The Experts below are selected from a list of 20043 Experts worldwide ranked by ideXlab platform
Bin Duan - One of the best experts on this subject based on the ideXlab platform.
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electrospun thymosin beta 4 loaded plga pla nanofiber microfiber hybrid yarns for Tendon Tissue engineering application
Materials Science and Engineering: C, 2020Co-Authors: Rong Zhou, Philipp N. Streubel, Bin Duan, Fang Zhou, Shaojuan ChenAbstract:Microfiber yarns (MY) have been widely employed to construct Tendon Tissue grafts. However, suboptimal ultrastructure and inappropriate environments for cell interactions limit their clinical application. Herein, we designed a modified electrospinning device to coat poly(lactic-co-glycolic acid) PLGA nanofibers onto polylactic acid (PLA) MY to generate PLGA/PLA hybrid yarns (HY), which had a well-aligned nanofibrous structure, resembling the ultrastructure of native Tendon Tissues and showed enhanced failure load compared to PLA MY. PLGA/PLA HY significantly improved the growth, proliferation, and Tendon-specific gene expressions of human adipose derived mesenchymal stem cells (HADMSC) compared to PLA MY. Moreover, thymosin beta-4 (Tβ4) loaded PLGA/PLA HY presented a sustained drug release manner for 28 days and showed an additive effect on promoting HADMSC migration, proliferation, and tenogenic differentiation. Collectively, the combination of Tβ4 with the nano-topography of PLGA/PLA HY might be an efficient strategy to promote tenogenesis of adult stem cells for Tendon Tissue engineering.
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Electrospun thymosin Beta-4 loaded PLGA/PLA nanofiber/ microfiber hybrid yarns for Tendon Tissue engineering application
Materials science & engineering. C Materials for biological applications, 2019Co-Authors: Rong Zhou, Philipp N. Streubel, Fang Zhou, Shaojuan Chen, Bin DuanAbstract:Microfiber yarns (MY) have been widely employed to construct Tendon Tissue grafts. However, suboptimal ultrastructure and inappropriate environments for cell interactions limit their clinical application. Herein, we designed a modified electrospinning device to coat poly(lactic-co-glycolic acid) PLGA nanofibers onto polylactic acid (PLA) MY to generate PLGA/PLA hybrid yarns (HY), which had a well-aligned nanofibrous structure, resembling the ultrastructure of native Tendon Tissues and showed enhanced failure load compared to PLA MY. PLGA/PLA HY significantly improved the growth, proliferation, and Tendon-specific gene expressions of human adipose derived mesenchymal stem cells (HADMSC) compared to PLA MY. Moreover, thymosin beta-4 (Tβ4) loaded PLGA/PLA HY presented a sustained drug release manner for 28 days and showed an additive effect on promoting HADMSC migration, proliferation, and tenogenic differentiation. Collectively, the combination of Tβ4 with the nano-topography of PLGA/PLA HY might be an efficient strategy to promote tenogenesis of adult stem cells for Tendon Tissue engineering.
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Living nanofiber yarn-based woven biotextiles for Tendon Tissue engineering using cell tri-culture and mechanical stimulation.
Acta biomaterialia, 2017Co-Authors: Ying Wang, Philipp N. Streubel, Bin DuanAbstract:Abstract Non-woven nanofibrous scaffolds have been developed for Tendon graft application by using electrospinning strategies. However, electrospun nanofibrous scaffolds face some obstacles and limitations, including suboptimal scaffold structure, weak tensile and suture-retention strengths, and compact structure for cell infiltration. In this work, a novel nanofibrous, woven biotextile, fabricated based on electrospun nanofiber yarns, was implemented as a Tissue engineered Tendon scaffold. Based on our modified electrospinning setup, polycaprolactone (PCL) nanofiber yarns were fabricated with reproducible quality, and were further processed into plain-weaving fabrics interlaced with polylactic acid (PLA) multifilaments. Nonwoven nanofibrous PCL meshes with random or aligned fiber structures were generated using typical electrospinning as comparative counterparts. The woven fabrics contained 3 D aligned microstructures with significantly larger pore size and obviously enhanced tensile mechanical properties than their nonwoven counterparts. The biological results revealed that cell proliferation and infiltration, along with the expression of Tendon-specific genes by human adipose derived mesenchymal stem cells (HADMSC) and human tenocytes (HT), were significantly enhanced on the woven fabrics compared with those on randomly-oriented or aligned nanofiber meshes. Co-cultures of HADMSC with HT or human umbilical vein endothelial cells (HUVEC) on woven fabrics significantly upregulated the functional expression of most tenogenic markers. HADMSC/HT/HUVEC tri-culture on woven fabrics showed the highest upregulation of most Tendon-associated markers than all the other mono- and co-culture groups. Furthermore, we conditioned the tri-cultured constructs with dynamic conditioning and demonstrated that dynamic stretch promoted total collagen secretion and tenogenic differentiation. Our nanofiber yarn-based biotextiles have significant potential to be used as engineered scaffolds to synergize the multiple cell interaction and mechanical stimulation for promoting Tendon regeneration. Statement of Significance Tendon grafts are essential for the treatment of various Tendon-related conditions due to the inherently poor healing capacity of native Tendon Tissues. In this study, we combined electrospun nanofiber yarns with textile manufacturing strategies to fabricate nanofibrous woven biotextiles with hierarchical features, aligned fibrous topography, and sufficient mechanical properties as Tendon Tissue engineered scaffolds. Comparing to traditional electrospun random or aligned meshes, our novel nanofibrous woven fabrics possess strong tensile and suture-retention strengths and larger pore size. We also demonstrated that the incorporation of Tendon cells and vascular cells promoted the tenogenic differentiation of the engineered Tendon constructs, especially under dynamic stretch. This study not only presents a novel Tissue engineered Tendon scaffold fabrication technique but also provides a useful strategy to promote Tendon differentiation and regeneration.
Wei Liu - One of the best experts on this subject based on the ideXlab platform.
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Tissue Engineering of Tendons: A Comparison of Muscle-Derived Cells, Tenocytes, and Dermal Fibroblasts as Cell Sources.
Plastic and reconstructive surgery, 2016Co-Authors: Bo Chen, Wei Liu, Jin-ping Ding, Wenjie Zhang, Guangdong Zhou, Yilin Cao, Bin WangAbstract:Background:The rapid development of Tendon Tissue-engineering technology may offer an alternative graft for reconstruction of severe Tendon losses. One critical factor for Tendon Tissue engineering is the optimization of seed cells. Little is known about the optimal cell source for engineered Tendon
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Fabrication of Electrospun Poly(L-Lactide-co-ɛ-Caprolactone)/Collagen Nanoyarn Network as a Novel, Three-Dimensional, Macroporous, Aligned Scaffold for Tendon Tissue Engineering
Tissue engineering. Part C Methods, 2013Co-Authors: Haoming Wang, Lei Song, Yang Xiang, Wei LiuAbstract:Tissue engineering techniques using novel scaffolding materials offer potential alternatives for managing Tendon disorders. An ideal Tendon Tissue engineered scaffold should mimic the three-dimensional (3D) structure of the natural extracellular matrix (ECM) of the native Tendon. Here, we propose a novel electrospun nanoyarn network that is morphologically and structurally similar to the ECM of native Tendon Tissues. The nanoyarn, random nanofiber, and aligned nanofiber scaffolds of a synthetic biodegradable polymer, poly(l-lactide-co-ɛ-caprolactone) [P(LLA-CL)], and natural collagen I complex were fabricated using electrospinning. These scaffolds were characterized in terms of fiber morphology, pore size, porosity, and chemical and mechanical properties for the purpose of culturing Tendon cells (TCs) for Tendon Tissue engineering. The results indicated a fiber diameter of 632±81 nm for the random nanofiber scaffold, 643±97 nm for the aligned nanofiber scaffold, and 641±68 nm for the nanoyarn scaffold. Th...
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fabrication of electrospun poly l lactide co e caprolactone collagen nanoyarn network as a novel three dimensional macroporous aligned scaffold for Tendon Tissue engineering
Tissue Engineering Part C-methods, 2013Co-Authors: Haoming Wang, Lei Song, Wei Liu, Yang Xiang, Qiang ZhouAbstract:Tissue engineering techniques using novel scaffolding materials offer potential alternatives for managing Tendon disorders. An ideal Tendon Tissue engineered scaffold should mimic the three-dimensional (3D) structure of the natural extracellular matrix (ECM) of the native Tendon. Here, we propose a novel electrospun nanoyarn network that is morphologically and structurally similar to the ECM of native Tendon Tissues. The nanoyarn, random nanofiber, and aligned nanofiber scaffolds of a synthetic biodegradable polymer, poly(L-lactide-co-e-caprolactone) [P(LLA-CL)], and natural collagen I complex were fabricated using electrospinning. These scaffolds were characterized in terms of fiber morphology, pore size, porosity, and chemical and mechanical properties for the purpose of culturing Tendon cells (TCs) for Tendon Tissue engineering. The results indicated a fiber diameter of 632 ± 81 nm for the random nanofiber scaffold, 643 ± 97 nm for the aligned nanofiber scaffold, and 641 ± 68 nm for the nanoyarn scaffold. The yarn in the nanoyarn scaffold was twisted by many nanofibers similar to the structure and inherent nanoscale organization of Tendons, indicating an increase in the diameter of 9.51 ± 3.62 μm. The nanoyarn scaffold also contained 3D aligned microstructures with large interconnected pores and high porosity. Fourier transform infrared analyses revealed the presence of collagen in the three scaffolds. The mechanical properties of the sample scaffolds indicated that the scaffolds had desirable mechanical properties for Tissue regeneration. Further, the results revealed that TC proliferation and infiltration, and the expression of Tendon-related ECM genes, were significantly enhanced on the nanoyarn scaffold compared with that on the random nanofiber and aligned nanofiber scaffolds. This study demonstrates that electrospun P(LLA-CL)/collagen nanoyarn is a novel, 3D, macroporous, aligned scaffold that has potential application in Tendon Tissue engineering.
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engineering human neo Tendon Tissue in vitro with human dermal fibroblasts under static mechanical strain
Biomaterials, 2009Co-Authors: Dan Deng, Wei Liu, Wenjie Zhang, Guangdong Zhou, Yang Yang, Lei Cui, Yilin CaoAbstract:Proper cell source is one of the key issues for Tendon engineering. Our previous study showed that dermal fibroblasts could be used to successfully engineer Tendon in vivo and tenocytes could engineer neo-Tendon in vitro with static strain. This study further investigated the possibility of engineering human neo-Tendon Tissue in vitro using dermal fibroblasts. Human dermal fibroblasts were seeded on polyglycolic acid (PGA) fibers pre-fixed on a U-shape as a mechanical loading group, or simply cultured in a dish as a tension-free group. In addition, human tenocytes were also seeded on PGA fibers with tension as a comparison to human dermal fibroblasts. The results showed that human neo-Tendon Tissue could be generated using dermal fibroblasts during in vitro culture under static strain and the Tissue structure became more mature with the increase of culture time. Longitudinally aligned collagen fibers and spindle shape cells were observed histologically and collagen fibril diameter and tensile strength increased with time and reached a peak at 14 weeks. In contrast, the dermal fibroblast-PGA constructs failed to form neo-Tendon, but formed disorganized fibrous Tissue in tension-free condition with significantly weaker strength and poor collagen fiber formation. Interestingly, neo-Tendon Tissues generated with human dermal fibroblasts were indistinguishable from the counterpart engineered with human tenocytes, which supports the viewpoint that human dermal fibroblasts is likely to replace tenocytes for future Tendon graft development in vitro with dynamic mechanical loading in a bioreactor system.
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in vitro Tendon engineering with avian tenocytes and polyglycolic acids a preliminary report
Tissue Engineering, 2006Co-Authors: Dejun Cao, Wei Liu, Lei Cui, Xian Wei, Yilin CaoAbstract:Although there are many reports of in vivo Tendon engineering using different animal models, only a few studies involve the short-term investigation of in vitro Tendon engineering. Our previous study demonstrated that functional Tendon Tissue could be engineered in vivo in a hen model using tenocytes and polyglycolic acid (PGA) fibers. This current study explored the feasibility of in vitro Tendon engineering using the same type of cells and scaffold material. Tenocytes were extracted from the Tendons of a hen's foot with enzyme digestion and cultured in DMEM plus 10% FBS. Unwoven PGA fibers were arranged into a cord-like construct and fixed on a U-shape spring, and tenocytes were then seeded on PGA fibers to generate a cell-PGA construct. In experimental group 1, 22 cell-scaffold constructs were fixed on the spring with no tension and collected at weeks 4 (n = 7), 6 (n = 7) and 10 (n = 8); in experimental group 2, five cell-scaffold constructs were fixed on the spring with a constant strain and collected after 6 weeks of culture. In the control group, three cell-free scaffolds were fixed on the spring without tension. The collected engineered Tendons were subjected to gross and histological examinations and biomechanical analysis. The results showed that Tendon Tissue could be generated during in vitro culture. In addition, the Tissue structure and mechanical property became more mature and stronger with the increase of culture time. Furthermore, application of constant strain could enhance Tissue maturation and improve mechanical property of the in vitro engineered Tendon (1.302 +/- 0.404 Mpa with tension vs 0.406 +/- 0.030 Mpa without tension at 6 weeks). Nevertheless, Tendon engineered with constant strain appeared much thinner in its diameter than Tendon engineered without mechanical loading. Additionally, its collagen fibers were highly compacted when compared to natural Tendon structure, suggesting that constant strain may not be the optimal means of mechanical load. Thus, application of dynamic mechanical load with a bioreactor to the construction of Tendon Tissue will be our next goal in this series of in vitro Tendon engineering study.
James Chang - One of the best experts on this subject based on the ideXlab platform.
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human flexor Tendon Tissue engineering in vivo effects of stem cell reseeding
Plastic and Reconstructive Surgery, 2013Co-Authors: Taliah Schmitt, Hung Pham, Colin Yi-loong Woon, Simon Farnebo, Paige M Fox, Joel A Bronstein, Anthony W Behn, James ChangAbstract:Background:Tissue-engineered human flexor Tendons may be an option to aid in reconstruction of complex upper extremity injuries with significant Tendon loss. The authors hypothesize that human adipose-derived stem cells remain viable following reseeding on human Tendon scaffolds in vivo and aid in g
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flexor Tendon Tissue engineering bioreactor cyclic strain increases construct strength
Tissue Engineering Part A, 2010Co-Authors: Jonathan Riboh, Hung Pham, Derek P. Lindsey, Sepideh Saber, Andrew Y Zhang, R L Smith, James ChangAbstract:Mutilating injuries of the hand and upper extremity result in Tendon losses too great to be replaced by autologous grafts. The goal of this study was to use Tissue engineering techniques to produce additional Tendon material. We used a custom bioreactor to apply cyclic mechanical loading onto Tissue-engineered Tendon constructs to study ultimate tensile stress (UTS) and elastic modulus (E). Constructs used were acellularized rabbit hindpaw flexor digitorum profundus equivalents reseeded with tenocytes or left unseeded. Tendon constructs were subjected to a stretch force of 1.25 N over a 5-day course. Seeded Tendon constructs that were exposed to bioreactor loading had a significantly increased UTS (71.17 +/- 14.15 N) compared to nonloaded controls (35.69 +/- 5.62 N) (p = 0.001). Similarly, seeded constructs exposed to bioreactor loading also had a significantly higher E (1091 +/- 169 MPa) compared to nonloaded controls (632 +/- 86 MPa) (p = 0.001). This study shows that cyclic loading of Tendon constructs increases the UTS and elastic modulus of seeded constructs. The use of the bioreactor may therefore accelerate the in vitro production of strong, nonimmunogenic Tendon material that can potentially be used clinically to reconstruct significant Tendon losses.
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flexor Tendon Tissue engineering temporal distribution of donor tenocytes versus recipient cells
Plastic and Reconstructive Surgery, 2009Co-Authors: Johan Thorfinn, Alphonsus K. S. Chong, Hung M. Pham, Sepideh Saber, Ioannis K Angelidis, Andrew Y Zhang, Gordon K Lee, James ChangAbstract:Background: Tissue-engineered Tendon material may address Tendon shortages in mutilating hand injuries. Tenocytes from rabbit flexor Tendon can be successfully seeded onto acellularized Tendons that are used as Tendon constructs. These constructs in vivo exhibit a population of tenocyte-like cells; however, it is not known to what extent these cells are of donor or recipient origin. Furthermore, the temporal distribution is also not known. Methods: Tenocytes from New Zealand male rabbits were cultured and seeded onto acellularized rabbit forepaw flexor Tendons (n = 48). These Tendon constructs were transplanted into female recipients. Tendons were examined after 3, 6, 12, and 30 weeks using fluorescent in situ hybridization to detect the Y chromosome in the male donor cells. One unseeded, acellularized allograft in each animal was used as a control. Results: The donor male tenocytes populate the epitenon and endotenon of the grafts at greater numbers than the recipient female tenocytes at 3 and 6 weeks. The donor and recipient tenocytes are present jointly in the grafts until 12 weeks. At 30 weeks, nearly all cells are recipient tenocyte-like cells. Conclusions: Donor male cells survive in decreasing numbers over time until 30 weeks. The presence of cells in Tissue-engineered Tendon grafts has been shown in prior studies to add to the strength of the constructs in vitro. This study shows that recipient cells can migrate into and repopulate the Tendon construct. Cell seeding onto Tendon material may create stronger constructs that will allow the initiation of motion earlier. (Plast. Reconstr. Surg. 124: 2019, 2009.)
Hongwei Ouyang - One of the best experts on this subject based on the ideXlab platform.
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Cell-material interactions in Tendon Tissue engineering.
Acta biomaterialia, 2018Co-Authors: Junxin Lin, Zi Yin, Wenyan Zhou, Shan Han, Varitsara Bunpetch, Kun Zhao, Chaozhong Liu, Hongwei OuyangAbstract:Abstract The interplay between cells and materials is a fundamental topic in biomaterial-based Tissue regeneration. One of the principles for biomaterial development in Tendon regeneration is to stimulate tenogenic differentiation of stem cells. To this end, efforts have been made to optimize the physicochemical and bio-mechanical properties of biomaterials for Tendon Tissue engineering. However, recent progress indicated that innate immune cells, especially macrophages, can also respond to the material cues and undergo phenotypical changes, which will either facilitate or hinder Tissue regeneration. This process has been, to some extent, neglected by traditional strategies and may partially explain the unsatisfactory outcomes of previous studies; thus, more researchers have turned their focus on developing and designing immunoregenerative biomaterials to enhance Tendon regeneration. In this review, we will first summarize the effects of material cues on tenogenic differentiation and paracrine secretion of stem cells. A brief introduction will also be made on how material cues can be manipulated for the regeneration of Tendon-to-bone interface. Then, we will discuss the characteristics and influences of macrophages on the repair process of Tendon healing and how they respond to different materials cues. These principles may benefit the development of novel biomaterials provided with combinative bioactive cues to activate tenogenic differentiation of stem cells and pro-resolving macrophage phenotype. Statement of Significance The progress achieved with the rapid development of biomaterial-based strategies for Tendon regeneration has not yielded broad benefits to clinical patients. In addition to the interplay between stem cells and biomaterials, the innate immune response to biomaterials also plays a determinant role in Tissue regeneration. Here, we propose that fine-tuning of stem cell behaviors and alternative activation of macrophages through material cues may lead to effective Tendon/ligament regeneration. We first review the characteristics of key material cues that have been manipulated to promote tenogenic differentiation and paracrine secretion of stem cells in Tendon regeneration. Then, we discuss the potentiality of corresponding material cues in activating macrophages toward a pro-resolving phenotype to promote Tissue repair.
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Col V siRNA Engineered Tenocytes for Tendon Tissue Engineering
PloS one, 2011Co-Authors: Guo Rong Zhang, Xiaohui Zou, Xing Hui Song, Lin-lin Wang, Hongwei OuyangAbstract:The presence of uniformly small collagen fibrils in Tendon repair is believed to play a major role in suboptimal Tendon healing. Collagen V is significantly elevated in healing Tendons and plays an important role in fibrillogenesis. The objective of this study was to investigate the effect of a particular chain of collagen V on the fibrillogenesis of Sprague-Dawley rat tenocytes, as well as the efficacy of Col V siRNA engineered tenocytes for Tendon Tissue engineering. RNA interference gene therapy and a scaffold free Tissue engineered Tendon model were employed. The results showed that scaffold free Tissue engineered Tendon had Tissue-specific Tendon structure. Down regulation of collagen V α1 or α2 chains by siRNAs (Col5α1 siRNA, Col5α2 siRNA) had different effects on collagen I and decorin gene expressions. Col5α1 siRNA treated tenocytes had smaller collagen fibrils with abnormal morphology; while those Col5α2 siRNA treated tenocytes had the same morphology as normal tenocytes. Furthermore, it was found that Tendons formed by coculture of Col5α1 siRNA treated tenocytes with normal tenocytes at a proper ratio had larger collagen fibrils and relative normal contour. Conclusively, it was demonstrated that Col V siRNA engineered tenocytes improved Tendon Tissue regeneration. And an optimal level of collagen V is vital in regulating collagen fibrillogenesis. This may provide a basis for future development of novel cellular- and molecular biology-based therapeutics for Tendon diseases.
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autologous tenocyte therapy for experimental achilles tendinopathy in a rabbit model
Tissue Engineering Part A, 2011Co-Authors: Jimin Chen, Hongwei Ouyang, Zhen Lin, Nathan J Pavlos, Allan Wang, Ming H ZhengAbstract:Background: Tendinopathy of the Achilles Tendon is a chronic degenerative condition that frequently does not respond to treatment. In the current study, we propose that autologous tenocytes therapy (ATT) is effective in treating Tendon degeneration in a collagenase-induced rabbit Achilles tendinopathy model. Methods: Chronic tendinopathy was created in the left Achilles Tendon of 44 rabbits by an intraTendonous injection of type I collagenase. Forty-two rabbits were randomly allocated into three groups of 14 and received control treatment; autologous tenocytes digested from Tendon Tissue; and autologous tenocytes digested from epitendineum Tissue. For cell tracking in vivo, the remaining two animals were injected with autologous tenocytes labeled with a nano-scale super-paramagnetic iron oxide (Feridex). Rabbits were sacrificed at 4 and 8 weeks after the therapeutic injection, and Tendon Tissue was analyzed by histology, immunostaining, and biomechanical testing to evaluate Tissue repair. Results: Autolog...
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Efficacy of hESC-MSCs in knitted silk-collagen scaffold for Tendon Tissue engineering and their roles.
Biomaterials, 2010Co-Authors: Jialin Chen, Zi Yin, Xiao Chen, Xiaohui Zou, Wei Liang Shen, Boon Chin Heng, Hongwei OuyangAbstract:Human embryonic stem cells (hESC) and their differentiated progenies are an attractive cell source for transplantation therapy and Tissue engineering. Nevertheless, the utility of these cells for Tendon Tissue engineering has not yet been adequately explored. This study incorporated hESC-derived mesenchymal stem cells (hESC-MSCs) within a knitted silk-collagen sponge scaffold, and assessed the efficacy of this Tissue-engineered construct in promoting Tendon regeneration. When subjected to mechanical stimulation in vitro, hESC-MSCs exhibited tenocyte-like morphology and positively expressed Tendon-related gene markers (e.g. Collagen type I & III, Epha4 and Scleraxis), as well as other mechano-sensory structures and molecules (cilia, integrins and myosin). In ectopic transplantation, the Tissue-engineered Tendon under in vivo mechanical stimulus displayed more regularly aligned cells and larger collagen fibers. This in turn resulted in enhanced Tendon regeneration in situ, as evidenced by better histological scores and superior mechanical performance characteristics. Furthermore, cell labeling and extracellular matrix expression assays demonstrated that the transplanted hESC-MSCs not only contributed directly to Tendon regeneration, but also exerted an environment-modifying effect on the implantation site in situ. Hence, Tissue-engineered Tendon can be successfully fabricated through seeding of hESC-MSCs within a knitted silk-collagen sponge scaffold followed by mechanical stimulation.
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Synergic Combination of Collagen Matrix with Knitted Silk Scaffold Regenerated Ligament with More Native Microstructure in Rabbit Model
IFMBE Proceedings, 2024Co-Authors: Xiao Chen, Zi Yin, Lin-lin Wang, Hongwei OuyangAbstract:A number of researches on ligament and Tendon Tissue engineering scaffold have been carried out. However, a scaffold which simultaneously possesses optimal strength, porous structure and biocompatible microenvironment is yet to be developed. This study aims to design a new practical ligament scaffold by synergic incorporation of silk material, knitting structure and collagen matrix.
Philipp N. Streubel - One of the best experts on this subject based on the ideXlab platform.
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electrospun thymosin beta 4 loaded plga pla nanofiber microfiber hybrid yarns for Tendon Tissue engineering application
Materials Science and Engineering: C, 2020Co-Authors: Rong Zhou, Philipp N. Streubel, Bin Duan, Fang Zhou, Shaojuan ChenAbstract:Microfiber yarns (MY) have been widely employed to construct Tendon Tissue grafts. However, suboptimal ultrastructure and inappropriate environments for cell interactions limit their clinical application. Herein, we designed a modified electrospinning device to coat poly(lactic-co-glycolic acid) PLGA nanofibers onto polylactic acid (PLA) MY to generate PLGA/PLA hybrid yarns (HY), which had a well-aligned nanofibrous structure, resembling the ultrastructure of native Tendon Tissues and showed enhanced failure load compared to PLA MY. PLGA/PLA HY significantly improved the growth, proliferation, and Tendon-specific gene expressions of human adipose derived mesenchymal stem cells (HADMSC) compared to PLA MY. Moreover, thymosin beta-4 (Tβ4) loaded PLGA/PLA HY presented a sustained drug release manner for 28 days and showed an additive effect on promoting HADMSC migration, proliferation, and tenogenic differentiation. Collectively, the combination of Tβ4 with the nano-topography of PLGA/PLA HY might be an efficient strategy to promote tenogenesis of adult stem cells for Tendon Tissue engineering.
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Electrospun thymosin Beta-4 loaded PLGA/PLA nanofiber/ microfiber hybrid yarns for Tendon Tissue engineering application
Materials science & engineering. C Materials for biological applications, 2019Co-Authors: Rong Zhou, Philipp N. Streubel, Fang Zhou, Shaojuan Chen, Bin DuanAbstract:Microfiber yarns (MY) have been widely employed to construct Tendon Tissue grafts. However, suboptimal ultrastructure and inappropriate environments for cell interactions limit their clinical application. Herein, we designed a modified electrospinning device to coat poly(lactic-co-glycolic acid) PLGA nanofibers onto polylactic acid (PLA) MY to generate PLGA/PLA hybrid yarns (HY), which had a well-aligned nanofibrous structure, resembling the ultrastructure of native Tendon Tissues and showed enhanced failure load compared to PLA MY. PLGA/PLA HY significantly improved the growth, proliferation, and Tendon-specific gene expressions of human adipose derived mesenchymal stem cells (HADMSC) compared to PLA MY. Moreover, thymosin beta-4 (Tβ4) loaded PLGA/PLA HY presented a sustained drug release manner for 28 days and showed an additive effect on promoting HADMSC migration, proliferation, and tenogenic differentiation. Collectively, the combination of Tβ4 with the nano-topography of PLGA/PLA HY might be an efficient strategy to promote tenogenesis of adult stem cells for Tendon Tissue engineering.
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Living nanofiber yarn-based woven biotextiles for Tendon Tissue engineering using cell tri-culture and mechanical stimulation.
Acta biomaterialia, 2017Co-Authors: Ying Wang, Philipp N. Streubel, Bin DuanAbstract:Abstract Non-woven nanofibrous scaffolds have been developed for Tendon graft application by using electrospinning strategies. However, electrospun nanofibrous scaffolds face some obstacles and limitations, including suboptimal scaffold structure, weak tensile and suture-retention strengths, and compact structure for cell infiltration. In this work, a novel nanofibrous, woven biotextile, fabricated based on electrospun nanofiber yarns, was implemented as a Tissue engineered Tendon scaffold. Based on our modified electrospinning setup, polycaprolactone (PCL) nanofiber yarns were fabricated with reproducible quality, and were further processed into plain-weaving fabrics interlaced with polylactic acid (PLA) multifilaments. Nonwoven nanofibrous PCL meshes with random or aligned fiber structures were generated using typical electrospinning as comparative counterparts. The woven fabrics contained 3 D aligned microstructures with significantly larger pore size and obviously enhanced tensile mechanical properties than their nonwoven counterparts. The biological results revealed that cell proliferation and infiltration, along with the expression of Tendon-specific genes by human adipose derived mesenchymal stem cells (HADMSC) and human tenocytes (HT), were significantly enhanced on the woven fabrics compared with those on randomly-oriented or aligned nanofiber meshes. Co-cultures of HADMSC with HT or human umbilical vein endothelial cells (HUVEC) on woven fabrics significantly upregulated the functional expression of most tenogenic markers. HADMSC/HT/HUVEC tri-culture on woven fabrics showed the highest upregulation of most Tendon-associated markers than all the other mono- and co-culture groups. Furthermore, we conditioned the tri-cultured constructs with dynamic conditioning and demonstrated that dynamic stretch promoted total collagen secretion and tenogenic differentiation. Our nanofiber yarn-based biotextiles have significant potential to be used as engineered scaffolds to synergize the multiple cell interaction and mechanical stimulation for promoting Tendon regeneration. Statement of Significance Tendon grafts are essential for the treatment of various Tendon-related conditions due to the inherently poor healing capacity of native Tendon Tissues. In this study, we combined electrospun nanofiber yarns with textile manufacturing strategies to fabricate nanofibrous woven biotextiles with hierarchical features, aligned fibrous topography, and sufficient mechanical properties as Tendon Tissue engineered scaffolds. Comparing to traditional electrospun random or aligned meshes, our novel nanofibrous woven fabrics possess strong tensile and suture-retention strengths and larger pore size. We also demonstrated that the incorporation of Tendon cells and vascular cells promoted the tenogenic differentiation of the engineered Tendon constructs, especially under dynamic stretch. This study not only presents a novel Tissue engineered Tendon scaffold fabrication technique but also provides a useful strategy to promote Tendon differentiation and regeneration.
