Diatom-Inspired Scaffold for Infected Bone Defect Therapy: Achieving Stable Photothermal Properties and Coordinated Antibacterial-Osteogenic Functions.

Abstract

Bone defect therapy frequently encounters bacterial infections and chronic inflammation, which impair bone regeneration and threaten implant stability. Iron oxide nanoparticles have attracted attention due to cost-effectiveness, biocompatibility, and metabolic safety. However, iron oxide nanoparticles still struggle to balance low-temperature efficient antibacterial activity, effective immunomodulation, and bone regeneration. Therefore, inspired by diatoms, a multifunctional bone repair scaffold based on chitosan-hydroxyapatite (CH) is developed by integrating the multifunctional properties of copper-doped iron goethite (Fe(Cu)OOH) nanoparticles and a mesoporous SiO₂ protective layer (CH/FeCu@SiO₂). The "cytoskeleton" CH scaffold stabilizes the nanoparticles and supports tissue growth. The "chloroplast" Fe(Cu)OOH and the " frustule" SiO₂ layer synergistically capture near-infrared (NIR) light to generate localized mild hyperthermia (≈42 °C), with the release of Cu²⁺ to achieve antibacterial effects (>99%). In addition, Fe(Cu)OOH exhibits enzyme-like antioxidant activity, scavenging reactive oxygen species (ROS) (69.20%) and thereby promoting M2 macrophage polarization (1.64-fold), which protects stem cells and creates osteogenic immune microenvironment. Moreover, the mild hyperthermia and ion release upregulate the TGF-β signaling pathway and inhibit osteoclast differentiation, promoting vascularized bone regeneration and defect repair (1.3-fold). Overall, this biomimetic scaffold, enabling synergistic antibacterial, immunomodulatory, and osteogenic activities, offers a promising therapeutic strategy for infectious bone defects treatment.