biostudies-literatureUnknown29Hao YTraumatic brain injury (TBI) can lead to severe neurotrauma, leading to long-term cognitive decline and even death. Massive neuronal loss and excessive neuroinflammation are critical issues in the treatment of secondary TBI. To tackle these challenges, we developed a GelMA and CSMA hydrogel loaded with Erythropoietin (EPO) and Interleukin-4 (IL-4), named GC/I/E. By directly loading the hydrogel with EPO, rapid neuroprotection and angiogenesis were achieved. Meanwhile, by loading Mesoporous silica nanoparticles (MSNs) with IL-4 (MSN@IL-4), sustained inflammation modulation during inflammation was attained. <i>In vitro</i> experiments demonstrated that GC/I/E hydrogel were biocompatible and could provide neuroprotection for HT22 cells in H₂O₂ environment, regulate RAW26Materials today. Bio101335https://www.ebi.ac.uk/biostudies/studies/S-EPMC11609671biostudies-literatureBioactive hydrogel synergizes neuroprotection, macrophage polarization, and angiogenesis to improve repair of traumatic brain injury.PMC11609671Liu HZhou LFeng LWang CHe XHao YGuo RCheng HYu XJin LfalseBioactive hydrogel synergizes neuroprotection, macrophage polarization, and angiogenesis to improve repair of traumatic brain injury.Traumatic brain injury (TBI) can lead to severe neurotrauma, leading to long-term cognitive decline and even death. Massive neuronal loss and excessive neuroinflammation are critical issues in the treatment of secondary TBI. To tackle these challenges, we developed a GelMA and CSMA hydrogel loaded with Erythropoietin (EPO) and Interleukin-4 (IL-4), named GC/I/E. By directly loading the hydrogel with EPO, rapid neuroprotection and angiogenesis were achieved. Meanwhile, by loading Mesoporous silica nanoparticles (MSNs) with IL-4 (MSN@IL-4), sustained inflammation modulation during inflammation was attained. <i>In vitro</i> experiments demonstrated that GC/I/E hydrogel were biocompatible and could provide neuroprotection for HT22 cells in H₂O₂ environment, regulate RAW262024-01-01T00:00:00Z2024 Dec2025-04-04T00:21:50.065Z2025-04-04T00:21:50.065ZS-EPMC116096713962404710.1016/j.mtbio.2024.101335