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Laurie R Goodrich - One of the best experts on this subject based on the ideXlab platform.
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Equine Models for the Investigation of Mesenchymal Stem Cell Therapies in Orthopaedic Disease
Operative Techniques in Sports Medicine, 2017Co-Authors: Aimee C. Colbath, David D. Frisbie, Steven W. Dow, John D. Kisiday, C. Wayne Mcilwraith, Laurie R GoodrichAbstract:Mesenchymal stem cells (MSCs) have emerged as a promising treatment for orthopaedic disease. Well-established equine models of posttraumatic osteoarthritis, focal Cartilage Healing, and tendonitis provide a platform for testing safety and efficacy of biologic therapies such as MSCs in a species with naturally occurring disease. Horses routinely experience similar conditions that mirror human musculoskeletal injury, including osteoarthritis, meniscal injuries, and Achilles tendinopathy, which provide relevant clinical models for therapeutic interventions. The use of MSCs in equine models of osteoarthritis and focal Cartilage Healing has yielded encouraging results. When MSCs have been used in equine models of tendonitis or tendonosis, most clinical and experimental studies have been consistently positive. Currently, the relationship among MSC lifespan, persistence within the injured site, administration methods, and treatment efficacy remains unclear, resulting in widespread interest in cell tracking. We conclude that equine models of musculoskeletal disease can provide important preclinical insights into the likely efficacy and mechanisms of activity of MSCs for the treatment of human orthopaedic injuries.
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Adeno-associated virus gene therapy vector scAAVIGF-I for transduction of equine articular chondrocytes and RNA-seq analysis.
Osteoarthritis and cartilage, 2015Co-Authors: D.d. Hemphill, C. W. Mcilwraith, R.a. Slayden, Richard J. Samulski, Laurie R GoodrichAbstract:Summary Objective IGF-I is one of several anabolic factors being investigated for the treatment of osteoarthritis (OA). Due to the short biological half-life, extended administration is required for more robust Cartilage Healing. Here we create a self-complimentary adeno-associated virus (AAV) gene therapy vector utilizing the transgene for IGF-I. Design Various biochemical assays were performed to investigate the cellular response to scAAVIGF-I treatment vs an scAAVGFP positive transduction control and a negative for transduction control culture. RNA-sequencing analysis was also performed to establish a differential regulation profile of scAAVIGF-I transduced chondrocytes. Results Biochemical analyses indicated an average media IGF-I concentration of 608 ng/ml in the scAAVIGF-I transduced chondrocytes. This increase in IGF-I led to increased expression of collagen type II and aggrecan and increased protein concentrations of cellular collagen type II and media glycosaminoglycan vs both controls. RNA-seq revealed a global regulatory pattern consisting of 113 differentially regulated GO categories including those for chondrocyte and Cartilage development and regulation of apoptosis. Conclusions This research substantiates that scAAVIGF-I gene therapy vector increased production of IGF-I to clinically relevant levels with a biological response by chondrocytes conducive to increased Cartilage Healing. The RNA-seq further established a set of differentially expressed genes and gene ontologies induced by the scAAVIGF-I vector while controlling for AAV infection. This dataset provides a static representation of the cellular transcriptome that, while only consisting of one time point, will allow for further gene expression analyses to compare additional Cartilage Healing therapeutics or a transient cellular response.
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genetic modification of chondrocytes with insulin like growth factor 1 enhances Cartilage Healing in an equine model
Journal of Bone and Joint Surgery-british Volume, 2007Co-Authors: Laurie R Goodrich, Chisa Hidaka, Paul D Robbins, Christopher H Evans, Alan J NixonAbstract:Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro . The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on Cartilage Healing in an equine femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of a single 15 mm Cartilage defect in each femoropatellar joint. One joint received 2 × 107 AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 107 naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated. Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months. Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, Cartilage Healing in the equine model. The equine model of Cartilage Healing closely resembles human clinical Cartilage repair. The results of this study suggest that Cartilage Healing can be enhanced through genetic modification of chondrocytes prior to transplantation.
Alan J Nixon - One of the best experts on this subject based on the ideXlab platform.
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matrix induced autologous chondrocyte implantation maci using a cell seeded collagen membrane improves Cartilage Healing in the equine model
Journal of Bone and Joint Surgery American Volume, 2017Co-Authors: Alan J Nixon, Michael S Scimeca, N Moran, Laila Begum, Holly D Sparks, Sean P Mcdonough, Gloria MatthewsAbstract:Background:Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has i
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a chondrocyte infiltrated collagen type i iii membrane maci implant improves Cartilage Healing in the equine patellofemoral joint model
Osteoarthritis and Cartilage, 2015Co-Authors: Alan J Nixon, E Rickey, T Butler, Michael S Scimeca, N Moran, Gloria MatthewsAbstract:Summary Autologous chondrocyte implantation (ACI) has improved outcome in long-term studies of joint repair in man. However, ACI requires sutured periosteal flaps to secure the cells, which precludes minimally-invasive implantation, and introduces complications with arthrofibrosis and graft hypertrophy. This study evaluated ACI on a collagen type I/III scaffold (matrix-induced autologous chondrocyte implantation; MACI ® ) in critical sized defects in the equine model. Methods Chondrocytes were isolated from horses, expanded and seeded onto a collagen I/III membrane (ACI-Maix™) and implanted into one of two 15-mm defects in the femoral trochlear ridge of six horses. Control defects remained empty as ungrafted debrided defects. The animals were examined daily, scored by second look arthroscopy at 12 weeks, and necropsy examination 6 months after implantation. Reaction to the implant was determined by lameness, and synovial fluid constituents and synovial membrane histology. Cartilage Healing was assessed by arthroscopic scores, gross assessment, repair tissue histology and immunohistochemistry, Cartilage glycosaminoglycan (GAG) and DNA assay, and mechanical testing. Results MACI ® implanted defects had improved arthroscopic second-look, gross Healing, and composite histologic scores, compared to spontaneously Healing empty defects. Cartilage GAG and DNA content in the defects repaired by MACI implant were significantly improved compared to controls. Mechanical properties were improved but remained inferior to normal Cartilage. There was minimal evidence of reaction to the implant in the synovial fluid, synovial membrane, subchondral bone, or Cartilage. Conclusions The MACI ® implant appeared to improve Cartilage Healing in a critical sized defect in the equine model evaluated over 6 months.
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autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full and partial thickness Cartilage defects in an equine model
Journal of Orthopaedic Research, 2011Co-Authors: Alan J Nixon, Laila Begum, Hussni O Mohammed, Barbara A Huibregtse, Michael Ocallaghan, Gloria MatthewsAbstract:Autologous chondrocyte implantation (ACI) has been used clinically for over 15 years and yet definitive evidence of chondrocyte persistence and direct impact on Cartilage repair in full-thickness lesions is scant and no data are available on ACI in partial-thickness defects in any animal model. This study assessed the effect of chondrocytes secured using periosteal overlay in partial- and full-thickness Cartilage defects in the equine model. Paired Cartilage defects 15 mm in diameter were made in the patellofemoral joint of 16 horse and repaired with ACI or periosteal flap alone. Response was assessed at 8 weeks by clinical, microradiographic, and histologic appearance, and by collagen type II immunohistochemistry, and proteoglycan and DNA quantification. ACI improved histologic scores in partial- and full-thickness Cartilage defects, including defect filling, attachment to the underlying subchondral bone, and presence of residual chondrocyte accumulations. For partial-thickness defects chondrocyte predominance, collagen type II content, and toluidine stained matrix were enhanced, and attachment to the surrounding Cartilage improved. DNA and PG content of grafted partial-thickness defects was improved by chondrocyte implantation. Periosteal patches alone did not induce Cartilage repair. This study indicated implantation of chondrocytes to Cartilage defects improved Healing with a combination of persisting chondrocyte regions, enhanced collagen type II formation, and better overall Cartilage Healing scores. Use of ACI in the more challenging partial-thickness defects also improved histologic indices and biochemical content. The equine model of Cartilage Healing closely resembles Cartilage repair in man, and results of this study confirm cell persistence and improved early Cartilage Healing events after ACI. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1121–1130, 2011
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Autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full‐ and partial‐thickness Cartilage defects in an equine model
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2011Co-Authors: Alan J Nixon, Laila Begum, Hussni O Mohammed, Barbara A Huibregtse, Michael O'callaghan, Gloria MatthewsAbstract:Autologous chondrocyte implantation (ACI) has been used clinically for over 15 years and yet definitive evidence of chondrocyte persistence and direct impact on Cartilage repair in full-thickness lesions is scant and no data are available on ACI in partial-thickness defects in any animal model. This study assessed the effect of chondrocytes secured using periosteal overlay in partial- and full-thickness Cartilage defects in the equine model. Paired Cartilage defects 15 mm in diameter were made in the patellofemoral joint of 16 horse and repaired with ACI or periosteal flap alone. Response was assessed at 8 weeks by clinical, microradiographic, and histologic appearance, and by collagen type II immunohistochemistry, and proteoglycan and DNA quantification. ACI improved histologic scores in partial- and full-thickness Cartilage defects, including defect filling, attachment to the underlying subchondral bone, and presence of residual chondrocyte accumulations. For partial-thickness defects chondrocyte predominance, collagen type II content, and toluidine stained matrix were enhanced, and attachment to the surrounding Cartilage improved. DNA and PG content of grafted partial-thickness defects was improved by chondrocyte implantation. Periosteal patches alone did not induce Cartilage repair. This study indicated implantation of chondrocytes to Cartilage defects improved Healing with a combination of persisting chondrocyte regions, enhanced collagen type II formation, and better overall Cartilage Healing scores. Use of ACI in the more challenging partial-thickness defects also improved histologic indices and biochemical content. The equine model of Cartilage Healing closely resembles Cartilage repair in man, and results of this study confirm cell persistence and improved early Cartilage Healing events after ACI. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1121–1130, 2011
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genetic modification of chondrocytes with insulin like growth factor 1 enhances Cartilage Healing in an equine model
Journal of Bone and Joint Surgery-british Volume, 2007Co-Authors: Laurie R Goodrich, Chisa Hidaka, Paul D Robbins, Christopher H Evans, Alan J NixonAbstract:Gene therapy with insulin-like growth factor-1 (IGF-1) increases matrix production and enhances chondrocyte proliferation and survival in vitro . The purpose of this study was to determine whether arthroscopically-grafted chondrocytes genetically modified by an adenovirus vector encoding equine IGF-1 (AdIGF-1) would have a beneficial effect on Cartilage Healing in an equine femoropatellar joint model. A total of 16 horses underwent arthroscopic repair of a single 15 mm Cartilage defect in each femoropatellar joint. One joint received 2 × 107 AdIGF-1 modified chondrocytes and the contralateral joint received 2 × 107 naive (unmodified) chondrocytes. Repairs were analysed at four weeks, nine weeks and eight months after surgery. Morphological and histological appearance, IGF-1 and collagen type II gene expression (polymerase chain reaction, in situ hybridisation and immunohistochemistry), collagen type II content (cyanogen bromide and sodium dodecyl sulphate-polyacrylamide gel electrophoresis), proteoglycan content (dimethylmethylene blue assay), and gene expression for collagen type I, matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, aggrecanase-1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-3 were evaluated. Genetic modification of chondrocytes significantly increased IGF-1 mRNA and ligand production in repair tissue for up to nine weeks following transplantation. The gross and histological appearance of IGF-1 modified repair tissue was improved over control defects. Gross filling of defects was significantly improved at four weeks, and a more hyaline-like tissue covered the lesions at eight months. Histological outcome at four and nine weeks post-transplantation revealed greater tissue filling of defects transplanted with genetically modified chondrocytes, whereas repair tissue in control defects was thin and irregular and more fibrous. Collagen type II expression in IGF-1 gene-transduced defects was increased 100-fold at four weeks and correlated with increased collagen type II immunoreaction up to eight months. Genetic modification of chondrocytes with AdIGF-1 prior to transplantation improved early (four to nine weeks), and to a lesser degree long-term, Cartilage Healing in the equine model. The equine model of Cartilage Healing closely resembles human clinical Cartilage repair. The results of this study suggest that Cartilage Healing can be enhanced through genetic modification of chondrocytes prior to transplantation.
Gloria Matthews - One of the best experts on this subject based on the ideXlab platform.
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matrix induced autologous chondrocyte implantation maci using a cell seeded collagen membrane improves Cartilage Healing in the equine model
Journal of Bone and Joint Surgery American Volume, 2017Co-Authors: Alan J Nixon, Michael S Scimeca, N Moran, Laila Begum, Holly D Sparks, Sean P Mcdonough, Gloria MatthewsAbstract:Background:Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has i
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a chondrocyte infiltrated collagen type i iii membrane maci implant improves Cartilage Healing in the equine patellofemoral joint model
Osteoarthritis and Cartilage, 2015Co-Authors: Alan J Nixon, E Rickey, T Butler, Michael S Scimeca, N Moran, Gloria MatthewsAbstract:Summary Autologous chondrocyte implantation (ACI) has improved outcome in long-term studies of joint repair in man. However, ACI requires sutured periosteal flaps to secure the cells, which precludes minimally-invasive implantation, and introduces complications with arthrofibrosis and graft hypertrophy. This study evaluated ACI on a collagen type I/III scaffold (matrix-induced autologous chondrocyte implantation; MACI ® ) in critical sized defects in the equine model. Methods Chondrocytes were isolated from horses, expanded and seeded onto a collagen I/III membrane (ACI-Maix™) and implanted into one of two 15-mm defects in the femoral trochlear ridge of six horses. Control defects remained empty as ungrafted debrided defects. The animals were examined daily, scored by second look arthroscopy at 12 weeks, and necropsy examination 6 months after implantation. Reaction to the implant was determined by lameness, and synovial fluid constituents and synovial membrane histology. Cartilage Healing was assessed by arthroscopic scores, gross assessment, repair tissue histology and immunohistochemistry, Cartilage glycosaminoglycan (GAG) and DNA assay, and mechanical testing. Results MACI ® implanted defects had improved arthroscopic second-look, gross Healing, and composite histologic scores, compared to spontaneously Healing empty defects. Cartilage GAG and DNA content in the defects repaired by MACI implant were significantly improved compared to controls. Mechanical properties were improved but remained inferior to normal Cartilage. There was minimal evidence of reaction to the implant in the synovial fluid, synovial membrane, subchondral bone, or Cartilage. Conclusions The MACI ® implant appeared to improve Cartilage Healing in a critical sized defect in the equine model evaluated over 6 months.
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autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full and partial thickness Cartilage defects in an equine model
Journal of Orthopaedic Research, 2011Co-Authors: Alan J Nixon, Laila Begum, Hussni O Mohammed, Barbara A Huibregtse, Michael Ocallaghan, Gloria MatthewsAbstract:Autologous chondrocyte implantation (ACI) has been used clinically for over 15 years and yet definitive evidence of chondrocyte persistence and direct impact on Cartilage repair in full-thickness lesions is scant and no data are available on ACI in partial-thickness defects in any animal model. This study assessed the effect of chondrocytes secured using periosteal overlay in partial- and full-thickness Cartilage defects in the equine model. Paired Cartilage defects 15 mm in diameter were made in the patellofemoral joint of 16 horse and repaired with ACI or periosteal flap alone. Response was assessed at 8 weeks by clinical, microradiographic, and histologic appearance, and by collagen type II immunohistochemistry, and proteoglycan and DNA quantification. ACI improved histologic scores in partial- and full-thickness Cartilage defects, including defect filling, attachment to the underlying subchondral bone, and presence of residual chondrocyte accumulations. For partial-thickness defects chondrocyte predominance, collagen type II content, and toluidine stained matrix were enhanced, and attachment to the surrounding Cartilage improved. DNA and PG content of grafted partial-thickness defects was improved by chondrocyte implantation. Periosteal patches alone did not induce Cartilage repair. This study indicated implantation of chondrocytes to Cartilage defects improved Healing with a combination of persisting chondrocyte regions, enhanced collagen type II formation, and better overall Cartilage Healing scores. Use of ACI in the more challenging partial-thickness defects also improved histologic indices and biochemical content. The equine model of Cartilage Healing closely resembles Cartilage repair in man, and results of this study confirm cell persistence and improved early Cartilage Healing events after ACI. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1121–1130, 2011
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Autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full‐ and partial‐thickness Cartilage defects in an equine model
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2011Co-Authors: Alan J Nixon, Laila Begum, Hussni O Mohammed, Barbara A Huibregtse, Michael O'callaghan, Gloria MatthewsAbstract:Autologous chondrocyte implantation (ACI) has been used clinically for over 15 years and yet definitive evidence of chondrocyte persistence and direct impact on Cartilage repair in full-thickness lesions is scant and no data are available on ACI in partial-thickness defects in any animal model. This study assessed the effect of chondrocytes secured using periosteal overlay in partial- and full-thickness Cartilage defects in the equine model. Paired Cartilage defects 15 mm in diameter were made in the patellofemoral joint of 16 horse and repaired with ACI or periosteal flap alone. Response was assessed at 8 weeks by clinical, microradiographic, and histologic appearance, and by collagen type II immunohistochemistry, and proteoglycan and DNA quantification. ACI improved histologic scores in partial- and full-thickness Cartilage defects, including defect filling, attachment to the underlying subchondral bone, and presence of residual chondrocyte accumulations. For partial-thickness defects chondrocyte predominance, collagen type II content, and toluidine stained matrix were enhanced, and attachment to the surrounding Cartilage improved. DNA and PG content of grafted partial-thickness defects was improved by chondrocyte implantation. Periosteal patches alone did not induce Cartilage repair. This study indicated implantation of chondrocytes to Cartilage defects improved Healing with a combination of persisting chondrocyte regions, enhanced collagen type II formation, and better overall Cartilage Healing scores. Use of ACI in the more challenging partial-thickness defects also improved histologic indices and biochemical content. The equine model of Cartilage Healing closely resembles Cartilage repair in man, and results of this study confirm cell persistence and improved early Cartilage Healing events after ACI. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1121–1130, 2011
M. Van Griensven - One of the best experts on this subject based on the ideXlab platform.
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State of the art and future perspectives of articular Cartilage regeneration: a focus on adipose‐derived stem cells and platelet‐derived products
Journal of tissue engineering and regenerative medicine, 2011Co-Authors: F. Hildner, Christian Albrecht, Christian Gabriel, H. Redl, M. Van GriensvenAbstract:Trauma, malposition and age-related degeneration of articular Cartilage often result in severe lesions that do not heal spontaneously. Many efforts over the last centuries have been undertaken to support Cartilage Healing, with approaches ranging from symptomatic treatment to structural Cartilage regeneration. Microfracture and matrix-associated autologous chondrocyte transplantation (MACT) can be regarded as one of the most effective techniques available today to treat traumatic Cartilage defects. Research is focused on the development of new biomaterials, which are intended to provide optimized physical and biochemical conditions for cell proliferation and Cartilage synthesis. New attempts have also been undertaken to replace chondrocytes with cells that are more easily available and cause less donor site morbidity, e.g. adipose derived stem cells (ASC). The number of in vitro studies on adult stem cells has rapidly increased during the last decade, indicating that many variables have yet to be optimized to direct stem cells towards the desired lineage. The present review gives an overview of the difficulties of Cartilage repair and current Cartilage repair techniques. Moreover, it reviews new fields of Cartilage tissue engineering, including stem cells, co-cultures and platelet-rich plasma (PRP).
Michael Sittinger - One of the best experts on this subject based on the ideXlab platform.
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Engineered cells and Cartilage Healing
Arthritis Research & Therapy, 2001Co-Authors: Thomas Häupl, Christian Kaps, G Gross, G.-r. Burmester, Michael SittingerAbstract:In chronic joint diseases, inflammation causes an imbalance in Cartilage matrix turnover shifting towards degradation. This process may be promoted by destructive invasion of synovial tissue into Cartilage as well as a switch in chondrocyte physiology. Furthermore, we could demonstrate a decrease in the expression of morphogenic factors, which are possibly supporting homeostasis and are probably released by the synovium in its function as Cartilage nursing tissue. Leading to progressive degradation and loss of the cartilaginous joint surface, chronic joint diseases eventually depend on replacement therapies. In recent years, methods for biological reconstruction of the articular surfaces with engineered Cartilage transplants evolved as an alternative to the established therapy of endoprosthetic arthroplasty. The basic principle of the various strategies is the delivery and integration of functionally active autologous chondrocytes or mesenchymal precursor cells within an appropriate carrier system further supported by differentiation promoting factors into the original anatomic site to restore tissue architecture and function. Using in vitro preformed implants appears to be particularly promising. This Cartilage engineering is usually based on application of biocompatible and resorbable embedding substances and/or scaffold materials. Results from gene expression analysis clearly favour three-dimensional instead of monolayer chondrocyte cultivation to enhance Cartilage matrix production in vitro. Implants of such constructs in the cartilaginous environment of the joint in rabbits or horses were found to produce Cartilage typic morphological patterns and matrix synthesis. Heterotopic implantation for example subcutaneously into immunocompromized nude mice may induce unspecific fibroblastoid invasion and implant destruction. Encapsulation experiments prevented this process of infiltration, leading to enhanced matrix production and Cartilage formation. As an alternative and avoiding artificial barriers, tissue maturation and stabilization may be supported by morphogenetic factors, which are representatives of the TGF-β family and key molecules in Cartilage and joint formation during development. Clonally expanded bone morphogentic protein (BMP)-7 transgenic primary chondrocytes demonstrated a qualitative switch in collagen expression from type I towards type II when cultured in alginate beads. Other markers of chondrocyte dedifferentiation were down-regulated also. Implantation subcutaneaously into nude mice revealed almost complete exclusion of host fibroblasts from the engineered Cartilage accompanied by improved implant maturation. Thus, the present results demonstrate that current artificial Cartilage transplants are already feasible for joint Cartilage repair. Nevertheless, treatment of severe joint defects faces specific problems, which are continuously addressed in ongoing studies: the fixation and integration of engineered Cartilage in joints; the transplant protection against chronic inflammatory degradation; and the required enormous mechanical stability. These challenges are particularly addressed by the current developments of composite grafts consisting of bone and Cartilage components for reconstruction of the subchondral bone. Furthermore, controlled use of morphogenetic growth factors will unfold great potential to stabilize transplants, promote regeneration and may also allow guided tissue repair starting from mesenchymal precursors or stem cells.