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Updated: Feb 10, 2026

Measuring Bone Remodeling and Recreating the Tumor-Bone Microenvironment Using Calvaria Co-culture and Histomorphometry
Published on: March 14, 2020
Sonocatalytic multifunctional hydrogel in-situ remodels the infectious microenvironment for eradicating refractory
Xinzi He1, Yaping Li2, Zhihui Xiang1
1Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, China; Zhejiang Key Laboratory of Motor System Disease Precision Research and Therapy, Hangzhou City, Zhejiang Province, China; Clinical Research Center of Motor System Disease of Zhejiang, China.
Abstract:
Osteomyelitis remains a formidable clinical challenge due to biofilm-associated antibiotic resistance, a hypoxic and immunosuppressive microenvironment, and progressive inflammatory bone destruction. To address these multifactorial barriers, we developed an ultrasound (US)-activatable injectable hydrogel, designated MIL-101(Fe)@ZnO@MM + PFO + Gel, which integrates sonodynamic catalysis, oxygen regulation, and immunomodulation within a single therapeutic platform. The core-shell nanostructure comprises MIL-101(Fe)@ZnO nanoflowers, synthesized via a seed-mediated growth process to couple the redox activity of iron with the peroxidase-like catalytic properties of ZnO. The core-shell nanostructure comprises MIL-101(Fe)@ZnO nanoflowers, synthesized via a seed-mediated growth process to couple the redox activity of iron with the peroxidase-like catalytic properties of ZnO. These nanozymes are camouflaged with a thiolated macrophage membrane (MM), dispersed in oxygen-enriched perfluorocarbon (PFO), and crosslinked within a quaternary ammonium-modified hydrogel matrix possessing biofilm-penetrating capability. Upon US irradiation, the hydrogel achieves deep biofilm penetration and generates abundant reactive oxygen species (ROS) through Fe/Zn synergistic catalysis, while PFO liquefaction releases oxygen to alleviate local hypoxia and potentiate the sonodynamic effect. In a rat model of methicillin-resistant Staphylococcus aureus (MRSA)-induced tibial osteomyelitis, this treatment markedly reduced bacterial load, substantially suppressed inflammatory infiltration and pro-inflammatory cytokine cascades, and effective mitigation of bone erosion. Collectively, MIL-101(Fe)@ZnO@MM + PFO + Gel+US offers a minimally invasive, spatiotemporally controlled platform for eradicating refractory infections and reprogramming the osteomyelitic microenvironment toward regeneration.
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