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Kyriacos A. Athanasiou - One of the best experts on this subject based on the ideXlab platform.
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Considerations for translation of tissue engineered Fibrocartilage from bench to bedside.
Journal of Biomechanical Engineering, 2019Co-Authors: Ryan P. Donahue, Erik A. Gonzalez-leon, Kyriacos A. AthanasiouAbstract:Fibrocartilage is found in the knee meniscus, the temporomandibular joint (TMJ) disc, the pubic symphysis, the annulus fibrosus of intervertebral disc, tendons, and ligaments. These tissues are notoriously difficult to repair due to their avascularity, and limited clinical repair and replacement options exist. Tissue engineering has been proposed as a route to repair and replace Fibrocartilages. Using the knee meniscus and TMJ disc as examples, this review describes how Fibrocartilages can be engineered toward translation to clinical use. Presented are Fibrocartilage anatomy, function, epidemiology, pathology, and current clinical treatments because they inform design criteria for tissue engineered Fibrocartilages. Methods for how native tissues are characterized histomorphologically, biochemically, and mechanically to set gold standards are described. Then, provided is a review of Fibrocartilage-specific tissue engineering strategies, including the selection of cell sources, scaffold or scaffold-free methods, and biochemical and mechanical stimuli. In closing, the Food and Drug Administration paradigm is discussed to inform researchers of both the guidance that exists and the questions that remain to be answered with regard to bringing a tissue engineered Fibrocartilage product to the clinic.
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combined use of chondroitinase abc tgf β1 and collagen crosslinking agent lysyl oxidase to engineer functional neotissues for Fibrocartilage repair
Biomaterials, 2014Co-Authors: Eleftherios Makris, Regina F Macbarb, Nikolaos K Paschos, Kyriacos A. AthanasiouAbstract:Patients suffering from damaged or diseased Fibrocartilages currently have no effective long-term treatment options. Despite their potential, engineered tissues suffer from inferior biomechanical integrity and an inability to integrate in vivo. The present study identifies a treatment regimen (including the biophysical agent chondroitinase-ABC, the biochemical agent TGF-β1, and the collagen crosslinking agent lysyl oxidase) to prime highly cellularized, scaffold-free neoFibrocartilage implants, effecting continued improvement in vivo. We show these agents drive in vitro neoFibrocartilage matrix maturation toward synergistically enhanced Young's modulus and ultimate tensile strength values, which were increased 245% and 186%, respectively, over controls. Furthermore, an in vitro Fibrocartilage defect model found this treatment regimen to significantly increase the integration tensile properties between treated neoFibrocartilage and native tissue. Through translating this technology to an in vivo Fibrocartilage defect model, our results indicate, for the first time, that a pre-treatment can prime neoFibrocartilage for significantly enhanced integration potential in vivo, with interfacial tensile stiffness and strength increasing by 730% and 745%, respectively, compared to integration values achieved in vitro. Our results suggest that specifically targeting collagen assembly and organization is a powerful means to augment overall neotissue mechanics and integration potential toward improved clinical feasibility.
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a chondroitinase abc and tgf β1 treatment regimen for enhancing the mechanical properties of tissue engineered Fibrocartilage
Acta Biomaterialia, 2013Co-Authors: Regina F Macbarb, Eleftherios Makris, Kyriacos A. AthanasiouAbstract:The development of functionally equivalent Fibrocartilage remains elusive despite efforts to engineer tissues such as knee meniscus, intervertebral disc and temporomandibular joint disc. Attempts to engineer these structures often fail to create tissues with mechanical properties on a par with native tissue, resulting in constructs unsuitable for clinical applications. The objective of this study was to engineer a spectrum of biomimetic Fibrocartilages representative of the distinct functional properties found in native tissues. Using the self-assembly process, different co-cultures of meniscus cells and articular chondrocytes were seeded into agarose wells and treated with the catabolic agent chondroitinase-ABC (C-ABC) and the anabolic agent transforming growth factor-β1 (TGF-β1) via a two-factor (cell ratio and bioactive treatment), full factorial study design. Application of both C-ABC and TGF-β1 resulted in a beneficial or positive increase in the collagen content of treated constructs compared to controls. Significant increases in both the collagen density and fiber diameter were also seen with this treatment, increasing these values by 32 and 15%, respectively, over control values. Mechanical testing found the combined bioactive treatment to synergistically increase the Young's modulus and ultimate tensile strength of the engineered Fibrocartilages compared to controls, with values reaching the lower spectrum of those found in native tissues. Together, these data demonstrate that C-ABC and TGF-β1 interact to develop a denser collagen matrix better able to withstand tensile loading. This study highlights a way to optimize the tensile properties of engineered Fibrocartilage using a biochemical and a biophysical agent together to create distinct Fibrocartilages with functional properties mimicking those of native tissue.
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Fibrochondrogenesis of hESCs: Growth Factor Combinations and Cocultures
Stem Cells and Development, 2009Co-Authors: Gwendolyn M. Hoben, Vincent P. Willard, Kyriacos A. AthanasiouAbstract:The successful differentiation of human embryonic stem cells (hESCs) to fibrochondrocyte-like cells and characterization of these differentiated cells is a critical step toward tissue engineering of musculoskeletal Fibrocartilages (e.g., knee meniscus, temporomandibular joint disc, and intervertebral disc). In this study, growth factors and primary cell cocultures were applied to hESC embryoid bodies (EBs) for 3 weeks and evaluated for their effect on the synthesis of critical Fibrocartilage matrix components: glycosaminoglycans (GAG) and collagens (types I, II, and VI). Changes in surface markers (CD105, CD44, SSEA, PDGFRα) after the differentiation treatments were also analyzed. The study was conducted in three phases: (1) examination of growth factors (TGF-β3, BMP-2, BMP-4, BMP-6, PDGF-BB, sonic hedgehog protein); (2) comparison of two cocultures (primary chondrocytes or fibrochondrocytes); and (3) the combination of the most effective growth factor and coculture regimen. TGF-β3 with BMP-4 yielded EBs ...
Lunquan Sun - One of the best experts on this subject based on the ideXlab platform.
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book shaped acellular Fibrocartilage scaffold with cell loading capability and chondrogenic inducibility for tissue engineered Fibrocartilage and bone tendon healing
ACS Applied Materials & Interfaces, 2019Co-Authors: Can Chen, Cheng Zheng, Yong Cao, Fei Liu, Yifu Tang, Yang Chen, Chunfeng D Zhao, Lunquan SunAbstract:Functional Fibrocartilage regeneration is a bottleneck during bone-tendon healing, and the currently available tissue-engineering strategies for Fibrocartilage regeneration are insufficient because of a lack of appropriate scaffold that can load large seeding-cells and induce chondrogenesis of stem cells. The acellular Fibrocartilage scaffold (AFS) contains active growth factors as well as tissue-specific epitopes for cell-matrix interactions, which make it a potential scaffold for tissue-engineered Fibrocartilage. A limitation to this scaffold is that its low porosity inhibits cells loading and infiltration. Here, inspired by book appearance, we sectioned native Fibrocartilage tissue (NFT) into book-shape to improve cells loading and infiltration, and then decellularized with four protocols: (1) 2% SDS for 6-h, (2) 2% SDS for 24-h, (3) 4 SDS for 6-h, (4) 4% SDS for 24-h, followed by nuclease digestion. The optimal protocol was screened with respect to microstructures, DNA residence, native ingredients reservation, and chondrogenic inducibility of the AFS. In vitro studies demonstrated that this screened scaffold is noncytotoxicity and low-immunogenicity, allows adipose-derived stromal cells (ASCs) attachment and proliferation, shows superior chondrogenic inducibility, and stimulates collagen or glycosaminoglycans secretion. The underlying mechanism for this chondrogenic inducibility may be related to hedgehog pathway activating. Additionally, a novel pattern for fabricating tissue-engineered Fibrocartilage was developed to enlarge seeding-cells loading, namely, cell-sheets sandwiched by book-shaped scaffold. In-vivo studies indicate that this screened scaffold alone could induce endogenous cells to satisfactorily regenerate Fibrocartilage at 16-week, as characterized by fibrocartilaginous extracellular matrix (ECM) deposition and good interface integration. Interleaving this book-shaped AFS with autologous ASCs-sheets significantly enhanced its ability to regenerate Fibrocartilage. Cell tracking demonstrated that fibrochondrocytes, osteoblasts, and osteocytes in the healing interface at postoperative 8-week partly originated from the sandwiched ASCs-sheets. On that basis, we propose the use of this book-shaped AFS and cell sheet technique for fabricating tissue-engineered Fibrocartilage to improve bone-tendon healing.
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Book-Shaped Acellular Fibrocartilage Scaffold with Cell-loading Capability and Chondrogenic Inducibility for Tissue-Engineered Fibrocartilage and Bone-Tendon Healing.
ACS Applied Materials & Interfaces, 2019Co-Authors: Can Chen, Cheng Zheng, Yong Cao, Fei Liu, Yifu Tang, Yang Chen, Chunfeng D Zhao, Lunquan SunAbstract:Functional Fibrocartilage regeneration is a bottleneck during bone–tendon healing, and the currently available tissue-engineering strategies for Fibrocartilage regeneration are insufficient because of a lack of appropriate scaffold that can load large seeding-cells and induce chondrogenesis of stem cells. The acellular Fibrocartilage scaffold (AFS) contains active growth factors as well as tissue-specific epitopes for cell-matrix interactions, which make it a potential scaffold for tissue-engineered Fibrocartilage. A limitation to this scaffold is that its low porosity inhibits cells loading and infiltration. Here, inspired by book appearance, we sectioned native Fibrocartilage tissue (NFT) into book-shape to improve cells loading and infiltration, and then decellularized with four protocols: (1) 2% SDS for 6-h, (2) 2% SDS for 24-h, (3) 4 SDS for 6-h, (4) 4% SDS for 24-h, followed by nuclease digestion. The optimal protocol was screened with respect to microstructures, DNA residence, native ingredients re...
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Book-Shaped Acellular Fibrocartilage Scaffold with Cell-loading Capability and Chondrogenic Inducibility for Tissue-Engineered Fibrocartilage and Bone–Tendon Healing
2019Co-Authors: Can Chen, Cheng Zheng, Yong Cao, Fei Liu, Yifu Tang, Yang Chen, Chunfeng Zhao, Lunquan SunAbstract:Functional Fibrocartilage regeneration is a bottleneck during bone–tendon healing, and the currently available tissue-engineering strategies for Fibrocartilage regeneration are insufficient because of a lack of appropriate scaffold that can load large seeding-cells and induce chondrogenesis of stem cells. The acellular Fibrocartilage scaffold (AFS) contains active growth factors as well as tissue-specific epitopes for cell-matrix interactions, which make it a potential scaffold for tissue-engineered Fibrocartilage. A limitation to this scaffold is that its low porosity inhibits cells loading and infiltration. Here, inspired by book appearance, we sectioned native Fibrocartilage tissue (NFT) into book-shape to improve cells loading and infiltration, and then decellularized with four protocols: (1) 2% SDS for 6-h, (2) 2% SDS for 24-h, (3) 4 SDS for 6-h, (4) 4% SDS for 24-h, followed by nuclease digestion. The optimal protocol was screened with respect to microstructures, DNA residence, native ingredients reservation, and chondrogenic inducibility of the AFS. In vitro studies demonstrated that this screened scaffold is noncytotoxicity and low-immunogenicity, allows adipose-derived stromal cells (ASCs) attachment and proliferation, shows superior chondrogenic inducibility, and stimulates collagen or glycosaminoglycans secretion. The underlying mechanism for this chondrogenic inducibility may be related to hedgehog pathway activating. Additionally, a novel pattern for fabricating tissue-engineered Fibrocartilage was developed to enlarge seeding-cells loading, namely, cell-sheets sandwiched by book-shaped scaffold. In-vivo studies indicate that this screened scaffold alone could induce endogenous cells to satisfactorily regenerate Fibrocartilage at 16-week, as characterized by fibrocartilaginous extracellular matrix (ECM) deposition and good interface integration. Interleaving this book-shaped AFS with autologous ASCs-sheets significantly enhanced its ability to regenerate Fibrocartilage. Cell tracking demonstrated that fibrochondrocytes, osteoblasts, and osteocytes in the healing interface at postoperative 8-week partly originated from the sandwiched ASCs-sheets. On that basis, we propose the use of this book-shaped AFS and cell sheet technique for fabricating tissue-engineered Fibrocartilage to improve bone–tendon healing
Michio Inada - One of the best experts on this subject based on the ideXlab platform.
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reconstruction of the triangular Fibrocartilage complex after surgery for treatment of synovial osteochondromatosis of the distal radioulnar joint
Journal of Hand Surgery (European Volume), 1990Co-Authors: Masami Maeda, Michio Inada, Akihiro Fukui, Yuji Inada, Susumu TamaiAbstract:Abstract Synovial osteochondromatosis of the hand is uncommon, except for tenosynovial chondromatosis of the digits. It is even more rare in the wrist joint. A patient with synovial osteochondromatosis of the distal radioulnar joint that involved the triangular Fibrocartilage complex is described. At operation, synovectomy, excision of osteochondral bodies, and removal of the entire triangular Fibrocartilage complex was done. The triangular Fibrocartilage complex was reconstructed using part of the extensor carpi ulnaris tendon. One year after operation, the patient had regained almost full range of motion and is without pain.
Can Chen - One of the best experts on this subject based on the ideXlab platform.
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book shaped acellular Fibrocartilage scaffold with cell loading capability and chondrogenic inducibility for tissue engineered Fibrocartilage and bone tendon healing
ACS Applied Materials & Interfaces, 2019Co-Authors: Can Chen, Cheng Zheng, Yong Cao, Fei Liu, Yifu Tang, Yang Chen, Chunfeng D Zhao, Lunquan SunAbstract:Functional Fibrocartilage regeneration is a bottleneck during bone-tendon healing, and the currently available tissue-engineering strategies for Fibrocartilage regeneration are insufficient because of a lack of appropriate scaffold that can load large seeding-cells and induce chondrogenesis of stem cells. The acellular Fibrocartilage scaffold (AFS) contains active growth factors as well as tissue-specific epitopes for cell-matrix interactions, which make it a potential scaffold for tissue-engineered Fibrocartilage. A limitation to this scaffold is that its low porosity inhibits cells loading and infiltration. Here, inspired by book appearance, we sectioned native Fibrocartilage tissue (NFT) into book-shape to improve cells loading and infiltration, and then decellularized with four protocols: (1) 2% SDS for 6-h, (2) 2% SDS for 24-h, (3) 4 SDS for 6-h, (4) 4% SDS for 24-h, followed by nuclease digestion. The optimal protocol was screened with respect to microstructures, DNA residence, native ingredients reservation, and chondrogenic inducibility of the AFS. In vitro studies demonstrated that this screened scaffold is noncytotoxicity and low-immunogenicity, allows adipose-derived stromal cells (ASCs) attachment and proliferation, shows superior chondrogenic inducibility, and stimulates collagen or glycosaminoglycans secretion. The underlying mechanism for this chondrogenic inducibility may be related to hedgehog pathway activating. Additionally, a novel pattern for fabricating tissue-engineered Fibrocartilage was developed to enlarge seeding-cells loading, namely, cell-sheets sandwiched by book-shaped scaffold. In-vivo studies indicate that this screened scaffold alone could induce endogenous cells to satisfactorily regenerate Fibrocartilage at 16-week, as characterized by fibrocartilaginous extracellular matrix (ECM) deposition and good interface integration. Interleaving this book-shaped AFS with autologous ASCs-sheets significantly enhanced its ability to regenerate Fibrocartilage. Cell tracking demonstrated that fibrochondrocytes, osteoblasts, and osteocytes in the healing interface at postoperative 8-week partly originated from the sandwiched ASCs-sheets. On that basis, we propose the use of this book-shaped AFS and cell sheet technique for fabricating tissue-engineered Fibrocartilage to improve bone-tendon healing.
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Book-Shaped Acellular Fibrocartilage Scaffold with Cell-loading Capability and Chondrogenic Inducibility for Tissue-Engineered Fibrocartilage and Bone-Tendon Healing.
ACS Applied Materials & Interfaces, 2019Co-Authors: Can Chen, Cheng Zheng, Yong Cao, Fei Liu, Yifu Tang, Yang Chen, Chunfeng D Zhao, Lunquan SunAbstract:Functional Fibrocartilage regeneration is a bottleneck during bone–tendon healing, and the currently available tissue-engineering strategies for Fibrocartilage regeneration are insufficient because of a lack of appropriate scaffold that can load large seeding-cells and induce chondrogenesis of stem cells. The acellular Fibrocartilage scaffold (AFS) contains active growth factors as well as tissue-specific epitopes for cell-matrix interactions, which make it a potential scaffold for tissue-engineered Fibrocartilage. A limitation to this scaffold is that its low porosity inhibits cells loading and infiltration. Here, inspired by book appearance, we sectioned native Fibrocartilage tissue (NFT) into book-shape to improve cells loading and infiltration, and then decellularized with four protocols: (1) 2% SDS for 6-h, (2) 2% SDS for 24-h, (3) 4 SDS for 6-h, (4) 4% SDS for 24-h, followed by nuclease digestion. The optimal protocol was screened with respect to microstructures, DNA residence, native ingredients re...
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Book-Shaped Acellular Fibrocartilage Scaffold with Cell-loading Capability and Chondrogenic Inducibility for Tissue-Engineered Fibrocartilage and Bone–Tendon Healing
2019Co-Authors: Can Chen, Cheng Zheng, Yong Cao, Fei Liu, Yifu Tang, Yang Chen, Chunfeng Zhao, Lunquan SunAbstract:Functional Fibrocartilage regeneration is a bottleneck during bone–tendon healing, and the currently available tissue-engineering strategies for Fibrocartilage regeneration are insufficient because of a lack of appropriate scaffold that can load large seeding-cells and induce chondrogenesis of stem cells. The acellular Fibrocartilage scaffold (AFS) contains active growth factors as well as tissue-specific epitopes for cell-matrix interactions, which make it a potential scaffold for tissue-engineered Fibrocartilage. A limitation to this scaffold is that its low porosity inhibits cells loading and infiltration. Here, inspired by book appearance, we sectioned native Fibrocartilage tissue (NFT) into book-shape to improve cells loading and infiltration, and then decellularized with four protocols: (1) 2% SDS for 6-h, (2) 2% SDS for 24-h, (3) 4 SDS for 6-h, (4) 4% SDS for 24-h, followed by nuclease digestion. The optimal protocol was screened with respect to microstructures, DNA residence, native ingredients reservation, and chondrogenic inducibility of the AFS. In vitro studies demonstrated that this screened scaffold is noncytotoxicity and low-immunogenicity, allows adipose-derived stromal cells (ASCs) attachment and proliferation, shows superior chondrogenic inducibility, and stimulates collagen or glycosaminoglycans secretion. The underlying mechanism for this chondrogenic inducibility may be related to hedgehog pathway activating. Additionally, a novel pattern for fabricating tissue-engineered Fibrocartilage was developed to enlarge seeding-cells loading, namely, cell-sheets sandwiched by book-shaped scaffold. In-vivo studies indicate that this screened scaffold alone could induce endogenous cells to satisfactorily regenerate Fibrocartilage at 16-week, as characterized by fibrocartilaginous extracellular matrix (ECM) deposition and good interface integration. Interleaving this book-shaped AFS with autologous ASCs-sheets significantly enhanced its ability to regenerate Fibrocartilage. Cell tracking demonstrated that fibrochondrocytes, osteoblasts, and osteocytes in the healing interface at postoperative 8-week partly originated from the sandwiched ASCs-sheets. On that basis, we propose the use of this book-shaped AFS and cell sheet technique for fabricating tissue-engineered Fibrocartilage to improve bone–tendon healing
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SR-FTIR as a tool for quantitative mapping of the content and distribution of extracellular matrix in decellularized book-shape bioscaffolds
BMC, 2018Co-Authors: Yongchun Zhou, Can Chen, Zhu Guo, Shanshan XieAbstract:Abstract Background To evaluate synchrotron radiation-based Fourier transform infrared microspectroscopy (SR-FTIR) as a tool for quantitative mapping of the content and distribution of the extracellular matrix in decellularized Fibrocartilage bioscaffolds, and to provide a new platform for quantitatively characterizing bioscaffolds for tissue engineering. Methods Fibrocartilage was harvested and cut into book-shape bioscaffolds (N = 54), which were then decellularized. The structures and distribution of collagen fibrous and intrinsic ultrastructure in decellularized Fibrocartilage bioscaffolds were evaluated by histological staining and scanning electron microscopy (SEM), respectively. The content of collagen and proteoglycan in the cellularized or decellularized bioscaffolds were also measured by SR-FTIR and biochemical assay. Results Book-shape Fibrocartilage decellularized bioscaffolds were successfully obtained. Histological examination revealed that the structure of extracellular matrix endured during decellularization. Histology and DNA quantification analysis confirmed substantial removal of cells during decellularization. SEM demonstrated that intrinsic ultrastructure of the Fibrocartilage bioscaffold was also well preserved. SR-FTIR quantitative analysis confirmed that decellularization had a significant effect on the content and distribution of collagen and proteoglycan in Fibrocartilage bioscaffolds, these results are confirmed with the biochemical assay results. Conclusion SR-FTIR imaging can capture the histological morphology of decellularized bioscaffolds. Moreover, it can be used for quantitative mapping of the content and distribution of collagen in the bioscaffolds
Brian D Adams - One of the best experts on this subject based on the ideXlab platform.
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Triangular Fibrocartilage injury : A laboratory model
The Journal of Hand Surgery, 1996Co-Authors: Brian D Adams, John E. Samani, Kathy A. HolleyAbstract:A potential injury mechanism for triangular Fibrocartilage tears and ulnar styloid fractures was investigated in cadaver specimens. The distal radioulnar joint was distracted to failure, thus applying a tensile force to the triangular Fibrocartilage. During distraction, strains in the triangular Fibrocartilage and the anatomic site of disruption were recorded with an image analysis system. Complete avulsion of the triangular Fibrocartilage from the ulnar head occurred in 7 of 10 specimens. No ulnar styloid fractures occurred. Although strains were high in the radial portion of the disk (28%), no tears occurred in the substance of the disk or at its attachment to the radius. These findings suggest that distal radioulnar joint distraction can cause avulsion of the triangular Fibrocartilage. However, ulnar styloid fractures and tears within the disk are more likely caused by injury mechanisms that include shear or compressive forces. Since complete avulsions of the triangular Fibrocartilage occurred without a fracture, the absence of a fracture does not rule out a destabilizing injury to the distal radioulnar joint.
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partial excision of the triangular Fibrocartilage complex articular disk a biomechanical study
Journal of Hand Surgery (European Volume), 1993Co-Authors: Brian D AdamsAbstract:Abstract A cadaver study was performed to evaluate the effects of partial and complete excisions of the articular disk of the triangular Fibrocartilage complex on the kinematics of the distal radioulnar joint and the structural integrity of the triangular Fibrocartilage. An excision that did not violate the peripheral 2 mm of the disk and that comprised less than two thirds of the disk area resulted in no significant kinematic or structural changes, but larger excisions produced measurable changes. These results provide further support for limited excision of central triangular Fibrocartilage complex tears.