Wang Yanan, Zhu Qiongjun, Chen Zhezhe, Wang Xiaoyu, Ma Boxuan, Wang Yao, Xiao Yun, Luo Rifang, Zhang Wenbin, Wang Yunbing, Fu Guosheng
Department of Cardiology, Sir Run Run Shaw Hospital School of Medicine, Zhejiang University, Hangzhou, 310016, China; Zhejiang Key Laboratory of Cardiovascular Intervention and Precision Medicine, Hangzhou, 310016, China; Engineering Research Center for Cardiovascular Innovative Devices of Zhejiang Province, Hangzhou, 310016, China.
National Engineering Research Center for Biomaterials and College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.
Biomaterials. 2026 Feb;325:123600. doi: 10.1016/j.biomaterials.2025.123600. Epub 2025 Aug 2.
Therapeutic-coated vascular stents are one of the key directions in the clinical treatment of atherosclerosis. However, vascular injury and implant stimulation trigger a feedback loop between coagulation and inflammation, impairing endothelial cell (EC) function, which is critical for long-term success in atherosclerotic vessels. Here, we designed a self-adaptive covalent coating stent that integrates thrombin-responsive release of apixaban as a coagulation modulator and an antioxidant polyphenol as an anti-inflammatory. This pathologic microenvironment-responsive coating regulates coagulation-inflammation loop post-implantation. The nanogels within the coating dynamically response to thrombin, the upstream initiator of coagulation-inflammation, to release apixaban in high thrombotic risk conditions while retaining it in low-risk states. Epigallocatechin gallate (EGCG), functioning as a cross-linker and the ROS scavagener, detaches in response to oxidative stress. As such, the coating enables blockade of coagulation-inflammation loop, synergistically protects ECs from inflammatory damage, promotes endothelial regeneration, and inhibits endothelial-to-mesenchymal transition (EndMT), efficiently modulating the inflammatory microenvironment via localized and coordinated regulation of coagulation-inflammation loop. Furthermore, the implantation in an atherosclerotic rabbit model demonstrated that the coating inhibits plaque deterioration linked to inflammation and endothelial damage. This dual-responsive strategy offers a promising avenue for therapeutic stents by mitigating the coagulation-inflammation loop and supporting endothelial repair in atherosclerotic vessels.
治疗性涂层血管支架是动脉粥样硬化临床治疗的关键方向之一。然而，血管损伤和植入刺激会引发凝血与炎症之间的反馈循环，损害内皮细胞（EC）功能，而内皮细胞功能对于动脉粥样硬化血管的长期成功治疗至关重要。在此，我们设计了一种自适应共价涂层支架，该支架整合了凝血酶响应释放的阿哌沙班作为凝血调节剂和一种抗氧化多酚作为抗炎剂。这种病理微环境响应涂层在植入后调节凝血-炎症循环。涂层内的纳米凝胶对凝血-炎症的上游启动因子凝血酶动态响应，在高血栓形成风险条件下释放阿哌沙班，而在低风险状态下保留它。表没食子儿茶素没食子酸酯（EGCG）作为交联剂和活性氧清除剂，会响应氧化应激而分离。因此，该涂层能够阻断凝血-炎症循环，协同保护内皮细胞免受炎症损伤，促进内皮再生，并抑制内皮-间充质转化（EndMT），通过对凝血-炎症循环的局部和协同调节有效调节炎症微环境。此外，在动脉粥样硬化兔模型中的植入表明，该涂层可抑制与炎症和内皮损伤相关的斑块恶化。这种双重响应策略通过减轻凝血-炎症循环并支持动脉粥样硬化血管中的内皮修复，为治疗性支架提供了一条有前景的途径。
