Yang Ying, Gao Peng, Wang Juan, Tu Qiufen, Bai Long, Xiong Kaiqin, Qiu Hua, Zhao Xin, Maitz Manfred F, Wang Huaiyu, Li Xiangyang, Zhao Qiang, Xiao Yin, Huang Nan, Yang Zhilu
Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane 4059, Australia.
Research (Wash D C). 2020 Apr 24;2020:9203906. doi: 10.34133/2020/9203906. eCollection 2020.
Stenting is currently the major therapeutic treatment for cardiovascular diseases. However, the nonbiogenic metal stents are inclined to trigger a cascade of cellular and molecular events including inflammatory response, thrombogenic reactions, smooth muscle cell hyperproliferation accompanied by the delayed arterial healing, and poor reendothelialization, thus leading to restenosis along with late stent thrombosis. To address prevalence critical problems, we present an endothelium-mimicking coating capable of rapid regeneration of a competently functioning new endothelial layer on stents through a stepwise metal (copper)-catechol-(amine) (MCA) surface chemistry strategy, leading to combinatorial endothelium-like functions with glutathione peroxidase-like catalytic activity and surface heparinization. Apart from the stable nitric oxide (NO) generating rate at the physiological level (2.2 × 10 mol/cm/min lasting for 60 days), this proposed strategy could also generate abundant amine groups for allowing a high heparin conjugation efficacy up to ∼1 g/cm, which is considerably higher than most of the conventional heparinized surfaces. The resultant coating could create an ideal microenvironment for bringing in enhanced anti-thrombogenicity, anti-inflammation, anti-proliferation of smooth muscle cells, re-endothelialization by regulating relevant gene expressions, hence preventing restenosis in vivo. We envision that the stepwise MCA coating strategy would facilitate the surface endothelium-mimicking engineering of vascular stents and be therefore helpful in the clinic to reduce complications associated with stenosis.
支架植入术是目前治疗心血管疾病的主要方法。然而，非生物源性金属支架容易引发一系列细胞和分子事件，包括炎症反应、血栓形成反应、平滑肌细胞过度增殖并伴有动脉愈合延迟以及内皮再形成不良，从而导致再狭窄和晚期支架血栓形成。为了解决这些普遍存在的关键问题，我们提出了一种模仿内皮的涂层，该涂层能够通过逐步的金属（铜）-儿茶酚-（胺）（MCA）表面化学策略在支架上快速再生功能正常的新内皮细胞层，从而实现具有谷胱甘肽过氧化物酶样催化活性和表面肝素化的组合内皮样功能。除了在生理水平上稳定的一氧化氮（NO）生成速率（2.2×10⁻⁶mol/cm²/min，持续60天）外，该策略还可以产生大量胺基，以实现高达约1μg/cm²的高肝素结合效率，这大大高于大多数传统的肝素化表面。所得涂层可以创造一个理想的微环境，通过调节相关基因表达来增强抗血栓形成、抗炎、抑制平滑肌细胞增殖和促进内皮再形成，从而在体内预防再狭窄。我们设想，逐步的MCA涂层策略将促进血管支架的表面内皮模仿工程，因此有助于临床减少与狭窄相关的并发症。
