An oxidized chondroitin sulfate-crosslinked and CuCDs-loaded decellularized bovine pericardium with improved anti-coagulation, pro-endothelialization and anti-calcification properties for BHVs

Abstract

With the growth of the elderly people and the development of transcatheter aortic valve replacement (TAVR) technology, bioprosthetic heart valves (BHVs) originating from the decellularized bovine pericardium (DBP) have become a favourable option for severe valvular heart disease (VHD). However, currently, available commercial bioprosthetic heart valves prepared from glutaraldehyde (GA)-crosslinked xenografts have limited durability because of various factors, including severe cytotoxicity, inflammatory response, poor pro-endothelialization ability and calcification. Therefore, the development of valve materials with better performance is urgent. In this work, we first synthesized Cu-doped carbon dots (CuCDs) with excellent biocompatibility and high stability using sodium citrate, ethylenediamine and copper chloride. Subsequently, oxidized chondroitin sulfate (OCS) was used to crosslink the decellularized bovine pericardium to obtain OCS–BP followed by loading CuCDs onto the surface of this OCS-fixed BP sample through amide bonds formed by an EDC/NHS-catalyzed reaction between the functional groups on CuCDs and OCS–BP to prepare the BHV (CuCDs–OCS–BP) with specific properties. Relevant experiments conducted both in vivo and in vitro indicate that CuCDs–OCS–BP with good stability showed improved mechanical properties, compliance and flexibility, encouraging HUVEC-cytocompatibility, excellent anti-blood cell adhesion, antithrombogenic properties, anti-inflammatory and anti-calcification properties, and a good endothelialisation ability due to the catalytic generation of endogenous nitric oxide. Overall, CuCDs–OCS–BP is a promising material for BHVs.