A robust mussel-inspired zwitterionic coating on biodegradable poly(L-lactide) stent with enhanced anticoagulant, anti-inflammatory, and anti-hyperplasia properties

Abstract

Endowing cardiovascular stents with multiple functionalities, such as anti–proliferative, and anti–inflammatory properties, is important for combating restenosis after stent implantation. The surface properties of stents play a key role in obtaining the desired post–implantation performance. Zwitterionic coatings are resistant to non–specific adsorption, and here, a mussel–inspired zwitterionic poly (carboxybetaine acrylate–co–dopamine methacrylate) copolymer (PCBDA) was synthesized and applied to the surface of a biodegradable poly(l–lactide) stent. To obtain a zwitterionic polymer coating, the surface of a PLA stent was pretreated by co–depositing polydopamine (PDA) and polyethyleneimine (PEI). The mussel–inspired catechol moieties in the PCBDA copolymer cross–linked with the PDA–PEI hybrid to form a robust PCBDA/PDA–PEI coating on the PLA stent. The zwitterionic PCBDA formed a hydration layer once it contacted blood, preventing the non–specific adsorption of serum proteins, which further blocked subsequent coagulation and inflammation. The anti–protein adsorption tests showed that the PCBDA/PDA–PEI coating resisted the non–specific adsorption of fibrinogen, which was a positive signal for enhanced anti–coagulation. Moreover, the platelet adhesion/activation tests confirmed its antithrombotic properties. The in vivo tissue response was also greatly suppressed due to the inhibited recognition of PCBDA/PDA–PEI–coated implants by macrophages. Interestingly, unlike traditional zwitterionic polymers, due to the introduction of adhesive catechol moieties, PCBDA supported the growth of endothelial cells, demonstrating its ability to selectively direct the fate of endothelial cells and smooth muscle cells. In vivo stent implantation results showed inhibited intimal hyperplasia due to the protection of PCBDA/PDA–PEI. Overall, due to the specific characteristics of the mussel–inspired PCBDA/PDA–PEI coating, anticoagulation, anti–inflammatory, and anti–proliferation properties were obtained; thus, it is expected that this coating can be used to inhibit restenosis and realize endothelialization after stent implantation.