Corilagin functionalized decellularized extracellular matrix as artificial blood vessels with improved endothelialization and anti-inflammation by reactive oxygen species scavenging

Abstract

Abstract The performance of biological-originated blood vessels in clinical remains disappointing due to fast occlusion caused by acute thrombosis or long-standing inflammation. How to prevent rapid degradation and inhibit acute inflammation but maintain their high bioactivity is still a significant challenge. As a bioactive polyphenol in various traditional Chinese medicine, Corilagin (Cor) exhibits excellent anticoagulant, anti-inflammatory and rapid ROS consumption properties. Inspired by abundant supramolecular interactions in organisms, we selected it to crosslink tissues via purely H-bonds to simulate these natural interactions without introducing potential toxic aldehyde or carboxyl groups. Results show that 2 mg/ml was selected as the optimal Cor concentration to form a stable crosslinking network (FI > 95%) and effectively delay their degradation. Cor modification not only enhances ECs adhesion and monolayer function via accelerating VEGF and TGF-β secretion but also promotes macrophage transformation from pro-inflammatory M1 phenotype to anti-inflammatory M2 ones. In vitro and ex-vivo studies implied that Cor-crosslinked samples exhibited low platelet accumulation and decreased thrombin generation. In vivo evaluation further confirmed that Cor-introducing could effectively consume ROS, thus exhibiting rapid endothelialization, suppressed inflammation and reduced mineral deposition. Overall, Cor crosslinking provided a bright future for blood vessels’ long-term patency and adapted to various blood-contacting surfaces.