Tendon Tissue Engineering

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Hongwei Ouyang - One of the best experts on this subject based on the ideXlab platform.

  • Cell-material interactions in Tendon Tissue Engineering.
    Acta biomaterialia, 2018
    Co-Authors: Junxin Lin, Zi Yin, Wenyan Zhou, Shan Han, Varitsara Bunpetch, Kun Zhao, Chaozhong Liu, Hongwei Ouyang
    Abstract:

    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.

  • Fetal and adult fibroblasts display intrinsic differences in Tendon Tissue Engineering and regeneration
    Scientific reports, 2014
    Co-Authors: Qiaomei Tang, Jialin Chen, Zi Yin, Hongwei Ouyang, Wei Liang Shen, Huanhuan Liu, Zhi Fang, Boon Chin Heng, Xiao Chen
    Abstract:

    Injured adult Tendons do not exhibit optimal healing through a regenerative process, whereas fetal Tendons can heal in a regenerative fashion without scar formation. Hence, we compared FFs (mouse fetal fibroblasts) and AFs (mouse adult fibroblasts) as seed cells for the fabrication of scaffold-free engineered Tendons. Our results demonstrated that FFs had more potential for Tendon Tissue Engineering, as shown by higher levels of Tendon-related gene expression. In the in situ AT injury model, the FFs group also demonstrated much better structural and functional properties after healing, with higher levels of collagen deposition and better microstructure repair. Moreover, fetal fibroblasts could increase the recruitment of fibroblast-like cells and reduce the infiltration of inflammatory cells to the injury site during the regeneration process. Our results suggest that the underlying mechanisms of better regeneration with FFs should be elucidated and be used to enhance adult Tendon healing. This may assist in the development of future strategies to treat Tendon injuries.

  • Tendon Injury: Role of Differentiation of Adult and Embryonic Derived Stem Cells
    Stem Cells and Cancer Stem Cells Volume 4, 2011
    Co-Authors: Chen Xiao, Boon Chin Heng, Hongwei Ouyang
    Abstract:

    Injuries to Tendon are particularly common in sports activities, but there is poor self-repair capability of this unique connective Tissue. As understanding of Tendon biology is critical for the development of innovative therapy for successful Tendon regeneration, the various cell sub-populations in Tendon as well as their niche in Tendon metabolism and pathology are described. Embryonic and adult stem cell-based Tendon Tissue Engineering approaches have achieved encouraging results. This chapter focuses on introducing two promising strategies: (i) stepwise differentiation of embryonic stem cells for Tendon Tissue Engineering, and (ii) incorporation of the matrix niche into Tendon stem cell differentiation for complete Tendon regeneration. Multifaceted technologies, such as incorporation of growth factors, bio-scaffolds, mechanical stimulation and genetic modification, are increasingly being utilized to control and direct stem cell differentiation, in the development of novel stem cell-based therapy for effective repair and regeneration of injured Tendons.

  • Col V siRNA Engineered Tenocytes for Tendon Tissue Engineering
    PloS one, 2011
    Co-Authors: Guo Rong Zhang, Xiaohui Zou, Xing Hui Song, Lin-lin Wang, Hongwei Ouyang
    Abstract:

    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.

  • Efficacy of hESC-MSCs in knitted silk-collagen scaffold for Tendon Tissue Engineering and their roles.
    Biomaterials, 2010
    Co-Authors: Jialin Chen, Zi Yin, Xiao Chen, Xiaohui Zou, Wei Liang Shen, Boon Chin Heng, Hongwei Ouyang
    Abstract:

    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.

Dianne Little - One of the best experts on this subject based on the ideXlab platform.

  • Meltblown Polymer Fabrics as Candidate Scaffolds for Rotator Cuff Tendon Tissue Engineering.
    Tissue engineering. Part A, 2017
    Co-Authors: Thomas Lee Jenkins, Sean Meehan, Behnam Pourdeyhimi, Dianne Little
    Abstract:

    Various biomaterial technologies are promising for Tissue Engineering, including electrospinning, but commercial scale-up of throughput is difficult. The goal of the study was to evaluate meltblown fabrics as candidate scaffolds for rotator cuff Tendon Tissue Engineering. Meltblown poly(lactic acid) fabrics were produced with several polymer crystallinities and airflow velocities [500(low), 900(medium) or 1400(high) m3air/h/m fabric]. Fiber diameter, alignment, and baseline bidirectional tensile mechanical properties were evaluated. Attachment and spreading of human adipose-derived stem cells (hASCs) were evaluated over 3 days immediately following seeding. After initial screening, the fabric with the greatest Young's modulus and yield stress was selected for 28-day in vitro culture and for evaluation of Tendon-like extracellular matrix production and development of mechanical properties. As expected, airflow velocity of the polymer during meltblowing demonstrated an inverse relationship with fiber diamet...

  • Aligned multilayered electrospun scaffolds for rotator cuff Tendon Tissue Engineering.
    Acta biomaterialia, 2015
    Co-Authors: Steven B. Orr, Abby Chainani, K.j. Hippensteel, Alysha Kishan, N. William Garrigues, David S. Ruch, Farshid Guilak, Christopher L. Gilchrist, Dianne Little
    Abstract:

    The rotator cuff consists of several Tendons and muscles that provide stability and force transmission in the shoulder joint. Whereas most rotator cuff tears are amenable to suture repair, the overall success rate of repair is low, and massive tears are prone to re-tear. Extracellular matrix (ECM) patches are used to augment suture repair, but they have limitations. Tissue-engineered approaches provide a promising solution for massive rotator cuff tears. Previous studies have shown that, compared to nonaligned scaffolds, aligned electrospun polymer scaffolds exhibit greater anisotropy and exert a greater tenogenic effect. Nevertheless, achieving rapid cell infiltration through the full thickness of the scaffold is challenging, and scaling to a translationally relevant size may be difficult. Our goal was to evaluate whether a novel method of alignment, combining a multilayered electrospinning technique with a hybrid of several electrospinning alignment techniques, would permit cell infiltration and collagen deposition through the thickness of poly(e-caprolactone) scaffolds following seeding with human adipose-derived stem cells. Furthermore, we evaluated whether multilayered aligned scaffolds enhanced collagen alignment, Tendon-related gene expression, and mechanical properties compared to multilayered nonaligned scaffolds. Both aligned and nonaligned multilayered scaffolds demonstrated cell infiltration and ECM deposition through the full thickness of the scaffold after only 28 days of culture. Aligned scaffolds displayed significantly increased expression of tenomodulin compared to nonaligned scaffolds and exhibited aligned collagen fibrils throughout the full thickness, the presence of which may account for the increased yield stress and Young’s modulus of cell-seeded aligned scaffolds along the axis of fiber alignment.

  • Multilayered electrospun scaffolds for Tendon Tissue Engineering.
    Tissue engineering. Part A, 2013
    Co-Authors: Abby Chainani, K.j. Hippensteel, Alysha Kishan, N. William Garrigues, David S. Ruch, Farshid Guilak, Dianne Little
    Abstract:

    Full-thickness rotator cuff tears are one of the most common causes of shoulder pain in people over the age of 65. High retear rates and poor functional outcomes are common after surgical repair, and currently available extracellular matrix scaffold patches have limited abilities to enhance new Tendon formation. In this regard, Tissue-engineered scaffolds may provide a means to improve repair of rotator cuff tears. Electrospinning provides a versatile method for creating nanofibrous scaffolds with controlled architectures, but several challenges remain in its application to Tissue Engineering, such as cell infiltration through the full thickness of the scaffold as well as control of cell growth and differentiation. Previous studies have shown that ligament-derived extracellular matrix may enhance differentiation toward a Tendon or ligament phenotype by human adipose stem cells (hASCs). In this study, we investigated the use of Tendon-derived extracellular matrix (TDM)-coated electrospun multilayered scaff...

Xiao Chen - One of the best experts on this subject based on the ideXlab platform.

  • Fos Promotes Early Stage Teno-Lineage Differentiation of Tendon Stem/Progenitor Cells in Tendon.
    Stem cells translational medicine, 2017
    Co-Authors: Jialin Chen, Ludvig J. Backman, Wei Zhang, Zi Yin, Huanhuan Liu, Erchen Zhang, Zeyu Liu, Ting Zhu, Xiao Chen
    Abstract:

    Stem cells have been widely used in Tendon Tissue Engineering. The lack of refined and controlled differentiation strategy hampers the Tendon repair and regeneration. This study aimed to find new e ...

  • Fetal and adult fibroblasts display intrinsic differences in Tendon Tissue Engineering and regeneration
    Scientific reports, 2014
    Co-Authors: Qiaomei Tang, Jialin Chen, Zi Yin, Hongwei Ouyang, Wei Liang Shen, Huanhuan Liu, Zhi Fang, Boon Chin Heng, Xiao Chen
    Abstract:

    Injured adult Tendons do not exhibit optimal healing through a regenerative process, whereas fetal Tendons can heal in a regenerative fashion without scar formation. Hence, we compared FFs (mouse fetal fibroblasts) and AFs (mouse adult fibroblasts) as seed cells for the fabrication of scaffold-free engineered Tendons. Our results demonstrated that FFs had more potential for Tendon Tissue Engineering, as shown by higher levels of Tendon-related gene expression. In the in situ AT injury model, the FFs group also demonstrated much better structural and functional properties after healing, with higher levels of collagen deposition and better microstructure repair. Moreover, fetal fibroblasts could increase the recruitment of fibroblast-like cells and reduce the infiltration of inflammatory cells to the injury site during the regeneration process. Our results suggest that the underlying mechanisms of better regeneration with FFs should be elucidated and be used to enhance adult Tendon healing. This may assist in the development of future strategies to treat Tendon injuries.

  • Efficacy of hESC-MSCs in knitted silk-collagen scaffold for Tendon Tissue Engineering and their roles.
    Biomaterials, 2010
    Co-Authors: Jialin Chen, Zi Yin, Xiao Chen, Xiaohui Zou, Wei Liang Shen, Boon Chin Heng, Hongwei Ouyang
    Abstract:

    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.

  • Stem cells for Tendon Tissue Engineering and regeneration
    Expert opinion on biological therapy, 2010
    Co-Authors: Zi Yin, Jialin Chen, Xiao Chen, Hongwei Ouyang
    Abstract:

    Importance of the field: Tendon injuries are common especially in sports activities, but Tendon is a unique connective Tissue with poor self-repair capability. With advances in stem cell biology, Tissue Engineering is becoming increasingly powerful for Tissue regeneration. Stem cells with capacity of multipotency and self-renewal are an ideal cell source for Tissue Engineering.Areas covered in this review: This review focus on discussing the potential strategies including inductive growth factors, bio-scaffolds, mechanical stimulation, genetic modification and co-culture techniques to direct Tendon-lineage differentiation of stem cells for complete Tendon regeneration. Attempting to use embryonic stem cells as seed cells for Tendon Tissue Engineering have achieved encouraging results. The combination of chemical and physical signals in stem cell microenvironment could be regulated to induce differentiation of the embryonic stem cells into Tendon.What the reader will gain: We summarize fundamental question...

  • Tendon Tissue Engineering with mesenchymal stem cells and biografts: an option for large Tendon defects?
    Frontiers in bioscience (Scholar edition), 2009
    Co-Authors: Xiao Chen, Xiaohui Zou, Guo Li Yin, Hongwei Ouyang
    Abstract:

    Abstract The most important factors in the Tissue Engineering approach to Tissue repair and regeneration are the use of appropriate cells and scaffolds. Mesenchymal stem cells (MSCs) are one of the most promising seed cells, which can be easily derived and have the potential to differentiate into various mesenchymal cell types as well as tenocytes in vitro and in vivo. Biological Tendon grafts are the most common choice in current clinical practice, as they possess physical structure, strength and biocompatibility. We review the latest research findings on MSC-based Tendon Tissue Engineering and recent advances in biological graft research.

Denitsa Docheva - One of the best experts on this subject based on the ideXlab platform.

  • Functionalized thermosensitive hydrogel combined with Tendon stem/progenitor cells as injectable cell delivery carrier for Tendon Tissue Engineering.
    Biomedical materials (Bristol England), 2018
    Co-Authors: Heyong Yin, Zexing Yan, Richard J Bauer, Jiang Peng, Matthias Schieker, Michael Nerlich, Denitsa Docheva
    Abstract:

    Thermosensitive hydrogels have been studied for potential application as promising alternative cell carriers in cell-based regenerative therapies. In this study, a thermosensitive butane diisocyanate (BDI)-collagen hydrogel (BC hydrogel) was designed as an injectable cell delivery carrier of Tendon stem/progenitor cells (TSPCs) for Tendon Tissue Engineering. We functionalized the BDI hydrogel with the addition of 20% (v/v) collagen I gel to obtain the thermosensitive BC hydrogel, which was then seeded with TSPCs derived from human Achilles Tendons. The BC hydrogel compatibility and TSPC behavior and molecular response to the 3D hydrogel were investigated. Collagen (COL) I gel served as a control group. Our findings demonstrated that the BC hydrogel was thermosensitive, and hardened above 25 °C. It supported TSPC survival, proliferation, and metabolic activity with satisfactory dimension stability and biocompatibility, as revealed by gel contraction assay, live/dead staining, DNA quantification, and resazurin metabolic assay. Phalloidin-based visualization of F-actin demonstrated that the TSPCs were stretched within COL I gel with classical spindle cell shapes; similar cell morphologies were also found in the BC hydrogel. The gene expression profile of TSPCs in the BC hydrogel was comparable with that in COL I gel. Moreover, the BC hydrogel supported capillary-like structure formation by human umbilical vein endothelial cells (HUVECs) in the hydrogel matrix. Taken together, these results suggest that the thermosensitive BC hydrogel holds great potential as an injectable cell delivery carrier of TSPCs for Tendon Tissue Engineering.

  • functionalized thermosensitive hydrogel combined with Tendon stem progenitor cells as injectable cell delivery carrier for Tendon Tissue Engineering
    Biomedical Materials, 2018
    Co-Authors: Heyong Yin, Zexing Yan, Richard J Bauer, Jiang Peng, Matthias Schieker, Michael Nerlich, Denitsa Docheva
    Abstract:

    Thermosensitive hydrogels have been studied for potential application as promising alternative cell carriers in cell-based regenerative therapies. In this study, a thermosensitive butane diisocyanate (BDI)-collagen hydrogel (BC hydrogel) was designed as an injectable cell delivery carrier of Tendon stem/progenitor cells (TSPCs) for Tendon Tissue Engineering. We functionalized the BDI hydrogel with the addition of 20% (v/v) collagen I gel to obtain the thermosensitive BC hydrogel, which was then seeded with TSPCs derived from human Achilles Tendons. The BC hydrogel compatibility and TSPC behavior and molecular response to the 3D hydrogel were investigated. Collagen (COL) I gel served as a control group. Our findings demonstrated that the BC hydrogel was thermosensitive, and hardened above 25 °C. It supported TSPC survival, proliferation, and metabolic activity with satisfactory dimension stability and biocompatibility, as revealed by gel contraction assay, live/dead staining, DNA quantification, and resazurin metabolic assay. Phalloidin-based visualization of F-actin demonstrated that the TSPCs were stretched within COL I gel with classical spindle cell shapes; similar cell morphologies were also found in the BC hydrogel. The gene expression profile of TSPCs in the BC hydrogel was comparable with that in COL I gel. Moreover, the BC hydrogel supported capillary-like structure formation by human umbilical vein endothelial cells (HUVECs) in the hydrogel matrix. Taken together, these results suggest that the thermosensitive BC hydrogel holds great potential as an injectable cell delivery carrier of TSPCs for Tendon Tissue Engineering.

Bin Duan - One of the best experts on this subject based on the ideXlab platform.

  • electrospun thymosin beta 4 loaded plga pla nanofiber microfiber hybrid yarns for Tendon Tissue Engineering application
    Materials Science and Engineering: C, 2020
    Co-Authors: Rong Zhou, Fang Zhou, Philipp N. Streubel, Shaojuan Chen, Bin Duan
    Abstract:

    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.

  • Electrospun thymosin Beta-4 loaded PLGA/PLA nanofiber/ microfiber hybrid yarns for Tendon Tissue Engineering application
    Materials science & engineering. C Materials for biological applications, 2019
    Co-Authors: Rong Zhou, Fang Zhou, Philipp N. Streubel, Shaojuan Chen, Bin Duan
    Abstract:

    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.