ENGINEERING THE HEALING OF THE RABBIT MEDIAL COLLATERAL LIGAMENT

A biological approach to improve healing of the medial collateral liga ment (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 sele ct those that exhibit the most positive effects on cell proliferation and extracellular matrix synthesis. The selected growth factors were a pplied in vivo to a rabbit model where the MCL was ruptured. Biomechan ical and histological evaluations are performed to determine whether t he selected growth factors can enhance the properties of the healed MC L, whether these improvements are dose dependent, and whether combinat ions of growth factors can enhance MCL healing to a greater extent tha n individual growth factors. In vitro studies showed that epidermal gr owth factor (EGF) and platelet derived growth factor-BE (PDGF-RB) have the greatest effect on ligament fibroblast proliferation, whereas tra nsforming growth factor-beta(1) (TGF-beta(1)) superiorly promotes extr acellular matrix synthesis. These growth factors were then applied in vivo at different dosages, in isolation and in combination, and the li gaments were evaluated six weeks post-operatively. Tensile testing of the femur-MCL-tibia complexes (FMTCs) revealed that the specimens trea ted with a high dose of PDGF-BB have ultimate load, ultimate elongatio n and energy absorbed to failure values that are significantly greater than those from the other groups. The high dose of PDGF-BB was more e ffective 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 th e 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.