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<p>Small extracellular vesicles (sEVs) represent a promising therapeutic modality for peripheral nerve repair. By modulating inflammation, promoting axonal regeneration, and supporting remyelination, sEVs play a multifaceted role in restoring nerve structure and function following injury. Hydrogels provide protective, sustained release vehicles that can control sEV dosing and prolong local retention in the therapeutic delivery site. In this review, we summarize recent progress on sEV-incorporated hydrogels, including injectable, self-healing, electroconductive, and ECM-derived hydrogels that go beyond passive loading strategies to achieve responsive and tissue-specific delivery. Current preclinical results demonstrate improved nerve regeneration and functional outcomes from enhanced Schwann-cell activation and immune modulation. However, challenges remain in fine-tuning sEV stability and release kinetics, as well as developing scalable manufacturing processes. Future strategies like staged-release depots and biosensing hydrogels are accelerating the translation of sEV-hydrogel systems. Overall, sEVs embedded in hydrogels form a promising next-generation platform for controlled, local nerve regeneration therapeutics.</p>

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Beyond encapsulation: advanced hydrogels for extracellular vesicle therapeutics in peripheral nervous system repair

  • 期刊论文

  • 发表日期：

    2026年2月13日

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  • Yuwei Zou,
  • Yue An,
  • Lili Zhang

摘要

Small extracellular vesicles (sEVs) represent a promising therapeutic modality for peripheral nerve repair. By modulating inflammation, promoting axonal regeneration, and supporting remyelination, sEVs play a multifaceted role in restoring nerve structure and function following injury. Hydrogels provide protective, sustained release vehicles that can control sEV dosing and prolong local retention in the therapeutic delivery site. In this review, we summarize recent progress on sEV-incorporated hydrogels, including injectable, self-healing, electroconductive, and ECM-derived hydrogels that go beyond passive loading strategies to achieve responsive and tissue-specific delivery. Current preclinical results demonstrate improved nerve regeneration and functional outcomes from enhanced Schwann-cell activation and immune modulation. However, challenges remain in fine-tuning sEV stability and release kinetics, as well as developing scalable manufacturing processes. Future strategies like staged-release depots and biosensing hydrogels are accelerating the translation of sEV-hydrogel systems. Overall, sEVs embedded in hydrogels form a promising next-generation platform for controlled, local nerve regeneration therapeutics.