Huang Xueyu, Zheng Cheng, Ding Kailei, Zhang Shumang, Lei Yang, Wei Qingrong, Yang Li, Wang Yunbing
National Engineering Research Center for Biomaterials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, PR China.
National Engineering Research Center for Biomaterials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, PR China.
Acta Biomater. 2022 Dec;154:244-258. doi: 10.1016/j.actbio.2022.10.036. Epub 2022 Oct 25.
Bioprosthetic heart valves (BHVs) have been widely used due to the revolutionary transcatheter aortic valve replacement (TAVR) techniques but suffer from a limited lifespan. Previous modification methods of BHVs mainly rely on glutaraldehyde precrosslinking and subsequent modification. In this study, we have engineered a Poly-2-Hydroxyethyl methacrylate (pHEMA) coated BHV based on co-crosslinking and co-polymerization strategies. Our BHV overcomes previous limitations of glutaraldehyde prefixation by introducing free molecules before crosslinking to achieve the crosslinking and allyl moiety immobilization simultaneously. Decellularized porcine pericardium and 2-Amino-4-pentenoic acid (APA) are firstly co-crosslinked by glutaraldehyde to obtain alkenylated porcine pericardium (APA-PP), then APA-PP is copolymerized with hydrophilic monomer 2-Hydroxyethyl methacrylate (HEMA) to prepare pHEMA grafted porcine pericardium (HEMA-PP). Compared with traditional glutaraldehyde crosslinked pericardium (GA), HEMA-PP exhibits decreased cytotoxicity and significantly increased endothelialial cells proliferation (7-folds higher than GA after 3-day incubation). In vitro and ex vivo hemocompatibility studies demonstrate the superiority of HEMA-PP in anti-thrombogenicity, where the platelet adhesion decreased by levels of approximately 89% compared to GA. Moreover, HEMA-PP maintains structurally stable with a low level of calcification in the subcutaneous model. The hydrodynamic performance and durability are proven to meet the requirements of ISO 5840-3. Altogether, HEMA-PP may have the potential for future clinical application. STATEMENT OF SIGNIFICANCE: Currently, bioprosthetic heart valves (BHVs) have drawbacks including cytotoxicity, calcification and thrombosis, which would accelerate structural valvular degeneration and limit the service life of BHVs. We developed a new modification strategy that could simultaneously improve the biocompatibility, anti-calcification and anti-thrombotic properties of BHVs. Moreover, the appropriate durability and hydrodynamic property demonstrated the potential of our strategy for clinical application. This work will potentially prolong the service life of BHVs and provide new insight for the modification of BHVs.
生物人工心脏瓣膜（BHVs）由于革命性的经导管主动脉瓣置换术（TAVR）技术而被广泛使用，但使用寿命有限。以前对BHVs的修饰方法主要依赖于戊二醛预交联及随后的修饰。在本研究中，我们基于共交联和共聚策略设计了一种聚甲基丙烯酸2-羟乙酯（pHEMA）涂层的BHVs。我们的BHVs通过在交联前引入游离分子以同时实现交联和烯丙基部分固定，克服了以前戊二醛预固定的局限性。首先将脱细胞猪心包和2-氨基-4-戊烯酸（APA）用戊二醛共交联以获得烯基化猪心包（APA-PP），然后将APA-PP与亲水性单体甲基丙烯酸2-羟乙酯（HEMA）共聚以制备pHEMA接枝猪心包（HEMA-PP）。与传统的戊二醛交联心包（GA）相比，HEMA-PP表现出细胞毒性降低且内皮细胞增殖显著增加（孵育3天后比GA高7倍）。体外和离体血液相容性研究证明了HEMA-PP在抗血栓形成方面的优越性，与GA相比，血小板粘附降低了约89%。此外，HEMA-PP在皮下模型中结构保持稳定且钙化水平较低。流体动力学性能和耐久性经证明符合ISO 5840-3的要求。总之，HEMA-PP可能具有未来临床应用的潜力。重要性声明：目前，生物人工心脏瓣膜（BHVs）存在细胞毒性、钙化和血栓形成等缺点，这会加速瓣膜结构退变并限制BHVs的使用寿命。我们开发了一种新的修饰策略，可同时改善BHVs的生物相容性、抗钙化和抗血栓形成特性。此外，适当的耐久性和流体动力学性能证明了我们的策略在临床应用中的潜力。这项工作可能会延长BHVs的使用寿命，并为BHVs的修饰提供新的见解。
