Dynamic stiffness enables stage-specific properties mediating functional endothelialization on vascular implants.

Abstract

Achieving healthy, functional endothelialization represents the goal of neointima healing in cardiovascular implants but remains challenging due to strategies that fail to adapt dynamically to complex material-tissue interactions. We develop a biomimetic coating with dynamic stiffness via layer-by-layer assembly of recombinant humanized type III collagen and cystamine-modified hyaluronic acid, followed by postcrosslinking. The coating incorporates ECM-mimetic components and exhibits tunable stiffness that dynamically decreases in response to microenvironmental stimuli such as glutathione and reactive oxygen species. It exhibits stage-specific properties: initially suppressing acute thrombosis and directing cell adhesion; then facilitating a confluent, functional endothelial monolayer; driving smooth muscle cell contractile phenotype; and inducing anti-inflammatory macrophage polarization. In vivo, stents coated with our coating suppressed neointimal hyperplasia, achieving neointimal healing with morphology and function resembling native endothelium at 12 months. These findings reveal how dynamic stiffness guides material-tissue responses and provide a promising approach to enhance vascular implant healing.