Abstract：
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.
摘要：
由于革命性的经导管主动脉瓣置换术（TAVR）技术，生物假体心脏瓣膜（BHV）已被广泛使用，但寿命有限。BHV以前的改性方法主要依靠戊二醛预交联和后续改性。在这项研究中,我们设计了一种基于共交联和共聚策略的聚-2-甲基丙烯酸羟乙酯（pHEMA）涂层BHV。我们的BHV通过在交联之前引入游离分子以同时实现交联和烯丙基部分固定，克服了戊二醛预固定的先前局限性。脱细胞猪心包与2-氨基-4-戊烯酸(APA)先通过戊二醛共交联得到烯化猪心包(APA-PP),然后将APA-PP与亲水单体甲基丙烯酸2-羟乙酯(HEMA)共聚制备pHEMA接枝猪心包(HEMA-PP)。与传统的戊二醛交联心包(GA)相比，HEMA-PP表现出降低的细胞毒性和显着增加的内皮细胞增殖（3天孵育后比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在皮下模型中保持低水平钙化的结构稳定。流体动力学性能和耐久性被证明符合ISO5840-3的要求。总之,HEMA-PP可能具有未来临床应用的潜力。重要声明：目前，生物人工心脏瓣膜（BHVs）有缺陷，包括细胞毒性，钙化和血栓形成，这会加速BHVs的结构性瓣膜变性并限制其使用寿命。我们开发了一种新的修饰策略，可以同时提高生物相容性，BHV的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特性证明了我们的临床应用策略的潜力.这项工作将有可能延长BHV的使用寿命，并为BHV的改装提供新的见解。
