Staged photothermal hydrogel containing manganese-doped bioactive glass nanoparticles promotes infected bone regeneration by engaging Schwann cell PI3K/AKT signaling and neuro-osteogenic coupling

Infected bone lesions are characterized by concurrent bacterial infection, persistent inflammatory infiltration, peripheral nerve damage, and impaired osteogenesis. However, most biomaterials address only antibacterial, anti-inflammatory, or osteogenic functions while overlooking nerve-bone crosstalk during tissue repair. Here, we engineered QOMB, an injectable photothermal hydrogel responsive to near-infrared (NIR) irradiation, by embedding manganese-doped bioactive glass nanoparticles (Mn-BGN) within a dynamically crosslinked network of gallic acid-grafted quaternized chitosan (QCSG) and oxidized sodium alginate (OSA). QOMB exerts synergistic photothermal antibacterial effects and promotes anti-inflammatory M2 macrophage polarization within inflammatory microenvironments. More importantly, ions released from Mn-BGN stimulate Schwann cells (SCs) to secrete abundant neurotrophic factors, thereby establishing a pro-regenerative paracrine niche that promotes osteogenic differentiation. Transcriptomic profiling and molecular validation demonstrated that stimulation with Mn-BGN-derived ionic cues activates PI3K/AKT signaling and enhances neurotrophic factor secretion by SCs. In a rat model of infected femoral condylar defects, QOMB administration combined with sequential NIR irradiation markedly suppressed local bacterial colonization, attenuated chronic inflammation, enhanced neurotrophic signaling, and accelerated de novo bone formation. These results support a material-Schwann cell-bone regulatory pathway that coordinates staged infection control and immune reprogramming with neuro-osteogenic repair.