Abstract
Embolization that deliberately blocks target blood vessels through the delivery of embolic agents has emerged as a preferred therapy for various vascular-related diseases. Although various embolic materials are available in clinical practice, including solid and liquid embolic agents, their effectiveness remains limited in target vessels with broad size ranges and complex architectures. These limitations pose challenges in achieving controlled and durable embolization at target sites. To address these issues, we develop an advanced physically/chemically dual-crosslinked hydrogel (DC-gel) composed of thermosensitive poly(ethylene glycol)-poly((D)-amino acid) copolymers and triethoxysilane-capped 4-arm poly(ethylene glycol) macromolecule crosslinkers, which exhibits superior injectability and high mechanical strength. The physically-crosslinked network is formed by a sol-gel transition mediated by thermosensitive copolymers, which ensures catheter injectability while being robust enough to retain DC-gel at the injected region. Subsequently, the controlled in-situ chemical-crosslinking mediated by macromolecule crosslinkers provides additional mechanical strength for durable vascular embolization. Furthermore, an oily contrast agent with an ultrahigh iodine amount (>60 wt%) is developed and incorporated into DC-gel to endow it with long-lasting imaging capabilities for real-time and post-operative visualization. In vivo experiments conducted on rabbit artery, vein and tumor models confirm that our DC-gel system achieves persistent embolization without recanalization or non-target embolization, which stems from its superior mechanical stability and long-term persistence obtained by the dual crosslinking strategy plus a moderate fibroinflammatory response induced by the poly((D)-amino acid) component. Overall, DC-gel represents a highly promising embolic material that addresses current limitations in embolization therapy, offering enhanced controllability, durability, and imaging capabilities for clinical applications.