Mesenchymal stem cell-loaded hydrogel to inhibit inflammatory reaction in surgical brain injury via mitochondria transfer

Neurosurgical procedures are the key therapeutic interventions for the cerebral hemorrhage and brain tumors. However, neurosurgical procedures inevitably cause surgical brain injury (SBI), which will induce hemorrhage and inflammation. Gelatin Sponges are still the primary hemostatic materials used in clinical, but their anti-inflammatory efficacy is poor. Herein, we developed a cross-linked gelatin hydrogel (GelMA) to load mesenchymal stem cells (MSC) and directly implant them to the SBI site. Upon contacting the SBI site, the GelMA showed better clotting performance than Gelatin Sponges. Moreover, the MSC can reduce oxidative stress and enhance mitochondrial fusion via mitochondria transfer, resulting in ameliorating mitochondrial damage and reducing inflammation. Thus, the GelMA containing MSC can effectively reduce brain edema and inflammation and improve neurological function in SBI mouse models. In addition, GelMA exhibits excellent hemocompatibility and low cytotoxicity. It also enhances the proliferation of MSCs and decelerates the rapid depletion of MSCs. Therefore, MSC-loaded GelMA exhibits excellent hemostatic and anti-inflammatory effects, making it a potential new-generation biomaterial for SBI.