) in cell-based tissue-engineering-products within a rabbit meniscus-ring was performed using a transparent dorsal skin fold chamber in nude mice. Observations were undertaken during a 14 days period. Cell preconditioning differed between experimental groups. Immunohistochemical analysis of the regenerated tissue in the meniscus-ring induced by cell loaded composite scaffolds for differentiation and anti-angiogenic factors were performed. Meniscus-pellets and MSC-/MC-based tissue-engineering-products induced angiogenesis. An accelerated vascularization was detected in the group of meniscus-pellets derived from the vascularized zone compared to avascular meniscus-pellets. In terms of cell-based tissue-engineering-products, chondrogenic preconditioning resulted in significantly increased vessel growth. MSC-constructs showed an accelerated angiogenesis. Immunohistochemical evaluation showed a progressive differentiation and lower content for anti-angiogenic endostatin in the precultured group. Preconditioning of MC-/MSC-based tissue-engineering-products is a promising tool to influence the angiogenic potential of tissue-engineering-products and to adapt these properties according to the aimed tissue qualities.

  2. 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.

  3. Stem Cells for Skeletal Muscle Tissue Engineering.

    Science.gov (United States)

    Pantelic, Molly N; Larkin, Lisa M

    2018-04-19

    Volumetric muscle loss (VML) is a debilitating condition wherein muscle loss overwhelms the body's normal physiological repair mechanism. VML is particularly common among military service members who have sustained war injuries. Because of the high social and medical cost associated with VML and suboptimal current surgical treatments, there is great interest in developing better VML therapies. Skeletal muscle tissue engineering (SMTE) is a promising alternative to traditional VML surgical treatments that use autogenic tissue grafts, and rather uses isolated stem cells with myogenic potential to generate de novo skeletal muscle tissues to treat VML. Satellite cells are the native precursors to skeletal muscle tissue, and are thus the most commonly studied starting source for SMTE. However, satellite cells are difficult to isolate and purify, and it is presently unknown whether they would be a practical source in clinical SMTE applications. Alternative myogenic stem cells, including adipose-derived stem cells, bone marrow-derived mesenchymal stem cells, perivascular stem cells, umbilical cord mesenchymal stem cells, induced pluripotent stem cells, and embryonic stem cells, each have myogenic potential and have been identified as possible starting sources for SMTE, although they have yet to be studied in detail for this purpose. These alternative stem cell varieties offer unique advantages and disadvantages that are worth exploring further to advance the SMTE field toward highly functional, safe, and practical VML treatments. The following review summarizes the current state of satellite cell-based SMTE, details the properties and practical advantages of alternative myogenic stem cells, and offers guidance to tissue engineers on how alternative myogenic stem cells can be incorporated into SMTE research.

  4. The Effects of Environmental Factors on Smooth Muscle Cells Differentiation from Adipose-Derived Stem Cells and Esophagus Tissues Engineering

    DEFF Research Database (Denmark)

    Wang, Fang

    Adipose-derived stem cells (ASCs) are increasingly being used for regenerative medicine and tissue engineering. Smooth muscle cells (SMCs) can be differentiated from ASCs. Oxygen is a key factor influencing the stem cell differentiation. Tissue engineered esophagus has been a preferred solution...... of esophagus was studied. Our results showed that both SMCs and ASCs could attach on the porcine esophageal acellular matrix (EAM) scaffold in vitro after 24 hours and survive until 7 days. Thus ASCs might be a substitute for SMCs in the construction of tissue engineered esophageal muscle layer....

  5. Numerical simulation of fluid field and in vitro three-dimensional fabrication of tissue-engineered bones in a rotating bioreactor and in vivo implantation for repairing segmental bone defects.

    Science.gov (United States)

    Song, Kedong; Wang, Hai; Zhang, Bowen; Lim, Mayasari; Liu, Yingchao; Liu, Tianqing

    2013-03-01

    In this paper, two-dimensional flow field simulation was conducted to determine shear stresses and velocity profiles for bone tissue engineering in a rotating wall vessel bioreactor (RWVB). In addition, in vitro three-dimensional fabrication of tissue-engineered bones was carried out in optimized bioreactor conditions, and in vivo implantation using fabricated bones was performed for segmental bone defects of Zelanian rabbits. The distribution of dynamic pressure, total pressure, shear stress, and velocity within the culture chamber was calculated for different scaffold locations. According to the simulation results, the dynamic pressure, velocity, and shear stress around the surface of cell-scaffold construction periodically changed at different locations of the RWVB, which could result in periodical stress stimulation for fabricated tissue constructs. However, overall shear stresses were relatively low, and the fluid velocities were uniform in the bioreactor. Our in vitro experiments showed that the number of cells cultured in the RWVB was five times higher than those cultured in a T-flask. The tissue-engineered bones grew very well in the RWVB. This study demonstrates that stress stimulation in an RWVB can be beneficial for cell/bio-derived bone constructs fabricated in an RWVB, with an application for repairing segmental bone defects.

  6. An integrated finite-element approach to mechanics, transport and biosynthesis in tissue engineering

    NARCIS (Netherlands)

    Sengers, B.G.; Oomens, C.W.J.; Baaijens, F.P.T.

    2004-01-01

    A finite-element approach was formulated, aimed at enabling an integrated study of mechanical and biochemical factors that control the functional development of tissue engineered constructs. A nonlinear biphasic displacement-velocity-pressure description was combined with adjective and diffusive

  7. Bone tissue engineering for spine fusion : An experimental study on ectopic and orthotopic implants in rats

    NARCIS (Netherlands)

    van Gaalen, SM; Dhert, WJA; van den Muysenberg, A; Oner, FC; van Blitterswijk, C; Verbout, AJ; de Bruijn, J.D.

    2004-01-01

    Alternatives to the use of autologous bone as a bone graft in spine surgery are needed. The purpose of this study was to examine tissue-engineered bone constructs in comparison with control scaffolds without cells in a posterior spinal implantation model in rats. Syngeneic bone marrow cells were

  8. Regeneration of the anterior cruciate ligament: Current strategies in tissue engineering

    Science.gov (United States)

    Nau, Thomas; Teuschl, Andreas

    2015-01-01

    Recent advancements in the field of musculoskeletal tissue engineering have raised an increasing interest in the regeneration of the anterior cruciate ligament (ACL). It is the aim of this article to review the current research efforts and highlight promising tissue engineering strategies. The four main components of tissue engineering also apply in several ACL regeneration research efforts. Scaffolds from biological materials, biodegradable polymers and composite materials are used. The main cell sources are mesenchymal stem cells and ACL fibroblasts. In addition, growth factors and mechanical stimuli are applied. So far, the regenerated ACL constructs have been tested in a few animal studies and the results are encouraging. The different strategies, from in vitro ACL regeneration in bioreactor systems to bio-enhanced repair and regeneration, are under constant development. We expect considerable progress in the near future that will result in a realistic option for ACL surgery soon. PMID:25621217

  9. [Tissue engineering with mesenchymal stem cells for cartilage and bone regeneration].

    Science.gov (United States)

    Schaefer, D J; Klemt, C; Zhang, X H; Stark, G B

    2000-09-01

    Tissue engineering offers the possibility to fabricate living substitutes for tissues and organs by combining histogenic cells and biocompatible carrier materials. Pluripotent mesenchymal stem cells are isolated and subcultured ex vivo and then their histogenic differentiation is induced by external factors. The fabrication of bone and cartilage constructs, their combinations and gene therapeutic approaches are demonstrated. Advantages and disadvantages of these methods are described by in vitro and in vitro testing. The proof of histotypical function after implantation in vivo is essential. The use of autologous cells and tissue engineering methods offers the possibility to overcome the disadvantages of classical tissue reconstruction--donor site morbidity of autologous grafts, immunogenicity of allogenic grafts and loosening of alloplastic implants. Furthermore, tissue engineering widens the spectrum of surgical indications in bone and cartilage reconstruction.

  10. 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.

  11. Effects of heat stimulation and l-ascorbic acid 2-phosphate supplementation on myogenic differentiation of artificial skeletal muscle tissue constructs.

    Science.gov (United States)

    Ikeda, Kazushi; Ito, Akira; Sato, Masanori; Kanno, Shota; Kawabe, Yoshinori; Kamihira, Masamichi

    2017-05-01

    Although skeletal muscle tissue engineering has been extensively studied, the physical forces produced by tissue-engineered skeletal muscles remain to be improved for potential clinical utility. In this study, we examined the effects of mild heat stimulation and supplementation of a l-ascorbic acid derivative, l-ascorbic acid 2-phosphate (AscP), on myoblast differentiation and physical force generation of tissue-engineered skeletal muscles. Compared with control cultures at 37°C, mouse C2C12 myoblast cells cultured at 39°C enhanced myotube diameter (skeletal muscle hypertrophy), whereas mild heat stimulation did not promote myotube formation (differentiation rate). Conversely, AscP supplementation resulted in an increased differentiation rate but did not induce skeletal muscle hypertrophy. Following combined treatment with mild heat stimulation and AscP supplementation, both skeletal muscle hypertrophy and differentiation rate were enhanced. Moreover, the active tension produced by the tissue-engineered skeletal muscles was improved following combined treatment. These findings indicate that tissue culture using mild heat stimulation and AscP supplementation is a promising approach to enhance the function of tissue-engineered skeletal muscles. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  12. 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

  13. Advancing biomaterials of human origin for tissue engineering

    Science.gov (United States)

    Chen, Fa-Ming; Liu, Xiaohua

    2015-01-01

    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

  14. Biomimetic nanoclay scaffolds for bone tissue engineering

    Science.gov (United States)

    Ambre, Avinash Harishchandra

    Tissue engineering offers a significant potential alternative to conventional methods for rectifying tissue defects by evoking natural regeneration process via interactions between cells and 3D porous scaffolds. Imparting adequate mechanical properties to biodegradable scaffolds for bone tissue engineering is an important challenge and extends from molecular to macroscale. This work focuses on the use of sodium montmorillonite (Na-MMT) to design polymer composite scaffolds having enhanced mechanical properties along with multiple interdependent properties. Materials design beginning at the molecular level was used in which Na-MMT clay was modified with three different unnatural amino acids and further characterized using Fourier Transform Infrared (FTIR) spectroscopy, X-ray diffraction (XRD). Based on improved bicompatibility with human osteoblasts (bone cells) and intermediate increase in d-spacing of MMT clay (shown by XRD), 5-aminovaleric acid modified clay was further used to prepare biopolymer (chitosan-polygalacturonic acid complex) scaffolds. Osteoblast proliferation in biopolymer scaffolds containing 5-aminovaleric acid modified clay was similar to biopolymer scaffolds containing hydroxyapatite (HAP). A novel process based on biomineralization in bone was designed to prepare 5-aminovaleric acid modified clay capable of imparting multiple properties to the scaffolds. Bone-like apatite was mineralized in modified clay and a novel nanoclay-HAP hybrid (in situ HAPclay) was obtained. FTIR spectroscopy indicated a molecular level organic-inorganic association between the intercalated 5-aminovaleric acid and mineralized HAP. Osteoblasts formed clusters on biopolymer composite films prepared with different weight percent compositions of in situ HAPclay. Human MSCs formed mineralized nodules on composite films and mineralized extracellular matrix (ECM) in composite scaffolds without the use of osteogenic supplements. Polycaprolactone (PCL), a synthetic polymer, was

  15. An Update to Space Biomedical Research: Tissue Engineering in Microgravity Bioreactors

    Directory of Open Access Journals (Sweden)

    Abolfazl Barzegari

    2012-03-01

    Full Text Available Introduction: The severe need for constructing replacement tissues in organ transplantation has necessitated the development of tissue engineering approaches and bioreactors that can bring these approaches to reality. The inherent limitations of conventional bioreactors in generating realistic tissue constructs led to the devise of the microgravity tissue engineering that uses Rotating Wall Vessel (RWV bioreactors initially developed by NASA. Methods: In this review article, we intend to highlight some major advances and accomplishments in the rapidly-growing field of tissue engineering that could not be achieved without using microgravity. Results: Research is now focused on assembly of 3 dimensional (3D tissue fragments from various cell types in human body such as chondrocytes, osteoblasts, embryonic and mesenchymal stem cells, hepatocytes and pancreas islet cells. Hepatocytes cultured under microgravity are now being used in extracorporeal bioartificial liver devices. Tissue constructs can be used not only in organ replacement therapy, but also in pharmaco-toxicology and food safety assessment. 3D models of various cancers may be used in studying cancer development and biology or in high-throughput screening of anticancer drug candidates. Finally, 3D heterogeneous assemblies from cancer/immune cells provide models for immunotherapy of cancer. Conclusion: Tissue engineering in (simulated microgravity has been one of the stunning impacts of space research on biomedical sciences and their applications on earth.

  16. Surface-modified polymers for cardiac tissue engineering.

    Science.gov (United States)

    Moorthi, Ambigapathi; Tyan, Yu-Chang; Chung, Tze-Wen

    2017-09-26

    Cardiovascular disease (CVD), leading to myocardial infarction and heart failure, is one of the major causes of death worldwide. The physiological system cannot significantly regenerate the capabilities of a damaged heart. The current treatment involves pharmacological and surgical interventions; however, less invasive and more cost-effective approaches are sought. Such new approaches are developed to induce tissue regeneration following injury. Hence, regenerative medicine plays a key role in treating CVD. Recently, the extrinsic stimulation of cardiac regeneration has involved the use of potential polymers to stimulate stem cells toward the differentiation of cardiomyocytes as a new therapeutic intervention in cardiac tissue engineering (CTE). The therapeutic potentiality of natural or synthetic polymers and cell surface interactive factors/polymer surface modifications for cardiac repair has been demonstrated in vitro and in vivo. This review will discuss the recent advances in CTE using polymers and cell surface interactive factors that interact strongly with stem cells to trigger the molecular aspects of the differentiation or formulation of cardiomyocytes for the functional repair of heart injuries or cardiac defects.

  17. 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. © 2013 Published by Elsevier Ltd.

  18. 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.

  19. Mechanostimulation Protocols for Cardiac Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Marco Govoni

    2013-01-01

    Full Text Available Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field.

  20. Articular cartilage: from formation to tissue engineering.

    Science.gov (United States)

    Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

    2016-05-26

    Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue.

  1. The Application of Tissue Engineering Procedures to Repair the Larynx

    Science.gov (United States)

    Ringel, Robert L.; Kahane, Joel C.; Hillsamer, Peter J.; Lee, Annie S.; Badylak, Stephen F.

    2006-01-01

    The field of tissue engineering/regenerative medicine combines the quantitative principles of engineering with the principles of the life sciences toward the goal of reconstituting structurally and functionally normal tissues and organs. There has been relatively little application of tissue engineering efforts toward the organs of speech, voice,…

  2. Functional tissue engineering : ten more years of progress

    NARCIS (Netherlands)

    Guilak, F.; Baaijens, F.P.T.

    2014-01-01

    "Functional tissue engineering" is a subset of the field of tissue engineering that was proposed by the United States National Committee on Biomechanics over a decade ago in order to place more emphasis on the roles of biomechanics and mechanobiology in tissue repair and regeneration. Over the past

  3. Tissue-engineered skin preserving the potential of epithelial cells to differentiate into hair after grafting.

    Science.gov (United States)

    Larouche, Danielle; Cuffley, Kristine; Paquet, Claudie; Germain, Lucie

    2011-03-01

    The aim of this study was to evaluate whether tissue-engineered skin produced in vitro was able to sustain growth of hair follicles in vitro and after grafting. Different tissues were designed. Dissociated newborn mouse keratinocytes or newborn mouse hair buds (HBs) were added onto dermal constructs consisting of a tissue-engineered cell-derived matrix elaborated from either newborn mouse or adult human fibroblasts cultured with ascorbic acid. After 7-21 days of maturation at the air-liquid interface, no hair was noticed in vitro. Epidermal differentiation was observed in all tissue-engineered skin. However, human fibroblast-derived tissue-engineered dermis (hD) promoted a thicker epidermis than mouse fibroblast-derived tissue-engineered dermis (mD). In association with mD, HBs developed epithelial cyst-like inclusions presenting outer root sheath-like attributes. In contrast, epidermoid cyst-like inclusions lined by a stratified squamous epithelium were present in tissues composed of HBs and hD. After grafting, pilo-sebaceous units formed and hair grew in skin elaborated from HBs cultured 10-26 days submerged in culture medium in association with mD. However, the number of normal hair follicles decreased with longer culture time. This hair-forming capacity after grafting was not observed in tissues composed of hD overlaid with HBs. These results demonstrate that epithelial stem cells can be kept in vitro in a permissive tissue-engineered dermal environment without losing their potential to induce hair growth after grafting.

  4. Sliding motion modulates stiffness and friction coefficient at the surface of tissue engineered cartilage.

    Science.gov (United States)

    Grad, S; Loparic, M; Peter, R; Stolz, M; Aebi, U; Alini, M

    2012-04-01

    Functional cartilage tissue engineering aims to generate grafts with a functional surface, similar to that of authentic cartilage. Bioreactors that stimulate cell-scaffold constructs by simulating natural joint movements hold great potential to generate cartilage with adequate surface properties. In this study two methods based on atomic force microscopy (AFM) were applied to obtain information about the quality of engineered graft surfaces. For better understanding of the molecule-function relationships, AFM was complemented with immunohistochemistry. Bovine chondrocytes were seeded into polyurethane scaffolds and subjected to dynamic compression, applied by a ceramic ball, for 1h daily [loading group 1 (LG1)]. In loading group 2 (LG2), the ball additionally oscillated over the scaffold, generating sliding surface motion. After 3 weeks, the surfaces of the engineered constructs were analyzed by friction force and indentation-type AFM (IT-AFM). Results were complemented and compared to immunohistochemical analyses. The loading type significantly influenced the mechanical and histological outcomes. Constructs of LG2 exhibited lowest friction coefficient and highest micro- and nanostiffness. Collagen type II and aggrecan staining were readily observed in all constructs and appeared to reach deeper areas in loaded (LG1, LG2) compared to unloaded scaffolds. Lubricin was specifically detected at the top surface of LG2. This study proposes a quantitative AFM-based functional analysis at the micrometer- and nanometer scale to evaluate the quality of cartilage surfaces. Mechanical testing (load-bearing) combined with friction analysis (gliding) can provide important information. Notably, sliding-type biomechanical stimuli may favor (re-)generation and maintenance of functional articular surfaces and support the development of mechanically competent engineered cartilage. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights

  5. Expediting the transition from replacement medicine to tissue engineering.

    Science.gov (United States)

    Coury, Arthur J

    2016-06-01

    In this article, an expansive interpretation of "Tissue Engineering" is proposed which is in congruence with classical and recent published definitions. I further simplify the definition of tissue engineering as: "Exerting systematic control of the body's cells, matrices and fluids." As a consequence, many medical therapies not commonly considered tissue engineering are placed in this category because of their effect on the body's responses. While the progress of tissue engineering strategies is inexorable and generally positive, it has been subject to setbacks as have many important medical therapies. Medical practice is currently undergoing a transition on several fronts (academics, start-up companies, going concerns) from the era of "replacement medicine" where body parts and functions are replaced by mechanical, electrical or chemical therapies to the era of tissue engineering where health is restored by regeneration generation or limitation of the body's tissues and functions by exploiting our expanding knowledge of the body's biological processes to produce natural, healthy outcomes.

  6. Tissue engineering: technological advances to improve its applications in reconstructive surgery.

    Science.gov (United States)

    Alberti, C

    2012-01-01

    Tremendous advances in biomaterials science and nanotechnologies, together with thorough research on stem cells, have recently promoted an intriguing development of regenerative medicine/tissue engineering. The nanotechnology represents a wide interdisciplinary field that implies the manipulation of different materials at nanometer level to achieve the creation of constructs that mimic the nanoscale-based architecture of native tissues. The purpose of this article is to highlight the significant new knowledges regarding this matter. To widen the range of scaffold materials resort has been carried out to either recombinant DNA technology-generated materials, such as a collagen-like protein, or the incorporation of bioactive molecules, such as RDG (arginine-glycine-aspartic acid), into synthetic products. Both the bottom-up and the top-down fabrication approaches may be properly used to respectively obtain sopramolecular architectures or, instead, micro-/nanostructures to incorporate them within a preexisting complex scaffold construct. Computer-aided design/manufacturing (CAD/CAM) scaffold technique allows to achieve patient-tailored organs. Stem cells, because of their peculiar properties - ability to proliferate, self-renew and specific cell-lineage differentiate under appropriate conditions - represent an attractive source for intriguing tissue engineering/regenerative medicine applications. New developments in the realization of different organs tissue engineering will depend on further progress of both the science of nanoscale-based materials and the knowledge of stem cell biology. Moreover the in vivo tissue engineering appears to be the logical step of the current research.

  7. A review of evolution of electrospun tissue engineering scaffold: From two dimensions to three dimensions.

    Science.gov (United States)

    Ngadiman, Nor Hasrul Akhmal; Noordin, M Y; Idris, Ani; Kurniawan, Denni

    2017-07-01

    The potential of electrospinning process to fabricate ultrafine fibers as building blocks for tissue engineering scaffolds is well recognized. The scaffold construct produced by electrospinning process depends on the quality of the fibers. In electrospinning, material selection and parameter setting are among many factors that contribute to the quality of the ultrafine fibers, which eventually determine the performance of the tissue engineering scaffolds. The major challenge of conventional electrospun scaffolds is the nature of electrospinning process which can only produce two-dimensional electrospun mats, hence limiting their applications. Researchers have started to focus on overcoming this limitation by combining electrospinning with other techniques to fabricate three-dimensional scaffold constructs. This article reviews various polymeric materials and their composites/blends that have been successfully electrospun for tissue engineering scaffolds, their mechanical properties, and the various parameters settings that influence the fiber morphology. This review also highlights the secondary processes to electrospinning that have been used to develop three-dimensional tissue engineering scaffolds as well as the steps undertaken to overcome electrospinning limitations.

  8. Three-Dimensional Bioprinting for Regenerative Dentistry and Craniofacial Tissue Engineering.

    Science.gov (United States)

    Obregon, F; Vaquette, C; Ivanovski, S; Hutmacher, D W; Bertassoni, L E

    2015-09-01

    Craniofacial tissues are organized with complex 3-dimensional (3D) architectures. Mimicking such 3D complexity and the multicellular interactions naturally occurring in craniofacial structures represents one of the greatest challenges in regenerative dentistry. Three-dimensional bioprinting of tissues and biological structures has been proposed as a promising alternative to address some of these key challenges. It enables precise manufacture of various biomaterials with complex 3D architectures, while being compatible with multiple cell sources and being customizable to patient-specific needs. This review describes different 3D bioprinting methods and summarizes how different classes of biomaterials (polymer hydrogels, ceramics, composites, and cell aggregates) may be used for 3D biomanufacturing of scaffolds, as well as craniofacial tissue analogs. While the fabrication of scaffolds upon which cells attach, migrate, and proliferate is already in use, printing of all the components that form a tissue (living cells and matrix materials together) to produce tissue constructs is still in its early stages. In summary, this review seeks to highlight some of the key advantages of 3D bioprinting technology for the regeneration of craniofacial structures. Additionally, it stimulates progress on the development of strategies that will promote the translation of craniofacial tissue engineering from the laboratory bench to the chair side. © International & American Associations for Dental Research 2015.

  9. Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

    Science.gov (United States)

    Chen, Guobao; Lv, Yonggang

    2015-01-01

    Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

  10. 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.

  11. Intervertebral Disc Tissue Engineering with Natural Extracellular Matrix-Derived Biphasic Composite Scaffolds.

    Directory of Open Access Journals (Sweden)

    Baoshan Xu

    Full Text Available Tissue engineering has provided an alternative therapeutic possibility for degenerative disc diseases. However, we lack an ideal scaffold for IVD tissue engineering. The goal of this study is to fabricate a novel biomimetic biphasic scaffold for IVD tissue engineering and evaluate the feasibility of developing tissue-engineered IVD in vitro and in vivo. In present study we developed a novel integrated biphasic IVD scaffold using a simple freeze-drying and cross-linking technique of pig bone matrix gelatin (BMG for the outer annulus fibrosus (AF phase and pig acellular cartilage ECM (ACECM for the inner nucleus pulposus (NP phase. Histology and SEM results indicated no residual cells remaining in the scaffold that featured an interconnected porous microstructure (pore size of AF and NP phase 401.4 ± 13.1 μm and 231.6 ± 57.2 μm, respectively. PKH26-labeled AF and NP cells were seeded into the scaffold and cultured in vitro. SEM confirmed that seeded cells could anchor onto the scaffold. Live/dead staining showed that live cells (green fluorescence were distributed in the scaffold, with no dead cells (red fluorescence being found. The cell-scaffold constructs were implanted subcutaneously into nude mice and cultured for 6 weeks in vivo. IVD-like tissue formed in nude mice as confirmed by histology. Cells in hybrid constructs originated from PKH26-labeled cells, as confirmed by in vivo fluorescence imaging system. In conclusion, the study demonstrates the feasibility of developing a tissue-engineered IVD in vivo with a BMG- and ACECM-derived integrated AF-NP biphasic scaffold. As well, PKH26 fluorescent labeling with in vivo fluorescent imaging can be used to track cells and analyse cell--scaffold constructs in vivo.

  12. Stimulating Learning with Integrated Assessments in Construction Education

    Directory of Open Access Journals (Sweden)

    Imriyas Kamardeen

    2014-09-01

    Full Text Available Quality of learning students experience is heavily dependent on the effectiveness of course design. Assessments are a key component in course design and students determine their level of involvement in a learning activity based on whether it is assessed or not. Assessments are therefore a powerful tool that lecturers can utilise to drive learning. However, designing effective assessments to stimulate learning is challenging in the presence of disciplinary, contextual dimensions. A case study approach is adopted to demonstrate how effective integrated assessment schemes may be developed and implemented for construction education. The scheme in the case study amalgamated case-based learning, online quizzes and adaptive eTests to provide a variety of assessments, aligned with lecture topics and contemporary real-word scenarios. It was found that the presence of both formative and summative tasks in the assessment scheme complemented each other, kept students constantly motivated and engaged in learning, and resulted in a good learning experience for them. The study provide evidence, and valuable insights and tips for lecturers in similar degree programs as to how they could modify pedagogical styles in their courses for better learning experiences for students and improved teaching ratings for themselves. Keywords: Pedagogy, Integrated assessment, Case-based learning, Online quiz, Adaptive eLearning

  13. Stimulating Learning with Integrated Assessments in Construction Education

    Directory of Open Access Journals (Sweden)

    Imriyas Kamardeen

    2014-09-01

    Full Text Available Quality of learning students experience is heavily dependent on the effectiveness of course design. Assessments are a key component in course design and students determine their level of involvement in a learning activity based on whether it is assessed or not. Assessments are therefore a powerful tool that lecturers can utilise to drive learning. However, designing effective assessments to stimulate learning is challenging in the presence of disciplinary, contextual dimensions. A case study approach is adopted to demonstrate how effective integrated assessment schemes may be developed and implemented for construction education. The scheme in the case study amalgamated case-based learning, online quizzes and adaptive eTests to provide a variety of assessments, aligned with lecture topics and contemporary real-word scenarios. It was found that the presence of both formative and summative tasks in the assessment scheme complemented each other, kept students constantly motivated and engaged in learning, and resulted in a good learning experience for them. The study provide evidence, and valuable insights and tips for lecturers in similar degree programs as to how they could modify pedagogical styles in their courses for better learning experiences for students and improved teaching ratings for themselves.   Keywords: Pedagogy, Integrated assessment, Case-based learning, Online quiz, Adaptive eLearning

  14. Reconstruction of structure and function in tissue engineering of solid organs: Toward simulation of natural development based on decellularization.

    Science.gov (United States)

    Zheng, Chen-Xi; Sui, Bing-Dong; Hu, Cheng-Hu; Qiu, Xin-Yu; Zhao, Pan; Jin, Yan

    2018-04-27

    Failure of solid organs, such as the heart, liver, and kidney, remains a major cause of the world's mortality due to critical shortage of donor organs. Tissue engineering, which uses elements including cells, scaffolds, and growth factors to fabricate functional organs in vitro, is a promising strategy to mitigate the scarcity of transplantable organs. Within recent years, different construction strategies that guide the combination of tissue engineering elements have been applied in solid organ tissue engineering and have achieved much progress. Most attractively, construction strategy based on whole-organ decellularization has become a popular and promising approach, because the overall structure of extracellular matrix can be well preserved. However, despite the preservation of whole structure, the current constructs derived from decellularization-based strategy still perform partial functions of solid organs, due to several challenges, including preservation of functional extracellular matrix structure, implementation of functional recellularization, formation of functional vascular network, and realization of long-term functional integration. This review overviews the status quo of solid organ tissue engineering, including both advances and challenges. We have also put forward a few techniques with potential to solve the challenges, mainly focusing on decellularization-based construction strategy. We propose that the primary concept for constructing tissue-engineered solid organs is fabricating functional organs based on intact structure via simulating the natural development and regeneration processes. Copyright © 2018 John Wiley & Sons, Ltd.

  15. The effect of scaffold pore size in cartilage tissue engineering.

    Science.gov (United States)

    Nava, Michele M; Draghi, Lorenza; Giordano, Carmen; Pietrabissa, Riccardo

    2016-07-26

    The effect of scaffold pore size and interconnectivity is undoubtedly a crucial factor for most tissue engineering applications. The aim of this study was to examine the effect of pore size and porosity on cartilage construct development in different scaffolds seeded with articular chondrocytes. We fabricated poly-L-lactide-co-trimethylene carbonate scaffolds with different pore sizes, using a solvent-casting/particulate-leaching technique. We seeded primary bovine articular chondrocytes on these scaffolds, cultured the constructs for 2 weeks and examined cell proliferation, viability and cell-specific production of cartilaginous extracellular matrix proteins, including GAG and collagen. Cell density significantly increased up to 50% with scaffold pore size and porosity, likely facilitated by cell spreading on the internal surface of bigger pores, and by increased mass transport of gases and nutrients to cells, and catabolite removal from cells, allowed by lower diffusion barriers in scaffolds with a higher porosity. However, both the cell metabolic activity and the synthesis of cartilaginous matrix proteins significantly decreased by up to 40% with pore size. We propose that the association of smaller pore diameters, causing 3-dimensional cell aggregation, to a lower oxygenation caused by a lower porosity, could have been the condition that increased the cell-specific synthesis of cartilaginous matrix proteins in the scaffold with the smallest pores and the lowest porosity among those tested. In the initial steps of in vitro cartilage engineering, the combination of small scaffold pores and low porosity is an effective strategy with regard to the promotion of chondrogenesis.

  16. Current Concepts in Tissue Engineering: Skin and Wound.

    Science.gov (United States)

    Tenenhaus, Mayer; Rennekampff, Hans-Oliver

    2016-09-01

    Pure regenerative healing with little to no donor morbidity remains an elusive goal for both surgeon and patient. The ability to engineer and promote the development of like tissue holds so much promise, and efforts in this direction are slowly but steadily advancing. Products selected and reviewed reflect historical precedence and importance and focus on current clinically available products in use. Emerging technologies we anticipate will further expand our therapeutic options are introduced. The topic of tissue engineering is incredibly broad in scope, and as such the authors have focused their review on that of constructs specifically designed for skin and wound healing. A review of pertinent and current clinically related literature is included. Products such as biosynthetics, biologics, cellular promoting factors, and commercially available matrices can be routinely found in most modern health care centers. Although to date no complete regenerative or direct identical soft-tissue replacement exists, currently available commercial components have proven beneficial in augmenting and improving some types of wound healing scenarios. Cost, directed specificity, biocompatibility, and bioburden tolerance are just some of the impending challenges to adoption. Quality of life and in fact the ability to sustain life is dependent on our most complex and remarkable organ, skin. Although pure regenerative healing and engineered soft-tissue constructs elude us, surgeons and health care providers are slowly gaining comfort and experience with concepts and strategies to improve the healing of wounds.

  17. 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

  18. Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Baei, Payam [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Jalili-Firoozinezhad, Sasan [Department of Biomedicine and Surgery, University Hospital Basel, University of Basel, Hebelstrasse 20, CH-4031 Basel (Switzerland); Department of Bioengineeringand IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa (Portugal); Rajabi-Zeleti, Sareh [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad [Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Baharvand, Hossein, E-mail: Baharvand@royaninstitute.org [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Developmental Biology, University of Science and Culture, ACECR, Tehran (Iran, Islamic Republic of); Aghdami, Nasser, E-mail: Nasser.Aghdami@royaninstitute.org [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of)

    2016-06-01

    Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14 days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues. - Highlights: • Thermosensitive electro-conductive hydrogels were prepared from CS and GNPs. • Gelation time and conductivity were tuned by varying concentration of GNPs. • CS-2GNP with gelation time of 25.7 min and conductivity of 0.13 S·m{sup −1} was selected for in vitro studies. • CS-2GNP supported active metabolism, migration and proliferation of MSCs. • Expression of cardiac markers increased about two-fold in CS-2GNP compared to CS.

  19. Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering

    International Nuclear Information System (INIS)

    Baei, Payam; Jalili-Firoozinezhad, Sasan; Rajabi-Zeleti, Sareh; Tafazzoli-Shadpour, Mohammad; Baharvand, Hossein; Aghdami, Nasser

    2016-01-01

    Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14 days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues. - Highlights: • Thermosensitive electro-conductive hydrogels were prepared from CS and GNPs. • Gelation time and conductivity were tuned by varying concentration of GNPs. • CS-2GNP with gelation time of 25.7 min and conductivity of 0.13 S·m"−"1 was selected for in vitro studies. • CS-2GNP supported active metabolism, migration and proliferation of MSCs. • Expression of cardiac markers increased about two-fold in CS-2GNP compared to CS.

  20. Proteomic differences between native and tissue-engineered tendon and ligament.

    Science.gov (United States)

    Kharaz, Yalda A; Tew, Simon R; Peffers, Mandy; Canty-Laird, Elizabeth G; Comerford, Eithne

    2016-05-01

    Tendons and ligaments (T/Ls) play key roles in the musculoskeletal system, but they are susceptible to traumatic or age-related rupture, leading to severe morbidity as well as increased susceptibility to degenerative joint diseases such as osteoarthritis. Tissue engineering represents an attractive therapeutic approach to treating T/L injury but it is hampered by our poor understanding of the defining characteristics of the two tissues. The present study aimed to determine differences in the proteomic profile between native T/Ls and tissue engineered (TE) T/L constructs. The canine long digital extensor tendon and anterior cruciate ligament were analyzed along with 3D TE fibrin-based constructs created from their cells. Native tendon and ligament differed in their content of key structural proteins, with the ligament being more abundant in fibrocartilaginous proteins. 3D T/L TE constructs contained less extracellular matrix (ECM) proteins and had a greater proportion of cellular-associated proteins than native tissue, corresponding to their low collagen and high DNA content. Constructs were able to recapitulate native T/L tissue characteristics particularly with regard to ECM proteins. However, 3D T/L TE constructs had similar ECM and cellular protein compositions indicating that cell source may not be an important factor for T/L tissue engineering. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Growing tissues in real and simulated microgravity: new methods for tissue engineering.

    Science.gov (United States)

    Grimm, Daniela; Wehland, Markus; Pietsch, Jessica; Aleshcheva, Ganna; Wise, Petra; van Loon, Jack; Ulbrich, Claudia; Magnusson, Nils E; Infanger, Manfred; Bauer, Johann

    2014-12-01

    Tissue engineering in simulated (s-) and real microgravity (r-μg) is currently a topic in Space medicine contributing to biomedical sciences and their applications on Earth. The principal aim of this review is to highlight the advances and accomplishments in the field of tissue engineering that could be achieved by culturing cells in Space or by devices created to simulate microgravity on Earth. Understanding the biology of three-dimensional (3D) multicellular structures is very important for a more complete appreciation of in vivo tissue function and advancing in vitro tissue engineering efforts. Various cells exposed to r-μg in Space or to s-μg created by a random positioning machine, a 2D-clinostat, or a rotating wall vessel bioreactor grew in the form of 3D tissues. Hence, these methods represent a new strategy for tissue engineering of a variety of tissues, such as regenerated cartilage, artificial vessel constructs, and other organ tissues as well as multicellular cancer spheroids. These aggregates are used to study molecular mechanisms involved in angiogenesis, cancer development, and biology and for pharmacological testing of, for example, chemotherapeutic drugs or inhibitors of neoangiogenesis. Moreover, they are useful for studying multicellular responses in toxicology and radiation biology, or for performing coculture experiments. The future will show whether these tissue-engineered constructs can be used for medical transplantations. Unveiling the mechanisms of microgravity-dependent molecular and cellular changes is an up-to-date requirement for improving Space medicine and developing new treatment strategies that can be translated to in vivo models while reducing the use of laboratory animals.

  2. 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.

  3. [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

  4. Design and characterization of a biodegradable double-layer scaffold aimed at periodontal tissue-engineering applications.

    Science.gov (United States)

    Requicha, João F; Viegas, Carlos A; Hede, Shantesh; Leonor, Isabel B; Reis, Rui L; Gomes, Manuela E

    2016-05-01

    The inefficacy of the currently used therapies in achieving the regeneration ad integrum of the periodontium stimulates the search for alternative approaches, such as tissue-engineering strategies. Therefore, the core objective of this study was to develop a biodegradable double-layer scaffold for periodontal tissue engineering. The design philosophy was based on a double-layered construct obtained from a blend of starch and poly-ε-caprolactone (30:70 wt%; SPCL). A SPCL fibre mesh functionalized with silanol groups to promote osteogenesis was combined with a SPCL solvent casting membrane aiming at acting as a barrier against the migration of gingival epithelium into the periodontal defect. Each layer of the double-layer scaffolds was characterized in terms of morphology, surface chemical composition, degradation behaviour and mechanical properties. Moreover, the behaviour of seeded/cultured canine adipose-derived stem cells (cASCs) was assessed. In general, the developed double-layered scaffolds demonstrated adequate degradation and mechanical behaviour for the target application. Furthermore, the biological assays revealed that both layers of the scaffold allow adhesion and proliferation of the seeded undifferentiated cASCs, and the incorporation of silanol groups into the fibre-mesh layer enhance the expression of a typical osteogenic marker. This study allowed an innovative construct to be developed, combining a three-dimensional (3D) scaffold with osteoconductive properties and with potential to assist periodontal regeneration, carrying new possible solutions to current clinical needs. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

  5. Modeling the Human Scarred Heart In Vitro: Toward New Tissue Engineered Models.

    Science.gov (United States)

    Deddens, Janine C; Sadeghi, Amir Hossein; Hjortnaes, Jesper; van Laake, Linda W; Buijsrogge, Marc; Doevendans, Pieter A; Khademhosseini, Ali; Sluijter, Joost P G

    2017-02-01

    Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An urgent need exists to improve the understanding of adverse cardiac remodeling in order to develop new therapeutic interventions that will prevent, reverse, or regenerate the fibrotic changes in the failing heart. With recent advances in both disease biology and cardiac tissue engineering, the translation of fundamental laboratory research toward the treatment of chronic heart failure patients becomes a more realistic option. Here, the current understanding of cardiac fibrosis and the great potential of tissue engineering are presented. Approaches using hydrogel-based tissue engineered heart constructs are discussed to contemplate key challenges for modeling tissue engineered cardiac fibrosis and to provide a future outlook for preclinical and clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Surface modification of polycaprolactone scaffolds fabricated via selective laser sintering for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Chen, Chih-Hao; Lee, Ming-Yih; Shyu, Victor Bong-Hang; Chen, Yi-Chieh; Chen, Chien-Tzung; Chen, Jyh-Ping

    2014-01-01

    Surface modified porous polycaprolactone scaffolds fabricated via rapid prototyping techniques were evaluated for cartilage tissue engineering purposes. Polycaprolactone scaffolds manufactured by selective laser sintering (SLS) were surface modified through immersion coating with either gelatin or collagen. Three groups of scaffolds were created and compared for both mechanical and biological properties. Surface modification with collagen or gelatin improved the hydrophilicity, water uptake and mechanical strength of the pristine scaffold. From microscopic observations and biochemical analysis, collagen-modified scaffold was the best for cartilage tissue engineering in terms of cell proliferation and extracellular matrix production. Chondrocytes/collagen-modified scaffold constructs were implanted subdermally in the dorsal spaces of female nude mice. Histological and immunohistochemical staining of the retrieved implants after 8 weeks revealed enhanced cartilage tissue formation. We conclude that collagen surface modification through immersion coating on SLS-manufactured scaffolds is a feasible scaffold for cartilage tissue engineering in craniofacial reconstruction. - Highlights: • Selective laser sintered polycaprolactone scaffolds are prepared. • Scaffolds are surface modified through immersion coating with gelatin or collagen. • Collagen-scaffold is the best for cartilage tissue engineering in vitro. • Chondrocytes/collagen-scaffold reveals enhanced cartilage tissue formation in vivo

  7. Surface modification of polycaprolactone scaffolds fabricated via selective laser sintering for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chih-Hao [Department of Chemical and Materials Engineering, Chang Gung University, Kweishan, Taoyuan 333, Taiwan, ROC (China); Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Craniofacial Research Center, Chang Gung University, Kweishann, Taoyuan 333, Taiwan, ROC (China); Lee, Ming-Yih [Graduate Institute of Medical Mechatronics, Chang Gung University, Kweishan, Taoyuan 333, Taiwan, ROC (China); Shyu, Victor Bong-Hang; Chen, Yi-Chieh; Chen, Chien-Tzung [Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Craniofacial Research Center, Chang Gung University, Kweishann, Taoyuan 333, Taiwan, ROC (China); Chen, Jyh-Ping, E-mail: jpchen@mail.cgu.edu.tw [Department of Chemical and Materials Engineering, Chang Gung University, Kweishan, Taoyuan 333, Taiwan, ROC (China); Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan 333, Taiwan, ROC (China)

    2014-07-01

    Surface modified porous polycaprolactone scaffolds fabricated via rapid prototyping techniques were evaluated for cartilage tissue engineering purposes. Polycaprolactone scaffolds manufactured by selective laser sintering (SLS) were surface modified through immersion coating with either gelatin or collagen. Three groups of scaffolds were created and compared for both mechanical and biological properties. Surface modification with collagen or gelatin improved the hydrophilicity, water uptake and mechanical strength of the pristine scaffold. From microscopic observations and biochemical analysis, collagen-modified scaffold was the best for cartilage tissue engineering in terms of cell proliferation and extracellular matrix production. Chondrocytes/collagen-modified scaffold constructs were implanted subdermally in the dorsal spaces of female nude mice. Histological and immunohistochemical staining of the retrieved implants after 8 weeks revealed enhanced cartilage tissue formation. We conclude that collagen surface modification through immersion coating on SLS-manufactured scaffolds is a feasible scaffold for cartilage tissue engineering in craniofacial reconstruction. - Highlights: • Selective laser sintered polycaprolactone scaffolds are prepared. • Scaffolds are surface modified through immersion coating with gelatin or collagen. • Collagen-scaffold is the best for cartilage tissue engineering in vitro. • Chondrocytes/collagen-scaffold reveals enhanced cartilage tissue formation in vivo.

  8. 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

  9. An Introduction to Tissue Engineering Using Hydrogels

    Science.gov (United States)

    Ballyns, Jeffrey J.; Doran, Robert F.; Archer, Shivaun D.; Bonassar, Lawrence J.

    2011-01-01

    Biotechnology has often been a favorite topic in popular culture. While this has provided students with some introduction to the futuristic potential of biotechnology and biomedical sciences, it does not often translate to activities that will excite and stimulate them academically. In this article, the authors present a three-part classroom…

  10. Artificial implant materials - role of biomaterials in the tissue engineering

    International Nuclear Information System (INIS)

    Lewandowska-Szumiel, M.

    2007-01-01

    Lecture presents different materials applicable in production of implants. All these materials should be sterilized, however some of them can be modified using by irradiation (e.g. polymers). Numerous examples of tissue engineering are presented

  11. 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...

  12. Engineering a concept: the creation of tissue engineering.

    Science.gov (United States)

    Williams, D

    1997-12-01

    Tissue engineering is a fashionable phrase and a new concept. This article analyses what is meant by this term and discusses some of the products that may emerge from the translation of this concept into clinical reality.

  13. The combination of meltblown and electrospinning for bone tissue engineering

    Czech Academy of Sciences Publication Activity Database

    Erben, J.; Pilařová, K.; Sanetrník, F.; Chvojka, J.; Jenčová, V.; Blažková, L.; Havlíček, J.; Novák, O.; Mikeš, P.; Prosecká, Eva; Lukáš, D.; Kuželová Kostaková, E.

    2015-01-01

    Roč. 143, mar 15 (2015), s. 172-176 ISSN 0167-577X Institutional support: RVO:68378041 Keywords : meltblown * electrospinning * tissue engineering * polycaprolactone Subject RIV: JI - Composite Materials Impact factor: 2.437, year: 2015

  14. Tissue engineering skin: a paradigm shift in wound care.

    Science.gov (United States)

    Mason, C

    2005-12-01

    Tissue-engineered skin for the treatment of burns and ulcers is a clinical success, but making it commercially viable is more problematic. This article examines the industry, its techniques and suggests the way forward.

  15. Alveolar bone tissue engineering using composite scaffolds for drug delivery

    Directory of Open Access Journals (Sweden)

    Tomonori Matsuno

    2010-08-01

    Full Text Available For many years, bone graft substitutes have been used to reconstruct bone defects in orthopedic and dental fields. However, synthetic bone substitutes such as hydroxyapatite or β-tricalcium phosphate have no osteoinductive or osteogenic abilities. Bone tissue engineering has also been promoted as an alternative approach to regenerating bone tissue. To succeed in bone tissue engineering, osteoconductive scaffolding biomaterials should provide a suitable environment for osteogenic cells and provide local controlled release of osteogenic growth factors. In addition, the scaffold for the bone graft substitute should biodegrade to replace the newly formed bone. Recent advances in bone tissue engineering have allowed the creation of composite scaffolds with tailored functional properties. This review focuses on composite scaffolds that consist of synthetic ceramics and natural polymers as drug delivery carriers for alveolar bone tissue engineering.

  16. 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.

  17. Extensive characterization and comparison of endothelial cells derived from dermis and adipose tissue : Potential use in tissue engineering

    NARCIS (Netherlands)

    Monsuur, H.N.; Weijers, E.M.; Niessen, F.B.; Gefen, A.; Koolwijk, P.; Gibbs, S.; van den Broek, L.J.

    2016-01-01

    Tissue-engineered constructs need to become quickly vascularized in order to ensure graft take. One way of achieving this is to incorporate endothelial cells (EC) into the construct. The adipose tissue stromal vascular fraction (adipose-SVF) might provide an alternative source for endothelial cells

  18. 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.

  19. Recent advances in hydrogels for cartilage tissue engineering.

    Science.gov (United States)

    Vega, S L; Kwon, M Y; Burdick, J A

    2017-01-30

    Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks), new techniques to process hydrogels (e.g. 3D printing) and better incorporation of biological signals (e.g. controlled release). This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

  20. Recent advances in hydrogels for cartilage tissue engineering

    Directory of Open Access Journals (Sweden)

    SL Vega

    2017-01-01

    Full Text Available Articular cartilage is a load-bearing tissue that lines the surface of bones in diarthrodial joints. Unfortunately, this avascular tissue has a limited capacity for intrinsic repair. Treatment options for articular cartilage defects include microfracture and arthroplasty; however, these strategies fail to generate tissue that adequately restores damaged cartilage. Limitations of current treatments for cartilage defects have prompted the field of cartilage tissue engineering, which seeks to integrate engineering and biological principles to promote the growth of new cartilage to replace damaged tissue. To date, a wide range of scaffolds and cell sources have emerged with a focus on recapitulating the microenvironments present during development or in adult tissue, in order to induce the formation of cartilaginous constructs with biochemical and mechanical properties of native tissue. Hydrogels have emerged as a promising scaffold due to the wide range of possible properties and the ability to entrap cells within the material. Towards improving cartilage repair, hydrogel design has advanced in recent years to improve their utility. Some of these advances include the development of improved network crosslinking (e.g. double-networks, new techniques to process hydrogels (e.g. 3D printing and better incorporation of biological signals (e.g. controlled release. This review summarises these innovative approaches to engineer hydrogels towards cartilage repair, with an eye towards eventual clinical translation.

  1. 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.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  3. Recent Progress of Fabrication of Cell Scaffold by Electrospinning Technique for Articular Cartilage Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Yingge Zhou

    2018-01-01

    Full Text Available As a versatile nanofiber manufacturing technique, electrospinning has been widely employed for the fabrication of tissue engineering scaffolds. Since the structure of natural extracellular matrices varies substantially in different tissues, there has been growing awareness of the fact that the hierarchical 3D structure of scaffolds may affect intercellular interactions, material transportation, fluid flow, environmental stimulation, and so forth. Physical blending of the synthetic and natural polymers to form composite materials better mimics the composition and mechanical properties of natural tissues. Scaffolds with element gradient, such as growth factor gradient, have demonstrated good potentials to promote heterogeneous cell growth and differentiation. Compared to 2D scaffolds with limited thicknesses, 3D scaffolds have superior cell differentiation and development rate. The objective of this review paper is to review and discuss the recent trends of electrospinning strategies for cartilage tissue engineering, particularly the biomimetic, gradient, and 3D scaffolds, along with future prospects of potential clinical applications.

  4. 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.

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

    Science.gov (United States)

    Scheller, E L; Krebsbach, P H; Kohn, D H

    2009-05-01

    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 development of a single tissue, hybrid organ or interface. Furthermore, combining the understanding of the interactions between molecules of the extracellular matrix and attached cells with an understanding of the gene expression needed to induce differentiation and tissue growth will provide the design basis for translating basic science into rationally developed components of this tissue engineering triad. Dental tissue engineers are interested in regeneration of teeth, oral mucosa, salivary glands, bone and periodontium. Many of these oral structures are hybrid tissues. For example, engineering the periodontium requires growth of alveolar bone, cementum and the periodontal ligament. Recapitulation of biological development of hybrid tissues and interfaces presents a challenge that exceeds that of engineering just a single tissue. Advances made in dental interface engineering will allow these tissues to serve as model systems for engineering other tissues or organs of the body. This review will begin by covering basic tissue engineering principles and strategic design of functional biomaterials. We will then explore the impact of biomaterials design on the status of craniofacial tissue engineering and current challenges and opportunities in dental tissue engineering.

  6. 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. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Tissue-Engineered Solutions in Plastic and Reconstructive Surgery: Principles and Practice

    Science.gov (United States)

    Al-Himdani, Sarah; Jessop, Zita M.; Al-Sabah, Ayesha; Combellack, Emman; Ibrahim, Amel; Doak, Shareen H.; Hart, Andrew M.; Archer, Charles W.; Thornton, Catherine A.; Whitaker, Iain S.

    2017-01-01

    Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering “holds the promise of revolutionizing patient care in the twenty-first century.” The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20–30 years from the start of basic science research to clinical utility

  8. Effects of Initial Seeding Density and Fluid Perfusion Rate on Formation of Tissue-Engineered Bone

    OpenAIRE

    GRAYSON, WARREN L.; BHUMIRATANA, SARINDR; CANNIZZARO, CHRISTOPHER; CHAO, P.-H. GRACE; LENNON, DONALD P.; CAPLAN, ARNOLD I.; VUNJAK-NOVAKOVIC, GORDANA

    2008-01-01

    We describe a novel bioreactor system for tissue engineering of bone that enables cultivation of up to six tissue constructs simultaneously, with direct perfusion and imaging capability. The bioreactor was used to investigate the relative effects of initial seeding density and medium perfusion rate on the growth and osteogenic differentiation patterns of bone marrow–derived human mesenchymal stem cells (hMSCs) cultured on three-dimensional scaffolds. Fully decellularized bovine trabecular bon...

  9. Towards biologically relevant synthetic designer matrices in 3D bioprinting for tissue engineering and regenerative medicine

    KAUST Repository

    Costa, Rú ben M.; Rauf, Sakandar; Hauser, Charlotte

    2017-01-01

    3D bioprinting is one of the most promising technologies in tissue engineering and regenerative medicine. As new printing techniques and bioinks are getting developed, new cellular constructs with high resolution and functionality arise. Different to bioinks of animal, algal or plant origin, synthesized bioinks are proposed as superior biomaterials because their characteristics are fully under control. In this review, we will highlight the potential of synthetic biomaterials to be used as bioinks in 3D bioprinting to produce functionally enhanced matrices.

  10. Towards biologically relevant synthetic designer matrices in 3D bioprinting for tissue engineering and regenerative medicine

    KAUST Repository

    Costa, Rúben M.

    2017-05-12

    3D bioprinting is one of the most promising technologies in tissue engineering and regenerative medicine. As new printing techniques and bioinks are getting developed, new cellular constructs with high resolution and functionality arise. Different to bioinks of animal, algal or plant origin, synthesized bioinks are proposed as superior biomaterials because their characteristics are fully under control. In this review, we will highlight the potential of synthetic biomaterials to be used as bioinks in 3D bioprinting to produce functionally enhanced matrices.

  11. Rapid prototyping for tissue-engineered bone scaffold by 3D printing and biocompatibility study.

    Science.gov (United States)

    He, Hui-Yu; Zhang, Jia-Yu; Mi, Xue; Hu, Yang; Gu, Xiao-Yu

    2015-01-01

    The prototyping of tissue-engineered bone scaffold (calcined goat spongy bone-biphasic ceramic composite/PVA gel) by 3D printing was performed, and the biocompatibility of the fabricated bone scaffold was studied. Pre-designed STL file was imported into the GXYZ303010-XYLE 3D printing system, and the tissue-engineered bone scaffold was fabricated by 3D printing using gel extrusion. Rabbit bone marrow stromal cells (BMSCs) were cultured in vitro and then inoculated to the sterilized bone scaffold obtained by 3D printing. The growth of rabbit BMSCs on the bone scaffold was observed under the scanning electron microscope (SEM). The effect of the tissue-engineered bone scaffold on the proliferation and differentiation of rabbit BMSCs using MTT assay. Universal testing machine was adopted to test the tensile strength of the bone scaffold. The leachate of the bone scaffold was prepared and injected into the New Zealand rabbits. Cytotoxicity test, acute toxicity test, pyrogenic test and intracutaneous stimulation test were performed to assess the biocompatibility of the bone scaffold. Bone scaffold manufactured by 3D printing had uniform pore size with the porosity of about 68.3%. The pores were well interconnected, and the bone scaffold showed excellent mechanical property. Rabbit BMSCs grew and proliferated on the surface of the bone scaffold after adherence. MTT assay indicated that the proliferation and differentiation of rabbit BMSCs on the bone scaffold did not differ significantly from that of the cells in the control. In vivo experiments proved that the bone scaffold fabricated by 3D printing had no acute toxicity, pyrogenic reaction or stimulation. Bone scaffold manufactured by 3D printing allows the rabbit BMSCs to adhere, grow and proliferate and exhibits excellent biomechanical property and high biocompatibility. 3D printing has a good application prospect in the prototyping of tissue-engineered bone scaffold.

  12. Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus.

    Science.gov (United States)

    Xiao, Yinghua; Friis, Elizabeth A; Gehrke, Stevin H; Detamore, Michael S

    2013-10-01

    Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context.

  13. Tissue-engineering-based Strategies for Regenerative Endodontics

    Science.gov (United States)

    Albuquerque, M.T.P.; Valera, M.C.; Nakashima, M.; Nör, J.E.; Bottino, M.C.

    2014-01-01

    Stemming from in vitro and in vivo pre-clinical and human models, tissue-engineering-based strategies continue to demonstrate great potential for the regeneration of the pulp-dentin complex, particularly in necrotic, immature permanent teeth. Nanofibrous scaffolds, which closely resemble the native extracellular matrix, have been successfully synthesized by various techniques, including but not limited to electrospinning. A common goal in scaffold synthesis has been the notion of promoting cell guidance through the careful design and use of a collection of biochemical and physical cues capable of governing and stimulating specific events at the cellular and tissue levels. The latest advances in processing technologies allow for the fabrication of scaffolds where selected bioactive molecules can be delivered locally, thus increasing the possibilities for clinical success. Though electrospun scaffolds have not yet been tested in vivo in either human or animal pulpless models in immature permanent teeth, recent studies have highlighted their regenerative potential both from an in vitro and in vivo (i.e., subcutaneous model) standpoint. Possible applications for these bioactive scaffolds continue to evolve, with significant prospects related to the regeneration of both dentin and pulp tissue and, more recently, to root canal disinfection. Nonetheless, no single implantable scaffold can consistently guide the coordinated growth and development of the multiple tissue types involved in the functional regeneration of the pulp-dentin complex. The purpose of this review is to provide a comprehensive perspective on the latest discoveries related to the use of scaffolds and/or stem cells in regenerative endodontics. The authors focused this review on bioactive nanofibrous scaffolds, injectable scaffolds and stem cells, and pre-clinical findings using stem-cell-based strategies. These topics are discussed in detail in an attempt to provide future direction and to shed light on

  14. PLDLA/PCL-T Scaffold for Meniscus Tissue Engineering.

    Science.gov (United States)

    Esposito, Andrea Rodrigues; Moda, Marlon; Cattani, Silvia Mara de Melo; de Santana, Gracy Mara; Barbieri, Juliana Abreu; Munhoz, Monique Moron; Cardoso, Túlio Pereira; Barbo, Maria Lourdes Peris; Russo, Teresa; D'Amora, Ugo; Gloria, Antonio; Ambrosio, Luigi; Duek, Eliana Aparecida de Rezende

    2013-04-01

    The inability of the avascular region of the meniscus to regenerate has led to the use of tissue engineering to treat meniscal injuries. The aim of this study was to evaluate the ability of fibrochondrocytes preseeded on PLDLA/PCL-T [poly(L-co-D,L-lactic acid)/poly(caprolactone-triol)] scaffolds to stimulate regeneration of the whole meniscus. Porous PLDLA/PCL-T (90/10) scaffolds were obtained by solvent casting and particulate leaching. Compressive modulus of 9.5±1.0 MPa and maximum stress of 4.7±0.9 MPa were evaluated. Fibrochondrocytes from rabbit menisci were isolated, seeded directly on the scaffolds, and cultured for 21 days. New Zealand rabbits underwent total meniscectomy, after which implants consisting of cell-free scaffolds or cell-seeded scaffolds were introduced into the medial knee meniscus; the negative control group consisted of rabbits that received no implant. Macroscopic and histological evaluations of the neomeniscus were performed 12 and 24 weeks after implantation. The polymer scaffold implants adapted well to surrounding tissues, without apparent rejection, infection, or chronic inflammatory response. Fibrocartilaginous tissue with mature collagen fibers was observed predominantly in implants with seeded scaffolds compared to cell-free implants after 24 weeks. Similar results were not observed in the control group. Articular cartilage was preserved in the polymeric implants and showed higher chondrocyte cell number than the control group. These findings show that the PLDLA/PCL-T 90/10 scaffold has potential for orthopedic applications since this material allowed the formation of fibrocartilaginous tissue, a structure of crucial importance for repairing injuries to joints, including replacement of the meniscus and the protection of articular cartilage from degeneration.

  15. Tissue engineering for human urethral reconstruction: systematic review of recent literature.

    Science.gov (United States)

    de Kemp, Vincent; de Graaf, Petra; Fledderus, Joost O; Ruud Bosch, J L H; de Kort, Laetitia M O

    2015-01-01

    Techniques to treat urethral stricture and hypospadias are restricted, as substitution of the unhealthy urethra with tissue from other origins (skin, bladder or buccal mucosa) has some limitations. Therefore, alternative sources of tissue for use in urethral reconstructions are considered, such as ex vivo engineered constructs. To review recent literature on tissue engineering for human urethral reconstruction. A search was made in the PubMed and Embase databases restricted to the last 25 years and the English language. A total of 45 articles were selected describing the use of tissue engineering in urethral reconstruction. The results are discussed in four groups: autologous cell cultures, matrices/scaffolds, cell-seeded scaffolds, and clinical results of urethral reconstructions using these materials. Different progenitor cells were used, isolated from either urine or adipose tissue, but slightly better results were obtained with in vitro expansion of urothelial cells from bladder washings, tissue biopsies from the bladder (urothelium) or the oral cavity (buccal mucosa). Compared with a synthetic scaffold, a biological scaffold has the advantage of bioactive extracellular matrix proteins on its surface. When applied clinically, a non-seeded matrix only seems suited for use as an onlay graft. When a tubularized substitution is the aim, a cell-seeded construct seems more beneficial. Considerable experience is available with tissue engineering of urethral tissue in vitro, produced with cells of different origin. Clinical and in vivo experiments show promising results.

  16. Restoring nervous system structure and function using tissue engineered living scaffolds

    Directory of Open Access Journals (Sweden)

    Laura A Struzyna

    2015-01-01

    Full Text Available Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following nervous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regeneration rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engineered "living scaffolds", which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

  17. Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

    Science.gov (United States)

    Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

    Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

  18. Colloquium: Modeling the dynamics of multicellular systems: Application to tissue engineering

    Science.gov (United States)

    Kosztin, Ioan; Vunjak-Novakovic, Gordana; Forgacs, Gabor

    2012-10-01

    Tissue engineering is a rapidly evolving discipline that aims at building functional tissues to improve or replace damaged ones. To be successful in such an endeavor, ideally, the engineering of tissues should be based on the principles of developmental biology. Recent progress in developmental biology suggests that the formation of tissues from the composing cells is often guided by physical laws. Here a comprehensive computational-theoretical formalism is presented that is based on experimental input and incorporates biomechanical principles of developmental biology. The formalism is described and it is shown that it correctly reproduces and predicts the quantitative characteristics of the fundamental early developmental process of tissue fusion. Based on this finding, the formalism is then used toward the optimization of the fabrication of tubular multicellular constructs, such as a vascular graft, by bioprinting, a novel tissue engineering technology.

  19. STEM CELL ORIGIN DIFFERENTLY AFFECTS BONE TISSUE ENGINEERING STRATEGIES.

    Directory of Open Access Journals (Sweden)

    Monica eMattioli-Belmonte

    2015-09-01

    Full Text Available Bone tissue engineering is a promising research area for the improvement of traditional bone grafting procedure drawbacks. Thanks to the capability of self-renewal and multi-lineage differentiation, stem cells are one of the major actors in tissue engineering approaches, and adult mesenchymal stem cells (MSCs are considered to be appropriate for regenerative medicine strategies. Bone marrow MSCs (BM-MSCs are the earliest- discovered and well-known stem cell population used in bone tissue engineering. However, several factors hamper BM-MSC clinical application and subsequently, new stem cell sources have been investigated for these purposes. The successful identification and combination of tissue engineering, scaffold, progenitor cells, and physiologic signalling molecules enabled the surgeon to design, recreate the missing tissue in its near natural form. On the basis of these considerations, we analysed the capability of two different scaffolds, planned for osteochondral tissue regeneration, to modulate differentiation of adult stem cells of dissimilar local sources (i.e. periodontal ligament, maxillary periosteum as well as adipose-derived stem cells, in view of possible craniofacial tissue engineering strategies. We demonstrated that cells are differently committed toward the osteoblastic phenotype and therefore, considering their peculiar features, they may alternatively represent interesting cell sources in different stem cell-based bone/periodontal tissue regeneration approaches.

  20. 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.

  1. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. 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. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Development and evaluation of a removable tissue-engineered muscle with artificial tendons.

    Science.gov (United States)

    Nakamura, Tomohiro; Takagi, Shunya; Kamon, Takafumi; Yamasaki, Ken-Ichi; Fujisato, Toshia

    2017-02-01

    Tissue-engineered skeletal muscles were potentially useful as physiological and biochemical in vitro models. Currently, most of the similar models were constructed without tendons. In this study, we aimed to develop a simple, highly versatile tissue-engineered muscle with artificial tendons, and to evaluate the contractile, histological and molecular dynamics during differentiation. C2C12 cells were embedded in a cold type-І collagen gel and placed between two artificial tendons on a silicone sheet. The construct shrank and tightly attached to the artificial tendons with differentiation, finally detaching from the silicone sheet within 1 week of culture onset. We successfully developed a tissue-engineered skeletal muscle with two artificial tendons from C2C12 myoblasts embedded in type-І collagen gel. The isometric twitch contractile force (TCF) significantly increased during differentiation. Time to Peak Tension (TPT) and Half-Relaxation Time (1/2RT) were significantly shortened during differentiation. Myogenic regulatory factors were maximally expressed at 2 weeks, and subsequently decreased at 3 weeks of culture. Histological analysis indicated that myotube formation increased markedly from 2 weeks and well-ordered sarcomere structures were observed on the surface of the 3D engineered muscle at 3 weeks of culture. These results suggested that robust muscle structure occurred by 3 weeks in the tissue-engineered skeletal muscle. Moreover, during the developmental process, the artificial tendons might contribute to well-ordered sarcomere formation. Our results indicated that this simple culture system could be used to evaluate the effects of various pharmacological and mechanical cues on muscle contractility in a variety of research areas. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  4. Chondroprotective supplementation promotes the mechanical properties of injectable scaffold for human nucleus pulposus tissue engineering.

    Science.gov (United States)

    Foss, Berit L; Maxwell, Thomas W; Deng, Ying

    2014-01-01

    A result of intervertebral disc (IVD) degeneration, the nucleus pulposus (NP) is no longer able to withstand applied load leading to pain and disability. The objective of this study is to fabricate a tissue-engineered injectable scaffold with chondroprotective supplementation in vitro to improve the mechanical properties of a degenerative NP. Tissue-engineered scaffolds were fabricated using different concentrations of alginate and calcium chloride and mechanically evaluated. Fabrication conditions were based on structural and mechanical resemblance to the native NP. Chondroprotective supplementation, glucosamine (GCSN) and chondroitin sulfate (CS), were added to scaffolds at concentrations of 0:0µg/mL (0:0-S), 125:100µg/mL (125:100-S), 250:200µg/mL (250:200-S), and 500:400µg/mL (500:400-S), GCSN and CS, respectively. Scaffolds were used to fabricate tissue-engineered constructs through encapsulation of human nucleus pulposus cells (HNPCs). The tissue-engineered constructs were collected at days 1, 14, and 28 for biochemical and biomechanical evaluations. Confocal microscopy showed HNPC viability and rounded morphology over the 28 day period. MTT analysis resulted in significant increases in cell proliferation for each group. Collagen type II ELISA quantification and compressive aggregate moduli (HA) showed increasing trends for both 250:200-S and the 500:400-S groups on Day 28 with significantly greater HA compared to 0:0-S group. Glycosaminoglycan and water content decreased for all groups. Results indicate the increased mechanical properties of the 250:200-S and the 500:400-S was due to production of a functional matrix. This study demonstrated potential for a chondroprotective supplemented injectable scaffold to restore biomechanical function of a degenerative disc through the production of a mechanically functional matrix. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro.

    Science.gov (United States)

    Martin, Neil R W; Turner, Mark C; Farrington, Robert; Player, Darren J; Lewis, Mark P

    2017-10-01

    The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly-controlled investigations into nutritional regulation of muscle physiology. © 2017 The Authors. Journal of Cellular Physiology Published by wiley periodicals, Inc.

  6. Decellularized matrices for cardiovascular tissue engineering.

    Science.gov (United States)

    Moroni, Francesco; Mirabella, Teodelinda

    2014-01-01

    Cardiovascular disease (CVD) is one of the leading causes of death in the Western world. The replacement of damaged vessels and valves has been practiced since the 1950's. Synthetic grafts, usually made of bio-inert materials, are long-lasting and mechanically relevant, but fail when it comes to "biointegration". Decellularized matrices, instead, can be considered biological grafts capable of stimulating in vivo migration and proliferation of endothelial cells (ECs), recruitment and differentiation of mural cells, finally, culminating in the formation of a biointegrated tissue. Decellularization protocols employ osmotic shock, ionic and non-ionic detergents, proteolitic digestions and DNase/RNase treatments; most of them effectively eliminate the cellular component, but show limitations in preserving the native structure of the extracellular matrix (ECM). In this review, we examine the current state of the art relative to decellularization techniques and biological performance of decellularized heart, valves and big vessels. Furthermore, we focus on the relevance of ECM components, native and resulting from decellularization, in mediating in vivo host response and determining repair and regeneration, as opposed to graft corruption.

  7. Introduction to tissue engineering and application for cartilage engineering.

    Science.gov (United States)

    de Isla, N; Huseltein, C; Jessel, N; Pinzano, A; Decot, V; Magdalou, J; Bensoussan, D; Stoltz, J-F

    2010-01-01

    Tissue engineering is a multidisciplinary field that applies the principles of engineering, life sciences, cell and molecular biology toward the development of biological substitutes that restore, maintain, and improve tissue function. In Western Countries, tissues or cells management for clinical uses is a medical activity governed by different laws. Three general components are involved in tissue engineering: (1) reparative cells that can form a functional matrix; (2) an appropriate scaffold for transplantation and support; and (3) bioreactive molecules, such as cytokines and growth factors that will support and choreograph formation of the desired tissue. These three components may be used individually or in combination to regenerate organs or tissues. Thus the growing development of tissue engineering needs to solve four main problems: cells, engineering development, grafting and safety studies.

  8. The self-assembling process and applications in tissue engineering

    Science.gov (United States)

    Lee, Jennifer K.; Link, Jarrett M.; Hu, Jerry C. Y.; Athanasiou, Kyriacos A.

    2018-01-01

    Tissue engineering strives to create neotissues capable of restoring function. Scaffold-free technologies have emerged that can recapitulate native tissue function without the use of an exogenous scaffold. This chapter will survey, in particular, the self-assembling and self-organization processes as scaffold-free techniques. Characteristics and benefits of each process are described, and key examples of tissues created using these scaffold-free processes are examined to provide guidance for future tissue engineering developments. This chapter aims to explore the potential of self-assembly and self-organization scaffold-free approaches, detailing the recent progress in the in vitro tissue engineering of biomimetic tissues with these methods, toward generating functional tissue replacements. PMID:28348174

  9. Skin Diseases Modeling using Combined Tissue Engineering and Microfluidic Technologies.

    Science.gov (United States)

    Mohammadi, Mohammad Hossein; Heidary Araghi, Behnaz; Beydaghi, Vahid; Geraili, Armin; Moradi, Farshid; Jafari, Parya; Janmaleki, Mohsen; Valente, Karolina Papera; Akbari, Mohsen; Sanati-Nezhad, Amir

    2016-10-01

    In recent years, both tissue engineering and microfluidics have significantly contributed in engineering of in vitro skin substitutes to test the penetration of chemicals or to replace damaged skins. Organ-on-chip platforms have been recently inspired by the integration of microfluidics and biomaterials in order to develop physiologically relevant disease models. However, the application of organ-on-chip on the development of skin disease models is still limited and needs to be further developed. The impact of tissue engineering, biomaterials and microfluidic platforms on the development of skin grafts and biomimetic in vitro skin models is reviewed. The integration of tissue engineering and microfluidics for the development of biomimetic skin-on-chip platforms is further discussed, not only to improve the performance of present skin models, but also for the development of novel skin disease platforms for drug screening processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Current Concepts in Scaffolding for Bone Tissue Engineering.

    Science.gov (United States)

    Ghassemi, Toktam; Shahroodi, Azadeh; Ebrahimzadeh, Mohammad H; Mousavian, Alireza; Movaffagh, Jebraeel; Moradi, Ali

    2018-03-01

    Bone disorders are of significant worry due to their increased prevalence in the median age. Scaffold-based bone tissue engineering holds great promise for the future of osseous defects therapies. Porous composite materials and functional coatings for metallic implants have been introduced in next generation of orthopedic medicine for tissue engineering. While osteoconductive materials such as hydroxyapatite and tricalcium phosphate ceramics as well as some biodegradable polymers are suggested, much interest has recently focused on the use of osteoinductive materials like demineralized bone matrix or bone derivatives. However, physiochemical modifications in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, mineralization and osteogenic differentiation are required. This paper reviews studies on bone tissue engineering from the biomaterial point of view in scaffolding. Level of evidence: I.

  11. 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

  12. Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

    Science.gov (United States)

    Alberti, C

    2016-01-01

    To prevent problematic outcomes of bowel-based bladder reconstructive surgery, such as prosthetic tumors and systemic metabolic complications, research works, to either regenerate and strengthen failing organ or build organ replacement biosubstitute, have been turned, from 90s of the last century, to both regenerative medicine and tissue engineering.Various types of acellular matrices, naturally-derived materials, synthetic polymers have been used for either "unseeded" (cell free) or autologous "cell seeded" tissue engineering scaffolds. Different categories of cell sources - from autologous differentiated urothelial and smooth muscle cells to natural or laboratory procedure-derived stem cells - have been taken into consideration to reach the construction of suitable "cell seeded" templates. Current clinically validated bladder tissue engineering approaches essentially consist of augmentation cystoplasty in patients suffering from poorly compliant neuropathic bladder. No clinical applications of wholly tissue engineered neobladder have been carried out to radical-reconstructive surgical treatment of bladder malignancies or chronic inflammation-due vesical coarctation. Reliable reasons why bladder tissue engineering clinical applications so far remain unusual, particularly imply the risk of graft ischemia, hence its both fibrous contraction and even worse perforation. Therefore, the achievement of graft vascular network (vasculogenesis) could allow, together with the promotion of host surrounding vessel sprouting (angiogenesis), an effective graft blood supply, so avoiding the ischemia-related serious complications.

  13. An economic survey of the emerging tissue engineering industry.

    Science.gov (United States)

    Lysaght, M J; Nguy, N A; Sullivan, K

    1998-01-01

    The contemporary scope of worldwide tissue engineering research and development was estimated by totaling the relevant annual spending and other economic parameters of firms involved the field. Operating expenses allocated to tissue engineering in 1997 exceed $450 million and fund the activities of nearly 2,500 scientists and support personnel. Growth rate is 22.5% per annum. Most activity is centered in the United States. Government spending in this field represents investment and valuation represents a remarkable act of faith in the future of a technology yet to produce its first significant revenue-generating product.

  14. HEPATIC TISSUE ENGINEERING (MODERN STATE OF THIS PROBLEM

    Directory of Open Access Journals (Sweden)

    Y.S. Gulay

    2014-01-01

    Full Text Available In this article it was discussed the problem of creation implanted hepatic tissue engineering designs as a modern stage of complex investigation for working out bioartifi cial liver support systems. It was determined that for the positive decision of numerous biological and technological problems it is necessary: to use matrices with determined properties, which mimic properties of hepatic extracellular matrix; to use technology for stereotype sowing of these matrices by both parenchymal and non-parenchymal hepatic cells and to improve the technologies for making and assembling of hepatic tissue-engineering designs.

  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...

  16. 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.

  17. Biodegradable electroactive materials for tissue engineering applications

    Science.gov (United States)

    Guimard, Nathalie Kathryn

    polymerization can be achieved at the surface of these functionalized films and that the extent of polymer immobilization appears to be affected by the presence of immobilized thiophene. The results reported in this dissertation lead the author to suggest that it is possible to generate biodegradable electroactive materials. Further, she believes that with additional optimization these materials may prove beneficial for the regeneration of peripheral nerves and possibly other tissues that respond favorably to electrical stimulation.

  18. Investigation of optical coherence tomography as an imaging modality in tissue engineering

    International Nuclear Information System (INIS)

    Yang Ying; Dubois, Arnaud; Qin Xiangpei; Li Jian; Haj, Alicia El; Wang, Ruikang K

    2006-01-01

    Monitoring cell profiles in 3D porous scaffolds presents a major challenge in tissue engineering. In this study, we investigate optical coherence tomography (OCT) as an imaging modality to monitor non-invasively both structures and cells in engineered tissue constructs. We employ time-domain OCT to visualize macro-structural morphology, and whole-field optical coherence microscopy to delineate the morphology of cells and constructs in a developing in vitro engineered bone tissue. The results show great potential for the use of OCT in non-invasive monitoring of cellular activities in 3D developing engineered tissues

  19. Towards a Tissue-Engineered Ligament: Design and Preliminary Evaluation of a Dedicated Multi-Chamber Tension-Torsion Bioreactor

    Directory of Open Access Journals (Sweden)

    Cédric P. Laurent

    2014-02-01

    Full Text Available Tissue engineering may constitute a promising alternative to current strategies in ligament repair, providing that suitable scaffolds and culture conditions are proposed. The objective of the present contribution is to present the design and instrumentation of a novel multi-chamber tension-torsion bioreactor dedicated to ligament tissue engineering. A preliminary biological evaluation of a new braided scaffold within this bioreactor under dynamic loading is reported, starting with the development of a dedicated seeding protocol validated from static cultures. The results of these preliminary biological characterizations confirm that the present combination of scaffold, seeding protocol and bioreactor may enable us to head towards a suitable ligament tissue-engineered construct.

  20. Tissue Engineered Skeletal Myofibers can Directly "Sense" Gravitational Force Changes

    Science.gov (United States)

    Vandenburgh, Herman H.; Shansky, J.; DelTatto, M.; Lee, Peter; 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. Embryonic avian muscle cells were isolated and BAMs tissue engineered as described previously. The myoblasts proliferate and fuse into aligned postmitotic myofibers after ten to fourteen days in vitro. A cylindrical muscle-like structure containing several thousand myofibers is formed which is approximately 30 mm in length, 2-3 mm in diameter, and attached at each end. For the Space Shuttle experiments, the BAMs were transferred to 55 mL bioreactor cartridges (6 BAMs/cartridge). At Kennedy Space Center, the cartridges were mounted in two Space Tissue Loss (STL) Modules (three to four cartridges per Module) and either maintained as ground controls or loaded in a Mid-Deck locker of the Space Shuttle. The BAM cartridges were continuously perfused during the experiment at 1.5 mL/ min with tissue culture medium. Eighteen BAMs were flown for nine days on Mission STS66 while eighteen BAMs served as ground controls. The complete experiment was repeated on Mission STS77 with twenty four BAMs in each group. BAMs could be maintained in a healthy state for at least 30 days in the perfusion bioreactor cartridges. The BAM muscle fibers directly detected both the

  1. Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration

    Directory of Open Access Journals (Sweden)

    Sethuraman Swaminathan

    2009-11-01

    Full Text Available Abstract Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves.

  2. Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration

    Science.gov (United States)

    2009-01-01

    Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves. PMID:19939265

  3. 3D Printing and Electrospinning of Composite Hydrogels for Cartilage and Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Arianna De Mori

    2018-03-01

    Full Text Available Injuries of bone and cartilage constitute important health issues costing the National Health Service billions of pounds annually, in the UK only. Moreover, these damages can become cause of disability and loss of function for the patients with associated social costs and diminished quality of life. The biomechanical properties of these two tissues are massively different from each other and they are not uniform within the same tissue due to the specific anatomic location and function. In this perspective, tissue engineering (TE has emerged as a promising approach to address the complexities associated with bone and cartilage regeneration. Tissue engineering aims at developing temporary three-dimensional multicomponent constructs to promote the natural healing process. Biomaterials, such as hydrogels, are currently extensively studied for their ability to reproduce both the ideal 3D extracellular environment for tissue growth and to have adequate mechanical properties for load bearing. This review will focus on the use of two manufacturing techniques, namely electrospinning and 3D printing, that present promise in the fabrication of complex composite gels for cartilage and bone tissue engineering applications.

  4. A tissue engineering strategy for the treatment of avascular necrosis of the femoral head.

    Science.gov (United States)

    Aarvold, A; Smith, J O; Tayton, E R; Jones, A M H; Dawson, J I; Lanham, S; Briscoe, A; Dunlop, D G; Oreffo, R O C

    2013-12-01

    Skeletal stem cells (SSCs) and impaction bone grafting (IBG) can be combined to produce a mechanically stable living bone composite. This novel strategy has been translated to the treatment of avascular necrosis of the femoral head. Surgical technique, clinical follow-up and retrieval analysis data of this translational case series is presented. SSCs and milled allograft were impacted into necrotic bone in five femoral heads of four patients. Cell viability was confirmed by parallel in vitro culture of the cell-graft constructs. Patient follow-up was by serial clinical and radiological examination. Tissue engineered bone was retrieved from two retrieved femoral heads and was analysed by histology, microcomputed tomography (μCT) and mechanical testing. Three patients remain asymptomatic at 22- to 44-month follow-up. One patient (both hips) required total hip replacement due to widespread residual necrosis. Retrieved tissue engineered bone demonstrated a mature trabecular micro-architecture histologically and on μCT. Bone density and axial compression strength were comparable to trabecular bone. Clinical follow-up shows this to be an effective new treatment for focal early stage avascular necrosis of the femoral head. Unique retrieval analysis of clinically translated tissue engineered bone has demonstrated regeneration of tissue that is both structurally and functionally analogous to normal trabecular bone. Copyright © 2013 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  5. 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.

  6. 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.; Von den Hoff, J.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

  7. Tissue engineered devices for ligament repair, replacement and ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-12-29

    Dec 29, 2009 ... These devices use a wide variety of materials and designs to replicate ligament mechanics and allow for new tissue regeneration. Key words: Anterior cruciate ligament (ACL), tissue engineering, cells, tensile, stress relaxation, polymer, allograft, xenograft. INTRODUCTION. The anterior cruciate ligament ...

  8. 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.

  9. Enzymatically biomineralized chitosan scaffolds for tissue-engineering applications.

    NARCIS (Netherlands)

    Dash, M.; Samal, S.K.; Douglas, T.E.L.; Schaubroeck, D.; Leeuwenburgh, S.C.G.; Voort, P. van der; Declercq, H.A.; Dubruel, P.

    2017-01-01

    Porous biodegradable scaffolds represent promising candidates for tissue-engineering applications because of their capability to be preseeded with cells. We report an uncrosslinked chitosan scaffold designed with the aim of inducing and supporting enzyme-mediated formation of apatite minerals in the

  10. Surface modification of polyester biomaterials for tissue engineering

    International Nuclear Information System (INIS)

    Jiao Yanpeng; Cui Fuzhai

    2007-01-01

    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. (topical review)

  11. 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

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

    Science.gov (United States)

    YUAN, Bo; ZHOU, Sheng-yuan; CHEN, Xiong-sheng

    2017-01-01

    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. PMID:28378568

  14. Cell based bone tissue engineering in jaw defects

    NARCIS (Netherlands)

    Meijer, Gert J.; de Bruijn, Joost Dick; Koole, Ron; van Blitterswijk, Clemens

    2008-01-01

    In 6 patients the potency of bone tissue engineering to reconstruct jaw defects was tested. After a bone marrow aspirate was taken, stem cells were cultured, expanded and grown for 7 days on a bone substitute in an osteogenic culture medium to allow formation of a layer of extracellular bone matrix.

  15. Tissue Engineering: Toward a New Era of Medicine.

    Science.gov (United States)

    Shafiee, Ashkan; Atala, Anthony

    2017-01-14

    The goal of tissue engineering is to mitigate the critical shortage of donor organs via in vitro fabrication of functional biological structures. Tissue engineering is one of the most prominent examples of interdisciplinary fields, where scientists with different backgrounds work together to boost the quality of life by addressing critical health issues. Many different fields, such as developmental and molecular biology, as well as technologies, such as micro- and nanotechnologies and additive manufacturing, have been integral for advancing the field of tissue engineering. Over the past 20 years, spectacular advancements have been achieved to harness nature's ability to cure diseased tissues and organs. Patients have received laboratory-grown tissues and organs made out of their own cells, thus eliminating the risk of rejection. However, challenges remain when addressing more complex solid organs such as the heart, liver, and kidney. Herein, we review recent accomplishments as well as challenges that must be addressed in the field of tissue engineering and provide a perspective regarding strategies in further development.

  16. 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

  17. Environmental regulation of valvulogenesis:implications for tissue engineering

    NARCIS (Netherlands)

    Riem Vis, P.W.; Kluin, J.; Sluijter, J.P.G.; Herwerden, van L.A.; Bouten, C.V.C.

    2011-01-01

    Ongoing research efforts aim at improving the creation of tissue-engineered heart valves for in vivo systemic application. Hence, in vitro studies concentrate on optimising culture protocols incorporating biological as well as biophysical stimuli for tissue development. Important lessons can be

  18. Tissue engineering of urethra: Systematic review of recent literature.

    Science.gov (United States)

    Žiaran, Stanislav; Galambošová, Martina; Danišovič, L'uboš

    2017-12-01

    The purpose of this article was to perform a systematic review of the recent literature on urethral tissue engineering. A total of 31 articles describing the use of tissue engineering for urethra reconstruction were included. The obtained results were discussed in three groups: cells, scaffolds, and clinical results of urethral reconstructions using these components. Stem cells of different origin were used in many experimental studies, but only autologous urothelial cells, fibroblasts, and keratinocytes were applied in clinical trials. Natural and synthetic scaffolds were studied in the context of urethral tissue engineering. The main advantage of synthetic ones is the fact that they can be obtained in unlimited amount and modified by different techniques, but scaffolds of natural origin normally contain chemical groups and bioactive proteins which increase the cell attachment and may promote the cell proliferation and differentiation. The most promising are smart scaffolds delivering different bioactive molecules or those that can be tubularized. In two clinical trials, only onlay-fashioned transplants were used for urethral reconstruction. However, the very promising results were obtained from animal studies where tubularized scaffolds, both non-seeded and cell-seeded, were applied. Impact statement The main goal of this article was to perform a systematic review of the recent literature on urethral tissue engineering. It summarizes the most recent information about cells, seeded or non-seeded scaffolds and clinical application with respect to regeneration of urethra.

  19. Human prenatal progenitors for pediatric cardiovascular tissue engineering

    NARCIS (Netherlands)

    Schmidt, D.

    2007-01-01

    Pediatric cardiovascular tissue engineering is a promising strategy to overcome the lack of autologous, growing replacements for the early repair of congenital malformations in order to prevent secondary damage to the immature heart. Therefore, cells should be harvested during pregnancy as soon as

  20. 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.

  1. 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

  2. Animal models for bone tissue engineering and modelling disease

    Science.gov (United States)

    Griffin, Michelle

    2018-01-01

    ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

  3. Poly(ether ester amide)s for tissue engineering

    NARCIS (Netherlands)

    Deschamps, A.A.; van Apeldoorn, Aart A.; de Bruijn, Joost Dick; Grijpma, Dirk W.; Feijen, Jan

    2003-01-01

    Poly(ether ester amide) (PEEA) copolymers based on poly(ethylene glycol) (PEG), 1,4-butanediol and dimethyl-7,12-diaza-6,13-dione-1,18-octadecanedioate were evaluated as scaffold materials for tissue engineering. A PEEA copolymer based on PEG with a molecular weight of 300 g/mol and 25 wt% of soft

  4. 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.

  5. 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

  6. Modeling collagen remodeling in tissue engineered cardiovascular tissues

    NARCIS (Netherlands)

    Soares, A.L.F.

    2012-01-01

    Commonly, heart valve replacements consist of non-living materials lacking the ability to grow, repair and remodel. Tissue engineering (TE) offers a promising alternative to these replacement strategies since it can overcome its disadvantages. The technique aims to create an autologous living tissue

  7. Mechanical design criteria for intervertebral disc tissue engineering.

    Science.gov (United States)

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

    2010-04-19

    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 behaviors, 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 where functional equivalence was achieved, and 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. Copyright 2009 Elsevier Ltd. All rights reserved.

  8. Meet the new meat: tissue engineered skeletal muscle

    NARCIS (Netherlands)

    Langelaan, M.L.P.; Boonen, K.J.M.; Polak, R.B.; Baaijens, F.P.T.; Post, M.J.; Schaft, van der D.W.J.

    2010-01-01

    Contemporary large-scale farming and transportation of livestock brings along a high risk of infectious animal diseases and environmental burden through greenhouse gas emission. A new approach to produce meat and thereby reducing these risks is found in tissue engineering of skeletal muscle. This

  9. Biocompatibility of hydrogel-based scaffolds for tissue engineering applications.

    Science.gov (United States)

    Naahidi, Sheva; Jafari, Mousa; Logan, Megan; Wang, Yujie; Yuan, Yongfang; Bae, Hojae; Dixon, Brian; Chen, P

    2017-09-01

    Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:23099792

  11. 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.

  12. Tissue engineered bone versus alloplastic commercial biomaterials in craniofacial reconstruction.

    Science.gov (United States)

    Lucaciu, Ondine; Băciuţ, Mihaela; Băciuţ, G; Câmpian, R; Soriţău, Olga; Bran, S; Crişan, B; Crişan, Liana

    2010-01-01

    This research was developed in order to demonstrate the tissue engineering method as an alternative to conventional methods for bone reconstruction, in order to overcome the frequent failures of alloplastic commercial biomaterials, allografts and autografts. Tissue engineering is an in vitro method used to obtain cell based osteoinductive bone grafts. This study evaluated the feasibility of creating tissue-engineered bone using mesenchymal cells seeded on a scaffold obtained from the deciduous red deer antler. We have chosen mesenchymal stem cells because they are easy to obtain, capable to differentiate into cells of mesenchymal origin (osteoblasts) and to produce tissue such as bone. As scaffold, we have chosen the red deer antler because it has a high level of porosity. We conducted a case control study, on three groups of mice type CD1--two study groups (n=20) and a control group (n=20). For the study groups, we obtained bone grafts through tissue engineering, using mesenchymal stem cells seeded on the scaffold made of deciduous red deer antler. Bone defects were surgically induced on the left parietal bone of all subjects. In the control group, we grafted the bone defects with commercial biomaterials (OsteoSet, Wright Medical Technology, Inc., Arlington, Federal USA). Subjects were sacrificed at two and four months, the healing process was morphologically and histologically evaluated using descriptive histology and the golden standard - histological scoring. The grafts obtained in vivo through tissue engineering using adult stem cell, seeded on the scaffold obtained from the red deer antler using osteogenic medium have proven their osteogenic properties.

  13. Construction of a cardiac conduction system subject to extracellular stimulation.

    Science.gov (United States)

    Clements, Clyde; Vigmond, Edward

    2005-01-01

    Proper electrical excitation of the heart is dependent on the specialized conduction system that coordinates the electrical activity from the atria to the ventricles. This paper describes the construction of a conduction system as a branching network of Purkinje fibers on the endocardial surface. Endocardial surfaces were extracted from an FEM model of the ventricles and transformed to 2D. A Purkinje network was drawn on top and the inverse transform performed. The underlying mathematics utilized one dimensional cubic Hermite finite elements. Compared to linear elements, the cubic Hermite solution was found to have a much smaller RMS error. Furthermore, this method has the advantage of enforcing current conservation at bifurcation and unification points, and allows for discrete coupling resistances.

  14. Repairing the Osteochondral Defect in Goat with the Tissue-Engineered Osteochondral Graft Preconstructed in a Double-Chamber Stirring Bioreactor

    Directory of Open Access Journals (Sweden)

    Yang Pei

    2014-01-01

    Full Text Available To investigate the reparative efficacy of tissue-engineered osteochondral (TEO graft for repairing the osteochondral defect in goat, we designed a double-chamber stirring bioreactor to construct the bone and cartilage composites simultaneously in one β-TCP scaffold and observed the reparative effect in vivo. The osteochondral defects were created in goats and all the animals were divided into 3 groups randomly. In groups A, the defect was treated with the TEO which was cultured with mechanical stimulation of stir; in group B, the defect was treated with TEO which was cultured without mechanical stimulation of stir; in groups C, the defect was treated without TEO. At 12 weeks and 24 weeks after operation, the reparative effects in different groups were assessed and compared. The results indicated that the reparative effect of the TEO cultured in the bioreactor was better than the control group, and mechanical stimulation of stir could further improve the reparative effect. We provided a feasible and effective method to construct the TEO for treatment of osteochondral defect using autologous BMSCs and the double-chamber bioreactor.

  15. Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering.

    Science.gov (United States)

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

    2007-08-01

    Engineering a functional replacement for the annulus fibrosus (AF) of the intervertebral disc is contingent upon recapitulation of AF structure, composition, and mechanical properties. In this study, we propose a new paradigm for AF tissue engineering that focuses on the reconstitution of anatomic fiber architecture and uses constitutive modeling to evaluate construct function. A modified electrospinning technique was utilized to generate aligned nanofibrous polymer scaffolds for engineering the basic functional unit of the AF, a single lamella. Scaffolds were tested in uniaxial tension at multiple fiber orientations, demonstrating a nonlinear dependence of modulus on fiber angle that mimicked the nonlinearity and anisotropy of native AF. A homogenization model previously applied to native AF successfully described scaffold mechanical response, and parametric studies demonstrated that nonfibrillar matrix, along with fiber connectivity, are key contributors to tensile mechanics for engineered AF. We demonstrated that AF cells orient themselves along the aligned scaffolds and deposit matrix that contributes to construct mechanics under loading conditions relevant to the in vivo environment. The homogenization model was applied to cell-seeded constructs and provided quantitative measures for the evolution of matrix and interfibrillar interactions. Finally, the model demonstrated that at fiber angles of the AF (28 degrees -44 degrees ), engineered material behaved much like native tissue, suggesting that engineered constructs replicate the physiologic behavior of the single AF lamella. Constitutive modeling provides a powerful tool for analysis of engineered AF neo-tissue and native AF tissue alike, highlighting key mechanical design criteria for functional AF tissue engineering.

  16. Review of vascularised bone tissue-engineering strategies with a focus on co-culture systems.

    Science.gov (United States)

    Liu, Yuchun; Chan, Jerry K Y; Teoh, Swee-Hin

    2015-02-01

    Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit poor cellular viability particularly at the core, leading to graft failure and lack of integration with host tissues. Various BTE approaches have been explored for improving vascularisation in tissue-engineered constructs and are briefly discussed in this review. Recent investigations relating to co-culture systems of endothelial and osteoblast-like cells have shown evidence of BTE efficacy in increasing vascularization in thick constructs. This review provides an overview of key concepts related to bone formation and then focuses on the current state of engineered vascularized co-culture systems using bone repair as a model. It will also address key questions regarding the generation of clinically relevant vascularized bone constructs as well as potential directions and considerations for research with the objective of pursuing engineered co-culture systems in other disciplines of vascularized regenerative medicine. The final objective is to generate serious and functional long-lasting vessels for sustainable angiogenesis that will enable enhanced cellular survival within thick voluminous bone grafts, thereby aiding in bone formation and remodelling in the long term. However, more evidence about the quality of blood vessels formed and its associated functional improvement in bone formation as well as a mechanistic understanding of their interactions are necessary for designing better therapeutic strategies for translation to clinical settings. Copyright © 2012 John Wiley & Sons, Ltd.

  17. Tissue engineering of cartilage using a mechanobioreactor exerting simultaneous mechanical shear and compression to simulate the rolling action of articular joints.

    Science.gov (United States)

    Shahin, Kifah; Doran, Pauline M

    2012-04-01

    The effect of dynamic mechanical shear and compression on the synthesis of human tissue-engineered cartilage was investigated using a mechanobioreactor capable of simulating the rolling action of articular joints in a mixed fluid environment. Human chondrocytes seeded into polyglycolic acid (PGA) mesh or PGA-alginate scaffolds were precultured in shaking T-flasks or recirculation perfusion bioreactors for 2.5 or 4 weeks prior to mechanical stimulation in the mechanobioreactor. Constructs were subjected to intermittent unconfined shear and compressive loading at a frequency of 0.05 Hz using a peak-to-peak compressive strain amplitude of 2.2% superimposed on a static axial compressive strain of 6.5%. The mechanical treatment was carried out for up to 2.5 weeks using a loading regime of 10 min duration each day with the direction of the shear forces reversed after 5 min and release of all loading at the end of the daily treatment period. Compared with shaking T-flasks and mechanobioreactor control cultures without loading, mechanical treatment improved the amount and quality of cartilage produced. On a per cell basis, synthesis of both major structural components of cartilage, glycosaminoglycan (GAG) and collagen type II, was enhanced substantially by up to 5.3- and 10-fold, respectively, depending on the scaffold type and seeding cell density. Levels of collagen type II as a percentage of total collagen were also increased after mechanical treatment by up to 3.4-fold in PGA constructs. Mechanical treatment had a less pronounced effect on the composition of constructs precultured in perfusion bioreactors compared with perfusion culture controls. This work demonstrates that the quality of tissue-engineered cartilage can be enhanced significantly by application of simultaneous dynamic mechanical shear and compression, with the greatest benefits evident for synthesis of collagen type II. Copyright © 2011 Wiley Periodicals, Inc.

  18. Potential applications of three-dimensional structure of silk fibroin/poly(ester-urethane) urea nanofibrous scaffold in heart valve tissue engineering

    Science.gov (United States)

    Du, Juan; Zhu, Tonghe; Yu, Haiyan; Zhu, Jingjing; Sun, Changbing; Wang, Jincheng; Chen, Sihao; Wang, Jihu; Guo, Xuran

    2018-07-01

    Tissue engineering heart valves (TEHV) are thought to have many advantages in low immunogenicity, good histocompatibility, excellent mechanical properties. In this paper, we reported the fabrication and characterization of a novel composite nanofibrous scaffold consisting of silk fibroin (SF) and poly(ester-urethane) urea (LDI-PEUU) by using electrospinning. Chemical and physical properties of scaffolds were evaluated using scanning electron microscopy, attenuated total reflectance Fourier transform infrared, X-ray diffraction, contact angle measurement, thermogravimetric analysis, biodegradation test and tensile strength analysis. We determined that the composite scaffolds supported the growth of human umbilical vein endothelial cell (HUVEC). The results of cell proliferation and cell morphology indicate that SF/LDI-PEUU nanofibers promoted cell viability, which supporting the application in tissue engineering. All results clarified that SF/LDI-PEUU (40:60) nanofibrous scaffolds meet the required specifications for tissue engineering and could be used as a promising construct for heart valve tissue engineering.

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

    Science.gov (United States)

    Jangö, Hanna

    2017-08-01

    This PhD-thesis is based on animal studies and comprises three original papers and unpublished data. The studies were con-ducted during my employment as a research fellow at the Department of Obstetrics and Gynecology, Herlev University Hospital, Denmark. New strategies for surgical reconstruction of pelvic organ pro-lapse (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(lacticco-glycolic acid) (MPEG-PLGA) and electrospun polycaprolactone (PCL) - with or without seeded muscle stem cells in the form of autologous fresh muscle fiber fragments (MFFs). To simulate different POP repair scenarios different animal models were used. In Study 1 and 2, MPEG-PLGA was evaluated in a native tissue re-pair model and a partial defect model of the rat abdominal wall. We found that the scaffold was fully degraded after eight weeks. Cells from added MFFs could be traced and had resulted in the formation of new striated muscle fibers. Also, biomechanical changes were found in the groups with added MFFs. In Study 3, the long-term degradable electrospun PCL scaffold was evaluated in three rat abdominal wall models representing different loads on the scaffold. Surprisingly, cells from the MFFs did not survive. After eight weeks, a marked inflammatory foreign-body response was observed with numerous giant cells located between and around the PCL fibers which appeared not to be degraded. This response caused a considerable increase in the thickness of the mesh, resulting in a neotissue

  20. 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.

  1. An Overview of Recent Patents on Musculoskeletal Interface Tissue Engineering

    Science.gov (United States)

    Rao, Rohit T.; Browe, Daniel P.; Lowe, Christopher J.; Freeman, Joseph W.

    2018-01-01

    Interface tissue engineering involves the development of engineered grafts that promote integration between multiple tissue types. Musculoskeletal tissue interfaces are critical to the safe and efficient transmission of mechanical forces between multiple musculoskeletal tissues e.g. between ligament and bone tissue. However, these interfaces often do not physiologically regenerate upon injury, resulting in impaired tissue function. Therefore, interface tissue engineering approaches are considered to be particularly relevant for the structural restoration of musculoskeletal tissues interfaces. In this article we provide an overview of the various strategies used for engineering musculoskeletal tissue interfaces with a specific focus on the recent important patents that have been issued for inventions that were specifically designed for engineering musculoskeletal interfaces as well as those that show promise to be adapted for this purpose. PMID:26577344

  2. 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.

  3. Electrospun nanofibrous materials for tissue engineering and drug delivery

    Directory of Open Access Journals (Sweden)

    Wenguo Cui, Yue Zhou and Jiang Chang

    2010-01-01

    Full Text Available The electrospinning technique, which was invented about 100 years ago, has attracted more attention in recent years due to its possible biomedical applications. Electrospun fibers with high surface area to volume ratio and structures mimicking extracellular matrix (ECM have shown great potential in tissue engineering and drug delivery. In order to develop electrospun fibers for these applications, different biocompatible materials have been used to fabricate fibers with different structures and morphologies, such as single fibers with different composition and structures (blending and core-shell composite fibers and fiber assemblies (fiber bundles, membranes and scaffolds. This review summarizes the electrospinning techniques which control the composition and structures of the nanofibrous materials. It also outlines possible applications of these fibrous materials in skin, blood vessels, nervous system and bone tissue engineering, as well as in drug delivery.

  4. Mathematical modeling in wound healing, bone regeneration and tissue engineering.

    Science.gov (United States)

    Geris, Liesbet; Gerisch, Alf; Schugart, Richard C

    2010-12-01

    The processes of wound healing and bone regeneration and problems in tissue engineering have been an active area for mathematical modeling in the last decade. Here we review a selection of recent models which aim at deriving strategies for improved healing. In wound healing, the models have particularly focused on the inflammatory response in order to improve the healing of chronic wound. For bone regeneration, the mathematical models have been applied to design optimal and new treatment strategies for normal and specific cases of impaired fracture healing. For the field of tissue engineering, we focus on mathematical models that analyze the interplay between cells and their biochemical cues within the scaffold to ensure optimal nutrient transport and maximal tissue production. Finally, we briefly comment on numerical issues arising from simulations of these mathematical models.

  5. 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.

  6. 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......) (MPEG-PLGA) and electrospun polycaprolactone (PCL) - with or without seeded muscle stem cells in the form of autologous fresh muscle fiber fragments (MFFs).To simulate different POP repair scenarios different animal models were used. In Study 1 and 2, MPEG-PLGA was evaluated in a native tissue repair...

  7. Cell Therapy and Tissue Engineering Products for Chondral Knee Injuries

    Directory of Open Access Journals (Sweden)

    Adriana Flórez Cabrera

    2017-07-01

    Full Text Available The articular cartilage is prone to suffer lesions of different etiology, being the articular cartilage lesions of the knee the most common. Although most conventional treatments reduce symptoms they lead to the production of fibrocartilage, which has different characteristics than the hyaline cartilage of the joint. There are few therapeutic approaches that promote the replacement of damaged tissue by functional hyaline cartilage. Among them are the so-called advanced therapies, which use cells and tissue engineering products to promote cartilage regeneration. Most of them are based on scaffolds made of different biomaterials, which seeded or not with endogenous or exogenous cells, can be used as cartilage artificial replacement to improve joint function. This paper reviews some therapeutic approaches focused on the regeneration of articular cartilage of the knee and the biomaterials used to develop scaffolds for cell therapy and tissue engineering of cartilage.

  8. Physical Limitations to Tissue Engineering of Intervertabral Disc Cells

    OpenAIRE

    Kobayashi, Shigeru; Baba, Hisatoshi; Takeno, Kenichi; Miyazaki, Tsuyoshi; Meir, Adam; Urban, Jill

    2010-01-01

    There is increasing interest in the using biological methods to repair degenerate discs. Biological repair depends on the disc maintaining a population of viable and active cells. Adequate nutrition of the disc influences the outcome of such therapies and, hence, must be considered to be a crucial parameter. Therefore, it is very important to maintain an appropriate physicochemical environment to achieve successful disc repair by biological methods and tissue engineering procedures.

  9. HEPATIC TISSUE ENGINEERING (MODERN STATE OF THIS PROBLEM)

    OpenAIRE

    Y.S. Gulay; M.E. Krasheninnikov; M.Y. Shagidulin; N.A. Onishchenko

    2014-01-01

    In this article it was discussed the problem of creation implanted hepatic tissue engineering designs as a modern stage of complex investigation for working out bioartifi cial liver support systems. It was determined that for the positive decision of numerous biological and technological problems it is necessary: to use matrices with determined properties, which mimic properties of hepatic extracellular matrix; to use technology for stereotype sowing of these matrices by both parenchymal and ...

  10. On the genealogy of tissue engineering and regenerative medicine.

    Science.gov (United States)

    Kaul, Himanshu; Ventikos, Yiannis

    2015-04-01

    In this article, we identify and discuss a timeline of historical events and scientific breakthroughs that shaped the principles of tissue engineering and regenerative medicine (TERM). We explore the origins of TERM concepts in myths, their application in the ancient era, their resurgence during Enlightenment, and, finally, their systematic codification into an emerging scientific and technological framework in recent past. The development of computational/mathematical approaches in TERM is also briefly discussed.

  11. Advancing biomaterials of human origin for tissue engineering

    OpenAIRE

    Chen, Fa-Ming; Liu, Xiaohua

    2015-01-01

    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 in...

  12. Emerging bone tissue engineering via Polyhydroxyalkanoate (PHA)-based scaffolds.

    Science.gov (United States)

    Lim, Janice; You, Mingliang; Li, Jian; Li, Zibiao

    2017-10-01

    Polyhydroxyalkanoates (PHAs) are a class of biodegradable polymers derived from microorganisms. On top of their biodegradability and biocompatibility, different PHA types can contribute to varying mechanical and chemical properties. This has led to increasing attention to the use of PHAs in numerous biomedical applications over the past few decades. Bone tissue engineering refers to the regeneration of new bone through providing mechanical support while inducing cell growth on the PHA scaffolds having a porous structure for tissue regeneration. This review first introduces the various properties PHA scaffold that make them suitable for bone tissue engineering such as biocompatibility, biodegradability, mechanical properties as well as vascularization. The typical fabrication techniques of PHA scaffolds including electrospinning, salt-leaching and solution casting are further discussed, followed by the relatively new technology of using 3D printing in PHA scaffold fabrication. Finally, the recent progress of using different types of PHAs scaffold in bone tissue engineering applications are summarized in intrinsic PHA/blends forms or as composites with other polymeric or inorganic hybrid materials. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Applications of Biomaterials in Corneal Endothelial Tissue Engineering.

    Science.gov (United States)

    Wang, Tsung-Jen; Wang, I-Jong; Hu, Fung-Rong; Young, Tai-Horng

    2016-11-01

    When corneal endothelial cells (CECs) are diseased or injured, corneal endothelium can be surgically removed and tissue from a deceased donor can replace the original endothelium. Recent major innovations in corneal endothelial transplantation include replacement of diseased corneal endothelium with a thin lamellar posterior donor comprising a tissue-engineered endothelium carried or cultured on a thin substratum with an organized monolayer of cells. Repairing CECs is challenging because they have restricted proliferative ability in vivo. CECs can be cultivated in vitro and seeded successfully onto natural tissue materials or synthetic polymeric materials as grafts for transplantation. The optimal biomaterials for substrata of CEC growth are being investigated. Establishing a CEC culture system by tissue engineering might require multiple biomaterials to create a new scaffold that overcomes the disadvantages of single biomaterials. Chitosan and polycaprolactone are biodegradable biomaterials approved by the Food and Drug Administration that have superior biological, degradable, and mechanical properties for culturing substratum. We successfully hybridized chitosan and polycaprolactone into blended membranes, and demonstrated that CECs proliferated, developed normal morphology, and maintained their physiological phenotypes. The interaction between cells and biomaterials is important in tissue engineering of CECs. We are still optimizing culture methods for the maintenance and differentiation of CECs on biomaterials.

  14. Recent Advances in Application of Biosensors in Tissue Engineering

    Science.gov (United States)

    Paul, Arghya; Lee, Yong-kyu; Jaffa, Ayad A.

    2014-01-01

    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. PMID:25165697

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

    Science.gov (United States)

    Ceccarelli, Gabriele; Presta, Rossella; Benedetti, Laura; Cusella De Angelis, Maria Gabriella; Lupi, Saturnino Marco; Rodriguez Y Baena, Ruggero

    2017-01-01

    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.

  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. 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.

  18. Photo-patterning of porous hydrogels for tissue engineering.

    Science.gov (United States)

    Bryant, Stephanie J; Cuy, Janet L; Hauch, Kip D; Ratner, Buddy D

    2007-07-01

    Since pore size and geometry strongly impact cell behavior and in vivo reaction, the ability to create scaffolds with a wide range of pore geometries that can be tailored to suit a particular cell type addresses a key need in tissue engineering. In this contribution, we describe a novel and simple technique to design porous, degradable poly(2-hydroxyethyl methacrylate) hydrogel scaffolds with well-defined architectures using a unique photolithography process and optimized polymer chemistry. A sphere-template was used to produce a highly uniform, monodisperse porous structure. To create a patterned and porous hydrogel scaffold, a photomask and initiating light were employed. Open, vertical channels ranging in size from 360+/-25 to 730+/-70 microm were patterned into approximately 700 microm thick hydrogels with pore diameters of 62+/-8 or 147+/-15 microm. Collagen type I was immobilized onto the scaffolds to facilitate cell adhesion. To assess the potential of these novel scaffolds for tissue engineering, a skeletal myoblast cell line (C2C12) was seeded onto scaffolds with 147 microm pores and 730 microm diameter channels, and analyzed by histology and digital volumetric imaging. Cell elongation, cell spreading and fibrillar formation were observed on these novel scaffolds. In summary, 3D architectures can be patterned into porous hydrogels in one step to create a wide range of tissue engineering scaffolds that may be tailored for specific applications.

  19. In vivo outcomes of tissue-engineered osteochondral grafts.

    Science.gov (United States)

    Bal, B Sonny; Rahaman, Mohamed N; Jayabalan, Prakash; Kuroki, Keiichi; Cockrell, Mary K; Yao, Jian Q; Cook, James L

    2010-04-01

    Tissue-engineered osteochondral grafts have been synthesized from a variety of materials, with some success at repairing chondral defects in animal models. We hypothesized that in tissue-engineered osteochondral grafts synthesized by bonding mesenchymal stem cell-loaded hydrogels to a porous material, the choice of the porous scaffold would affect graft healing to host bone, and the quality of cell restoration at the hyaline cartilage surface. Bone marrow-derived allogeneic mesenchymal stem cells were suspended in hydrogels that were attached to cylinders of porous tantalum metal, allograft bone, or a bioactive glass. The tissue-engineered osteochondral grafts, thus created were implanted into experimental defects in rabbit knees. Subchondral bone restoration, defect fill, bone ingrowth-implant integration, and articular tissue quality were compared between the three subchondral materials at 6 and 12 weeks. Bioactive glass and porous tantalum were superior to bone allograft in integrating to adjacent host bone, regenerating hyaline-like tissue at the graft surface, and expressing type II collagen in the articular cartilage.

  20. 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.

  1. 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.

  2. In vivo tissue engineering: Part I. Concept genesis and guidelines for its realization.

    Science.gov (United States)

    Zdrahala, R J; Zdrahala, I J

    1999-10-01

    A loss of function of an organ often represents a life-threatening situation. Transplantations are successful, but "replacement" availability, its compatibility with the host, and subsequent healing often pose serious questions. Tissue engineering, where a carefully prepared scaffold is populated, in vitro, by cells to form an artificial organ, addresses some of the problems mentioned above. Trauma associated with the implant introduction to the host often complicates the process. The novel concept of in vivo tissue engineering which is designed to mediate the healing and tissue regeneration process by providing an in vitro formed porous, microcellular scaffold is proposed. The scaffold (part or entire organ) is then populated by cells either spontaneously (the surrounding cells will spread and populate to inhabit the scaffold) or by cellular augmentation (encapsulated cells are delivered to this in statu nascendi scaffold). Minimally traumatic arthroscopic surgery combined with a unique polymer delivery system is envisioned for the introduction of this implant to a site to be repaired. Such an approach will require the formation of polymer in-situ, in a reasonable time. The scaffold-forming polymers will be, in principle, biodegradable. We propose to utilize biodegradable polyurethane systems for in vivo tissue engineering. Diversity of their structure/property relationships, relative "ease" of their preparation, and excellent biocompatibility predetermine polyurethanes to be the materials of choice. This paper describes the genesis of this concept and potentials for its realization. It is intended to initiate and stimulate discussion among the related scientific disciplines to form a basis for this field. The synthesis, application, and biodegradation of selected polyurethanes and variety of its medical utilization will be discussed in upcoming papers.

  3. Tissue Engineering of the Urethra: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies.

    Science.gov (United States)

    Versteegden, Luuk R M; de Jonge, Paul K J D; IntHout, Joanna; van Kuppevelt, Toin H; Oosterwijk, Egbert; Feitz, Wout F J; de Vries, Rob B M; Daamen, Willeke F

    2017-10-01

    Urethra repair by tissue engineering has been extensively studied in laboratory animals and patients, but is not routinely used in clinical practice. To systematically investigate preclinical and clinical evidence of the efficacy of tissue engineering for urethra repair in order to stimulate translation of preclinical studies to the clinic. A systematic search strategy was applied in PubMed and EMBASE. Studies were independently screened for relevance by two reviewers, resulting in 80 preclinical and 23 clinical studies of which 63 and 13 were selected for meta-analysis to assess side effects, functionality, and study completion. Analyses for preclinical and clinical studies were performed separately. Full circumferential and inlay procedures were assessed independently. Evaluated parameters included seeding of cells and type of biomaterial. Meta-analysis revealed that cell seeding significantly reduced the probability of encountering side effects in preclinical studies. Remarkably though, cells were only sparsely used in the clinic (4/23 studies) and showed no significant reduction of side effects. ln 21 out of 23 clinical studies, decellularized templates were used, while in preclinical studies other biomaterials showed promising outcomes as well. No direct comparison to current clinical practice could be made due to the limited number of randomized controlled studies. Due to a lack of controlled (pre)clinical studies, the efficacy of tissue engineering for urethra repair could not be determined. Meta-analysis outcome measures were similar to current treatment options described in literature. Surprisingly, it appeared that favorable preclinical results, that is inclusion of cells, were not translated to the clinic. Improved (pre)clinical study designs may enhance clinical translation. We reviewed all available literature on urethral tissue engineering to assess the efficacy in preclinical and clinical studies. We show that improvements to (pre)clinical study

  4. Mag-seeding of rat bone marrow stromal cells into porous hydroxyapatite scaffolds for bone tissue engineering.

    Science.gov (United States)

    Shimizu, Kazunori; Ito, Akira; Honda, Hiroyuki

    2007-09-01

    Bone tissue engineering has been investigated as an alternative strategy for autograft transplantation. In the process of tissue engineering, cell seeding into three-dimensional (3-D) scaffolds is the first step for constructing 3-D tissues. We have proposed a methodology of cell seeding into 3-D porous scaffolds using magnetic force and magnetite nanoparticles, which we term Mag-seeding. In this study, we applied this Mag-seeding technique to bone tissue engineering using bone marrow stromal cells (BMSCs) and 3-D hydroxyapatite (HA) scaffolds. BMSCs were magnetically labeled with our original magnetite cationic liposomes (MCLs) having a positive surface charge to improve adsorption to cell surface. Magnetically labeled BMSCs were seeded onto a scaffold, and a 1-T magnet was placed under the scaffold. By using Mag-seeding, the cells were successfully seeded into the internal space of scaffolds with a high cell density. The cell seeding efficiency into HA scaffolds by Mag-seeding was approximately threefold larger than that by static-seeding (conventional method, without a magnet). After a 14-d cultivation period using the osteogenic induction medium by Mag-seeding, the level of two representative osteogenic markers (alkaline phosphatase and osteocalcin) were significantly higher than those by static-seeding. These results indicated that Mag-seeding of BMSCs into HA scaffolds is an effective approach to bone tissue engineering.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-03-01

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  7. In vitro comparison of human fibroblasts from intact and ruptured ACL for use in tissue engineering

    Directory of Open Access Journals (Sweden)

    T Brune

    2007-12-01

    Full Text Available The present study compares fibroblasts extracted from intact and ruptured human anterior cruciate ligaments (ACL for creation of a tissue engineered ACL-construct, made of porcine small intestinal submucosal extracellular matrix (SIS-ECM seeded with these ACL cells. The comparison is based on histological, immunohistochemical and RT-PCR analyses. Differences were observed between cells in a ruptured ACL (rACL and cells in an intact ACL (iACL, particularly with regard to the expression of integrin subunits and smooth muscle actin (SMA. Despite these differences in the cell source, both cell populations behaved similarly when seeded on an SIS-ECM scaffold, with similar cell morphology, connective tissue organization and composition, SMA and integrin expression. This study shows the usefulness of naturally occurring scaffolds such as SIS-ECM for the study of cell behaviour in vitro, and illustrates the possibility to use autologous cells extracted from ruptured ACL biopsies as a source for tissue engineered ACL constructs.

  8. In vitro cartilage tissue engineering using cancellous bone matrix gelatin as a biodegradable scaffold

    International Nuclear Information System (INIS)

    Yang Bo; Yin Zhanhai; Cao Junling; Shi Zhongli; Zhang Zengtie; Liu Fuqiang; Song Hongxing; Caterson, Bruce

    2010-01-01

    In this study, we constructed tissue-engineered cartilage using allogeneic cancellous bone matrix gelatin (BMG) as a scaffold. Allogeneic BMG was prepared by sequential defatting, demineralization and denaturation. Isolated rabbit chondrocytes were seeded onto allogeneic cancellous BMG, and cell-BMG constructs were harvested after 1, 3 and 6 weeks for evaluation by hematoxylin and eosin staining for overall morphology, toluidine blue for extracellular matrix (ECM) proteoglycans, immunohistochemical staining for collagen type II and a transmission electron microscope for examining cellular microstructure on BMG. The prepared BMG was highly porous with mechanical strength adjustable by duration of demineralization and was easily trimmed for tissue repair. Cancellous BMG showed favorable porosity for cell habitation and metabolism material exchange with larger pore sizes (100-500 μm) than in cortical BMG (5-15 μm), allowing cell penetration. Cancellous BMG also showed good biocompatibility, which supported chondrocyte proliferation and sustained their differentiated phenotype in culture for up to 6 weeks. Rich and evenly distributed cartilage ECM proteoglycans and collagen type II were observed around chondrocytes on the surface and inside the pores throughout the cancellous BMG. Considering the large supply of banked bone allografts and relatively convenient preparation, our study suggests that allogeneic cancellous BMG is a promising scaffold for cartilage tissue engineering.

  9. Restoring nervous system structure and function using tissue engineered living scaffolds

    Institute of Scientific and Technical Information of China (English)

    Laura A Struzyna; James P Harris; Kritika S Katiyar; H Isaac Chen; D KacyCullen

    2015-01-01

    Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner-vous system injury or neurodegenerative disease. Disconnection of axon pathways – the long-distance ifbers connecting specialized regions of the central nervous system or relaying peripheral signals – is a common feature of many neurological disorders and injury. However, functional axonal regenera-tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi-neered “living scaffolds”, which are preformed three-dimensional constructs consisting of living neural cells in a deifned, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration – mimicking key developmental mechanisms– or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal clusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in preclinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

  10. Current strategies in multiphasic scaffold design for osteochondral tissue engineering: A review.

    Science.gov (United States)

    Yousefi, Azizeh-Mitra; Hoque, Md Enamul; Prasad, Rangabhatala G S V; Uth, Nicholas

    2015-07-01

    The repair of osteochondral defects requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using specifically designed scaffold-cell constructs. Biphasic and triphasic approaches utilize two or three different architectures, materials, or composites to produce a multilayered construct. This article gives an overview of some of the current strategies in multiphasic/gradient-based scaffold architectures and compositions for tissue engineering of osteochondral defects. In addition, the application of finite element analysis (FEA) in scaffold design and simulation of in vitro and in vivo cell growth outcomes has been briefly covered. FEA-based approaches can potentially be coupled with computer-assisted fabrication systems for controlled deposition and additive manufacturing of the simulated patterns. Finally, a summary of the existing challenges associated with the repair of osteochondral defects as well as some recommendations for future directions have been brought up in the concluding section of this article. © 2014 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2016-08-01

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

  12. In vitro cartilage tissue engineering using cancellous bone matrix gelatin as a biodegradable scaffold

    Energy Technology Data Exchange (ETDEWEB)

    Yang Bo; Yin Zhanhai; Cao Junling; Shi Zhongli; Zhang Zengtie; Liu Fuqiang [College of Medicine, Xi' an Jiaotong University, Yanta West Road, No 76, Yanta District, Xi' an, Shaanxi Province 710061 (China); Song Hongxing [Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Caterson, Bruce, E-mail: caojl@mail.xjtu.edu.c [Connective Tissue Biology Laboratories, Cardiff School of Biosciences, Cardiff University, Biomedical Building, Museum Avenue, Cardiff, CF10 3US (United Kingdom)

    2010-08-01

    In this study, we constructed tissue-engineered cartilage using allogeneic cancellous bone matrix gelatin (BMG) as a scaffold. Allogeneic BMG was prepared by sequential defatting, demineralization and denaturation. Isolated rabbit chondrocytes were seeded onto allogeneic cancellous BMG, and cell-BMG constructs were harvested after 1, 3 and 6 weeks for evaluation by hematoxylin and eosin staining for overall morphology, toluidine blue for extracellular matrix (ECM) proteoglycans, immunohistochemical staining for collagen type II and a transmission electron microscope for examining cellular microstructure on BMG. The prepared BMG was highly porous with mechanical strength adjustable by duration of demineralization and was easily trimmed for tissue repair. Cancellous BMG showed favorable porosity for cell habitation and metabolism material exchange with larger pore sizes (100-500 {mu}m) than in cortical BMG (5-15 {mu}m), allowing cell penetration. Cancellous BMG also showed good biocompatibility, which supported chondrocyte proliferation and sustained their differentiated phenotype in culture for up to 6 weeks. Rich and evenly distributed cartilage ECM proteoglycans and collagen type II were observed around chondrocytes on the surface and inside the pores throughout the cancellous BMG. Considering the large supply of banked bone allografts and relatively convenient preparation, our study suggests that allogeneic cancellous BMG is a promising scaffold for cartilage tissue engineering.

  13. Natural marine sponges for bone tissue engineering: The state of art and future perspectives.

    Science.gov (United States)

    Granito, Renata Neves; Custódio, Márcio Reis; Rennó, Ana Claudia Muniz

    2017-08-01

    Marine life and its rich biodiversity provide a plentiful resource of potential new products for the society. Remarkably, marine organisms still remain a largely unexploited resource for biotechnology applications. Among them, marine sponges are sessile animals from the phylum Porifera dated at least from 580 million years ago. It is known that molecules from marine sponges present a huge therapeutic potential in a wide range of applications mainly due to its antitumor, antiviral, anti-inflammatory, and antibiotic effects. In this context, this article reviews all the information available in the literature about the potential of the use of marine sponges for bone tissue engineering applications. First, one of the properties that make sponges interesting as bone substitutes is their structural characteristics. Most species have an efficient interconnected porous architecture, which allows them to process a significant amount of water and facilitates the flow of fluids, mimicking an ideal bone scaffold. Second, sponges have an organic component, the spongin, which is analogous to vertebral collagen, the most widely used natural polymer for tissue regeneration. Last, osteogenic properties of marine sponges is also highlighted by their mineral content, such as biosilica and other compounds, that are able to support cell growth and to stimulate bone formation and mineralization. This review focuses on recent studies concerning these interesting properties, as well as on some challenges to be overcome in the bone tissue engineering field. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1717-1727, 2017. © 2016 Wiley Periodicals, Inc.

  14. Electrically polarized PLLA nanofibers as neural tissue engineering scaffolds with improved neuritogenesis.

    Science.gov (United States)

    Barroca, Nathalie; Marote, Ana; Vieira, Sandra I; Almeida, Abílio; Fernandes, Maria H V; Vilarinho, Paula M; da Cruz E Silva, Odete A B

    2018-07-01

    Tissue engineering is evolving towards the production of smart platforms exhibiting stimulatory cues to guide tissue regeneration. This work explores the benefits of electrical polarization to produce more efficient neural tissue engineering platforms. Poly (l-lactic) acid (PLLA)-based scaffolds were prepared as solvent cast films and electrospun aligned nanofibers, and electrically polarized by an in-lab built corona poling device. The characterization of the platforms by thermally stimulated depolarization currents reveals a polarization of 60 × 10 -10 C cm -2 that is stable on poled electrospun nanofibers for up to 6 months. Further in vitro studies using neuroblastoma cells reveals that platforms' polarization potentiates Retinoic Acid-induced neuronal differentiation. Additionally, in differentiating embryonic cortical neurons, poled aligned nanofibers further increased neurite outgrowth by 30% (+70 μm) over non-poled aligned nanofibers, and by 50% (+100 μm) over control conditions. Therefore, the synergy of topographical cues and electrical polarization of poled aligned nanofibers places them as promising biocompatible and bioactive platforms for neural tissue regeneration. Given their long lasting induced polarization, these PLLA poled nanofibrous scaffolds can be envisaged as therapeutic devices of long shelf life for neural repair applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Embroidered polymer-collagen hybrid scaffold variants for ligament tissue engineering.

    Science.gov (United States)

    Hoyer, M; Drechsel, N; Meyer, M; Meier, C; Hinüber, C; Breier, A; Hahner, J; Heinrich, G; Rentsch, C; Garbe, L-A; Ertel, W; Schulze-Tanzil, G; Lohan, A

    2014-10-01

    Embroidery techniques and patterns used for scaffold production allow the adaption of biomechanical scaffold properties. The integration of collagen into embroidered polylactide-co-caprolactone [P(LA-CL)] and polydioxanone (PDS) scaffolds could stimulate neo-tissue formation by anterior cruciate ligament (ACL) cells. Therefore, the aim of this study was to test embroidered P(LA-CL) and PDS scaffolds as hybrid scaffolds in combination with collagen hydrogel, sponge or foam for ligament tissue engineering. ACL cells were cultured on embroidered P(LA-CL) and PDS scaffolds without or with collagen supplementation. Cell adherence, vitality, morphology and ECM synthesis were analyzed. Irrespective of thread size, ACL cells seeded on P(LA-CL) scaffolds without collagen adhered and spread over the threads, whereas the cells formed clusters on PDS and larger areas remained cell-free. Using the collagen hydrogel, the scaffold colonization was limited by the gel instability. The collagen sponge layers integrated into the scaffolds were hardly penetrated by the cells. Collagen foams increased scaffold colonization in P(LA-CL) but did not facilitate direct cell-thread contacts in the PDS scaffolds. The results suggest embroidered P(LA-CL) scaffolds as a more promising basis for tissue engineering an ACL substitute than PDS due to superior cell attachment. Supplementation with a collagen foam presents a promising functionalization strategy. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Mathematical Modeling of Uniaxial Mechanical Properties of Collagen Gel Scaffolds for Vascular Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Ramiro M. Irastorza

    2015-01-01

    Full Text Available Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.. When Akaike criterion is used, the best is the Mooney-Rivlin inspired model.

  17. Synthesis of biodegradable and electroactive multiblock polylactide and aniline pentamer copolymer for tissue engineering applications.

    Science.gov (United States)

    Huang, Lihong; Zhuang, Xiuli; Hu, Jun; Lang, Le; Zhang, Peibiao; Wang, Yu; Chen, Xuesi; Wei, Yen; Jing, Xiabin

    2008-03-01

    To obtain one biodegradable and electroactive polymer as the scaffold for tissue engineering, the multiblock copolymer PLAAP was designed and synthesized with the condensation polymerization of hydroxyl-capped poly( l-lactide) (PLA) and carboxyl-capped aniline pentamer (AP). The PLAAP copolymer exhibited excellent electroactivity, solubility, and biodegradability. At the same time, as one scaffold material, PLAAP copolymer possesses certain mechanical properties with the tensile strength of 3 MPa, tensile Young 's modulus of 32 MPa, and breaking elongation rate of 95%. We systematically studied the compatibility of PLAAP copolymer in vitro and proved that the electroactive PLAAP copolymer was innocuous, biocompatible, and helpful for the adhesion and proliferation of rat C6 cells. Moreover, the PLAAP copolymer stimulated by electrical signals was demonstrated as accelerating the differentiation of rat neuronal pheochromocytoma PC-12 cells. This biodegradable and electroactive PLAAP copolymer thus possessed the properties in favor of the long-time application in vivo as nerve repair scaffold materials in tissue engineering.

  18. Mathematical modeling of uniaxial mechanical properties of collagen gel scaffolds for vascular tissue engineering.

    Science.gov (United States)

    Irastorza, Ramiro M; Drouin, Bernard; Blangino, Eugenia; Mantovani, Diego

    2015-01-01

    Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.). When Akaike criterion is used, the best is the Mooney-Rivlin inspired model.

  19. Tissue engineering applications: cartilage lesions repair by the use of autologous chondrocytes

    Directory of Open Access Journals (Sweden)

    L. De Franceschi

    2011-09-01

    Full Text Available Promising new therapies based on tissue engineering have been recently developed for cartilage repair. The association of biomaterials with autologous chondrocytes expanded in vitro can represent a useful tool to regenerate this tissue. The scaffolds utilised in such therapeutical applications should provide a pre-formed three-dimensional shape, prevent cells from floating out of the defect, have sufficient mechanical strength, facilitate uniform spread of cells and stimulate the phenotype of transplanted cells. Hyaff®-11 is a hyaluronic-acid based biodegradable polymer, that has been shown to provide successful cell carrier for tissue-engineered repair. From our findings we can state that human chondrocytes seeded on Hyaff®-11 are able to maintain in vitro the characteristic of differentiated cells, expressing and producing collagen type II and aggrecan which are the main markers of cartilage phenotype, down-regulating collagen type I. Moreover, it seems to be a useful scaffold for cartilage repair both in animal models and clinical trials in humans, favouring the formation of a hyaline-like tissue. In the light of these data, we can hypothesise, for the future, the use of autologous chondrocyte transplantation together with gene therapy as a treatment for rheumatic diseases such as osteoarthritis.

  20. Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Jahnavi, S [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Trivandrum, Kerala 695012 (India); Saravanan, U [Department of Civil Engineering, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Arthi, N [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Bhuvaneshwar, G S [Department of Engineering Design, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Kumary, T V [Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Trivandrum, Kerala 695012 (India); Rajan, S [Madras Medical Mission, Institute of Cardio-Vascular Diseases, Mogappair, Chennai, Tamil Nadu 600037 (India); Verma, R S, E-mail: vermars@iitm.ac.in [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India)

    2017-04-01

    Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44{sup +}, αSMA{sup +}, Vimentin{sup +} and CD105{sup −} human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. - Highlights: • We report detailed biological and mechanical investigations of a Bio-Hybrid scaffold. • Optimized polymer thickness yielded desired biological and mechanical properties. • Bio-Hybrid scaffold revealed hVIC proliferation with dense ECM deposition. • Biaxial testing indicated that Bio-Hybrid scaffolds are mechanically stronger than native valves. • Bio-Hybrid scaffold is a promising material for autologous valve tissue engineering.

  1. Functional stability of endothelial cells on a novel hybrid scaffold for vascular tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Pankajakshan, Divya; Krishnan, Lissy K [Thrombosis Research Unit, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojapura, Trivandrum 695 012 (India); Krishnan V, Kalliyana, E-mail: lissykk@sctimst.ac.i [Division of Polymer Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojapura, Trivandrum 695 012 (India)

    2010-12-15

    Porous and pliable conduits made of biodegradable polymeric scaffolds offer great potential for the development of blood vessel substitutes but they generally lack signals for cell proliferation, survival and maintenance of a normal phenotype. In this study we have prepared and evaluated porous poly({epsilon}-caprolactone) (PCL) integrated with fibrin composite (FC) to get a biomimetic hybrid scaffold (FC PCL) with the biological properties of fibrin, fibronectin (FN), gelatin, growth factors and glycosaminoglycans. Reduced platelet adhesion on a human umbilical vein endothelial cell-seeded hybrid scaffold as compared to bare PCL or FC PCL was observed, which suggests the non-thrombogenic nature of the tissue-engineered scaffold. Analysis of real-time polymerase chain reaction (RT-PCR) after 5 days of endothelial cell (EC) culture on a hybrid scaffold indicated that the prothrombotic von Willebrand factor and plasminogen activator inhibitor (PAI) were quiescent and stable. Meanwhile, dynamic expressions of tissue plasminogen activator (tPA) and endothelial nitric oxide synthase indicated the desired cell phenotype on the scaffold. On the hybrid scaffold, shear stress could induce enhanced nitric oxide release, which implicates vaso-responsiveness of EC grown on the tissue-engineered construct. Significant upregulation of mRNA for extracellular matrix (ECM) proteins, collagen IV and elastin, in EC was detected by RT-PCR after growing them on the hybrid scaffold and FC-coated tissue culture polystyrene (FC TCPS) but not on FN-coated TCPS. The results indicate that the FC PCL hybrid scaffold can accomplish a remodeled ECM and non-thrombogenic EC phenotype, and can be further investigated as a scaffold for cardiovascular tissue engineering. (communication)

  2. Tissue-Engineered Tendon for Enthesis Regeneration in a Rat Rotator Cuff Model

    Directory of Open Access Journals (Sweden)

    Michael J. Smietana

    2017-06-01

    Full Text Available Healing of rotator cuff (RC injuries with current suture or augmented scaffold techniques fails to regenerate the enthesis and instead forms a weaker fibrovascular scar that is prone to subsequent failure. Regeneration of the enthesis is the key to improving clinical outcomes for RC injuries. We hypothesized that the utilization of our tissue-engineered tendon to repair either an acute or a chronic full-thickness supraspinatus tear would regenerate a functional enthesis and return the biomechanics of the tendon back to that found in native tissue. Engineered tendons were fabricated from bone marrow-derived mesenchymal stem cells utilizing our well-described fabrication technology. Forty-three rats underwent unilateral detachment of the supraspinatus tendon followed by acute (immediate or chronic (4 weeks retracted repair by using either our engineered tendon or a trans-osseous suture technique. Animals were sacrificed at 8 weeks. Biomechanical and histological analyses of the regenerated enthesis and tendon were performed. Statistical analysis was performed by using a one-way analysis of variance with significance set at p < 0.05. Acute repairs using engineered tendon had improved enthesis structure and lower biomechanical failures compared with suture repairs. Chronic repairs with engineered tendon had a more native-like enthesis with increased fibrocartilage formation, reduced scar formation, and lower biomechanical failure compared with suture repair. Thus, the utilization of our tissue-engineered tendon showed improve enthesis regeneration and improved function in chronic RC repairs compared with suture repair. Clinical Significance: Our engineered tendon construct shows promise as a clinically relevant method for repair of RC injuries.

  3. Functional stability of endothelial cells on a novel hybrid scaffold for vascular tissue engineering

    International Nuclear Information System (INIS)

    Pankajakshan, Divya; Krishnan, Lissy K; Krishnan V, Kalliyana

    2010-01-01

    Porous and pliable conduits made of biodegradable polymeric scaffolds offer great potential for the development of blood vessel substitutes but they generally lack signals for cell proliferation, survival and maintenance of a normal phenotype. In this study we have prepared and evaluated porous poly(ε-caprolactone) (PCL) integrated with fibrin composite (FC) to get a biomimetic hybrid scaffold (FC PCL) with the biological properties of fibrin, fibronectin (FN), gelatin, growth factors and glycosaminoglycans. Reduced platelet adhesion on a human umbilical vein endothelial cell-seeded hybrid scaffold as compared to bare PCL or FC PCL was observed, which suggests the non-thrombogenic nature of the tissue-engineered scaffold. Analysis of real-time polymerase chain reaction (RT-PCR) after 5 days of endothelial cell (EC) culture on a hybrid scaffold indicated that the prothrombotic von Willebrand factor and plasminogen activator inhibitor (PAI) were quiescent and stable. Meanwhile, dynamic expressions of tissue plasminogen activator (tPA) and endothelial nitric oxide synthase indicated the desired cell phenotype on the scaffold. On the hybrid scaffold, shear stress could induce enhanced nitric oxide release, which implicates vaso-responsiveness of EC grown on the tissue-engineered construct. Significant upregulation of mRNA for extracellular matrix (ECM) proteins, collagen IV and elastin, in EC was detected by RT-PCR after growing them on the hybrid scaffold and FC-coated tissue culture polystyrene (FC TCPS) but not on FN-coated TCPS. The results indicate that the FC PCL hybrid scaffold can accomplish a remodeled ECM and non-thrombogenic EC phenotype, and can be further investigated as a scaffold for cardiovascular tissue engineering. (communication)

  4. Methods of Monitoring Cell Fate and Tissue Growth in Three-Dimensional Scaffold-Based Strategies for In Vitro Tissue Engineering.

    Science.gov (United States)

    Leferink, Anne M; van Blitterswijk, Clemens A; Moroni, Lorenzo

    2016-08-01

    In the field of tissue engineering, there is a need for methods that allow assessing the performance of tissue-engineered constructs noninvasively in vitro and in vivo. To date, histological analysis is the golden standard to retrieve information on tissue growth, cellular distribution, and cell fate on tissue-engineered constructs after in vitro cell culture or on explanted specimens after in vivo applications. Yet, many advances have been made to optimize imaging techniques for monitoring tissue-engineered constructs with a sub-mm or μm resolution. Many imaging modalities have first been developed for clinical applications, in which a high penetration depth has been often more important than lateral resolution. In this study, we have reviewed the current state of the art in several imaging approaches that have shown to be promising in monitoring cell fate and tissue growth upon in vitro culture. Depending on the aimed tissue type and scaffold properties, some imaging methods are more applicable than others. Optical methods are mostly suited for transparent materials such as hydrogels, whereas magnetic resonance-based methods are mostly applied to obtain contrast between hard and soft tissues regardless of their transparency. Overall, this review shows that the field of imaging in scaffold-based tissue engineering is developing at a fast pace and has the potential to overcome the limitations of destructive endpoint analysis.

  5. Preparation of Laponite Bioceramics for Potential Bone Tissue Engineering Applications

    Science.gov (United States)

    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. PMID:24955961

  6. Porous magnesium-based scaffolds for tissue engineering

    International Nuclear Information System (INIS)

    Yazdimamaghani, Mostafa; Razavi, Mehdi; Vashaee, Daryoosh; Moharamzadeh, Keyvan; Boccaccini, Aldo R.; Tayebi, Lobat

    2017-01-01

    Significant amount of research efforts have been dedicated to the development of scaffolds for tissue engineering. Although at present most of the studies are focused on non-load bearing scaffolds, many scaffolds have also been investigated for hard tissue repair. In particular, metallic scaffolds are being studied for hard tissue engineering due to their suitable mechanical properties. Several biocompatible metallic materials such as stainless steels, cobalt alloys, titanium alloys, tantalum, nitinol and magnesium alloys have been commonly employed as implants in orthopedic and dental treatments. They are often used to replace and regenerate the damaged bones or to provide structural support for healing bone defects. Among the common metallic biomaterials, magnesium (Mg) and a number of its alloys are effective because of their mechanical properties close to those of human bone, their natural ionic content that may have important functional roles in physiological systems, and their in vivo biodegradation characteristics in body fluids. Due to such collective properties, Mg based alloys can be employed as biocompatible, bioactive, and biodegradable scaffolds for load-bearing applications. Recently, porous Mg and Mg alloys have been specially suggested as metallic scaffolds for bone tissue engineering. With further optimization of the fabrication techniques, porous Mg is expected to make a promising hard substitute scaffold. The present review covers research conducted on the fabrication techniques, surface modifications, properties and biological characteristics of Mg alloys based scaffolds. Furthermore, the potential applications, challenges and future trends of such degradable metallic scaffolds are discussed in detail. - Highlights: • A porous 3D material provides the required pathways for cells to grow, proliferate, and differentiate • Porous magnesium and Mg alloys could be used as load-bearing scaffolds • Porous magnesium and Mg alloys are good

  7. Approaches to improve angiogenesis in tissue-engineered skin.

    Science.gov (United States)

    Sahota, Parbinder S; Burn, J Lance; Brown, Nicola J; MacNeil, Sheila

    2004-01-01

    A problem with tissue-engineered skin is clinical failure due to delays in vascularization. The aim of this study was to explore a number of simple strategies to improve angiogenesis/vascularization using a tissue-engineered model of skin to which small vessel human dermal microvascular endothelial cells were added. For the majority of these studies, a modified Guirguis chamber was used, which allowed the investigation of several variables within the same experiment using the same human dermis; cell type, angiogenic growth factors, the influence of keratinocytes and fibroblasts, mechanical penetration of the human dermis, the site of endothelial cell addition, and the influence of hypoxia were all examined. A qualitative scoring system was used to assess the impact of these factors on the penetration of endothelial cells throughout the dermis. Similar results were achieved using freshly isolated small vessel human dermal microvascular endothelial cells or an endothelial cell line and a minimum cell seeding density was identified. Cell penetration was not influenced by the addition of angiogenic growth factors (vascular endothelial growth factor and basic fibroblast growth factor); similarly, including epidermal keratinocytes or dermal fibroblasts did not encourage endothelial cell entry, and neither did mechanical introduction of holes throughout the dermis. Two factors were identified that significantly enhanced endothelial cell penetration into the dermis: hypoxia and the site of endothelial cell addition. Endothelial cells added from the papillary surface entered into the dermis much more effectively than when cells were added to the reticular surface of the dermis. We conclude that this model is valuable in improving our understanding of how to enhance vascularization of tissue-engineered grafts.

  8. Porous magnesium-based scaffolds for tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Yazdimamaghani, Mostafa [School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078 (United States); Razavi, Mehdi [Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA 94304 (United States); Vashaee, Daryoosh [Electrical and Computer Engineering Department, North Carolina State University, Raleigh, NC 27606 (United States); Moharamzadeh, Keyvan [School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield (United Kingdom); Marquette University School of Dentistry, Milwaukee, WI 53233 (United States); Boccaccini, Aldo R. [Institute of Biomaterials, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058 Erlangen (Germany); Tayebi, Lobat, E-mail: lobat.tayebi@marquette.edu [Marquette University School of Dentistry, Milwaukee, WI 53233 (United States)

    2017-02-01

    Significant amount of research efforts have been dedicated to the development of scaffolds for tissue engineering. Although at present most of the studies are focused on non-load bearing scaffolds, many scaffolds have also been investigated for hard tissue repair. In particular, metallic scaffolds are being studied for hard tissue engineering due to their suitable mechanical properties. Several biocompatible metallic materials such as stainless steels, cobalt alloys, titanium alloys, tantalum, nitinol and magnesium alloys have been commonly employed as implants in orthopedic and dental treatments. They are often used to replace and regenerate the damaged bones or to provide structural support for healing bone defects. Among the common metallic biomaterials, magnesium (Mg) and a number of its alloys are effective because of their mechanical properties close to those of human bone, their natural ionic content that may have important functional roles in physiological systems, and their in vivo biodegradation characteristics in body fluids. Due to such collective properties, Mg based alloys can be employed as biocompatible, bioactive, and biodegradable scaffolds for load-bearing applications. Recently, porous Mg and Mg alloys have been specially suggested as metallic scaffolds for bone tissue engineering. With further optimization of the fabrication techniques, porous Mg is expected to make a promising hard substitute scaffold. The present review covers research conducted on the fabrication techniques, surface modifications, properties and biological characteristics of Mg alloys based scaffolds. Furthermore, the potential applications, challenges and future trends of such degradable metallic scaffolds are discussed in detail. - Highlights: • A porous 3D material provides the required pathways for cells to grow, proliferate, and differentiate • Porous magnesium and Mg alloys could be used as load-bearing scaffolds • Porous magnesium and Mg alloys are good

  9. Micrometer scale guidance of mesenchymal stem cells to form structurally oriented large-scale tissue engineered cartilage.

    Science.gov (United States)

    Chou, Chih-Ling; Rivera, Alexander L; Williams, Valencia; Welter, Jean F; Mansour, Joseph M; Drazba, Judith A; Sakai, Takao; Baskaran, Harihara

    2017-09-15

    Current clinical methods to treat articular cartilage lesions provide temporary relief of the symptoms but fail to permanently restore the damaged tissue. Tissue engineering, using mesenchymal stem cells (MSCs) combined with scaffolds and bioactive factors, is viewed as a promising method for repairing cartilage injuries. However, current tissue engineered constructs display inferior mechanical properties compared to native articular cartilage, which could be attributed to the lack of structural organization of the extracellular matrix (ECM) of these engineered constructs in comparison to the highly oriented structure of articular cartilage ECM. We previously showed that we can guide MSCs undergoing chondrogenesis to align using microscale guidance channels on the surface of a two-dimensional (2-D) collagen scaffold, which resulted in the deposition of aligned ECM within the channels and enhanced mechanical properties of the constructs. In this study, we developed a technique to roll 2-D collagen scaffolds containing MSCs within guidance channels in order to produce a large-scale, three-dimensional (3-D) tissue engineered cartilage constructs with enhanced mechanical properties compared to current constructs. After rolling the MSC-scaffold constructs into a 3-D cylindrical structure, the constructs were cultured for 21days under chondrogenic culture conditions. The microstructure architecture and mechanical properties of the constructs were evaluated using imaging and compressive testing. Histology and immunohistochemistry of the constructs showed extensive glycosaminoglycan (GAG) and collagen type II deposition. Second harmonic generation imaging and Picrosirius red staining indicated alignment of neo-collagen fibers within the guidance channels of the constructs. Mechanical testing indicated that constructs containing the guidance channels displayed enhanced compressive properties compared to control constructs without these channels. In conclusion, using a novel

  10. Sequentially-crosslinked bioactive hydrogels as nano-patterned substrates with customizable stiffness and degradation for corneal tissue engineering applications.

    Science.gov (United States)

    Rizwan, Muhammad; Peh, Gary S L; Ang, Heng-Pei; Lwin, Nyein Chan; Adnan, Khadijah; Mehta, Jodhbir S; Tan, Wui Siew; Yim, Evelyn K F

    2017-03-01

    Naturally-bioactive hydrogels like gelatin provide favorable properties for tissue-engineering but lack sufficient mechanical strength for use as implantable tissue engineering substrates. Complex fabrication or multi-component additives can improve material strength, but often compromises other properties. Studies have shown gelatin methacrylate (GelMA) as a bioactive hydrogel with diverse tissue growth applications. We hypothesize that, with suitable material modifications, GelMA could be employed for growth and implantation of tissue-engineered human corneal endothelial cell (HCEC) monolayer. Tissue-engineered HCEC monolayer could potentially be used to treat corneal blindness due to corneal endothelium dysfunction. Here, we exploited a sequential hybrid (physical followed by UV) crosslinking to create an improved material, named as GelMA+, with over 8-fold increase in mechanical strength as compared to regular GelMA. The presence of physical associations increased the subsequent UV-crosslinking efficiency resulting in robust materials able to withstand standard endothelium insertion surgical device loading. Favorable biodegradation kinetics were also measured in vitro and in vivo. We achieved hydrogels patterning with nano-scale resolution by use of oxygen impermeable stamps that overcome the limitations of PDMS based molding processes. Primary HCEC monolayers grown on GelMA+ carrier patterned with pillars of optimal dimension demonstrated improved zona-occludin-1 expression, higher cell density and cell size homogeneity, which are indications of functionally-superior transplantable monolayers. The hybrid crosslinking and fabrication approach offers potential utility for development of implantable tissue-engineered cell-carrier constructs with enhanced bio-functional properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone.

    Science.gov (United States)

    Sulaiman, Shamsul Bin; Keong, Tan Kok; Cheng, Chen Hui; Saim, Aminuddin Bin; Idrus, Ruszymah Bt Hj

    2013-06-01

    Various materials have been used as scaffolds to suit different demands in tissue engineering. One of the most important criteria is that the scaffold must be biocompatible. This study was carried out to investigate the potential of HA or TCP/HA scaffold seeded with osteogenic induced sheep marrow cells (SMCs) for bone tissue engineering. HA-SMC and TCP/HA-SMC constructs were induced in the osteogenic medium for three weeks prior to implantation in nude mice. The HA-SMC and TCP/HA-SMC constructs were implanted subcutaneously on the dorsum of nude mice on each side of the midline. These constructs were harvested after 8 wk of implantation. Constructs before and after implantation were analyzed through histological staining, scanning electron microscope (SEM) and gene expression analysis. The HA-SMC constructs demonstrated minimal bone formation. TCP/HA-SMC construct showed bone formation eight weeks after implantation. The bone formation started on the surface of the ceramic and proceeded to the centre of the pores. H&E and Alizarin Red staining demonstrated new bone tissue. Gene expression of collagen type 1 increased significantly for both constructs, but more superior for TCP/HA-SMC. SEM results showed the formation of thick collagen fibers encapsulating TCP/HA-SMC more than HA-SMC. Cells attached to both constructs surface proliferated and secreted collagen fibers. The findings suggest that TCP/HA-SMC constructs with better osteogenic potential compared to HA-SMC constructs can be a potential candidate for the formation of tissue engineered bone.

  12. Silk scaffolds in bone tissue engineering: An overview.

    Science.gov (United States)

    Bhattacharjee, Promita; Kundu, Banani; Naskar, Deboki; Kim, Hae-Won; Maiti, Tapas K; Bhattacharya, Debasis; Kundu, Subhas C

    2017-11-01

    Bone tissue plays multiple roles in our day-to-day functionality. The frequency of accidental bone damage and disorder is increasing worldwide. Moreover, as the world population continues to grow, the percentage of the elderly population continues to grow, which results in an increased number of bone degenerative diseases. This increased elderly population pushes the need for artificial bone implants that specifically employ biocompatible materials. A vast body of literature is available on the use of silk in bone tissue engineering. The current work presents an overview of this literature from materials and fabrication perspective. As silk is an easy-to-process biopolymer; this allows silk-based biomaterials to be molded into diverse forms and architectures, which further affects the degradability. This makes silk-based scaffolds suitable for treating a variety of bone reconstruction and regeneration objectives. Silk surfaces offer active sites that aid the mineralization and/or bonding of bioactive molecules that facilitate bone regeneration. Silk has also been blended with a variety of polymers and minerals to enhance its advantageous properties or introduce new ones. Several successful works, both in vitro and in vivo, have been reported using silk-based scaffolds to regenerate bone tissues or other parts of the skeletal system such as cartilage and ligament. A growing trend is observed toward the use of mineralized and nanofibrous scaffolds along with the development of technology that allows to control scaffold architecture, its biodegradability and the sustained releasing property of scaffolds. Further development of silk-based scaffolds for bone tissue engineering, taking them up to and beyond the stage of human trials, is hoped to be achieved in the near future through a cross-disciplinary coalition of tissue engineers, material scientists and manufacturing engineers. The state-of-art of silk biomaterials in bone tissue engineering, covering their wide

  13. The Role of Bioreactors in Ligament and Tendon Tissue Engineering.

    Science.gov (United States)

    Mace, James; Wheelton, Andy; Khan, Wasim S; Anand, Sanj

    2016-01-01

    Bioreactors are pivotal to the emerging field of tissue engineering. The formation of neotissue from pluripotent cell lineages potentially offers a source of tissue for clinical use without the significant donor site morbidity associated with many contemporary surgical reconstructive procedures. Modern bioreactor design is becoming increasingly complex to provide a both an expandable source of readily available pluripotent cells and to facilitate their controlled differentiation into a clinically applicable ligament or tendon like neotissue. This review presents the need for such a method, challenges in the processes to engineer neotissue and the current designs and results of modern bioreactors in the pursuit of engineered tendon and ligament.

  14. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Synthesis of electroactive tetraaniline grafted polyethylenimine for tissue engineering

    Science.gov (United States)

    Dong, Shilei; Han, Lu; Cai, Muhang; Li, Luhai; Wei, Yan

    2015-07-01

    Tetraaniline grafted polyethylenimine (AT-PEI) was successfully synthesized in this study. Proton Nuclear Magnetic Resonance (1H NMR) Spectroscopy was used to determine the structure of carboxyl-capped aniline tetramer (AT-COOH) and AT-PEI. UV-Vis spectroscopy and Fourier transform infrared (FT-IR) spectroscopy were employed to characterize the absorption spectrum of the obtained AT-PEI samples. The morphology of AT-PEI copolymers in aqueous solution was determined by Scanning electron microscope (SEM). Moreover, AT-PEI copolymers demonstrated excellent solubility in aqueous solution and possessed electroactivity by cyclic voltammogram (CV) curves, which showed its potential application in the field of tissue engineering.

  16. The influence of environmental factors on bone tissue engineering.

    Science.gov (United States)

    Szpalski, Caroline; Sagebin, Fabio; Barbaro, Marissa; Warren, Stephen M

    2013-05-01

    Bone repair and regeneration are dynamic processes that involve a complex interplay between the substrate, local and systemic cells, and the milieu. Although each constituent plays an integral role in faithfully recreating the skeleton, investigators have long focused their efforts on scaffold materials and design, cytokine and hormone administration, and cell-based therapies. Only recently have the intangible aspects of the milieu received their due attention. In this review, we highlight the important influence of environmental factors on bone tissue engineering. Copyright © 2012 Wiley Periodicals, Inc.

  17. Nanoscale biomaterial interface modification for advanced tissue engineering applications

    International Nuclear Information System (INIS)

    Safonov, V; Zykova, A; Smolik, J; Rogovska, R; Donkov, N; Goltsev, A; Dubrava, T; Rassokha, I; Georgieva, V

    2012-01-01

    Recently, various stem cells, including mesenchymal stem cells (MSCs), have been found to have considerable potential for application in tissue engineering and future advanced therapies due to their biological capability to differentiate into specific lineages. Modified surface properties, such as composition, nano-roughness and wettability, affect the most important processes at the biomaterial interface. The aim of the present is work is to study the stem cells' (MSCs) adhesive potential, morphology, phenotypical characteristics in in vitro tests, and to distinguish betwen the different factors influencing the cell/biomaterial interaction, such as nano-topography, surface chemistry and surface free energy.

  18. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Gao X

    2015-11-01

    Full Text Available Xiang Gao,1,2,* Xiaohong Zhang,3,* Jinlin Song,1,2 Xiao Xu,4 Anxiu Xu,1 Mengke Wang,4 Bingwu Xie,1 Enyi Huang,2 Feng Deng,1,2 Shicheng Wei2–41College of Stomatology, 2Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing, 3Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, 4Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, Peking University School and Hospital of Stomatology, Beijing, People’s Republic of China*These authors contributed equally to this workAbstract: The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than

  19. Highly porous scaffolds of PEDOT:PSS for bone tissue engineering.

    Science.gov (United States)

    Guex, Anne Géraldine; Puetzer, Jennifer L; Armgarth, Astrid; Littmann, Elena; Stavrinidou, Eleni; Giannelis, Emmanuel P; Malliaras, George G; Stevens, Molly M

    2017-10-15

    Conjugated polymers have been increasingly considered for the design of conductive materials in the field of regenerative medicine. However, optimal scaffold properties addressing the complexity of the desired tissue still need to be developed. The focus of this study lies in the development and evaluation of a conductive scaffold for bone tissue engineering. In this study PEDOT:PSS scaffolds were designed and evaluated in vitro using MC3T3-E1 osteogenic precursor cells, and the cells were assessed for distinct differentiation stages and the expression of an osteogenic phenotype. Ice-templated PEDOT:PSS scaffolds presented high pore interconnectivity with a median pore diameter of 53.6±5.9µm and a total pore surface area of 7.72±1.7m 2 ·g -1 . The electrical conductivity, based on I-V curves, was measured to be 140µS·cm -1 with a reduced, but stable conductivity of 6.1µS·cm -1 after 28days in cell culture media. MC3T3-E1 gene expression levels of ALPL, COL1A1 and RUNX2 were significantly enhanced after 4weeks, in line with increased extracellular matrix mineralisation, and osteocalcin deposition. These results demonstrate that a porous material, based purely on PEDOT:PSS, is suitable as a scaffold for bone tissue engineering and thus represents a promising candidate for regenerative medicine. Tissue engineering approaches have been increasingly considered for the repair of non-union fractions, craniofacial reconstruction or large bone defect replacements. The design of complex biomaterials and successful engineering of 3-dimensional tissue constructs is of paramount importance to meet this clinical need. Conductive scaffolds, based on conjugated polymers, present interesting candidates to address the piezoelectric properties of bone tissue and to induce enhanced osteogenesis upon implantation. However, conductive scaffolds have not been investigated in vitro in great measure. To this end, we have developed a highly porous, electrically conductive scaffold

  20. Computational fluid dynamics modeling of momentum transport in rotating wall perfused bioreactor for cartilage tissue engineering.

    Science.gov (United States)

    Cinbiz, Mahmut N; Tığli, R Seda; Beşkardeş, Işil Gerçek; Gümüşderelioğlu, Menemşe; Colak, Uner

    2010-11-01

    In this study, computational fluid dynamics (CFD) analysis of a rotating-wall perfused-vessel (RWPV) bioreactor is performed to characterize the complex hydrodynamic environment for the simulation of cartilage development in RWPV bioreactor in the presence of tissue-engineered cartilage constructs, i.e., cell-chitosan scaffolds. Shear stress exerted on chitosan scaffolds in bioreactor was calculated for different rotational velocities in the range of 33-38 rpm. According to the calculations, the lateral and lower surfaces were exposed to 0.07926-0.11069 dyne/cm(2) and 0.05974-0.08345 dyne/cm(2), respectively, while upper surfaces of constructs were exposed to 0.09196-0.12847 dyne/cm(2). Results validate adequate hydrodynamic environment for scaffolds in RWPV bioreactor for cartilage tissue development which concludes the suitability of operational conditions of RWPV bioreactor. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Mesenchymal stem cell cultivation in electrospun scaffolds: mechanistic modeling for tissue engineering.

    Science.gov (United States)

    Paim, Ágata; Tessaro, Isabel C; Cardozo, Nilo S M; Pranke, Patricia

    2018-03-05

    Tissue engineering is a multidisciplinary field of research in which the cells, biomaterials, and processes can be optimized to develop a tissue substitute. Three-dimensional (3D) architectural features from electrospun scaffolds, such as porosity, tortuosity, fiber diameter, pore size, and interconnectivity have a great impact on cell behavior. Regarding tissue development in vitro, culture conditions such as pH, osmolality, temperature, nutrient, and metabolite concentrations dictate cell viability inside the constructs. The effect of different electrospun scaffold properties, bioreactor designs, mesenchymal stem cell culture parameters, and seeding techniques on cell behavior can be studied individually or combined with phenomenological modeling techniques. This work reviews the main culture and scaffold factors that affect tissue development in vitro regarding the culture of cells inside 3D matrices. The mathematical modeling of the relationship between these factors and cell behavior inside 3D constructs has also been critically reviewed, focusing on mesenchymal stem cell culture in electrospun scaffolds.

  2. A novel customizable modular bioreactor system for whole-heart cultivation under controlled 3D biomechanical stimulation.

    Science.gov (United States)

    Hülsmann, Jörn; Aubin, Hug; Kranz, Alexander; Godehardt, Erhardt; Munakata, Hiroshi; Kamiya, Hiroyuki; Barth, Mareike; Lichtenberg, Artur; Akhyari, Payam

    2013-09-01

    In the last decade, cardiovascular tissue engineering has made great progress developing new strategies for regenerative medicine applications. However, while tissue engineered heart valves are already entering the clinical routine, tissue engineered myocardial substitutes are still restrained to experimental approaches. In contrast to the heart valves, tissue engineered myocardium cannot be repopulated in vivo because of its biological complexity, requiring elaborate cultivation conditions ex vivo. Although new promising approaches-like the whole-heart decellularization concept-have entered the myocardial tissue engineering field, bioreactor technology needed for the generation of functional myocardial tissue still lags behind in the sense of user-friendly, flexible and low cost systems. Here, we present a novel customizable modular bioreactor system that can be used for whole-heart cultivation. Out of a commercially obtainable original equipment manufacturer platform we constructed a modular bioreactor system specifically aimed at the cultivation of decellularized whole-hearts through perfusion and controlled 3D biomechanical stimulation with a simple but highly flexible operation platform based on LabVIEW. The modular setup not only allows a wide range of variance regarding medium conditioning under controlled 3D myocardial stretching but can also easily be upgraded for e.g. electrophysiological monitoring or stimulation, allowing for a tailor-made low-cost myocardial bioreactor system.

  3. Protocols for the in vitro design of animal articular cartilage based on tissue engineering methods

    Directory of Open Access Journals (Sweden)

    Diego Correa

    2002-01-01

    Full Text Available The articular cartilage is the structure that covers the joint ends. It has some specific tasks crucial to the correct joint physiology. It may experience a large amount of injuries that could generate considerable disabilities. Unfortunately its selfrepair capacity is too limited; therefore, many treatments have been developed with partial success, given the suboptimal biomechanical behavior of the resultant tissue. Given that, Tissue Engineering offers an alternative, based on the design of a new tissue with biological and biomechanical features which resembles the native tissue. In this work, the authors describe the methodologies followed to accomplish that goal, studying the chondrocytes harvesting, the cellular cultures, the scaffold seeding processes, the mechanical stimulation and the structural and biomechanical evaluation. Finally, exposed some of the preliminary results, as a experimental validation of the methods proposed are.

  4. Osteoinductive peptide-functionalized nanofibers with highly ordered structure as biomimetic scaffolds for bone tissue engineering.

    Science.gov (United States)

    Gao, Xiang; Zhang, Xiaohong; Song, Jinlin; Xu, Xiao; Xu, Anxiu; Wang, Mengke; Xie, Bingwu; Huang, Enyi; Deng, Feng; Wei, Shicheng

    2015-01-01

    The construction of functional biomimetic scaffolds that recapitulate the topographical and biochemical features of bone tissue extracellular matrix is now of topical interest in bone tissue engineering. In this study, a novel surface-functionalized electrospun polycaprolactone (PCL) nanofiber scaffold with highly ordered structure was developed to simulate the critical features of native bone tissue via a single step of catechol chemistry. Specially, under slightly alkaline aqueous solution, polydopamine (pDA) was coated on the surface of aligned PCL nanofibers after electrospinning, followed by covalent immobilization of bone morphogenetic protein-7-derived peptides onto the pDA-coated nanofiber surface. Contact angle measurement, Raman spectroscopy, and X-ray photoelectron spectroscopy confirmed the presence of pDA and peptides on PCL nanofiber surface. Our results demonstrated that surface modification with osteoinductive peptides could improve cytocompatibility of nanofibers in terms of cell adhesion, spreading, and proliferation. Most importantly, Alizarin Red S staining, quantitative real-time polymerase chain reaction, immunostaining, and Western blot revealed that human mesenchymal stem cells cultured on aligned nanofibers with osteoinductive peptides exhibited enhanced osteogenic differentiation potential than cells on randomly oriented nanofibers. Furthermore, the aligned nanofibers with osteoinductive peptides could direct osteogenic differentiation of human mesenchymal stem cells even in the absence of osteoinducting factors, suggesting superior osteogenic efficacy of biomimetic design that combines the advantages of osteoinductive peptide signal and highly ordered nanofibers on cell fate decision. The presented peptide-decorated bone-mimic nanofiber scaffolds hold a promising potential in the context of bone tissue engineering.

  5. Use of autologous tissue engineered skin to treat porcine full-thickness skin defects

    Institute of Scientific and Technical Information of China (English)

    CAI Xia; CAO Yi-lin; CUI Lei; LIU Wei; GUAN Wen-xiang

    2005-01-01

    Objective: To explore a feasible method to repair full-thickness skin defects utilizing tissue engineered techniques. Methods: The Changfeng hybrid swines were used and the skin specimens were cut from the posterior limb girdle region, from which the keratinocytes and fibroblasts were isolated and harvested by trypsin, EDTA, and type II collagenase. The cells were seeded in Petri dishes for primary culture. When the cells were in logarithmic growth phase, they were treated with trypsin to separate them from the floor of the tissue culture dishes. A biodegradable material, Pluronic F-127, was prefabricated and mixed with these cells, and then the cell-Pluronic compounds were seeded evenly into a polyglycolic acid (PGA). Then the constructs were replanted to the autologous animals to repair the full-thickness skin defects. Histology and immunohistochemistry of the neotissue were observed in 1, 2, 4, and 8 postoperative weeks. Results: The cell-Pluronic F-127-PGA compounds repaired autologous full-thickness skin defects 1 week after implantation. Histologically, the tissue engineered skin was similar to the normal skin with stratified epidermis overlying a moderately thick collageneous dermis. Three of the structural proteins in the epidermal basement membrane zone, type IV collagen, laminin, and type VII collagen were detected using immunohistochemical methods. Conclusions: By studying the histology and immunohistochemistry of the neotissue, the bioengineered skin graft holds great promise for improving healing of the skin defects.

  6. Design and characterization of a biodegradable composite scaffold for ligament tissue engineering.

    Science.gov (United States)

    Hayami, James W S; Surrao, Denver C; Waldman, Stephen D; Amsden, Brian G

    2010-03-15

    Herein we report on the development and characterization of a biodegradable composite scaffold for ligament tissue engineering based on the fundamental morphological features of the native ligament. An aligned fibrous component was used to mimic the fibrous collagen network and a hydrogel component to mimic the proteoglycan-water matrix of the ligament. The composite scaffold was constructed from cell-adherent, base-etched, electrospun poly(epsilon-caprolactone-co-D,L-lactide) (PCLDLLA) fibers embedded in a noncell-adherent photocrosslinked N-methacrylated glycol chitosan (MGC) hydrogel seeded with primary ligament fibroblasts. Base etching improved cellular adhesion to the PCLDLLA material. Cells within the MGC hydrogel remained viable (72 +/- 4%) during the 4-week culture period. Immunohistochemistry staining revealed ligament ECM markers collagen type I, collagen type III, and decorin organizing and accumulating along the PCLDLLA fibers within the composite scaffolds. On the basis of these results, it was determined that the composite scaffold design was a viable alternative to the current approaches used for ligament tissue engineering and merits further study. (c) 2009 Wiley Periodicals, Inc.

  7. Human umbilical cord mesenchymal stem cells: osteogenesis in vivo as seed cells for bone tissue engineering.

    Science.gov (United States)

    Diao, Yinze; Ma, Qingjun; Cui, Fuzhai; Zhong, Yanfeng

    2009-10-01

    Mesenchymal stem cells (MSCs) are ideal seed cells for bone tissue engineering. However, intrinsic deficiencies exist for the autologous transplantation strategy of constructing artificial bone with MSCs derived from bone marrow of patients. In this study, MSCs-like cells were isolated from human umbilical cords and were expanded in vitro. Flow cytometric analysis revealed that cells from the fourth passage were positive for CD29, CD44, CD71, CD73, CD90, and CD105 whereas they were negative for CD14, CD34, CD45, and CD117. Furthermore, these cells expressed HLA-A, B, C (MHC-I), but not HLA-DP, DQ, DR (MHC-II), or costimulatory molecules such as CD80 and CD86. Following incubation in specific inductive media for 3 weeks, cultured cells were shown to possess potential to differentiate into adipogenic, osteogenic or chondrogenic lineages in vitro. The umbilical cord-derived MSCs (UC-MSCs) were loaded with a biomimetic artificial bone scaffold material before being implanted subcutaneously in the back of Balb/c nude mice for four to twelve weeks. Our results revealed that UC-MSCs loaded with the scaffold displayed capacity of osteogenic differentiation leading to osteogenesis with human origin in vivo. As a readily available source of seed cells for bone tissue engineering, UC-MSCs should have broad application prospects.

  8. Silk fibroin based biomimetic artificial extracellular matrix for hepatic tissue engineering applications

    International Nuclear Information System (INIS)

    Kasoju, Naresh; Bora, Utpal

    2012-01-01

    Hepatic tissue engineering, which aims to construct artificial liver tissues, requires a suitable extracellular matrix (ECM) for growth and proliferation of metabolically active hepatocytes. The current paper describes the development of a biomimetic artificial ECM, for hepatic tissue engineering applications, by mimicking the architectural features and biochemical composition of native ECM. Electrospinning was chosen as the fabrication technique of choice, while regenerated silk fibroin (RSF) and galactosylated chitosan (GalCS) were chosen as materials of choice. Poly(ethylene oxide) was used as a processing aid. Methodical optimization studies were performed to obtain smooth and continuous nanofibers with homogenous size distribution. Extensive characterization studies were performed to determine its morphological, physical, chemical/structural, thermal and cytotoxicity properties. Subsequently, detailed in vitro hepatocyte compatibility studies were performed using HepG2 cell line. Remarkably, the studies revealed that the growth, viability, metabolic activity and proliferation of hepatocytes were relatively superior on RSF–GalCS scaffold than on pure RSF