This study proposes to systematically investigate the capacity of a bone matrix derived chondrogenic factor to induce in vivo cartilage repair within an articular cartilage defect. The bioactive agent, a 31,000 dalton protein designated Chondrogenic Stimulating Activity (CSA), was identified by assay in embryonic limb bud cell cultures where it induced cartilage differentiation. Effective in vivo use of this highly soluble chondrogenic factor is dependent upon its availability at critical periods during the tissue repair process. The fabrication of controlled delivery release vehicles will utilize techniques involving chemical bonding and/or physical entrapment of the active factor into inert biodegradable implant devices. The chondrogenic potential of the biomatrix vehicles containing immobilized CSA is initially screened by implantation into ectopic intramuscular sites. The cartilage tissue induced by these implants will be quantitatively evaluated by histological and biochemical methods. It is hypothesized that immobilized CSA implants which stimulate ectopic chondrogenesis can effectively enhance the limited repair capacity of damaged articular cartilage. The CSA-mediated regeneration of a stable, phenotypically functional and well integrated cartilage tissue within an articular cartilage defect site is the principal objective of this proposal. The ability of formatted CSA to induce a functional cartilage repair will be evaluated by producing 3.2 mm full thickness defects in the articular surface of femoral condyles of adult New Zealand white rabbits. The extent of cartilage repair will be assessed by quantitative histological, immunochemical and biochemical analysis as well as by mechanical testing using confined compression creep. Additionally, the role of continuous passive motion (CPM) in promoting the healing of full thickness defects will also be studied in conjunction with immobilized CSA using a similar experimental model. The long-term goal of this proposal is to develop practical techniques which utilize purified soluble CSA in the repair of cartilagenous defects with ultimate application to the clinical problems of joint trauma and degeneration.
| Solchaga, Luis A; Tognana, Enrico; Penick, Kitsie et al. (2006) A rapid seeding technique for the assembly of large cell/scaffold composite constructs. Tissue Eng 12:1851-63 |
| Solchaga, Luis A; Temenoff, Johnna S; Gao, Jizong et al. (2005) Repair of osteochondral defects with hyaluronan- and polyester-based scaffolds. Osteoarthritis Cartilage 13:297-309 |
