PDF(Pubmed)
Abstract：
With the aging of the population in worldwide, valvular heart disease has become one of the most prominent life-threatening diseases in human health, and heart valve replacement surgery is one of the therapeutic methods for valvular heart disease. Currently, commercial bioprosthetic heart valves (BHVs) for clinical application are prepared with xenograft heart valves or pericardium crosslinked by glutaraldehyde. Due to the residual cell toxicity from glutaraldehyde, heterologous antigens, and immune response, there are still some drawbacks related to the limited lifespan of bioprosthetic heart valves, such as thrombosis, calcification, degeneration, and defectiveness of re-endothelialization. Therefore, the problems of calcification, defectiveness of re-endothelialization, and poor biocompatibility from the use of bioprosthetic heart valve need to be solved. In this study, hydrogel hybrid heart valves with improved anti-calcification and re-endothelialization were prepared by taking decellularized porcine heart valves as scaffolds following grafting with double bonds. Then, the anti-biofouling zwitterionic monomers 2-methacryloyloxyethyl phosphorylcholine (MPC) and vascular endothelial growth factor (VEGF) were utilized to obtain a hydrogel-coated hybrid heart valve (PEGDA-MPC-DHVs@VEGF). The results showed that fewer platelets and thrombi were observed on the surface of the PEGDA-MPC-DHVs@VEGF. Additionally, the PEGDA-MPC-DHVs@VEGF exhibited excellent collagen stability, biocompatibility and re-endothelialization potential. Moreover, less calcification deposition and a lower immune response were observed in the PEGDA-MPC-DHVs@VEGF compared to the glutaraldehyde-crosslinked DHVs (Glu-DHVs) after subcutaneous implantation in rats for 30 days. These studies demonstrated that the strategy of zwitterionic hydrogels loaded with VEGF may be an effective approach to improving the biocompatibility, anti-calcification and re-endothelialization of bioprosthetic heart valves.
摘要：
随着世界人口的老龄化,心脏瓣膜病已成为人类健康中最突出的威胁生命的疾病之一,心脏瓣膜置换术是心脏瓣膜病的治疗方法之一。目前,用于临床应用的商业生物人工心脏瓣膜（BHV）是用戊二醛交联的异种移植心脏瓣膜或心包制备的。由于戊二醛残留的细胞毒性，异源抗原，和免疫反应，仍然存在一些与生物人工心脏瓣膜寿命有限有关的缺点，如血栓形成，钙化,变性,和再内皮化的缺陷。因此,钙化的问题，再内皮化的缺陷，使用生物人工心脏瓣膜需要解决生物相容性差的问题。在这项研究中,通过将脱细胞猪心脏瓣膜作为双键移植后的支架来制备具有改善的抗钙化和再内皮化的水凝胶混合心脏瓣膜。然后，抗生物污染两性离子单体2-甲基丙烯酰氧基乙基磷酰胆碱（MPC）和血管内皮生长因子（VEGF）用于获得水凝胶涂层的混合心脏瓣膜（PEGDA-MPC-DHVs@VEGF）。结果显示,在PEGDA-MPC-DHVs@VEGF的表面观察到较少的血小板和血栓。此外,PEGDA-MPC-DHVs@VEGF表现出优异的胶原稳定性,生物相容性和再内皮化潜力。此外，在大鼠皮下植入30天后,与戊二醛交联的DHV(Glu-DHV)相比,在PEGDA-MPC-DHV@VEGF中观察到较少的钙化沉积和较低的免疫应答.这些研究表明，负载VEGF的两性离子水凝胶的策略可能是提高生物相容性的有效途径。生物人工心脏瓣膜的抗钙化和再内皮化。
