A combined strategy to reduce restenosis for vascular tissue engineering applications

Biodegradable polymers including poly(l-lactic acid) (PLLA) have been used to develop cardiovascular prostheses such as vascular grafts and stents. However, implant-associated thrombosis, inflammation, and restenosis are still major obstacles for the utility of these devices. The lack of an endothelial cell (EC) lining (endothelialization) on the implants and the responses of the immune systems toward the implants have been associated with these complications. In our research strategy, we have combined the drug delivery principle with the strategies of tissue engineering, the controlled release of anti-inflammation drugs and enhanced endothelialization, to reduce the implant-associated adverse responses. We first integrated curcumin, an anti-inflammatory drug and anti-smooth muscle cell (SMC) proliferative drug, with PLLA. This curcumin-loaded PLLA material was then modified using adsorptive coating of adhesive proteins such as fibronectin, collagen-I, vitronectin, laminin, and matrigel to improve the endothelial cell (EC) adhesion and proliferation, and ECs were seeded on top of these modified surfaces. Our results showed steady drug release kinetics over the period of 50 days from curcumin-loaded PLLA materials. Additionally, integration of curcumin in PLLA increased the roughness of the scaffold at the nanometric scale using an atomic force microscopic analysis. Moreover, coating with fibronectin on curcumin-loaded PLLA surfaces gave the highest EC adhesion and proliferation compared to other adhesive proteins using PicoGreen DNA assays. The ability of our strategy to release the curcumin for producing anti-inflammation and anti-proliferation responses and to improve EC adhesion and growth after EC seeding suggests this strategy may reduce implant-associated adverse responses and be a better approach for vascular tissue engineering applications.