Therapeutic Potential of Injectable Supramolecular Hydrogels With Neural Stem Cell Exosomes and Hydroxypropyl Methylcellulose for Post-Stroke Neurological Recovery.

BACKGROUND: Stroke has significantly contributed to the global mortality rate over the years, emphasizing the urgency of finding effective treatment strategies. Neural stem cell (NSC)-derived exosomes have the potential to improve neurological recovery after stroke; however, their therapeutic efficacy is hindered by their rapid clearance and limited duration of action. This study presents an innovative drug delivery method: a hydrogel based on NSC exosomes and hydroxypropyl methylcellulose (HPMC), which is intended to offer a continuous release, thereby enhancing and prolonging neurological improvement. RESULTS: We developed a nanohydrogel (Exo-HPMC) by integrating Buyang Huanwu Decoction (BHD) -preconditioned NSC-derived exosomes with HPMC. This study thoroughly investigated the controlled-release capabilities and rheological properties of Exo-HPMC. Our findings show that Exo-HPMC enables effective sustained exosome release, significantly extending their retention in mice. When administered to mice with middle cerebral artery occlusion (MCAO), Exo-HPMC facilitated notable post-stroke neurorepair. Behavioral assessments and immunofluorescence staining demonstrated that exosomes significantly promoted angiogenesis and nerve regeneration in stroke-affected areas, thereby reversing programmed cell death. CONCLUSION: The Exo-HPMC nanohydrogel presents a groundbreaking approach for stroke therapy. Ensuring a controlled and prolonged release of NSC-derived exosomes over two weeks, significantly enhances the therapeutic potential of exosomes for ischemic stroke treatment.