Spatiotemporally coordinated immunometabolic-hyperthermia therapy for diabetic bone defect regeneration
5 affiliations
- 1Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China
- 2School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
- 3Department of Orthopedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; Corresponding author.
- 4School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; Corresponding author.
- 5The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; Corresponding author.
Abstract
Diabetic bone defects (DBDs) are typified by persistent inflammation, oxidative stress, and microbial infection within the diabetic microenvironment, which collectively hinder osteogenesis and angiogenesis. Herein, we introduce an Immunometabolic–Hyperthermia Therapy (IMHT) strategy based on a dual-functional nanoplatform, namely a polydopamine/itaconate-incorporated agarose/gelatin (PIAG) hydrogel. This system is fabricated by incorporating itaconic acid (ITA) into polydopamine (PDA) nanoparticles through in situ polymerization, followed by encapsulation within a gelatin/agarose matrix. ITA primarily provides immunometabolic regulation, while PDA enables a tunable photothermal response. Upon localized photothermal heating (∼50 °C), the PIAG hydrogel effectively disrupts bacterial biofilms, with photothermal treatment providing the dominant antibacterial effect and ITA offering an additional supportive contribution. Upon mild photothermal activation (∼41 °C), IMHT mitigates excessive reactive oxygen species (ROS) generation, inhibits neutrophil extracellular trap (NET) formation, and reprograms macrophages toward an M2-like reparative phenotype through JAK1/STAT1 pathway inhibition. The resulting pro-regenerative immune milieu enhances fibroblast growth factor-2 (FGF-2) secretion, while heat-induced activation of HSP90 stabilizes FGF-2/FGFR1 signaling, further promoting osteogenic differentiation and endothelial migration. Overall, the spatiotemporally coordinated antibacterial, immunometabolic, and regenerative regulation realized by IMHT offers a comprehensive and effective strategy for the repair of diabetic bone defects.
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BibTeX
@article{wang2026spatiotemporally,
title = {{Spatiotemporally coordinated immunometabolic-hyperthermia therapy for diabetic bone defect regeneration}},
author = {Lingtian Wang and Xingyu Peng and Lulu Zheng and Yuqing Liu and Lei Chen and Xiaokun Li and Zhouguang Wang},
journal = {Materials Today Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103767},
url = {https://doi.org/10.1016/j.mtbio.2026.103767},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Spatiotemporally coordinated immunometabolic-hyperthermia therapy for diabetic bone defect regeneration
AU - Lingtian Wang
AU - Xingyu Peng
AU - Lulu Zheng
AU - Yuqing Liu
AU - Lei Chen
AU - Xiaokun Li
AU - Zhouguang Wang
PY - 2026
DA - 2026/10/20
JO - Materials Today Bio
DO - 10.1016/j.mtbio.2026.103767
UR - https://doi.org/10.1016/j.mtbio.2026.103767
AB - Diabetic bone defects (DBDs) are typified by persistent inflammation, oxidative stress, and microbial infection within the diabetic microenvironment, which collectively hinder osteogenesis and angiogenesis. Herein, we introduce an Immunometabolic–Hyperthermia Therapy (IMHT) strategy based on a dual-functional nanoplatform, namely a polydopamine/itaconate-incorporated agarose/gelatin (PIAG) hydrogel. This system is fabricated by incorporating itaconic acid (ITA) into polydopamine (PDA) nanoparticles through in situ polymerization, followed by encapsulation within a gelatin/agarose matrix. ITA primarily provides immunometabolic regulation, while PDA enables a tunable photothermal response. Upon localized photothermal heating (∼50 °C), the PIAG hydrogel effectively disrupts bacterial biofilms, with photothermal treatment providing the dominant antibacterial effect and ITA offering an additional supportive contribution. Upon mild photothermal activation (∼41 °C), IMHT mitigates excessive reactive oxygen species (ROS) generation, inhibits neutrophil extracellular trap (NET) formation, and reprograms macrophages toward an M2-like reparative phenotype through JAK1/STAT1 pathway inhibition. The resulting pro-regenerative immune milieu enhances fibroblast growth factor-2 (FGF-2) secretion, while heat-induced activation of HSP90 stabilizes FGF-2/FGFR1 signaling, further promoting osteogenic differentiation and endothelial migration. Overall, the spatiotemporally coordinated antibacterial, immunometabolic, and regenerative regulation realized by IMHT offers a comprehensive and effective strategy for the repair of diabetic bone defects.
SN - 2590-0064
ER -