用红细胞膜对脱细胞基质进行大规模表面改性,促进心脏瓣膜的原位再生

IF 10.1 1区 工程技术 Q1 ENGINEERING, MULTIDISCIPLINARY Engineering Pub Date : 2024-10-01 DOI:10.1016/j.eng.2024.04.019
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引用次数: 0

摘要

原位再生是构建组织工程心脏瓣膜(TEHV)的一种前景广阔的策略。目前,脱细胞心脏瓣膜(DHV)被广泛用作TEHV支架。然而,脱细胞心脏瓣膜的血液相容性有限,内皮化困难,导致血栓形成和移植失败。红细胞膜(RBCM)具有良好的生物相容性和长期循环稳定性,被广泛应用于纳米颗粒的伪装给药,但目前还没有将其大规模应用于脱细胞细胞外基质(ECM)改性的报道。我们首次利用逐层组装策略将 RBCM 固定在 DHV 表面,构建了创新的 TEHV 支架。我们的研究结果表明,该支架能有效防止血浆蛋白吸附、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,从而显著改善了 DHV 的血液相容性。此外,RBCM 改性还能显著提高 DHV 的机械性能和酶稳定性。大鼠皮下包埋和腹主动脉植入模型表明,该支架可调节巨噬细胞极化为抗炎和促进建模的 M2 表型,并在早期促进内皮化和 ECM 重塑,而不会导致血栓形成和钙化。新型 TEHV 性能卓越,可以克服临床常用假体的局限性。
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Large-Scale Surface Modification of Decellularized Matrix with Erythrocyte Membrane for Promoting In Situ Regeneration of Heart Valve
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.
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来源期刊
Engineering
Engineering Environmental Science-Environmental Engineering
自引率
1.60%
发文量
335
审稿时长
35 days
期刊介绍: Engineering, an international open-access journal initiated by the Chinese Academy of Engineering (CAE) in 2015, serves as a distinguished platform for disseminating cutting-edge advancements in engineering R&D, sharing major research outputs, and highlighting key achievements worldwide. The journal's objectives encompass reporting progress in engineering science, fostering discussions on hot topics, addressing areas of interest, challenges, and prospects in engineering development, while considering human and environmental well-being and ethics in engineering. It aims to inspire breakthroughs and innovations with profound economic and social significance, propelling them to advanced international standards and transforming them into a new productive force. Ultimately, this endeavor seeks to bring about positive changes globally, benefit humanity, and shape a new future.
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