The use of growth factors, gene therapy and tissue engineering to improve meniscal healing

The meniscus plays important roles in the knee joint, including load transmission at the tibiofemoral articulation, shock absorption, lubrication, and stabilization of the knee joint, though its healing capacity remains limited. Meniscal healing requires the proliferation of meniscal fibrochondrocytes from either an intrinsic source at the site of injury or an extrinsic source from the blood supply or synovium. We have characterized the effects of various doses of nine growth factors on the meniscal fibrochondrocyte proliferation and collagen and non-collagen synthesis, and identified epidermal growth factor (EGF), transforming growth factor alpha (TGFα), basic fibroblast growth factor (bFGF) and platelet derived growth factor AB (PDGF-AB) as candidate molecules to improve meniscal healing. The direct administration of the human recombinant growth factor protein is likely to be limited by the short biological half-life of these proteins and the rapid clearance of the injected proteins. We have therefore evaluated the feasibility of gene therapy and tissue engineering to deliver marker genes into the meniscus and found that direct and myoblast mediated ex vivo gene transfer can be used to deliver high levels and persistent expression of these growth factors into the injured meniscus. This study will help in the development of strategies to improve meniscal healing using new innovative technologies such as gene therapy approaches.