Chen Chong, Zhang Chunle, Yu Tao, Qin Yumei, Chen Yu, Xiong Yan, Luo Rifang, Wang Yunbing, Fu Ping
Department of Nephrology, Institute of Kidney Diseases, West China Hospital of Sichuan University, Chengdu, 610041, PR China.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, PR China.
Biomaterials. 2026 Jan;324:123486. doi: 10.1016/j.biomaterials.2025.123486. Epub 2025 Jun 6.
During cardiovascular-stent endothelialization, application of an endothelium-mimetic coating is desirable to establish a conducive microenvironment that promotes endothelialization, thereby reducing the risks of in-stent thrombosis and restenosis. In this study, we construct an endothelium-mimetic coating on vascular stents assisted by metal-phenolic networks (MPNs). The functional components are integrated through a layer-by-layer self-assembly technique with positively charged polyethyleneimine, negatively charged hyaluronic acid (HA), and MPNs composed of epigallocatechin gallate and Cu as a sandwiched assisting interlayer. Vasoactive nitric oxide (NO) released by Cu catalysis along with the glycocalyx major component HA modification on the surface, endow vascular stents with protective functionalities similar to that of natural endothelial cells. The presence of cation-anion electrolytes and polyphenols enhances the loading, stability, and uniformity of the coating through various interactions such as electrostatic adsorption, hydrogen bonding, π-π stacking, and covalent crosslinking of phenol-aldehyde-amine. Systematic in-vitro and in-vivo studies demonstrate that this coating significantly reduces platelet adhesion and activation and thrombus formation, selectively promotes endothelial cells proliferation and regulates the behaviour of smooth muscle cells, and mitigates inflammatory responses by the synergistic effects of NO catalytic release and glycocalyx functionalization. In-vivo stent implantation experiment reveals that, compared to bare stents, this coating accelerates stent endothelialization and inhibits intimal hyperplasia of vessels. Three months after implantation, the lumen loss rate of the coated stent is only one-third of that of the bare stent. Overall, the MPNs-assisted construction of multi-layered endothelium-mimetic polyelectrolyte coatings with a dual-modality strategy integrating contact therapy via glycocalyx functionalization and gas therapy via NO generation provides innovative insights for the development of next-generation stents. The proposed method can serve as a universal surface-modification strategy to enhance the biocompatibility of implantable cardiovascular devices.
在心血管支架内皮化过程中，应用内皮模拟涂层有助于建立促进内皮化的有利微环境，从而降低支架内血栓形成和再狭窄的风险。在本研究中，我们在金属-酚网络（MPN）辅助下在血管支架上构建了内皮模拟涂层。功能成分通过层层自组装技术与带正电荷的聚乙烯亚胺、带负电荷的透明质酸（HA）以及由表没食子儿茶素没食子酸酯和铜组成的MPN作为夹心辅助中间层进行整合。铜催化释放的血管活性一氧化氮（NO）以及表面糖萼主要成分HA的修饰，赋予血管支架与天然内皮细胞相似的保护功能。阳离子-阴离子电解质和多酚的存在通过静电吸附、氢键、π-π堆积以及酚醛胺的共价交联等各种相互作用增强了涂层的负载量、稳定性和均匀性。系统的体外和体内研究表明，这种涂层显著降低血小板粘附、活化和血栓形成，选择性促进内皮细胞增殖并调节平滑肌细胞行为，并通过NO催化释放和糖萼功能化的协同作用减轻炎症反应。体内支架植入实验表明，与裸支架相比，这种涂层加速了支架内皮化并抑制血管内膜增生。植入三个月后，涂层支架的管腔损失率仅为裸支架的三分之一。总体而言，MPN辅助构建具有双模态策略的多层内皮模拟聚电解质涂层，该策略通过糖萼功能化的接触疗法和通过NO生成的气体疗法相结合，为下一代支架的开发提供了创新思路。所提出的方法可作为一种通用的表面改性策略，以提高可植入心血管装置的生物相容性。
