Abstract：
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.
摘要：
目前商业戊二醛（GA）-交联的生物瓣膜小叶（BVL）患有血栓栓塞并发症，钙化,和有限的耐用性，这是BVL临床应用的主要绊脚石。因此，开发新型BVL将是增强BVL的耐久性和缓解血栓栓塞并发症的迫切需要。在这项研究中,据报道，双交联剂（氧化多糖和天然活性交联剂）的快速有效的协作策略，以实现增强机械，和结构稳定性，BVL具有优异的血液相容性和抗钙化性能。二醛黄原胶（AXG）表现出优异的热稳定性，酸碱，盐,首先引入酶解交联去细胞猪心包(D-PP),然后再引入具有良好抗炎性能的姜黄素,抗凝,抗肝纤维化，和抗动脉粥样硬化的协同交联和多官能化D-PP获得AXG+Cur-PP。结构表征的综合评价，血液相容性,内皮化潜能，力学性能和组分稳定性表明,AXG+Cur-PP具有较好的抗血栓形成性能和内皮化潜能,更温和的免疫反应，与GA交联的PP相比，优异的抗钙化性能和增强的机械性能。总的来说,这种协同交联策略提供了一种新的解决方案，以实现BVL具有增强的机械性能和优异的抗凝血，抗炎,抗钙化,和促进内皮细胞增殖的能力。
