Wang Xin, Yang Hantao, Wang Yaoben, Wang Yang, Hu Xuanbo, Huang Jiaxin, Chen Zhiyong, Chen Yu, Ding Jiandong, Yu Lin
State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Shanghai Stomatological Hospital & School of Stomatology, Fudan University, Shanghai, 200438, China.
Shanghai Geriatric Medical Center, 2560 Chunshen Road, Shanghai, 201104, China.
Bioact Mater. 2025 Jul 9;53:141-160. doi: 10.1016/j.bioactmat.2025.06.049. eCollection 2025 Nov.
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(-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(-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.
通过输送栓塞剂故意阻塞靶血管的栓塞术已成为治疗各种血管相关疾病的首选疗法。尽管临床实践中有多种栓塞材料可供使用，包括固体和液体栓塞剂，但它们在尺寸范围广泛且结构复杂的靶血管中的有效性仍然有限。这些限制给在靶部位实现可控且持久的栓塞带来了挑战。为了解决这些问题，我们开发了一种先进的物理/化学双重交联水凝胶（DC-凝胶），它由热敏聚（乙二醇）-聚（氨基酸）共聚物和三乙氧基硅烷封端的四臂聚（乙二醇）大分子交联剂组成，具有卓越的可注射性和高机械强度。物理交联网络由热敏共聚物介导的溶胶-凝胶转变形成，这确保了导管可注射性，同时又足够坚固以将DC-凝胶保留在注射区域。随后，由大分子交联剂介导的可控原位化学交联为持久的血管栓塞提供了额外的机械强度。此外，还开发了一种碘含量超高（>60 wt%）的油性造影剂并将其掺入DC-凝胶中，使其具有持久的成像能力，用于实时和术后可视化。在兔动脉、静脉和肿瘤模型上进行的体内实验证实，我们的DC-凝胶系统实现了持久栓塞，没有再通或非靶栓塞，这源于其双重交联策略获得的卓越机械稳定性和长期持久性，以及聚（氨基酸）成分诱导的适度纤维炎症反应。总体而言，DC-凝胶是一种非常有前途的栓塞材料，解决了当前栓塞治疗中的局限性，为临床应用提供了增强的可控性、耐久性和成像能力。
