Injectable Supramolecular Hybrid Hydrogel Delivers IL-1β-Stimulated Exosomes to Target Neuroinflammation

Long-term neuroinflammation is a major barrier to neurological recovery after cerebral ischemia-reperfusion injury (CIRI). Here, a thermosensitive injectable supra-molecular hybrid hydrogel is developed to sustainably deliver exosomes derived from interleukin-1 ss-stimulated bone marrow stromal cells (BMSCs) (ss Exos) with improved exosome production and anti-inflammatory capacity for neuroinflammation inhibition and neurological recovery. The supramolecular hydrogel displays self-healing and injectable features, along with high biocompatibility and tissue-like softness. The ss Exos effectively reduce the lipopolysaccharide-induced inflammatory responses in the immortalized mouse microglia (BV2) cell line, and the in situ formed hydrogel improves the exosome retention in the ischemic core area. More remarkably, in the middle cerebral artery occlusion in vivo model, glial scar formation and neuronal loss are significantly reduced by regulating neuroinflammation using the released ss Exos. Therefore, the combination of interleukin-1 ss-stimulated exosomes with injectable supramolecular hydrogel provides an appealing strategy for treating central nervous system diseases.

Automated summary

In this study, a thermosensitive injectable supra-molecular hybrid hydrogel was developed to deliver interleukin-1β-stimulated exosomes derived from bone marrow stromal cells (BMSCs) for neuroinflammation inhibition and neurological recovery after cerebral ischemia-reperfusion injury (CIRI). The hydrogel showed self-healing and injectable properties, as well as high biocompatibility and softness similar to tissue. The released exosomes effectively reduced inflammatory responses in microglia cells and improved retention in the ischemic core area, leading to reduced glial scar formation and neuronal loss in vivo.