Du Zeyu, Huang Yuting, Ma Qing, Zhang Wentai, Fu Yan, Huang Nan, Li Xin, Yang Zhilu, Tian Wenjie
School of Materials Science and Engineering, Key Lab of Advanced Technology for Materials of Education Ministry, Southwest Jiaotong University, Chengdu, Sichuan, 610031, China.
Dongguan Key Laboratory of Smart Biomaterials and Regenerative Medicine, The Tenth Affiliated Hospital, Southern Medical University, Dongguan, Guangdong, 523059, China.
Bioact Mater. 2025 Apr 1;50:1-13. doi: 10.1016/j.bioactmat.2025.03.019. eCollection 2025 Aug.
Surfaces with enduring and superior antithrombotic properties are essential for long-term blood-contacting devices. While current surface engineering strategies integrating anticoagulants and antiplatelet agents show promise in mimicking the non-thrombogenic properties of the endothelium, their long-term effectiveness remains limited. Here, we report an easy-to-perform, dual-biomimetic surface engineering strategy for tailoring long-acting endothelium-mimicking anti-thrombotic surfaces. We first designed a foot protein-5 (Mefp-5) mimic rich in amine and clickable alkynyl groups to polymerize-deposit a chemical robust coating onto the surface through a mussel-inspired adhesion mechanism. Then, a clickable nitric oxide (NO, an antiplatelet agent)-generating enzyme and the anticoagulant heparin were sequentially co-grafted onto the chemical robust coatings via click chemistry and carbodiimide chemistry. Our results demonstrate that this engineered surface achieved an impressive NO catalytic release efficiency of up to 88 %, while heparin retained 86 % of its bioactivity even after one month of exposure to PBS containing NO donor. Both and experiments confirmed that this robust endothelium-mimicking coating substantially reduces thrombosis formation. Overall, our long-acting endothelium-mimicking anti-thrombotic coatings present a promising and feasible strategy to address thrombosis-related challenges associated with blood-contacting devices.
具有持久且卓越抗血栓性能的表面对于长期与血液接触的设备至关重要。虽然目前整合抗凝剂和抗血小板药物的表面工程策略在模拟内皮细胞的非血栓形成特性方面显示出前景,但其长期有效性仍然有限。在此,我们报告一种易于实施的双仿生表面工程策略,用于定制长效模拟内皮细胞的抗血栓表面。我们首先设计了一种富含胺基和可点击炔基的足蛋白-5(Mefp-5)模拟物,通过受贻贝启发的粘附机制在表面聚合沉积一层化学稳定性高的涂层。然后,通过点击化学和碳二亚胺化学,将一种可点击的一氧化氮(NO,一种抗血小板药物)生成酶和抗凝剂肝素依次共接枝到化学稳定性高的涂层上。我们的结果表明,这种工程表面实现了高达88%的令人印象深刻的NO催化释放效率,而即使在暴露于含有NO供体的PBS中一个月后,肝素仍保留其86%的生物活性。体外和体内实验均证实,这种坚固的模拟内皮细胞涂层可显著减少血栓形成。总体而言,我们的长效模拟内皮细胞抗血栓涂层为解决与血液接触设备相关的血栓形成相关挑战提供了一种有前景且可行的策略。