An engineering-reinforced extracellular vesicle–integrated hydrogel with an ROS-responsive release pattern mitigates spinal cord injury

• DOI: 10.1126/sciadv.ads3398
• Publication Date: 2025-04-02T20:33:04Z
• Authors: Jian Cao; Xunqi Zhang; Jing Guo; Jiahe Wu; Lingmin Lin; Xurong Lin; Jiafu Mu; Tianchen Huang; Manning Zhu; Lan Ma; Weihang Zhou; Xinchi Jiang; Xuhua Wang; Shiqing Feng; Zhen Gu; Jian-Qing Gao
• Keywords: Phenylboronic acid

The local delivery of mesenchymal stem cell–derived extracellular vesicles (EVs) via hydrogel has emerged as an effective approach for spinal cord injury (SCI) treatment. However, achieving on-demand release EVs from to address dynamically changing pathology remains challenging. Here, we used a series engineering methods further enhance EVs’ efficacy and optimize their pattern hydrogel. Specifically, the pro-angiogenic, neurotrophic, anti-inflammatory effects were reinforced through three-dimensional culture dexamethasone (Dxm) encapsulation. Then, prepared Dxm-loaded 3EVs (3EVs-Dxm) membrane modified with ortho-dihydroxy groups (-2OH) formed EV-integrated (3EVs-Dxm-Gel) cross-link phenylboronic acid–modified hyaluronic acid tannic acid. ester in 3EVs-Dxm-Gel enabled immobilization reactive oxygen species–responsive EVs. Topical injection SCI rats notably mitigated severity promoted functional recovery, which may offer opportunities EV-based therapeutics central nervous system injury.