Modular assembly of nanocomposite hydrogel with NIR-responsive black phosphorus release and mild photothermal synergy for enhanced regenerative microenvironment and accelerated infectious bone repair

Infectious bone defects remain a clinical challenge due to the lack of spatiotemporal control over bacterial infection, immune microenvironment modulation, vascular regeneration, and osteogenic differentiation. Herein, we engineered a modularly assembled 808 nm near-infrared (NIR)-responsive therapeutic system with three functional modules, including a 3D-printed honeycomb-mimetic poly(lactic acid) (HP) framework as a mechanically supportive module, collagen-graphene oxide-black phosphorus (CGB) nanocomposite hydrogel as an ECM-mimetic filling module, and NIR-responsive black phosphorus (BP)-release module. Under NIR-induced mild photothermal effects, CGB@HP hydrogel exhibited NIR-responsive BP-release, BP’s degradation into PO 4 3− , and upregulation of heat shock protein 47, thus promoting antibacterial activity, osteogenesis and angiogenesis capacities, and induction of macrophage polarization toward the pro-reparative M2 phenotype. In vivo validation in a rat model of infectious critical-sized bone defects further demonstrated that the CGB@HP system accelerated bone healing by attenuating local inflammation, upregulating pro-healing factor secretion, recruiting endogenous stem cells, and stimulating vascular regeneration. Collectively, this work introduces a modular NIR-responsive platform that leverages synergistic physical (mild photothermal therapy) and chemical (BP release/degradation) cues to remodel the damaged tissue microenvironment. By integrating structural support, bioactive molecule delivery, and NIR-responsive immunomodulation, this modular assembly offers a promising strategy and broad implications for infectious bone regeneration through the combination of multifunctional modules into a construct.