Hyaluronic Acid Nanoparticle Composite Films Confer Favorable Time-dependent Biofunctions For Vavcular Wound Healing

Vascular stent implantation is the main treatment of coronary artery disease.Surface modification of coronary stents to prevent thrombosis and restenosis,promote endothelization has become a new hot spot.However,bioactive coatings on implants have not yet developed enough to meet the time-ordered biological requirements of vascular stent.In the first month after vascular stent implantation,the pathological changes in the injured vascular tissue are complex and time-ordered.Therefore,vascular stents possessing time-dependent biofunctions with early phase anticoagulant and anti-inflammatory properties,and later stage inhibitory effects on smooth muscle cell proliferation alongside the promotion of endothelial cell adhesion might meet the requirements of vascular repair.In this study,we fabricated three types of hyaluronic acid nanoparticles(HA-NPs)by subjecting HA and polyetherimide to ethyl(dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide coupling reaction.The HA-NPs prepared by HA with a molecular weight of 100-kD showed the best stability in a hyaluronidase environment.HA-NP composite films(HA-NCFs)were then fabricated by co-immobilizing selected HA-NPs(100-kD)and HA molecules(100-kD)through amide reaction on PDA/HD coated316 L stainless steel surfaces.The detachment behavior of HA-NPs(100-kD)in PBS for 20 days indicated HA-NPs(100-kD)gradually detaching from the surface..In vitro tests(anticoagulant and anti-inflammatory tests,endothelial cells and smooth muscle cells seeding,bacterial adhesion test)indicated that the newly fabricated HA-NCFs had inhibitory effects on the adhesion of fibrinogen,platelets,macrophages,bacteria,SMCs and ECs.As HA-NPs detaching from the surface,the HA-NCFs showed excellent comprehensive biocompatibility gradually,promoting adhesion and proliferation of ECs while still exerting inhibitory effects on platelets,macrophages,and SMCs.Finally,in vivo SS wire implantation test(aortic implantation in healthy Sprague-Dawley rats)showed that HA-NCFs possessed anti-inflammatory properties,inhibited the proliferation of smooth muscle cells,and promoted re-endothelialization.In particular,HA-NCFs with time-dependent biofunctions showed better anti-restenosiseffects than those of surfaces modified with molecular HA,which exhibited constant biocompatibility.This study provides an important basis for the construction of novel HA-NP composite films with favorable time-dependent biofunctions to meet the time-ordered biological requirements of vascular stent.