Local Spinal Cord Injury Treatment Using a Dental Pulp Stem Cell Encapsulated H2S Releasing Multifunctional Injectable Hydrogel

Spinal cord injury (SCI) commonly induces nerve damage and nerve cell degeneration. In this work, a novel dental pulp stem cells (DPSCs) encapsulated thermoresponsive injectable hydrogel with sustained hydrogen sulfide (H2S) delivery is demonstrated for SCI repair. For controlled and sustained H2S gas therapy, a clinically tested H2S donor (JK) loaded octysilane functionalized mesoporous silica nanoparticles (OMSNs) are incorporated into the thermosensitive hydrogel made from Pluronic F127 (PF‐127). The JK‐loaded functionalized MSNs (OMSF@JK) promote preferential M2‐like polarization of macrophages and neuronal differentiation of DPSCs in vitro. OMSF@JK incorporated PF‐127 injectable hydrogel (PF‐OMSF@JK) has a soft consistency similar to that of the human spinal cord and thus, shows a high cytocompatibility with DPSCs. The cross‐sectional micromorphology of the hydrogel shows a continuous porous structure. Last, the PF‐OMSF@JK composite hydrogel considerably improves the in vivo SCI regeneration in Sprague–Dawley rats through a reduction in inflammation and neuronal differentiation of the incorporated stem cells as confirmed using western blotting and immunohistochemistry. The highly encouraging in vivo results prove that this novel design on hydrogel is a promising therapy for SCI regeneration with the potential for clinical translation. A thermoresponsive hydrogel is designed for a dual‐pronged local therapy of spinal cord injuries (SCI). The composite hydrogel system can deliver H2S gas as well as encapsulating stem cells and enables improved SCI healing through precise modulation of injury site inflammation as demonstrated by a thorough in vitro and in vivo investigation.