Hu Mengyue, Peng Xu, Yue Lunli, Ding Hongmei, Yu Xiaoshuang, Wan Chang, Cheng Can, Yu Xixun
College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, P.R. China.
Experimental and Research Animal Institute, Sichuan University, Chengdu 610065, P.R. China.
Biomater Sci. 2022 Sep 27;10(19):5535-5551. doi: 10.1039/d2bm00736c.
Commercial biological valve leaflets (BVLs) crosslinked with glutaraldehyde (GA) are at risk of accelerating damage and even failure, owing to the high cell toxicity of GA, acute thrombosis, and calcification in clinical applications. In this study, a novel joint strategy of double crosslinking agents (dialdehyde pectin (AP) and carbodiimide) and heparin-loaded hydrogel coating was developed, endowing BVLs with excellent mechanical properties and multiple performances. Herein, AP played two essential roles, the crosslinking agent and the main component of the hydrogel coating. Both experimental and theoretical results indicated that the mechanical properties and stability of double-crosslinked BVLs were comparable to those of GA, and heparin loaded in hydrogel coating could improve the hemocompatibility of AP + EDC/NHS-PP. Further, cytocompatibility and tests showed that compared with GA-PP, AP + EDC/NHS + CS + Hep-PP has exhibited good endothelialization ability, mild immune response and anti-calcification performance and therefore prompts it to be an extremely valuable candidate for more durable and multifunctional BVLs.
与戊二醛（GA）交联的商用生物瓣膜小叶（BVLs）在临床应用中存在加速损伤甚至失效的风险，这是由于GA的高细胞毒性、急性血栓形成和钙化。在本研究中，开发了一种新型的双交联剂（二醛果胶（AP）和碳二亚胺）与载肝素水凝胶涂层的联合策略，赋予BVLs优异的机械性能和多种性能。在此，AP发挥了两个重要作用，即交联剂和水凝胶涂层的主要成分。实验和理论结果均表明，双交联BVLs的机械性能和稳定性与GA相当，水凝胶涂层中负载的肝素可改善AP + EDC/NHS-PP的血液相容性。此外，细胞相容性测试表明，与GA-PP相比，AP + EDC/NHS + CS + Hep-PP具有良好的内皮化能力、轻微的免疫反应和抗钙化性能，因此促使其成为更耐用和多功能BVLs的极具价值的候选材料。
