In situ regeneration is a promising strategy for constructing tissue engineering heart valves (TEHVs). Currently, the decellularized heart valve (DHV) is extensively employed as a TEHV scaffold. Nevertheless, DHV exhibits limited blood compatibility and notable difficulties in endothelialization, resulting in thrombosis and graft failure. The red blood cell membrane (RBCM) exhibits excellent biocompatibility and prolonged circulation stability and is extensively applied in the camouflage of nanoparticles for drug delivery; however, there is no report on its application for large-scale modification of decellularized extracellular matrix (ECM). For the first time, we utilized a layer-by-layer assembling strategy to immobilize RBCM on the surface of DHV and construct an innovative TEHV scaffold. Our findings demonstrated that the scaffold significantly improved the hemocompatibility of DHV by effectively preventing plasma protein adsorption, activated platelet adhesion, and erythrocyte aggregation, and induced macrophage polarization toward the M2 phenotype in vitro. Moreover, RBCM modification significantly enhanced the mechanical properties and enzymatic stability of DHV. The rat models of subcutaneous embedding and abdominal aorta implantation showed that the scaffold regulated the polarization of macrophages into the anti-inflammatory and pro-modeling M2 phenotype and promoted endothelialization and ECM remodeling in the early stage without thrombosis and calcification. The novel TEHV exhibits excellent performance and can overcome the limitations of commonly used clinical prostheses.

中文翻译：

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红细胞膜对脱细胞基质进行大规模表面修饰促进心脏瓣膜原位再生


原位再生是构建组织工程心脏瓣膜 （TEHV） 的一种很有前途的策略。目前，脱细胞心脏瓣膜 （DHV） 被广泛用作 TEHV 支架。然而，DHV 表现出有限的血液相容性和明显的内皮化困难，导致血栓形成和移植失败。红细胞膜 （RBCM） 表现出优异的生物相容性和持久的循环稳定性，广泛用于纳米颗粒的伪装以进行药物递送;然而，没有关于其在脱细胞细胞外基质 （ECM） 的大规模修饰中的应用的报道。我们首次利用逐层组装策略将 RBCM 固定在 DHV 表面，并构建了创新的 TEHV 支架。我们的研究结果表明，该支架通过有效阻止血浆蛋白吸附、活化血小板粘附和红细胞聚集，并在体外诱导巨噬细胞向 M2 表型极化，显着改善了 DHV 的血液相容性。此外，RBCM 修饰显着增强了 DHV 的机械性能和酶稳定性。皮下包埋和腹主动脉植入大鼠模型显示，支架调节巨噬细胞极化为抗炎和促建模 M2 表型，并在早期促进内皮化和 ECM 重塑，无血栓形成和钙化。新型 TEHV 表现出优异的性能，可以克服临床常用修复体的局限性。