Zhao Yanming, Sun Rujie, Wang Zitian, Ma Shaohua, Wang Runming, Li Feiran, Geng Hongya
Institute of Biomedical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong 518055, China.
Key Laboratory of Active Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education Institutes, Shenzhen, Guangdong 518055, China.
ACS Appl Bio Mater. 2025 Sep 15;8(9):7587-7615. doi: 10.1021/acsabm.5c01269. Epub 2025 Aug 31.
Controllable neuromodulation leveraging multimodal triggers synergized with hydrogels represents a transformative therapeutic strategy for pro-regenerative neural repair. Strategic incorporation of programmable neuromodulatory interventions and engineered hydrogels within localized neural niches is critical for clinical translation, characterized by lower invasiveness and greater therapeutic efficacy. This review elucidates the physiochemical features of hydrogels, systematically classifying hydrogel-based neuromodulation into five distinct modes (electrical, ionic, biomechanical, optical, and biochemical) and highlighting the intrinsic multidimensional structural and chemical engineering employed to enhance neuromodulatory performance. Key principles of hydrogel design and fabrication are provided from the perspective of tissue-implant interactions, such as mechanical compatibility, electrointegration, adhesion, and wireless activation. Hydrogels embedded with low-impedance organic and inorganic components, such as conductive polymers and noble metals, are investigated to provide high-level evidence to enable precise cellular stimulation for intrinsic nerve repair, neural prosthesis, and brain-machine interface. Crucially, this review highlights the synergistic integration of these principles into multimodal, closed-loop systems, which combine functions like electrophysiological sensing with on-demand biochemical release for intelligent, autonomous therapies. Finally, this review confronts the critical challenges for clinical translation and discusses future directions, including the potential of artificial intelligence-driven materials design to accelerate the development of next-generation neural interfaces.
利用多模态触发因素与水凝胶协同作用的可控神经调节代表了一种用于促进再生性神经修复的变革性治疗策略。将可编程神经调节干预措施和工程水凝胶战略性地整合到局部神经微环境中对于临床转化至关重要，其特点是侵入性更低且治疗效果更佳。本综述阐明了水凝胶的物理化学特性，将基于水凝胶的神经调节系统地分为五种不同模式（电、离子、生物力学、光学和生化），并强调了为增强神经调节性能而采用的内在多维结构和化学工程。从组织 - 植入物相互作用的角度提供了水凝胶设计和制造的关键原则，如机械兼容性、电整合、粘附和无线激活。对嵌入低阻抗有机和无机成分（如导电聚合物和贵金属）的水凝胶进行了研究，以提供高级证据，实现对内在神经修复、神经假体和脑机接口的精确细胞刺激。至关重要的是，本综述强调了将这些原则协同整合到多模态闭环系统中，该系统将电生理传感等功能与按需生化释放相结合，以实现智能、自主治疗。最后，本综述面对临床转化的关键挑战并讨论未来方向，包括人工智能驱动的材料设计加速下一代神经接口开发的潜力。
