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<p>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&#xa0;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<sub>4</sub><sup>3−</sup>, 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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月9日

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  • Xiangru Chen,
  • Zhiwei Sun,
  • Zhi Zheng,
  • Yinghao Cao,
  • Zhou Wan,
  • Heyan Huang,
  • Qianlong Huang,
  • Changmao Zhang,
  • Jiajia Chang,
  • Hui Chen,
  • Changyan Jiang,
  • Qijun Xu,
  • Yanqing Yang,
  • Chuchao Zhou

摘要

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 PO43−, 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.

Graphical Abstract