Muscle-based gene therapy and tissue engineering for treatment of growth plate injuries.

Growth plate injuries may lead to a progressive angular deformity or longitudinal growth disturbance. The authors investigated the feasibility of gene therapy and tissue engineering based on autologous muscle-and adenoviral-mediated gene transfer of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) to treat tibial physeal defects in rabbits. The medial half of the left proximal tibial growth plate was completely excised in 44 6-week-old New Zealand white rabbits. Four experimental groups were created: no treatment (I), autologous muscle interposition (II), autologous muscle interposition injected with adIGF-1 (III), and autologous muscle interposition injected with adBMP-2 (IV). Radiographic and histologic assessments were obtained postoperatively. Significant tibial shortening and a compact osseous bridge were observed in groups I and IV. Growth plates remained open in groups II and III. This experiment demonstrates that IGF-1 had a supportive effect on physeal chondrocytes, while BMP-2 caused increased osteogenic activity in the injured growth plates.

Fractures in large-segment allografts.

Sixteen of thirty-five large-segment allografts that had been implanted after resection for neoplastic conditions, and had been followed for a minimum of thirty-six months, were found to have fractured at a mean of twenty-six months after the implantation. Thirteen of the fractures were treated operatively, and we found a lack of vascularization and soft-tissue attachments to the graft at the fracture site. For seven fractured grafts, there were radiographic and clinical signs of union with the host bone. Eight of the sixteen grafts that had fractured were salvaged with one or more autogenous bone grafts, and two healed spontaneously. Thus, twenty-nine of the thirty-five grafting procedures were considered to have been successful in that the initial objective--provision of a functional segment for skeletal replacement--had been achieved. Multivariate analysis revealed a significant correlation for fracture in patients who were receiving chemotherapy when internal fixation of the graft had included devices that penetrated the cortices of the graft (p < 0.05).

Immunolocalization of selected cytokines and proteases in canine articular cartilage after transarticular loading.

Cytokines and proteases are thought to play a role in the destruction of cartilage and the development of osteoarthritis. The purpose of this study was to document chronological involvement of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), stromelysin (MMP-3), fibronectin, and alteration in the chondroitin sulphate sulfation pattern. Canine patellae underwent a closed-joint impact to induce the development of osteoarthritis. The animals were killed at 2, 12, 24, and 52 weeks. The patellar damage included cracks in the superficial zone of cartilage and the zone of the calcified cartilage-bone interface, vertical step-off fractures in the zone of calcified cartilage, and loss of proteoglycan around the cracks in the deep and superficial zones of cartilage. With avidin-biotin immunohistochemistry, these specimens were stained with antibodies to IL-1 beta, TNF-alpha, MMP-3, fibronectin, and altered proteoglycan sulfate with the monoclonal antibody 3-B-3. Three of the four specimens obtained at 2 weeks demonstrated a strong cellular and weak matrix staining pattern for IL-1 beta, TNF-alpha, MMP-3, and fibronectin around the cracks in the superficial and transitional zones of cartilage. No consistent staining pattern was noted in the cracks in the deep zone. None of the specimens obtained at 12, 24, or 52 weeks stained for these antibodies. No staining for the abnormal sulfation with the 3-B-3 antibody was evident in any specimen. The specimens obtained at 52 weeks showed healing of the step-off fractures and a filling-in of the proteoglycan loss. This model probably reflects the short-term cartilaginous changes in the patella after trauma; thus, only transient elevations in the cytokines and proteases were evident.