Abstract：
Tissue-engineered heart valve (TEHV) has emerged as a prospective alternative to conventional valve prostheses. The decellularized heart valve (DHV) represents a promising TEHV scaffold that preserves the natural three-dimensional structure and retains essential biological activity. However, the limited mechanical strength, fast degradation, poor hemocompatibility, and lack of endothelialization of DHV restrict its clinical use, which is necessary for ensuring its long-term durability. Herein, we used oxidized chondroitin sulfate (ChS), one of the main components of the extracellular matrix with various biological activities, to cross-link DHV to overcome the above problems. In addition, the ChS-adipic dihydrazide was used to react with residual aldehyde groups, thus preventing potential calcification. The results indicated notable enhancements in mechanical properties and resilience against elastase and collagenase degradation in vitro as well as the ability to withstand extended periods of storage without compromising the structural integrity of valve scaffolds. Additionally, the newly cross-linked valves exhibited favorable hemocompatibility in vitro and in vivo, thereby demonstrating exceptional biocompatibility. Furthermore, the scaffolds exhibited traits of gradual degradation and resistance to calcification through a rat subcutaneous implantation model. In the rat abdominal aorta implantation model, the scaffolds demonstrated favorable endothelialization, commendable patency, and a diminished pro-inflammatory response. As a result, the newly constructed DHV scaffold offers a compelling alternative to traditional valve prostheses, which potentially advances the field of TEHV.
摘要：
组织工程心脏瓣膜（TEHV）已成为常规瓣膜假体的潜在替代品。脱细胞心脏瓣膜（DHV）代表了一种有前途的TEHV支架，可保留天然的三维结构并保留基本的生物活性。然而,有限的机械强度，快速降解，血液相容性差，DHV缺乏内皮化限制了其临床应用，这是必要的，以确保其长期耐久性。在这里，我们使用氧化硫酸软骨素（ChS），细胞外基质的主要成分之一，具有各种生物活性，交联DHV以克服上述问题。此外,ChS-己二酸二酰肼用于与残留的醛基反应，从而防止潜在的钙化。结果表明，在体外对弹性蛋白酶和胶原酶降解的机械性能和弹性以及承受长时间储存而不损害瓣膜支架的结构完整性的能力方面显着增强。此外,新交联的瓣膜在体外和体内表现出良好的血液相容性，从而证明了优异的生物相容性。此外，通过大鼠皮下植入模型，支架表现出逐渐降解和抗钙化的特征。在大鼠腹主动脉植入模型中,支架表现出良好的内皮化，值得称赞的通畅，和减少的促炎反应。因此,新建的DHV支架为传统瓣膜假体提供了引人注目的替代方案，这可能会推进TEHV领域。
