Engineering the healing of the rabbit medial collateral ligament.

Abstract

A biological approach to improve healing of the medial collateral ligament (MCL) was investigated by exploring the use of therapeutic growth factors based on in vitro and in vivo experiments. The in vitro cell culture studies involved screening a variety of growth factors to select those that exhibit the most positive effects on cell proliferation and extracellular matrix synthesis. The selected growth factors were applied in vivo to a rabbit model where the MCL was ruptured. Biomechanical and histological evaluations are performed to determine whether the selected growth factors can enhance the properties of the healed MCL, whether these improvements are dose dependent, and whether combinations of growth factors can enhance MCL healing to a greater extent than individual growth factors. In vitro studies showed that epidermal growth factor (EGF) and platelet derived growth factor-BB (PDGF-BB) have the greatest effect on ligament fibroblast proliferation, whereas transforming growth factor-beta 1 (TGF-beta 1) superiorly promotes extracellular matrix synthesis. These growth factors were then applied in vivo at different dosages, in isolation and in combination, and the ligaments were evaluated six weeks post-operatively. Tensile testing of the femur-MCL-tibia complexes (FMTCs) revealed that the specimens treated with a high dose of PDGF-BB have ultimate load, ultimate elongation and energy absorbed to failure values that are significantly greater than those from the other groups. The high dose of PDGF-BB was more effective than the low dose, indicating a dose dependency. The addition of TGF-beta 1 to PDGF-BB did not lead to any further increases in the structural properties of the FMTC. These encouraging results suggest that PDGF-BB may be a potential growth factor to enhance the quality of the healing ligament.