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A dual-crosslinking modification strategy as an alternative to glutaraldehyde for preparing valve materials
1College of Polymer Science and Engineering, Sichuan University, Chengdu, 610065, PR China.
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The longevity and applicability of glutaraldehyde cross-linked commercial bioprosthetic heart valves (BHVs) that are the first choice for the transcatheter heart valve replacement (THVR) remain limited due to thrombus accumulation, calcification, inflammatory reactions and poor endothelialization. In this study, we first performed the prefunctionalization treatment of dual crosslinking by carboxymethylated λ-carrageenan and 4-pentenoic acid on decellularized bovine pericardium; subsequently, we conducted a post-functionalization treatment by dual modification of immobilizing the cyclodextrin (CD)/rutin and organic selenium onto above-mentioned doubly cross-linked (DC) bovine pericardium through the amidation reaction; finally, we obtained the anticipated bioprosthetic heart valve with multiple functions (DC + CD/Rutin+Se-BP). Uniaxial tensile tests demonstrated that this doubly cross-linked BHV exhibited superior mechanical properties compared with glutaraldehyde-treated bovine pericardium, which is expected to increase its structural stability and service life. By introducing the CD/Rutin complex and organic selenium, DC + CD/Rutin+Se-BP not only exhibited the ability to inhibit the adsorption of plasma proteins, platelet aggregation and thrombosis but also presented the excellent anti-inflammatory and anti-calcification characteristics both in vitro and in vivo. Furthermore, DC + CD/Rutin+Se-BP also exhibited stable in situ nitric oxide (NO) catalytic release ability due to the immobilization of organic selenium, which endowed bioprosthetic heart valve with excellent compatibility with human umbilical vein endothelial cells (HUVECs) and facilitated the long-term promotion of its endothelialization process. In summary, this approach combining dual cross-linking and dual modification provides a promising strategy for future design of BHVs, and DC + CD/Rutin+Se-BP exhibits a bright prospect in the clinical applications of BHVs.
