PEGNB-Heparin-Liposome composite hydrogels for in situ spraying and ultra-fast adhesion: meeting the challenges of endothelial repair of vascular injury

Carotid atherosclerosis is an essential cause of transient cerebral ischemia, stroke, and other cerebrovascular diseases, and carotid endarterectomy (CEA) is currently the most effective treatment for removing plaque and restoring the vascular lumen. However, the CEA disrupts the integrity and functionality of the endothelium and predisposes it to complications such as restenosis and thrombosis. Hydrogels can closely mimic the natural extracellular matrix, allowing a wide tuning of physical and chemical properties. These properties make hydrogels the most promising candidate materials for the repair of vascular injured intima. In this study, a multifunctional intimal repair hydrogel of poly(ethylene glycol)-norbornene (PEGNB)/ Heparin/ Liposome is proposed with the advantages of ultra-rapid adhesion to the wet tissue of the vascular inner wall, maintenance of adhesion stability under continuous erosion by blood flow. The hydrogel was supplemented with poly(vinyl butyral) (PVB) to reduce its swelling rate, and Rapamycin (RAPA) was encapsulated in this study as the drug into the cationic liposomes. This composite multifunctional (PNHB@Lip(RAPA)) hydrogel has exhibited outstanding anti-coagulation properties, markedly suppressed the proliferation and migration of SMCs, and displayed favourable cytocompatibility and blood compatibility. Concurrently, the capacity of the PNHB@Lip(RAPA) hydrogel to stimulate endovascular regeneration and deter restenosis and thrombus formation was validated through carotid intima damage repair experiments. These findings collectively indicate that the PNHB@Lip(RAPA) hydrogel represents a promising material for intimal injury repair, offering innovative insights into intimal repair methodologies. Statement of Significance Carotid atherosclerosis is a leading cause of transient cerebral ischemia, stroke, and cerebrovascular disorders. Although carotid endarterectomy (CEA) effectively removes plaques, it damages endothelial integrity, increasing the risk of restenosis and thrombosis. To address this, we developed PNHB@Lip(RAPA), a multifunctional intimal repair hydrogel composed of PEGNB, heparin, and rapamycin-encapsulated liposomes. This hydrogel rapidly adheres to wet vascular walls, resists blood flow erosion, and exhibits low swelling. The hydrogel demonstrates superior anticoagulation, inhibits smooth muscle cell proliferation and migration, and shows favourable cytocompatibility. Experimental results confirm its ability to promote endovascular regeneration while preventing restenosis and thrombosis. In summary, PNHB@Lip(RAPA) hydrogel is a promising material for intimal repair, offering innovative solutions to improve CEA postoperative outcomes.