Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.
Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.
ACS Appl Mater Interfaces. 2023 Aug 16;15(32):38247-38263. doi: 10.1021/acsami.3c05984. Epub 2023 Aug 7.
Coronary atherosclerosis is closely related to inflammation and oxidative stress. Owing to poor biocompatibility, lack of personalized treatment, and late toxic side effects, traditional drug-eluting stent intervention, releasing antiproliferative drugs, can delay endothelial repair and cause late thrombosis. The inflammation caused by atherosclerosis results in an acidic microenvironment and oxidative stress, which can be considered as triggers for precise and intelligent treatment. Here, we used catechol hyaluronic acid (C-HA) and cystamine (Cys) to prepare C-HA-Cys hydrogel coatings by amide reaction. The HS-releasing donor allicin was loaded in the hydrogel to form an intelligent biomimetic coating. The disulfide bond of Cys made the cross-linked network redox-responsive to the inflammation and oxidative stress in the microenvironment by releasing the drug and HS intelligently to combat the side effects of stent implantation. This study evaluated the hemocompatibility, anti-inflammatory capacity, vascular wall cytocompatibility, and in vivo histocompatibility of this intelligent hydrogel coating. Furthermore, the effect of HS released from the coating on atherosclerosis-related signaling pathways such as CD31 and cystathionine γ-lyase (CSE), CD36, and ACAT-1 was investigated. Our results indicate that the C-HA-Cys-Allicin hydrogel coating could be manufactured on the surface of vascular interventional devices to achieve a precise response to the microenvironment of the lesion to release drug, which can attain the purpose of prevention of in-stent restenosis and ensure the effectiveness and safety of the application of interventional devices.
冠状动脉粥样硬化与炎症和氧化应激密切相关。由于传统的药物洗脱支架干预具有较差的生物相容性、缺乏个性化治疗以及晚期毒性副作用,其释放抗增殖药物会延迟内皮修复并导致晚期血栓形成。动脉粥样硬化引起的炎症导致酸性微环境和氧化应激,可以被认为是精确和智能治疗的触发因素。在这里,我们使用儿茶酚透明质酸(C-HA)和半胱胺(Cys)通过酰胺反应制备 C-HA-Cys 水凝胶涂层。将 HS 释放供体大蒜素负载到水凝胶中,形成智能仿生涂层。Cys 的二硫键通过智能地释放药物和 HS 使交联网络对微环境中的炎症和氧化应激具有氧化还原响应性,从而对抗支架植入的副作用。本研究评估了这种智能水凝胶涂层的血液相容性、抗炎能力、血管壁细胞相容性和体内组织相容性。此外,还研究了涂层释放的 HS 对与动脉粥样硬化相关的信号通路(如 CD31 和胱硫醚γ-裂解酶(CSE)、CD36 和 ACAT-1)的影响。我们的结果表明,可以在血管介入器械的表面制造 C-HA-Cys-大蒜素水凝胶涂层,以实现对病变微环境的精确响应,从而释放药物,达到预防支架内再狭窄的目的,并确保介入器械应用的有效性和安全性。