PDF(Pubmed)
Abstract：
Bioprosthetic heart valve (BHV) replacement has been the predominant treatment for severe heart valve diseases over decades. Most clinically available BHVs are crosslinked by glutaraldehyde (GLUT), while the high toxicity of residual GLUT could initiate calcification, severe thrombosis, and delayed endothelialization. Here, we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of BHVs. In particular, recombinant humanized collagen type III (rhCOLIII), which was precisely customized with anti-coagulant and pro-endothelialization bioactivity, was first incorporated into the polyvinyl alcohol (PVA)-based hydrogel via hydrogen bond interactions. Then, tannic acid was introduced to enhance the mechanical performance of PVA-based hydrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of substrates. In vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLIII and TA possessed long-term anti-coagulant, accelerated endothelialization, mild inflammatory response and anti-calcification properties. Therefore, our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.
摘要：
几十年来，生物人工心脏瓣膜（BHV）置换一直是严重心脏瓣膜疾病的主要治疗方法。大多数临床可用的BHV通过戊二醛（GLUT）交联，而残余GLUT的高毒性可引发钙化，严重血栓形成,延迟内皮化。这里,我们解释了一种机械整合坚固的水凝胶-组织混合体，以提高BHV的性能。特别是,重组人源化III型胶原蛋白（rhCOLIII），这是精确定制的抗凝血和促内皮化生物活性，首先通过氢键相互作用结合到聚乙烯醇(PVA)基水凝胶中。然后，引入单宁酸以增强PVA基水凝胶的机械性能以及水凝胶层与生物衍生组织之间的界面结合，这是由于对各种基材具有很强的亲和力。体外和体内实验结果证实，由坚固的PVA基水凝胶包埋的rhCOLIII和TA修饰的GLUT交联的BHVs具有长期抗凝剂，加速内皮化，轻度炎症反应和抗钙化特性。因此,我们的机械整合稳健的水凝胶-组织混合策略显示了增强BHV植入后的服务功能和延长使用寿命的潜力.
