Application Of No-released Endothelial Functional Biomimetic Coating In Cardiovascular Stents

Cardiovascular disease is known as the number one killer of human health due to its high mortality and disability rate.Interventional therapy has become one of the commonly used methods for the treatment of coronary heart disease due to its minimally invasive,high curative effect,low risk,and rapid recovery advantages.In the nearly 40 years since the development of interventional therapy for cardiovascular diseases,it has experienced from simple balloon dilatation to bare metal vascular stent placement,and then to the advent of drug eluting stent(DES).The rate of in-stent restenosis also dropped from 60%to about 20-30%and then to below 10%.However,the drugs released by DES inhibited the intimal hyperplasia and at the same time inhibited the regeneration and repair of the vascular endothelial layer,leading to the occurrence of late thrombosis(LST)and in-stent restenosis(ISR).The endothelial cell layer is a natural barrier between blood and vascular tissue.It relies on the synergistic effect of active proteins,heparin on the endothelial cell membrane,sustained release of nitric oxide(NO)and other active factors to inhibit blood coagulation,inhibit the proliferation of SMC,and promote the self-repair of damaged endothelium.Therefore,in this study,the endothelial functional biomimetic coating with NO catalytic release was applied to the vascular stent to solve the complications in the clinical application of the vascular stent.In the second chapter of this article,regarding the high requirement of cardiac and vascular implants in tissue engineering,a novel concept of surface chemistry strategy featuring multiple functions is proposed in this study,which provides glutathione peroxidase(GPx)-like catalytic activity and allows secondary reactions for grafting functional biomolecules.The suggested strategy is the fabrication of a metal-catechol-(amine)network(MCAN)containing copper ions with GPx-like activity,amine-bearing hexamethylenediamine(HD)and wet adhesive catechol dopamine(DA).With a simple one-step molecular/ion co-assembly,the developed copper-DA-HD(CuII-DA/HD)network can be used to catalyze the generation of therapeutic nitric oxide(NO)gas in a durable and dose-controllable manner.The primary amine groups in the CuII-DA/HD network facilitate the secondary immobilization of bivalirudin(BVLD)to further provide an antithrombotic activity as supplement to the functions of NO.The CuII-DA/HD-BVLD coating functionalized on cardiovascular stents successfully improved thromboresistance,anti-restenosis,and promotes re-endothelialization in vivo.With regard to the ease of operation and low cost,the synergetic modification using MCAN strategy is of great potential for developing multifunctional blood-contacting materials/devices.In the third chapter of this article.To address in-stent restenosis(ISR)associated with neointimal hyperplasia or in-stent thrombosis,we developed a 'pseudo-endothelium' for vascular stents inspired by the importance and functions of native endothelium for cardiovascular system.The pseudo-endothelium is based on a de novo designed hydrogel.It is mechanically tough and could preserve integrity on the stents during angioplasty.Due to its physiochemical similarities to subendothelial extracellular matrix,the pseudo-endothelium facilitated the adhesion and growth of endothelial cells.Besides,it is non-thrombotic and capable of inhibiting undesired smooth muscle cells thanks to the bestowed endothelial functions.In vivo study demonstrated that vascular stents encapsulated by our pseudoendothelium promoted rapid formation of a native endothelium and impressively suppressed ISR.We expect that such pseudo-endothelium will open a new avenue to the surface engineering of vascular implants for better clinical outcomes.