BIOINTERACTIVE POLYMERS AND TISSUE ENGINEERED BLOOD-VESSELS

The regulation of endothelial cell (EC) and smooth muscle cell (SMC) p roliferation following vascular interventions is critical to clinical efficacy. Our laboratory has developed a method of impregnating biomat erials with suspensions containing bioactive proteins resulting in the capability of differentially modulating EC and SMC growth in vitro an d in vivo following implantation. We have previously reported that 60 mu internodal distance ePTFE grafts impregnated with fibrin glue (FG) containing FGF-1 and heparin develop confluent endothelialization with transiently increased EC and SMC proliferation after 4 weeks in dogs. Thoraco-abdominal implants after 20 weeks were developed significantl y thicker (139 mu) inner capsules in response to the FGF. To minimize SMC proliferation we studied the effects of FGF-1, heparin, and thromb in concentrations on SMC growth in vitro. FG caused a 182% increase (P < 0.001) in DNA synthesis. Heparin within FG diminished this effect i n a dose-dependant manner, with complete inhibition of FG-induced grow th at 500 U ml(-1) (versus FG alone, P < 0.001). FGF-1 within FG witho ut heparin had no effect, but together, FGF-1 caused a dose-dependant growth increase while increasing heparin concentrations initially incr eased and then decreased proliferation. FGF-1 and heparin in the mediu m of quiescent SMCs had similar effects. Only thrombin concentrations > 3.2 U ml(-1) stimulated SMC growth and this stimulation was blocked by heparin. A synergism between FGF and heparin on EC proliferation wa s also found but without EC growth inhibition in response to higher co ncentrations of heparin. It is thus possible to modulate the relative proliferative activity of ECs versus SMCs by altering the FGF:heparin ratio. This same system may be useful with other proteins to induce ot her local affects by the applied protein or systemic affects following release of that protein.