National Engineering Research Center for Biomaterials and College of Biomedical Engineering, Sichuan University, 29 Wangjiang Road, Chengdu, 610064, China.
Venus Medtech (Hangzhou) Inc., China.
Biomaterials. 2023 May;296:122070. doi: 10.1016/j.biomaterials.2023.122070. Epub 2023 Feb 27.
Transcatheter heart valve replacement (THVR) is a novel treatment modality for severe heart valves diseases and has become the main method for the treatment of heart valve diseases in recent years. However, the lifespan of the commercial glutaraldehyde cross-linked bioprosthetic heart valves (BHVs) used in THVR can only serve for 10-15 years, and the essential reason for the failure of the valve leaflet material is due to these problems such as calcification, coagulation, and inflammation caused by glutaraldehyde cross-linking. Herein, a kind of novel non-glutaraldehyde cross-linking agent bromo-bicyclic-oxazolidine (OX-Br) has been designed and synthesized with both crosslinking ability and in-situ atom transfer radical polymerization (ATRP) function. Then OX-Br treated porcine pericardium (OX-Br-PP) are stepwise modified with co-polymer brushes of reactive oxygen species (ROS) response anti-inflammatory drug conjugated block and anti-adhesion polyzwitterion polymer block through the in-situ ATRP reaction to obtain the functional BHV material MPQ@OX-PP. Along with the great mechanical properties and anti-enzymatic degradation ability similar to glutaraldehyde-crosslinked porcine pericardium (Glut-PP), good biocompatibility, improved anti-inflammatory effect, robust anti-coagulant ability and superior anti-calcification property have been verified for MPQ@OX-PP by a series of in vitro and in vivo investigations, indicating the excellent application potential as a multifunctional heart valve cross-linking agent for OX-Br. Meanwhile, the strategy of synergistic effect with in situ generations of reactive oxygen species-responsive anti-inflammatory drug blocks and anti-adhesion polymer brushes can effectively meet the requirement of multifaceted performance of bioprosthetic heart valves and provide a valuable reference for other blood contacting materials and functional implantable materials with great comprehensive performance.
经导管心脏瓣膜置换术（THVR）是一种治疗严重心脏瓣膜疾病的新方法，近年来已成为心脏瓣膜疾病治疗的主要方法。然而，用于 THVR 的商业戊二醛交联生物瓣（BHV）的使用寿命只能持续 10-15 年，而导致瓣叶材料失效的根本原因是戊二醛交联引起的钙化、凝固和炎症等问题。在此，设计并合成了一种具有交联能力和原位原子转移自由基聚合（ATRP）功能的新型非戊二醛交联剂溴代双环恶唑烷（OX-Br）。然后通过原位 ATRP 反应，将 OX-Br 处理的猪心包（OX-Br-PP）依次修饰为具有活性氧（ROS）响应抗炎药物共轭嵌段和抗粘连聚两性离子聚合物嵌段的共聚物刷，得到功能 BHV 材料 MPQ@OX-PP。与戊二醛交联猪心包（Glut-PP）具有相似的机械性能和抗酶降解能力、良好的生物相容性、改善的抗炎效果、强大的抗凝血能力和优异的抗钙化性能，通过一系列体外和体内研究验证了 MPQ@OX-PP 的优异应用潜力，作为 OX-Br 的多功能心脏瓣膜交联剂。同时，ROS 响应性抗炎药物嵌段和抗粘连聚合物刷的原位生成的协同效应策略可以有效地满足生物瓣多方面性能的要求，并为其他血液接触材料和具有综合性能的功能性植入材料提供了有价值的参考。
