Dual-function Injectable Hydrogel with Exosome-Cerium Oxide Nanocomposite Mediates Brain Infarction Therapy

Area of Science:

• Biomaterials Science
• Neuroscience
• Nanotechnology

Background:

• Ischemic stroke is a major cause of death and disability.
• Current therapies have limitations in addressing post-stroke complications like oxidative stress and neuroinflammation.
• Effective strategies are needed for sustained therapeutic delivery to the brain.

Purpose of the Study:

• To develop an injectable hydrogel for sustained co-delivery of exosomes and cerium oxide nanoparticles (EXO@CeO2).
• To investigate the therapeutic potential of EXO@CeO2-loaded hydrogel in mitigating oxidative stress, neuroinflammation, and promoting neurovascular repair after ischemic stroke.

Main Methods:

• Development of a dual-modified hyaluronic acid-based injectable hydrogel.
• Loading of exosome-cerium oxide nanocomposite (EXO@CeO2) into the hydrogel for sustained release.
• In vitro evaluation using oxygen-glucose deprivation models to assess ROS scavenging, apoptosis, mitochondrial function, and inflammatory cytokine modulation.
• In vivo evaluation in a murine photothrombotic stroke model to assess effects on oxidative stress, microglial polarization, cerebral blood flow, and neurobehavioral function.

Main Results:

• EXO@CeO2 effectively scavenged reactive oxygen species (ROS), reduced apoptosis, and stabilized mitochondrial membrane potential in vitro.
• The nanocomposite modulated inflammation by downregulating pro-inflammatory cytokines (IL-1β, IL-6) and upregulating IL-10.
• In vivo, the hydrogel alleviated acute cerebral oxidative stress and promoted M1 to M2 microglial polarization.
• Treatment improved local cerebral blood flow and led to sustained neurobehavioral recovery.

Conclusions:

• The injectable hydrogel enables sustained co-delivery of exosomes and cerium oxide for ischemic stroke therapy.
• This dual strategy combines antioxidant effects with exosome-mediated reparative functions.
• The approach effectively mitigates acute oxidative damage and promotes long-term neurovascular repair, offering a promising therapeutic avenue for ischemic stroke.