Hydrogel-encapsulated extracellular vesicles for the regeneration of spinal cord injury

Spinal cord injury (SCI) is a severe neurological condition that affects motor, sensory, and autonomous functions due to inflammation, axonal regeneration impairment, and neuronal death. Current treatments are insufficient, necessitating effective strategies to promote neuronal regeneration and repair. Regenerative treatments, including cell and extracellular vesicle (EV) transplantation, offer potential for improved functional recovery by promoting new neuron growth and protecting existing ones. EV-based therapies face limitations like short half-life and poor accumulation. Encapsulating EVs in hydrogels overcomes these limitations by maintaining bioactivity, protecting against clearance, and enabling sustained release at the target site. Hydrogel-encapsulated EVs promote neuroregeneration by improving functional recovery, reducing inflammation, and enhancing neuronal regeneration after SCI. This review provides an overview of the current research status, challenges, and future clinical opportunities of hydrogel-encapsulated EVs in SCI treatment. It emphasizes their potential in neuroprotection and functional recovery by describing their underlying mechanisms of action.

• 1
  Hydrogel-encapsulated EVs enhance exosome efficacy by maintaining bioactivity, protecting EVs from rapid clearance, and facilitating sustained release at the target site.
• 2
  Hydrogel-encapsulated MSCs-exosomes enhanced tissue repair and significant functional recovery after SCI by activating the PTEN/PI3K/AKT/mTOR pathway, leading to myelin-associated axonal regeneration, enhanced neurogenesis, and reduced neuroinflammation.
• 3
  Hypoxia preconditioned hUCMSCs-derived exosomes loaded by adhesive hyaluronic acid hydrogel promoted angiogenesis, nerve regeneration, and functional recovery after SCI by activation of HIF-1α and overexpression of VEGF.