Background: In osteochondral defects, subchondral bone, as a load-bearing structure, is believed to be important for bone and cartilage regeneration.
Hypothesis: A stiff scaffold creates better conditions for bone formation and cartilage regeneration than does a softer one.
Study Design: Controlled laboratory study.
Methods: Critical osteochondral defects were created in the femoral condyles of 24 sheep. Subchondral bone was reconstructed with a stiff scaffold or a modified softer one, with untreated defects serving as controls. The repair response was evaluated with mechanical, histological, and histomorphometrical techniques at 3 and 6 months postoperatively.
Results: The elastic modulus of regenerated fibrocartilage over the stiff scaffold tended to be higher than in the soft scaffold group (61% vs 46% of healthy cartilage) at 3 months. No difference was determined at 6 months; all were well below healthy cartilage. Treated defects showed substantial degradation of the soft scaffold with surrounding sclerotic bone at 3 and 6 months. In contrast, degradation of the stiff scaffold was slower and occurred together with continuous osseous replacement.
Conclusion: Stiff scaffolds were found to improve bone regeneration. In contrast, soft scaffolds provided less support, and consequently subchondral bone became sclerotic. Although regenerated cartilage formed over the stiff scaffolds at 3 months, and these exhibited better mechanical properties than did the soft scaffold group, the mechanical properties in both treated groups were the same at 6 months, not dissimilar to that of tissue formed in the untreated specimens and inferior to native articular cartilage.
Clinical Relevance: The results imply that subchondral defect filling in clinical settings advances bone regeneration and should have a comparable stiffness to that of healthy subchondral bone rather than being too flexible. Degradation of resorbable materials and consequently the loss of stiffness may compromise the healing of critical defects.
Background: Donor-site morbidity, limited numbers of cells, loss of phenotype during ex vivo expansion, and age-related decline in chondrogenic activity present critical obstacles to the use of autologous chondrocyte implantation for cartilage repair. Chondrocytes from juvenile cadaveric donors may represent an alternative to autologous cells.
Hypothesis/Purpose: The authors hypothesized that juvenile chondrocyte would show stronger and more stable chondrogenic activity than adult cells in vitro and that juvenile cells pose little risk of immunologic incompatibility in adult hosts.
Study Design: Controlled laboratory study.
Methods: Cartilage samples were from juvenile (<13 years old) and adult (>13 years old) donors. The chondrogenic activity of freshly isolated human articular chondrocytes and of expanded cells after monolayer culture was measured by proteoglycan assay, gene expression analysis, and histology. Lymphocyte proliferation assays were used to assess immunogenic activity.
Results: Proteoglycan content in neocartilage produced by juvenile chondrocytes was 100-fold higher than in neocartilage produced by adult cells. Collagen type II and type IX mRNA in fresh juvenile chondrocytes were 100- and 700-fold higher, respectively, than in adult chondrocytes. The distributions of collagens II and IX were similar in native juvenile cartilage and in neocartilage made by juvenile cells. Juvenile cells grew significantly faster in monolayer cultures than adult cells (P = .002) and proteoglycan levels produced in agarose culture was significantly higher in juvenile cells than in adult cells after multiple passages (P < .001). Juvenile chondrocytes did not stimulate lymphocyte proliferation.
Conclusion: These results document a dramatic age-related decline in human chondrocyte chondrogenic potential and show that allogeneic juvenile chondrocytes do not stimulate an immunologic response in vivo.
Clinical Relevance: Juvenile human chondrocytes have greater potential to restore articular cartilage than adult cells, and may be transplanted without the fear of rejection, suggesting a new allogeneic approach to restoring articular cartilage in older individuals.
Background: The use of mesenchymal stem cells (MSCs) to treat osteochondral defects caused by sports injuries or disease is of particular interest. However, there is a lack of studies in large-animal models examining the benefits of chondrogenic predifferentiation in vitro for repair of chronic osteochondral defects.
Hypothesis: Chondrogenic in vitro predifferentiation of autologous MSCs embedded in a collagen I hydrogel currently in clinical trial use for matrix-associated autologous chondrocyte transplantation facilitates the regeneration of a chronic osteochondral defect in an ovine stifle joint.
Study Design: Controlled laboratory study.
Methods: The optimal predifferentiation period of ovine MSCs within the type I collagen hydrogel in vitro was defined by assessment of several cellular and molecular biological parameters. For the animal study, osteochondral lesions (diameter 7 mm) were created at the medial femoral condyles of the hind legs in 10 merino sheep. To achieve a chronic defect model, implantation of the ovine MSCs/hydrogel constructs was not performed until 6 weeks after defect creation. The 40 defects were divided into 4 treatment groups: (1) chondrogenically predifferentiated ovine MSC/hydrogel constructs (preMSC-gels), (2) undifferentiated ovine MSC/hydrogel constructs (unMSC-gels), (3) cell-free collagen hydrogels (CF-gels), and (4) untreated controls (UCs). Evaluation followed after 6 months.
Results: With regard to proteoglycan content, cell count, gel contraction, apoptosis, compressive properties, and progress of chondrogenic differentiation, a differentiation period of 14 days in vitro was considered optimal. After 6 months in vivo, the defects treated with preMSC-gels showed significantly better histologic scores with morphologic characteristics of hyaline cartilage such as columnarization and presence of collagen type II.
Conclusion: Matrix-associated autologous chondrocyte transplantation with predifferentiated MSCs may be a promising approach for repair of focal, chronic osteochondral defects.
Clinical Relevance: The results suggest an encouraging method for future treatment of focal osteochondral defects to prevent progression to osteoarthritis.
