Ulvan mediated VE cadherin antibody and REDV peptide co-modification to improve endothelialization potential of bioprosthetic heart valves
Ulvan mediated VE cadherin antibody and REDV peptide co-modification to improve endothelialization potential of bioprosthetic heart valves
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Ulvan介导的VE钙粘蛋白抗体和REDV肽共修饰可提高生物人工心脏瓣膜的内皮化潜力
DOI：
10.1016/j.msec.2021.112337
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发表时间：
2021-08-11
影响因子：
7.9
通讯作者：
Wang, Jian'an
中科院分区：
文献类型：
--
作者：
Liu, Xianbao;Yu, Kaixiang;Wang, Jian'an
人口老龄化和退行性瓣膜疾病发病率的快速增加导致了人工生物心脏瓣膜（BHV）的更多使用。由于钙化、凝血和降解，目前临床使用的戊二醛交联生物瓣膜的耐久性较差。去细胞化可以通过去除异种细胞来部分减少钙化，但也可能导致血栓形成，这可以通过进一步的表面修饰来解决。天然硫酸多糖石莼多糖具有抗血栓形成和抗炎的特性，并且可以通过其肝素结合位点表现为类肝素以抑制蛋白质。VE-钙粘蛋白抗体和Arg-Glu-Asp-Val（REDV）肽可以促进选择性内皮细胞附着、粘附和增殖。在这项研究中，我们功能化去细胞猪心包膜（DPP）与石莼多糖，REDV，和VE-钙粘蛋白抗体（U-R-VE）。石莼多糖被共价修饰以作为VE-钙粘蛋白抗体的保护性涂层和间隔物，并抑制REDV。在体外试验中，我们发现，功能化显着和选择性地促进粘附和内皮细胞的生长，同时减少血小板粘附，炎症，体外钙化的DPP。在体内皮下植入模型中，与未修饰的心包相比，UR-VE修饰的DPP表现出更大的内皮化潜力和生物相容性。因此，U-R-VE修饰为制备具有增强的内皮化潜力的BHV的问题提供了有希望的解决方案。
An aging population and a rapid increase in the incidence of degenerative valve diseases have led to greater use of bioprosthetic heart valves (BHVs). The durability of glutaraldehyde cross-linked bioprostheses currently available for clinical use is poor due to calcification, coagulation, and degradation. Decellularization can partially reduce calcification by removal of xenogenic cells, but can also lead to thrombosis, which can be addressed by further surface modification. The natural sulfated polysaccharide ulvan possesses antithrombotic and anti-inflammatory properties, and can behave as a heparinoid to immobilize proteins through their heparin binding sites. VE-cadherin antibody and the Arg-Glu-Asp-Val (REDV) peptide can facilitate selective endothelial cell attachment, adhesion and proliferation. In this study, we functionalized decellularized porcine pericardium (DPP) with ulvan, REDV, and VE-cadherin antibody (U-R-VE). Ulvan was covalently modified to act as a protective coating and spacer for VE-cadherin antibody, and to immobilize REDV. In in vitro tests, we found that functionalization significantly and selectively promoted adhesion and growth of endothelial cells while reducing platelet adhesion, inflammation, and in vitro calcification of DPPs. In an in vivo subdermal implantation model, UR-VE modified DPP exhibited greater endothelialization potential and biocompatibility compared with unmodified pericardium. Thus, U-R-VE modification provides a promising solution to the problem of preparing BHVs with enhanced endothelialization potential.