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 transm ission at the tibiofemoral articulation, shock absorption, lubrication, and stabilization of the knee joint, though its healing capacity remains limit ed. Meniscal healing requires the proliferation of meniscal fibrochondrocyt es from either an intrinsic source at the site of injury or an extrinsic so urce from the blood supply or synovium. We have characterized the effects o f various doses of nine growth factors on the meniscal fibrochondrocyte pro liferation and collagen and non-collagen synthesis, and identified epiderma l growth factor (EGF), transforming growth factor alpha (TGF alpha), basic fibroblast growth factor (bFGF) and platelet derived growth factor AB (PDGF -AB) as candidate molecules to improve meniscal healing. The direct adminis tration of the human recombinant growth factor protein is likely to be limi ted by the short biological half-life of these proteins and the rapid clear ance of the injected proteins. We have therefore evaluated the feasibility of gene therapy and tissue engineering to deliver marker genes into the men iscus and found that direct and myoblast mediated ex vivo gene transfer can be used to deliver high levels and persistent expression of these growth f actors into the injured meniscus. This study will help in the development o f strategies to improve meniscal healing using new innovative technologies such as gene therapy approaches. (C) 2000 Elsevier Science S.A. All rights reserved.