Thrombin-regulated multi-functional hydrogel coating for decellularized extracellular matrix materials to enhance the anticoagulant and endothelialization properties.

Abstract

Valvular heart disease (VHD) is a leading global health concern, contributing to significant mortality rates and imposing substantial economic burdens annually. To date, numerous bioprosthetic heart valves (BHVs) based on decellularized extracellular matrix (dECM) have been engineered as prosthetic solutions for the treatment of VHD. However, the irreversible deterioration of BHVs, driven by thrombosis, inflammatory responses, and calcification, represents a persistent and unresolved clinical concern. Moreover, the simultaneous optimization of multiple properties through a single technological approach presents a formidable challenge for BHVs. Herin, a dual regulation strategy based on functional hydrogel encapsulated with self-regulating bioreactors has been proposed to develop functional BHV materials, which involve nanoparticle-coated architectures with the intrinsic feedback mechanism. Specifically, a self-feedback thrombin-responsive peptide nanoparticle delivery system encapsulated with anticoagulant apixaban (Thr NPs) has been employed. Meanwhile, with the nanoparticles as bridging agents, the functional hydrogel coatings can be formed to provide passive defense against biofouling, while the three-dimensional network structures serve as the high-capacity reservoir for drug delivery. The excellent biocompatibility, superior anticoagulation, reduced calcification, and minimal inflammation are demonstrated for the developed BHV materials by a series of investigations in vitro and in vivo. Notably, the carotid artery implantation and endo-covered stent model are established to further confirm the blood compatibility and the enhancement of endothelialization of the developed BHV materials after implantation. It is expected that this dual regulation strategy might provide a good reference for the self-feedback biomedical material design and the application of blood-contact materials.