Cartilage Defects (cartilage + defect)

Distribution by Scientific Domains

Kinds of Cartilage Defects

  • articular cartilage defect
  • full-thickness cartilage defect


  • Selected Abstracts


    A Cell-Free Collagen Type I Device for the Treatment of Focal Cartilage Defects

    ARTIFICIAL ORGANS, Issue 1 2010
    Karsten Gavenis
    Abstract The purpose of this study was to evaluate the potential value of a cell-free collagen type I gel plug for the treatment of focal cartilage defects. Cellular migration and proliferation was addressed in vitro, and the formation of repair tissue in a nude mouse-based defect model. A cell-free plug made of collagen type I was placed in the center of an incubation plate. Surrounding space was filled with a collagen type I gel (Arthro Kinetics, Esslingen, Germany) seeded with 2 × 105 human articular chondrocytes/mL gel. After cultivation for up to 6 weeks in vitro, samples were subject to histological and immunohistochemical staining and gene expression analysis. Subsequently, chondral defects of human osteochondral blocks were treated with the plug, and specimens were cultivated subcutaneously in nude mice for 6 weeks. The repair tissue was evaluated macroscopically, and collagen type II production was investigated immunohistochemically. In vitro, morphology of immigrated cells did not show any differences, as did collagen type II gene expression. After 4 weeks, the plug was homogeneously inhabited. After 6 weeks of cultivation in nude mice, collagen gel plug treatment led to a macroscopically excellent repair tissue. Histological staining revealed a tight bonding, and the collagen gel plug started to be remodeled. We conclude that the novel collagen gel plug device offers an environment favorable for the migration of articular chondrocytes and leads to a good-quality repair tissue in the nude mouse model. The arthroscopic transplantation of a collagen gel plug may be one option in the treatment of focal cartilage defects. [source]


    Repair of porcine articular cartilage defect with a biphasic osteochondral composite,

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2007
    Ching-Chuan Jiang
    Abstract Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with ,-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress,relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1277,1290, 2007 [source]


    Repair of porcine articular cartilage defect with autologous chondrocyte transplantation

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2005
    Hongsen Chiang
    Abstract Articular cartilage is known to have poor healing capacity after injury. Autologous chondral grafting remains the mainstay to treat well-defined, full-thickness, symptomatic cartilage defects. We demonstrated the utilization of gelatin microbeads to deliver autologous chondrocytes for in vivo cartilage generation. Chondrocytes were harvested from the left forelimbs of 12 Lee-Sung pigs. The cells were expanded in monolayer culture and then seeded onto gelatin microbeads or left in monolayer. Shortly before implantation, the cell-laden beads were mixed with collagen type I gel, while the cells in monolayer culture were collected and re-suspended in culture medium. Full-thickness cartilage defects were surgically created in the weight-bearing surface of the femoral condyles of both knees, covered by periosteal patches taken from proximal tibia, and sealed with a porcine fibrin glue. In total, 48 condyles were equally allotted to experimental, control, and null groups that were filled beneath the patch with chondrocyte-laden beads in gel, chondrocytes in plain medium solution, or nothing, respectively. The repair was examined 6 months post-surgery on the basis of macroscopic appearance, histological scores based on the International Cartilage Repair Society Scale, and the proportion of characteristic chondrocytes. Tensile stress-relaxation behavior was determined from uniaxial indentation tests. The experimental group scored higher than the control group in the categories of matrix nature, cell distribution pattern, and absence of mineralization, with similar surface smoothness. Both the experimental and control groups were superior to the null group in the above-mentioned categories. Viable cell populations were equal in all groups, but the proportion of characteristic chondrocytes was highest in the experimental group. Matrix stiffness was ranked as null > native cartilage > control > experimental group. Transplanted autologous chondrocytes survive and could yield hyaline-like cartilage. The application of beads and gel for transplantation helped to retain the transferred cells in situ and maintain a better chondrocyte phenotype. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source]


    Adhesion of perichondrial cells to a polylactic acid scaffold

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2003
    Alexander Giurea
    Abstract The number of chondrogenic cells available locally is an important factor in the repair process for cartilage defects. Previous studies demonstrated that the number of transplanted rabbit perichondrial cells (PC) remaining in a cartilage defect in vivo, after being carried into the site in a polylactic acid (PLA) scaffold, declined markedly within two days. This study examined the ability of in vitro culture of PC/PLA constructs to enhance subsequent biomechanical stability of the cells and the matrix content in an in vitro screening assay. PC/PLA constructs were analyzed after 1 h, 1 and 2 weeks of culture. The biomechanical adherence of PC to the PLA scaffold was tested by subjecting the PC/PLA constructs to a range of flow velocities (0.25,25 mm/s), spanning the range estimated to occur under conditions of construct insertion in vivo. The adhesion of PC to the PLA carrier was increased significantly by 1 and 2 weeks of incubation, with 25 mm/s flow causing a 57% detachment of cells after 1 h of seeding, but only 7% and 16% after 1 and 2 weeks of culture, respectively (p > 0.001). This adherence was associated with marked deposition of glycosaminoglycan and collagen. These findings suggest that pre-incubation of PC-laden PLA scaffolds markedly enhances the stability of the indwelling cells. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]


    A retrospective analysis of two independent prospective cartilage repair studies: autogenous perichondrial grafting versus subchondral drilling 10 years post-surgery

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2002
    Phianne S. J. M. Bouwmeester
    Background: Experimental data indicate that perichondrial grafting to restore articular cartilage defects will result in repair with hyaline-like cartilage. In contrast, debridement and drilling results in repair with fibro-cartilage. In this retrospective study the longterm clinical results of both procedures were compared to evaluate the theoretical benefit of repair with hyaline-like tissue. Methods: From two independent studies patients were selected with a cartilage defect in their knee. The selection was performed using strict inclusion criteria published elsewhere [Bouwmeester et al. Int. Orthop. 21 (1997) 313]. The patients were treated with either a perichondrium transplantation (PT group, n = 14) or with an ,open' debridement and drilling procedure (DD group, n = 11). The results of both procedures after 10,11 years were evaluated using the Hospital for Special Surgery Knee Score (HSSS), X-ray examination, clinical examination and visual analogue scales (VAS) for pain during walking and at rest. Results: Both procedures resulted in a general improvement compared to the situation before the operation. After an average of 10 years in the PT group there were three failures, in the DD group none, success rates were 78% and 100%, respectively. When comparing the successful PT patients with the DD patients, there were no differences in HSSS and VAS data. Both groups showed an equal number of irregular operation surface sites on X-ray (PT 9/11 versus DD 8/10). Conclusions: This study shows that clinically at 10 years follow-up no difference was observed between debridement and drilling and perichondrium transplantation for treatment of an isolated cartilage defect. This raises questions about ongoing research to develop methods in order to improve the results of debridement and drilling as therapy for an isolated cartilage defect in a young patient (, 40 years). © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]


    Enhanced treatment of articular cartilage defect of the knee by intra-articular injection of Bcl-xL-engineered mesenchymal stem cells in rabbit model

    JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 2 2010
    Bin Hu
    Abstract Direct intra-articular injection of mesenchymal stem cells (MSCs) has been proposed as a potential cell therapy for cartilage defects. This cell therapy relies on the survival of the implanted MSCs. However, the arduous local environment may limit cell viability after implantation, which would restrict the cells' regenerative capacity. Thus, it is necessary to reinforce the implanted cells against the unfavourable microenvironment in order to improve the efficacy of cell therapy. We examined whether the transduction of an anti-apoptotic protein, Bcl-xL, into MSCs could prevent cell death and improve the implantation efficiency of MSCs in a rabbit model. Our current findings demonstrate that the group treated with Bcl-xL-engineered MSCs could improve cartilage healing both morphologically and histologically when compared with the controls. These results suggest that intra-articular injection of Bcl-xL-engineered MSCs is a potential non-invasive therapeutic method for effectively treating cartilage defects of the knee. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Gene therapy for cartilage defects

    THE JOURNAL OF GENE MEDICINE, Issue 12 2005
    Magali Cucchiarini
    Abstract Focal defects of articular cartilage are an unsolved problem in clinical orthopaedics. These lesions do not heal spontaneously and no treatment leads to complete and durable cartilage regeneration. Although the concept of gene therapy for cartilage damage appears elegant and straightforward, current research indicates that an adaptation of gene transfer techniques to the problem of a circumscribed cartilage defect is required in order to successfully implement this approach. In particular, the localised delivery into the defect of therapeutic gene constructs is desirable. Current strategies aim at inducing chondrogenic pathways in the repair tissue that fills such defects. These include the stimulation of chondrocyte proliferation, maturation, and matrix synthesis via direct or cell transplantation-mediated approaches. Among the most studied candidates, polypeptide growth factors have shown promise to enhance the structural quality of the repair tissue. A better understanding of the basic scientific aspects of cartilage defect repair, together with the identification of additional molecular targets and the development of improved gene-delivery techniques, may allow a clinical translation of gene therapy for cartilage defects. The first experimental steps provide reason for cautious optimism. Copyright © 2005 John Wiley & Sons, Ltd. [source]


    The influence of sex on the chondrogenic potential of muscle-derived stem cells: Implications for cartilage regeneration and repair

    ARTHRITIS & RHEUMATISM, Issue 12 2008
    Tomoyuki Matsumoto
    Objective To explore possible differences in muscle-derived stem cell (MDSC) chondrogenic differentiation in vitro and articular cartilage regeneration in vivo between murine male MDSCs (M-MDSCs) and female MDSCs (F-MDSCs). Methods Three different populations of M- and F-MDSCs (n = 3 of each sex) obtained via preplate technique, which separates cells based on their variable adhesion characteristics, were compared for their in vitro chondrogenic potential using pellet culture. Cells were assayed with and without retroviral transduction to express bone morphogenetic protein 4 (BMP-4). The influence of both expression of stem cell marker Sca1 and in vitro expansion on the chondrogenic potential of M- and F-MDSCs was also determined. Additionally, BMP-4,transduced M- and F-MDSCs were applied to a full-thickness articular cartilage defect (n = 5 each) on the femur of a nude rat, and the quality of the repaired tissue was evaluated by macroscopic and histologic examination. Results With and without BMP-4 gene transduction, M-MDSCs produced significantly larger pellets with a richer extracellular matrix, compared with F-MDSCs. Sca1 purification influenced the chondrogenic potential of MDSCs, especially M-MDSCs. Long-term culture did not affect the chondrogenic potential of M-MDSCs but did influence F-MDSCs. M-MDSCs repaired articular cartilage defects more effectively than did F-MDSCs at all time points tested, as assessed both macroscopically and histologically. Conclusion Our findings demonstrate that sex influences the chondrogenic differentiation and articular cartilage regeneration potential of MDSCs. Compared with female MDSCs, male MDSCs display more chondrogenic differentiation and better cartilage regeneration potential. [source]


    Formation of cartilage repair tissue in articular cartilage defects pretreated with microfracture and covered with cell-free polymer-based implants,

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2009
    Christoph Erggelet
    Abstract The aim of our study was to evaluate the mid-term outcome of a cell-free polymer-based cartilage repair approach in a sheep cartilage defect model in comparison to microfracture treatment. Cell-free, freeze-dried implants (chondrotissue®) made of a poly-glycolic acid (PGA) scaffold and hyaluronan were immersed in autologous serum and used for covering microfractured full-thickness articular cartilage defects of the sheep (n,=,4). Defects treated with microfracture only served as controls (n,=,4). Six months after implantation, cartilage implants and controls were analyzed by immunohistochemical staining of type II collagen, histological staining of proteoglycans, and histological scoring. Histological analysis showed the formation of a cartilaginous repair tissue rich in proteoglycans. Histological scoring documented significant improvement of repair tissue formation when the defects were covered with the cell-free implant, compared to controls treated with microfracture. Immunohistochemistry showed that the cell-free implant induced cartilaginous repair tissue and type II collagen. Controls treated with microfracture showed marginal formation of a mixed-type repair tissue consisting of cartilaginous tissue and fibro-cartilage. Covering of microfractured defects with the cell-free polymer-based cartilage implant is suggested to be a promising treatment option for cartilage defects and improves the regeneration of articular cartilage. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1353,1360, 2009 [source]


    Repair of porcine articular cartilage defect with a biphasic osteochondral composite,

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 10 2007
    Ching-Chuan Jiang
    Abstract Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with ,-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress,relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1277,1290, 2007 [source]


    Safety of, and biological and functional response to, a novel metallic implant for the management of focal full-thickness cartilage defects: Preliminary assessment in an animal model out to 1 year

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2006
    Carl A. Kirker-Head
    Abstract Focal full-thickness cartilage lesions of the human medial femoral condyle (MFC) can cause pain and functional impairment. Affected middle-aged patients respond unpredictably to existing treatments and knee arthroplasty may be required, prompting risk of revision. This study assesses the safety of, and biological and functional response to, a metallic resurfacing implant which may delay or obviate the need for traditional arthroplasty. The anatomic contour of the surgically exposed MFC of six adult goats was digitally mapped and an 11 mm diameter full-thickness osteochondral defect was created. An anchor-based Co,Cr resurfacing implant, matching the mapped articular contour, was implanted. Each goat's contralateral unoperated femorotibial joint was used as a control. Postoperative outcome was assessed by lameness examination, radiography, arthroscopy, synoviocentesis, necropsy, and histology up to 26 (n,=,3) or 52 (n,=,3) weeks. By postoperative week (POW) 4, goats demonstrated normal range of motion, no joint effusion, and only mild lameness in the operated limb. By POW 26 the animals were sound with only occasional very mild lameness. Arthroscopy at POW 14 revealed moderate synovial inflammation and a chondral membrane extending centrally across the implant surface. Radiographs at POWs 14 to 52 implied implant stability in the operated joints, as well as subchondral bone remodeling and mild exostosis formation in the operated and contralateral unoperated joints of some goats. By POW 26, histology revealed new trabecular bone abutting the implant. At POWs 26 and 52 MFC cartilage was metachromatic and intact in the operated and unoperated femorotibial joints. Proximal tibiae of some operated and unoperated limbs demonstrated limited subchondral bone remodeling and foci of articular cartilage fibrillation and thinning. The chondral membrane crossing the prosthesis possessed a metachromatic matrix containing singular and clustered chondrocytes. Our data imply the safety, biocompatibility, and functionality of the implant. Focal articular damage was documented in the operated joints at POWs 26 and 52, but lesions were much reduced over those previously reported in untreated defects. Expanded animal or preclinical human studies are justified. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source]


    Repair of porcine articular cartilage defect with autologous chondrocyte transplantation

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2005
    Hongsen Chiang
    Abstract Articular cartilage is known to have poor healing capacity after injury. Autologous chondral grafting remains the mainstay to treat well-defined, full-thickness, symptomatic cartilage defects. We demonstrated the utilization of gelatin microbeads to deliver autologous chondrocytes for in vivo cartilage generation. Chondrocytes were harvested from the left forelimbs of 12 Lee-Sung pigs. The cells were expanded in monolayer culture and then seeded onto gelatin microbeads or left in monolayer. Shortly before implantation, the cell-laden beads were mixed with collagen type I gel, while the cells in monolayer culture were collected and re-suspended in culture medium. Full-thickness cartilage defects were surgically created in the weight-bearing surface of the femoral condyles of both knees, covered by periosteal patches taken from proximal tibia, and sealed with a porcine fibrin glue. In total, 48 condyles were equally allotted to experimental, control, and null groups that were filled beneath the patch with chondrocyte-laden beads in gel, chondrocytes in plain medium solution, or nothing, respectively. The repair was examined 6 months post-surgery on the basis of macroscopic appearance, histological scores based on the International Cartilage Repair Society Scale, and the proportion of characteristic chondrocytes. Tensile stress-relaxation behavior was determined from uniaxial indentation tests. The experimental group scored higher than the control group in the categories of matrix nature, cell distribution pattern, and absence of mineralization, with similar surface smoothness. Both the experimental and control groups were superior to the null group in the above-mentioned categories. Viable cell populations were equal in all groups, but the proportion of characteristic chondrocytes was highest in the experimental group. Matrix stiffness was ranked as null > native cartilage > control > experimental group. Transplanted autologous chondrocytes survive and could yield hyaline-like cartilage. The application of beads and gel for transplantation helped to retain the transferred cells in situ and maintain a better chondrocyte phenotype. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source]


    Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2003
    Chisa Hidaka
    Background: Cartilage has a limited capacity to heal. Although chondrocyte transplantation is a useful therapeutic strategy, the repair process can be lengthy. Previously we have shown that over expression of bone morphogenetic protein-7 (BMP-7) in chondrocytes by adenovirus-mediated gene transfer leads to increased matrix synthesis and cartilage-like tissue formation in vitro. In this context we hypothesized that implantation of genetically modified chondrocytes expressing BMP-7 would accelerate the formation of hyaline-like repair tissue in an equine model of cartilage defect repair. Methods: Chondrocytes treated with adenovirus vector encoding BMP-7 (AdBMP-7) or as control, an adenovirus vector encoding an irrelevant gene (Escherichia coli cytosine deaminase, AdCD) were implanted into extensive (15 mm diameter) articular cartilage defects in the patellofemoral joints of 10 horses. Biopsies were performed to evaluate early healing at 4 weeks. At the terminal time point of 8 months, repairs were assessed for morphology, MRI appearance, compressive strength, biochemical composition and persistence of implanted cells. Results: Four weeks after surgery AdBMP-7-treated repairs showed an increased level of BMP-7 expression and accelerated healing, with markedly more hyaline-like morphology than control. Quantitative real-time polymerase chain reaction (PCR) analysis of the repair tissue 8 months after surgery showed that few implanted cells persisted. By this time, the controls had healed similarly to the AdBMP-7-treated defects, and no difference was detected in the morphologic, biochemical or biomechanical properties of the repair tissues from the two treatment groups. Conclusions: Implantation of genetically modified chondrocytes expressing BMP-7 accelerates the appearance of hyaline-like repair tissue in experimental cartilage defects. Clinical relevance: Rehabilitation after cell-based cartilage repair can be prolonged, leading to decreased patient productivity and quality of life. This study shows the feasibility of using genetically modified chondrocytes to accelerate cartilage healing. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]


    Adhesion of perichondrial cells to a polylactic acid scaffold

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2003
    Alexander Giurea
    Abstract The number of chondrogenic cells available locally is an important factor in the repair process for cartilage defects. Previous studies demonstrated that the number of transplanted rabbit perichondrial cells (PC) remaining in a cartilage defect in vivo, after being carried into the site in a polylactic acid (PLA) scaffold, declined markedly within two days. This study examined the ability of in vitro culture of PC/PLA constructs to enhance subsequent biomechanical stability of the cells and the matrix content in an in vitro screening assay. PC/PLA constructs were analyzed after 1 h, 1 and 2 weeks of culture. The biomechanical adherence of PC to the PLA scaffold was tested by subjecting the PC/PLA constructs to a range of flow velocities (0.25,25 mm/s), spanning the range estimated to occur under conditions of construct insertion in vivo. The adhesion of PC to the PLA carrier was increased significantly by 1 and 2 weeks of incubation, with 25 mm/s flow causing a 57% detachment of cells after 1 h of seeding, but only 7% and 16% after 1 and 2 weeks of culture, respectively (p > 0.001). This adherence was associated with marked deposition of glycosaminoglycan and collagen. These findings suggest that pre-incubation of PC-laden PLA scaffolds markedly enhances the stability of the indwelling cells. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]


    Effects of a cultured autologous chondrocyte-seeded type II collagen scaffold on the healing of a chondral defect in a canine model

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2003
    C. R. Lee
    Using a previously established canine model for repair of articular cartilage defects, this study evaluated the 15-week healing of chondral defects (i.e., to the tidemark) implanted with an autologous articular chondrocyte-seeded type II collagen scaffold that had been cultured in vitro for four weeks prior to implantation. The amount and composition of the reparative tissue were compared to results from our prior studies using the same animal model in which the following groups were analyzed: defects implanted with autologous chondrocyte-seeded collagen scaffolds that had been cultured in vitro for approximately 12 h prior to implantation, defects implanted with autologous chondrocytes alone, and untreated defects. Chondrocytes, isolated from articular cartilage harvested from the left knee joint of six adult canines, were expanded in number in monolayer for three weeks, seeded into porous type II collagen scaffolds, cultured for an additional four weeks in vitro and then implanted into chondral defects in the trochlear groove of the right knee joints. The percentages of specific tissue types filling the defects were evaluated histomorphometrically and certain mechanical properties of the repair tissue were determined. The reparative tissue filled 88 ± 6% (mean ± SEM; range 70,100%) of the cross-sectional area of the original defect, with hyaline cartilage accounting for 42 ± 10% (range 7,67%) of defect area. These values were greater than those reported previously for untreated defects and defects implanted with a type II collagen scaffold seeded with autologous chondrocytes within 12 h prior to implantation. Most striking, was the decreased amount of fibrous tissue filling the defects in the current study, 5 ± 5% (range 0,26%) as compared to previous treatments. Despite this improvement, indentation testing of the repair tissue formed in this study revealed that the compressive stiffness of the repair tissue was well below (20-fold lower stiffness) that of native articular cartilage. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]


    A retrospective analysis of two independent prospective cartilage repair studies: autogenous perichondrial grafting versus subchondral drilling 10 years post-surgery

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2002
    Phianne S. J. M. Bouwmeester
    Background: Experimental data indicate that perichondrial grafting to restore articular cartilage defects will result in repair with hyaline-like cartilage. In contrast, debridement and drilling results in repair with fibro-cartilage. In this retrospective study the longterm clinical results of both procedures were compared to evaluate the theoretical benefit of repair with hyaline-like tissue. Methods: From two independent studies patients were selected with a cartilage defect in their knee. The selection was performed using strict inclusion criteria published elsewhere [Bouwmeester et al. Int. Orthop. 21 (1997) 313]. The patients were treated with either a perichondrium transplantation (PT group, n = 14) or with an ,open' debridement and drilling procedure (DD group, n = 11). The results of both procedures after 10,11 years were evaluated using the Hospital for Special Surgery Knee Score (HSSS), X-ray examination, clinical examination and visual analogue scales (VAS) for pain during walking and at rest. Results: Both procedures resulted in a general improvement compared to the situation before the operation. After an average of 10 years in the PT group there were three failures, in the DD group none, success rates were 78% and 100%, respectively. When comparing the successful PT patients with the DD patients, there were no differences in HSSS and VAS data. Both groups showed an equal number of irregular operation surface sites on X-ray (PT 9/11 versus DD 8/10). Conclusions: This study shows that clinically at 10 years follow-up no difference was observed between debridement and drilling and perichondrium transplantation for treatment of an isolated cartilage defect. This raises questions about ongoing research to develop methods in order to improve the results of debridement and drilling as therapy for an isolated cartilage defect in a young patient (, 40 years). © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source]


    Enhanced treatment of articular cartilage defect of the knee by intra-articular injection of Bcl-xL-engineered mesenchymal stem cells in rabbit model

    JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 2 2010
    Bin Hu
    Abstract Direct intra-articular injection of mesenchymal stem cells (MSCs) has been proposed as a potential cell therapy for cartilage defects. This cell therapy relies on the survival of the implanted MSCs. However, the arduous local environment may limit cell viability after implantation, which would restrict the cells' regenerative capacity. Thus, it is necessary to reinforce the implanted cells against the unfavourable microenvironment in order to improve the efficacy of cell therapy. We examined whether the transduction of an anti-apoptotic protein, Bcl-xL, into MSCs could prevent cell death and improve the implantation efficiency of MSCs in a rabbit model. Our current findings demonstrate that the group treated with Bcl-xL-engineered MSCs could improve cartilage healing both morphologically and histologically when compared with the controls. These results suggest that intra-articular injection of Bcl-xL-engineered MSCs is a potential non-invasive therapeutic method for effectively treating cartilage defects of the knee. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Sheep embryonic stem-like cells transplanted in full-thickness cartilage defects

    JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 3 2009
    Maria Dattena
    Abstract Articular cartilage regeneration is limited. Embryonic stem (ES) cell lines provide a source of totipotent cells for regenerating cartilage. Anatomical, biomechanical, physiological and immunological similarities between humans and sheep make this animal an optimal experimental model. This study examines the repair process of articular cartilage in sheep after transplantation of ES-like cells isolated from inner cell masses (ICMs) derived from in vitro -produced (IVP) vitrified embryos. Thirty-five ES-like colonies from 40 IVP embryos, positive for stage-specific embryonic antigens (SSEAs), were pooled in groups of two or three, embedded in fibrin glue and transplanted into osteochondral defects in the medial femoral condyles of 14 ewes. Empty defect (ED) and cell-free glue (G) in the controlateral stifle joint served as controls. The Y gene sequence was used to detect ES-like cells in the repair tissue by in situ hybridization (ISH). Two ewes were euthanized at 1 month post-operatively, three each at 2 and 6 months and four at 12 months. Repairing tissue was examined by biomechanical, macroscopic, histological, immunohistochemical (collagen type II) and ISH assays. Scores of all treatments showed no statistical significant differences among treatment groups at a given time period, although ES-like grafts showed a tendency toward a better healing process. ISH was positive in all ES-like specimens. This study demonstrates that ES-like cells transplanted into cartilage defects stimulate the repair process to promote better organization and tissue bulk. However, the small number of cells applied and the short interval between surgery and euthanasia might have negatively affected the results. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study

    JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 1 2009
    Wan-Ju Li
    Abstract The aim of this study was to evaluate a cell-seeded nanofibrous scaffold for cartilage repair in vivo. We used a biodegradable poly(,-caprolactone) (PCL) nanofibrous scaffold seeded with allogeneic chondrocytes or xenogeneic human mesenchymal stem cells (MSCs), or acellular PCL scaffolds, with no implant as a control to repair iatrogenic, 7 mm full-thickness cartilage defects in a swine model. Six months after implantation, MSC-seeded constructs showed the most complete repair in the defects compared to other groups. Macroscopically, the MSC-seeded constructs regenerated hyaline cartilage-like tissue and restored a smooth cartilage surface, while the chondrocyte-seeded constructs produced mostly fibrocartilage-like tissue with a discontinuous superficial cartilage contour. Incomplete repair containing fibrocartilage or fibrous tissue was found in the acellular constructs and the no-implant control group. Quantitative histological evaluation showed overall higher scores for the chondrocyte- and MSC-seeded constructs than the acellular construct and the no-implant groups. Mechanical testing showed the highest equilibrium compressive stress of 1.5 MPa in the regenerated cartilage produced by the MSC-seeded constructs, compared to 1.2 MPa in the chondrocyte-seeded constructs, 1.0 MPa in the acellular constructs and 0.2 MPa in the no-implant group. No evidence of immune reaction to the allogeneically- and xenogeneically-derived regenerated cartilage was observed, possibly related to the immunosuppressive activities of MSCs, suggesting the feasibility of allogeneic or xenogeneic transplantation of MSCs for cell-based therapy. Taken together, our results showed that biodegradable nanofibrous scaffolds seeded with MSCs effectively repair cartilage defects in vivo, and that the current approach is promising for cartilage repair. Copyright © 2008 John Wiley & Sons, Ltd. [source]


    Nanostructured Materials for Skeletal Repair

    MACROMOLECULAR SYMPOSIA, Issue 1 2010
    Joerg Brandt
    Abstract The treatment of bone and cartilage defects with bioengineered constructs of artificial scaffolds and autogenous cells became the main challenge of contemporary regenerative medicine. Early defect repair may prevent secondary injury. Recent studies could prove that bone and cartilage cells are sensitive to microscale and nanoscale patterns of surface topography and chemical structure. Nanostructured materials provide an environment for tissue regeneration mimicking the physiological range of extracellular matrix. The article reviews several studies substantiating the superiority of nanostructured materials for bone and cartilage repair along with own results on cell attachment. [source]


    Local stimulation of articular cartilage repair by transplantation of encapsulated chondrocytes overexpressing human fibroblast growth factor 2 (FGF-2) in vivo,

    THE JOURNAL OF GENE MEDICINE, Issue 1 2006
    Gunter Kaul
    Abstract Background Defects of articular cartilage are an unsolved problem in orthopaedics. In the present study, we tested the hypothesis that gene transfer of human fibroblast growth factor 2 (FGF-2) via transplantation of encapsulated genetically modified articular chondrocytes stimulates chondrogenesis in cartilage defects in vivo. Methods Lapine articular chondrocytes overexpressing a lacZ or a human FGF-2 gene sequence were encapsulated in alginate and further characterized. The resulting lacZ or FGF-2 spheres were applied to cartilage defects in the knee joints of rabbits. In vivo, cartilage repair was assessed qualitatively and quantitatively at 3 and 14 weeks after implantation. Results In vitro, bioactive FGF-2 was secreted, leading to a significant increase in the cell numbers in FGF-2 spheres. In vivo, FGF-2 continued to be expressed for at least 3 weeks without leading to differences in FGF-2 concentrations in the synovial fluid between treatment groups. Histological analysis revealed no adverse pathologic effects on the synovial membrane at any time point. FGF-2 gene transfer enhanced type II collagen expression and individual parameters of chondrogenesis, such as the cell morphology and architecture of the new tissue. Overall articular cartilage repair was significantly improved at both time points in vivo. Conclusions The data suggest that localized overexpression of FGF-2 enhances the repair of cartilage defects via stimulation of chondrogenesis, without adverse effects on the synovial membrane. These results may lead to the development of safe gene-based therapies for human articular cartilage defects. Copyright © 2005 John Wiley & Sons, Ltd. [source]


    Gene therapy for cartilage defects

    THE JOURNAL OF GENE MEDICINE, Issue 12 2005
    Magali Cucchiarini
    Abstract Focal defects of articular cartilage are an unsolved problem in clinical orthopaedics. These lesions do not heal spontaneously and no treatment leads to complete and durable cartilage regeneration. Although the concept of gene therapy for cartilage damage appears elegant and straightforward, current research indicates that an adaptation of gene transfer techniques to the problem of a circumscribed cartilage defect is required in order to successfully implement this approach. In particular, the localised delivery into the defect of therapeutic gene constructs is desirable. Current strategies aim at inducing chondrogenic pathways in the repair tissue that fills such defects. These include the stimulation of chondrocyte proliferation, maturation, and matrix synthesis via direct or cell transplantation-mediated approaches. Among the most studied candidates, polypeptide growth factors have shown promise to enhance the structural quality of the repair tissue. A better understanding of the basic scientific aspects of cartilage defect repair, together with the identification of additional molecular targets and the development of improved gene-delivery techniques, may allow a clinical translation of gene therapy for cartilage defects. The first experimental steps provide reason for cautious optimism. Copyright © 2005 John Wiley & Sons, Ltd. [source]


    Ligament and bone pathologic abnormalities more frequent in neuropathic joint disease in comparison with degenerative arthritis of the foot and ankle: Implications for understanding rapidly progressive joint degeneration,

    ARTHRITIS & RHEUMATISM, Issue 8 2010
    Jill Halstead
    Objective The variable disease progression of osteoarthritis (OA) and the basis for rapid joint deterioration in some subgroups of patients are poorly understood. To explore an anatomic basis for rapidly progressive OA, this observational study compared the magnetic resonance imaging (MRI) patterns of disease between patients with neuropathic joint disease (NJD) and patients with degenerative arthritis of the ankle and foot. Methods MR images of the foot and ankle of patients with early NJD (n = 7) and patients with OA (n = 15) were assessed. The anonomized MR images were dichotomously scored by a musculoskeletal radiologist for the presence of the following abnormalities per bone (of a total of 14 bones): cartilage defects, bone cysts, bone marrow edema, fractures, joint debris, joint effusions, tendinopathy, tendinitis, and ligament tears. Results Although the degree of cartilage damage and joint cyst formation was comparable between the groups, the degree of ligament tears, or change in MRI signal intensity in the ligaments, was significantly greater in patients with NJD compared with patients with OA (median of 3 tears versus 0, of 14 total bones; P < 0.01). Moreover, in patients with early NJD compared with patients with OA, there was a significantly greater degree of diffuse bone marrow edema (median of 6.5 tarsal bones versus 2 adjacent bones, of 14 total bones; P < 0.01), a greater number of bone fractures (median 4 versus 0; P < 0.01), and more frequent bone debris (median 4.5 versus 0; P = 0.013). Conclusion This analysis of NJD in the foot and ankle shows the predominance of bone and ligament abnormalities in NJD compared with the pattern of involvement in OA. These findings highlight the importance of structures other than articular cartilage in OA of the ankle and foot, and suggest that rapid joint degeneration in NJD may be more ligamentogenic or osteogenic in nature. [source]


    Subchondral bone and cartilage damage: A prospective study in older adults

    ARTHRITIS & RHEUMATISM, Issue 7 2010
    Dawn Doré
    Objective There is limited longitudinal evidence relating subchondral bone changes to cartilage damage and loss. The aim of this study was to describe the association between baseline tibial bone area and tibial subchondral bone mineral density (BMD) with tibial cartilage defect development and cartilage volume loss. Methods A total of 341 subjects (mean age 63 years, range 52,79 years) underwent measurement at baseline and ,2.7 years later. Tibial knee cartilage volume, cartilage defects (graded on a scale of 0,4), and bone area were determined using T1-weighted fat suppression magnetic resonance imaging. Tibial subchondral BMD was determined using dual x-ray absorptiometry. Results In multivariable analysis, baseline bone area positively predicted cartilage defect development at the medial and lateral tibial sites (odds ratio [OR] 1.6 per 1 SD increase, 95% confidence interval [95% CI] 1.0, 2.6, and OR 2.4 per 1 SD increase, 95% CI 1.4, 4.0, respectively) and cartilage volume loss at the medial tibial site (, = ,34.9 per 1 SD increase, 95% CI ,49.8, ,20.1). In contrast, baseline subchondral BMD positively predicted cartilage defect development at the medial tibial site only (OR 1.6 per 1 SD increase, 95% CI 1.2, 2.1) and was not associated with cartilage loss. Conclusion The results of this study demonstrated that bone area predicted medial and lateral cartilage defect development and medial cartilage volume loss, while subchondral BMD predicted medial defect development but not cartilage loss. These associations were independent of each other, indicating there are multiple mechanisms by which subchondral bone changes may lead to cartilage damage. [source]


    Tetracycline-regulated bone morphogenetic protein 2 gene expression in lentivirally transduced primary rabbit chondrocytes for treatment of cartilage defects

    ARTHRITIS & RHEUMATISM, Issue 7 2010
    Daniela Wübbenhorst
    Objective Treatment of cartilage defects is still challenging, primarily because of the poor self-healing capacity of articular cartilage. Gene therapy approaches have gained considerable attention, but, depending on the vector system used, they can lead to either limited or unrestrained gene expression, and therefore regulation of gene expression is necessary. This study was undertaken to construct an efficient tetracycline (Tet),regulated, lentivirally mediated system for the expression of growth factor bone morphogenetic protein 2 (BMP-2) in primary rabbit chondrocytes that will allow for the induction and termination of growth factor gene expression once cartilage regeneration is complete. Methods Chondrogenic ATDC5 cells and primary rabbit chondrocytes were lentivirally transduced with different tetracycline-on (Tet-On),regulated, self-inactivating vectors for the induction of expression of enhanced green fluorescent protein (eGFP) or BMP-2, using either a 1-vector system or a 2-vector system. Results Expression of eGFP was induced on ATDC5 cells and chondrocytes. The highest induction rate and highest level of gene expression were reached when the spleen focus-forming virus long terminal repeat promoter was used to drive the reverse transactivator expression, after the addition of doxycycline, in chondrocytes. An up to 20-fold induction of Tet-mediated BMP-2 expression was observed on ATDC5 cells. The extent of induction and expression level of BMP-2 in chondrocytes were similar between the 1-vector system, and 2-vector system,infected cells (mean ± SD 15.5 ± 1.1 ng/ml and 14.6 ± 0.4 ng/ml, respectively). In addition, prolonged induction and switching-off of BMP-2 expression, as well as repeated induction, were demonstrated. Production of proteoglycans, as shown by Alcian blue staining, demonstrated the functionality of the lentivirally expressed BMP-2 under induced conditions. Conclusion The lentivirally mediated Tet-On system is an effective strategy for efficient, repeatedly inducible expression of BMP-2 in primary rabbit chondrocytes. Therefore, use of this system in in vivo experiments may be a promising approach as a treatment strategy for cartilage defects. [source]


    Denuded subchondral bone and knee pain in persons with knee osteoarthritis

    ARTHRITIS & RHEUMATISM, Issue 12 2009
    Kirsten Moisio
    Objective It is unclear how articular cartilage loss contributes to pain in patients with knee osteoarthritis (OA). Full-thickness cartilage defects expose the subchondral bone plate. The relationship between denuded bone and pain has not been examined. The aim of this study was to investigate whether the percent of denuded bone is associated with moderate-to-severe knee pain or frequent knee pain and longitudinally with frequent knee pain 2 years after the baseline evaluation. Methods We studied 182 persons with knee OA (305 knees). Applying specialized magnetic resonance imaging techniques, manual segmentation was used to compute cartilage-covered and denuded bone areas for each surface. Moderate-to-severe knee pain was defined as a score of ,40 mm on a knee-specific 100-mm visual analog scale, and frequent knee pain was defined as pain on most days during the past month. Logistic regression and generalized estimating equations were used in analyses, adjusting for age, sex, body mass index, and bone marrow lesions. Results Cross-sectional analyses revealed that moderate-to-severe knee pain was associated with percent denuded bone in the medial compartment (adjusted odds ratio [OR] 3.90, 95% confidence interval [95% CI] 1.33,11.47), in the medial and patellar surfaces together, and in the lateral and patellar surfaces. Frequent knee pain was associated with percent denuded bone in the patellar surface (adjusted OR 3.11, 95% CI 1.24,7.81), in the medial and patellar surfaces, and in the lateral and patellar surfaces. Longitudinal analyses (in 168 knees without frequent knee pain at baseline) revealed that percent denuded bone in the medial and patellar surfaces was associated with frequent incident knee pain (adjusted OR 4.19, 95% CI 1.56,11.22). Conclusion These results support a relationship between subchondral bone plate exposure and prevalent and incident knee pain in patients with knee OA. [source]


    A Cell-Free Collagen Type I Device for the Treatment of Focal Cartilage Defects

    ARTIFICIAL ORGANS, Issue 1 2010
    Karsten Gavenis
    Abstract The purpose of this study was to evaluate the potential value of a cell-free collagen type I gel plug for the treatment of focal cartilage defects. Cellular migration and proliferation was addressed in vitro, and the formation of repair tissue in a nude mouse-based defect model. A cell-free plug made of collagen type I was placed in the center of an incubation plate. Surrounding space was filled with a collagen type I gel (Arthro Kinetics, Esslingen, Germany) seeded with 2 × 105 human articular chondrocytes/mL gel. After cultivation for up to 6 weeks in vitro, samples were subject to histological and immunohistochemical staining and gene expression analysis. Subsequently, chondral defects of human osteochondral blocks were treated with the plug, and specimens were cultivated subcutaneously in nude mice for 6 weeks. The repair tissue was evaluated macroscopically, and collagen type II production was investigated immunohistochemically. In vitro, morphology of immigrated cells did not show any differences, as did collagen type II gene expression. After 4 weeks, the plug was homogeneously inhabited. After 6 weeks of cultivation in nude mice, collagen gel plug treatment led to a macroscopically excellent repair tissue. Histological staining revealed a tight bonding, and the collagen gel plug started to be remodeled. We conclude that the novel collagen gel plug device offers an environment favorable for the migration of articular chondrocytes and leads to a good-quality repair tissue in the nude mouse model. The arthroscopic transplantation of a collagen gel plug may be one option in the treatment of focal cartilage defects. [source]


    Potential of Fortified Fibrin/Hyaluronic Acid Composite Gel as a Cell Delivery Vehicle for Chondrocytes

    ARTIFICIAL ORGANS, Issue 6 2009
    Sang-Hyug Park
    Abstract Numerous treatment methods have been applied for use in cartilage repair, including abrasion, drilling, and microfracture. Although chondrocyte transplantation is the preferred treatment, it has some shortcomings, such as difficulty of application (large and posterior condylar regions), poor chondrocyte distribution, and potential cell leakage from the defect region. The cell delivery system of the tissue engineering technique can be used to overcome these shortcomings. We chose fibrin/hyaluronan (HA) composite gel as an effective cell delivery system to resolve these issues. Both components are derived from natural extracellular matrix. In the first trial, fortified fibrin/HA composite gels with rabbit chondrocytes were tested by implantation in nude mice. At 4 weeks, glycosaminoglycan contents in the fibrin/HA composite (0.186 ± 0.006 mg/mg) were significantly higher than those in the presence of fibrin alone (0.153 ± 0.017 mg/mg). As a next step, we applied the fibrin/HA composite gel to animal cartilage defects using full thickness cartilage defect rabbit models. The fibrin/HA composite gel with rabbit chondrocytes (allogenic) was implanted into the experimental group, and the control group was implanted with the fibrin/HA composite gel alone. Implanted chondrocytes with the fibrin/HA composite showed improved cartilage formation. In conclusion, the key to successful regeneration of cartilage is to provide the repair site with a sufficient supply of chondrogenic cells with a suitable delivery vehicle to ensure maximal differentiation and deposition of the proper extracellular matrix. This study suggests the feasibility of tissue-engineered cartilage formation using fibrin/HA composite gel. [source]