College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, PR China.
College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, PR China; Experimental and Research Animal Institute, Sichuan University, Chengdu 610065, PR China.
Carbohydr Polym. 2023 Jun 15;310:120724. doi: 10.1016/j.carbpol.2023.120724. Epub 2023 Feb 18.
Currently commercial glutaraldehyde (GA)-crosslinked bioprosthetic valve leaflets (BVLs) suffer from thromboembolic complications, calcification, and limited durability, which are the major stumbling block to wider clinical application of BVLs. Thus, developing new-style BVLs will be an urgent need to enhance the durability of BVLs and alleviate thromboembolic complications. In this study, a quick and effective collaborative strategy of the double crosslinking agents (oxidized polysaccharide and natural active crosslinking agent) was reported to realize enhanced mechanical, and structural stability, excellent hemocompatibility and anti-calcification properties of BVLs. Dialdehyde xanthan gum (AXG) exhibiting excellent stability to heat, acid-base, salt, and enzymatic hydrolysis was first introduced to crosslink decellularized porcine pericardium (D-PP) and then curcumin with good properties of anti-inflammatory, anti-coagulation, anti-liver fibrosis, and anti-atherosclerosis was used to synergistically crosslink and multi-functionalize D-PP to obtain AXG + Cur-PP. A comprehensive evaluation of structural characterization, hemocompatibility, endothelialization potential, mechanical properties and component stability showed that AXG + Cur-PP exhibited better anti-thrombotic properties and endothelialization potential, milder immune responses, excellent anti-calcification properties and enhanced mechanical properties compared with GA-crosslinked PP. Overall, this cooperative crosslinking strategy provides a novel solution to achieve BVLs with enhanced mechanical properties and excellent anti-coagulation, anti-inflammatory, anti-calcification, and the ability to promote endothelial cell proliferation.
目前，商业戊二醛（GA）交联生物瓣叶（BVL）存在血栓栓塞并发症、钙化和耐用性有限等问题，这是 BVL 更广泛临床应用的主要障碍。因此，开发新型 BVL 将是增强 BVL 耐用性和减轻血栓栓塞并发症的迫切需要。在这项研究中，报道了一种快速有效的双交联剂（氧化多糖和天然活性交联剂）协同策略，以实现 BVL 的机械和结构稳定性增强、出色的血液相容性和抗钙化性能。首先，将具有良好的热稳定性、酸碱稳定性、盐稳定性和酶解稳定性的双醛黄原胶（AXG）用于交联脱细胞猪心包（D-PP），然后使用具有抗炎、抗凝、抗肝纤维化和抗动脉粥样硬化作用的姜黄素协同交联和多功能化 D-PP，得到 AXG+Cur-PP。结构表征、血液相容性、内皮化潜力、力学性能和成分稳定性的综合评价表明，与 GA 交联的 PP 相比，AXG+Cur-PP 具有更好的抗血栓形成性能和内皮化潜力、更温和的免疫反应、出色的抗钙化性能和增强的力学性能。总体而言，这种协同交联策略为实现具有增强的机械性能和出色的抗凝、抗炎、抗钙化以及促进内皮细胞增殖能力的 BVL 提供了一种新的解决方案。
