金属–酚表面化学应用于可降解聚三亚甲基碳酸酯改性构建一氧化氮催化释放涂层

Metal-Phenolic-(Amine) Surface Chemistry for Generating Nitric Oxide on Biodegradable Polymer Matrix Vascular Stent Coating

摘要: 聚三亚甲基碳酸酯(PTMC)因其具有表面溶蚀性特点、良好的生物相容性以及药物缓释性在可降解植入器械如血管支架表面改性上表现出广阔的应用前景。基于金属–酚表面化学构建的一氧化氮(NO)催化释放功能涂层已经被证实应用血管支架表面改性具有抗凝血、抑制平滑肌细胞增殖和促进内皮再生等多重生物学功能。然而，该NO催化释放涂层能否应用于可降解PTMC材料表面改性还未有过报道。因此，本研究采用旋涂的方法在支架材料表面首先制备PTMC涂层，随后基于金属–酚表面化学，利用没食子酸(gallic acid, GA)和硒代胱胺(selenocystamine, SeCA)共价结合形成网络结构，以Cu²⁺作为交联剂将上述网络结构进行交联，探究PTMC涂层表面构建具有Cu^II-GA/SeCA网络结构的NO催化涂层。研究结果证明，得益于GA多酚具有的广谱材料粘附特性，在PTMC涂层表面成功地构建了Cu^II-GA/SeCA涂层，且实现了NO催化释放速率在2~6.2 × 10⁻¹⁰ mol × cm⁻² × min⁻¹之间可调控。催化释放的NO通过特异性上调血小板环磷酸鸟苷(cGMP)表达抑制血小板的粘附与激活，证实了基于金属–酚表面化学的NO-催化释放涂层能应用于可降解聚合物涂层表面改性。

Abstract: Polytrimethylene carbonate (PTMC) shows broad application prospects in surface modification of degradable implantable devices such as vascular stents due to its surface erosion characteristics, good biocompatibility and drug slow release. The functional coating for the catalytic release of nitric oxide (NO) based on metal-phenol surface chemistry has been proven to have multiple biological functions such as anticoagulation, inhibition of smooth muscle cell proliferation, and promotion of endothelial regeneration by surface modification of vascular stents. However, it has not been reported whether the NO catalytic release coating can be applied to the surface modification of degradable PTMC materials. Therefore, in this study, the spin coating method was used to first prepare the PTMC coating on the surface of the stent material, and then based on the metal-phenol surface chemistry, the use of gallic acid (GA) and selenocystamine (SeCA) covalently combined to form network structure, using Cu²⁺ as a cross-linking agent to cross-link the above-mentioned network structure, and explore the construction of a NO catalytic coating with Cu^II-GA/SeCA network structure on the surface of the PTMC coating. The research results prove that, thanks to the broad-spectrum material adhesion characteristics of GA polyphenols, Cu^II-GA/SeCA coatings were successfully constructed on the surface of PTMC coatings, and the NO catalytic release rate was adjusted between 2~6.2 × 10⁻¹⁰ mol × cm⁻² × min⁻¹. Catalytic release of NO inhibits platelet adhe-sion and activation by specifically up-regulating the expression of platelet cyclic guanosine phos-phate (cGMP), confirming that the NO-catalytic release coating based on metal-phenolic-(amine) surface chemistry can be applied to the surface of degradable polymer coatings modified.