UCLA

Graft rejection is an immunological response facilitated by the host T lymphocytes and this process could engender tissue destruction and alloantibody production. Allograft recipients must adhere to a rigorous immunosuppressant administration to avoid post-operative complications to the graft. Herein, an acellular drug-eluting vascular graft platform was proposed to alleviate the requirement for systemic drug administration via the targeted delivery of tacrolimus. The graft inner layer and drug-carrying matrix were electrospun with poly(L-lactide-co-caprolactone)/poly(D,L-lactic-co-glycolic acid) as the inner layer and poly(carbonate-urethane) as the outer layer. Mechanical characterization and degradation kinetics of the engineered graft were performed and the optimal material composition was determined. In vitro cytocompatibility assays utilizing endothelial cells, macrophages, and T-cells of primary sources were done and the optimal drug loading concentration was identified. The anastomosis of the drug-eluting vascular graft into the femoral artery of rats was performed to assess its in vivo tissue integration and therapeutic capability. This experimental approach was devised as a proof-of-concept study prior to an elaborate organ transplantation model. The graft maintained a high patency rate and a sustained concentration of tacrolimus after a month of implantation, therefore proving the feasibility of a novel biomaterial-mediated immunomodulation modality.