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

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.