National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
J Mater Chem B. 2019 Mar 7;7(9):1427-1434. doi: 10.1039/c8tb02565g. Epub 2019 Feb 5.
Transcatheter aortic valve implantation (TAVI) has been developed years ago for patients who cannot undergo a surgical aortic valve replacement (SAVR). Although TAVI possesses the advantages of lower trauma and simpler manipulation compared to SAVR, the need for storage in glutaraldehyde (GLU) and a tedious intraoperative assembly process have caused great inconvenience for its further application. A pre-mounted TAVI valve assembled by mounting a dry valve frame to a delivery system is expected to address these problems. However, the currently used GLU treated leaflet cannot unfold normally after being crimped for a long-term and loses its function when the BHV is assembled to the catheter. Besides, its cytotoxicity and immune response after implantation are still problems to be solved. In the present study, a hydrogel hybrid porcine pericardium (HHPP) approach was developed to endow the BHVs with a favorable unfolding property and good biocompatibility. Three monomers with different charge characteristics (sodium acrylate, 2-methacryloyloxyethyl phosphorylcholine, and acryloyloxyethyltrimethyl ammonium chloride) were complexed with GLU treated PP (GLU-PP) to form three kinds of HHPPs (SAAH-PP, MPCH-PP, and DACH-PP). The results of the crimping simulation experiment showed that all HHPPs could quickly recover in PBS after being folded for 10 days, while the traditional BHVs (GLU-PP) could not recover under the same conditions. Bovine serum albumin adsorption and platelet adhesion test showed that SAAH-PP and MPCH-PP had good anti-adhesion abilities. A cell culture study indicated that all the three HHPPs promoted HUVEC growth and proliferation. In vivo biocompatibility studies showed that the immune response induced by MPCH-PP was reduced compared to that by GLU-PP. These studies demonstrated that the strategy of MPC hydrogel hybridization may be an effective approach to prepare a pre-mounted TAVI valve with improved biocompatibility.
经导管主动脉瓣植入术（TAVI）是多年前为不能接受外科主动脉瓣置换术（SAVR）的患者开发的。虽然 TAVI 与 SAVR 相比具有创伤小、操作简单的优点，但需要在戊二醛（GLU）中储存以及繁琐的术中组装过程，给其进一步应用带来了极大的不便。通过将干瓣膜框架安装到输送系统上来组装预安装的 TAVI 瓣膜，有望解决这些问题。然而，目前使用的 GLU 处理的瓣叶在长期卷曲后不能正常展开，并在 BHV 与导管组装时失去功能。此外，其植入后的细胞毒性和免疫反应仍然是需要解决的问题。在本研究中，开发了一种水凝胶杂化猪心包（HHPP）方法，以使 BHV 具有良好的展开性能和良好的生物相容性。三种具有不同电荷特性的单体（丙烯酸钠、2-甲基丙烯酰氧乙基磷酸胆碱和丙烯酰氧乙基三甲基氯化铵）与 GLU 处理的 PP（GLU-PP）复合，形成三种 HHPP（SAAH-PP、MPCH-PP 和 DACH-PP）。卷曲模拟实验结果表明，所有 HHPP 在折叠 10 天后在 PBS 中都能迅速恢复，而在相同条件下传统的 BHV（GLU-PP）则不能恢复。牛血清白蛋白吸附和血小板黏附试验表明，SAAH-PP 和 MPCH-PP 具有良好的抗黏附能力。细胞培养研究表明，三种 HHPP 均能促进 HUVEC 的生长和增殖。体内生物相容性研究表明，与 GLU-PP 相比，MPCH-PP 引起的免疫反应减少。这些研究表明，MPC 水凝胶杂化策略可能是一种有效的方法，可制备具有改善生物相容性的预安装 TAVI 瓣膜。
