Self-adaptive covalent coating for vascular stents: Coordinated coagulation-inflammation regulation to support re-endothelialization for atherosclerosis control

  • Biomaterials. 2026 Feb:325:123600. doi: 10.1016/j.biomaterials.2025.123600.
Yanan Wang  1 ,  Qiongjun Zhu  1 ,  Zhezhe Chen  1 ,  Xiaoyu Wang  1 ,  Boxuan Ma  1 ,  Yao Wang  1 ,  Yun Xiao  1 ,  Rifang Luo  2 ,  Wenbin Zhang  3 ,  Yunbing Wang  4 ,  Guosheng Fu  5
Affiliations
  • 1. 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.
  • 2. National Engineering Research Center for Biomaterials and College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China.
  • 3. 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. Electronic address: [email protected].
  • 4. National Engineering Research Center for Biomaterials and College of Biomedical Engineering, Sichuan University, Chengdu, 610065, China. Electronic address: [email protected].
  • 5. 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. Electronic address: [email protected].
PMID: 40753783 DOI: 10.1016/j.biomaterials.2025.123600
Abstract

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.

Keywords
Cardiovascular stent; Coagulation-inflammation interaction; Re-endothelialization.
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