A1 Refereed original research article in a scientific journal
Regulating macrophage glucose metabolism homeostasis via mitochondrial rheostats by short fiber-microsphere scaffolds for bone repair
Authors: Zhuang, Pengzhen; Chen, Yu; Zhang, Yu; Yang, Wu; Zuo, Guilai; Rosenholm, Jessica M.; Wang, Zhongmin; Wang, Juan; Cui, Wenguo; Zhang, Hongbo
Publisher: KEAI PUBLISHING LTD
Publishing place: BEIJING
Publication year: 2025
Journal: Bioactive Materials
Journal name in source: BIOACTIVE MATERIALS
Journal acronym: BIOACT MATER
Volume: 49
First page : 399
Last page: 417
Number of pages: 19
eISSN: 2452-199X
DOI: https://doi.org/10.1016/j.bioactmat.2025.03.008
Web address : https://doi.org/10.1016/j.bioactmat.2025.03.008
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/491809631
The alterations in glucose metabolism flux induced by mitochondrial function changes are crucial for regulating bone immune homeostasis. The restoration of mitochondrial homeostasis, serving as a pivotal rheostat for balancing glucose metabolism in immune cells, can effectively mitigate inflammation and initiate osteogenesis. Herein, an ion-activated mitochondrial rheostat fiber-microsphere polymerization system (FM@CeZnHA) was innovatively constructed. Physical-chemical and molecular biological methods confirmed that CeZnHA, characterized by a rapid degradation rate, releases Ce/Zn ions that restore mitochondrial metabolic homeostasis and M1/M2 balance of macrophages through swift redox reactions. This process reduces the glycolysis level of macrophages by down-regulating the NF-kappa B p65 signaling pathway, enhances their mitochondrial metabolic dependence, alleviates excessive early inflammatory responses, and promptly initiates osteogenesis. The FM network provided a stable platform for macrophage glycolytic transformation and simulated extracellular matrix microenvironment, continuously restoring mitochondrial homeostasis and accelerating ossification center formation through the release of metal ions from the internal CeZnHA for efficient bone immune cascade reactions. This strategy of bone immunity mediated by the restoration of macrophage mitochondrial metabolic function and glucose metabolic flux homeostasis opens up a new approach to treating bone defects.
Downloadable publication This is an electronic reprint of the original article. |  |
Funding information in the publication:
Pengzhen Zhuang and Yu Chen contributed equally to this work. This work was supported by the Program of Shanghai Academic/Technology Research Leader (22XD1422600), the Research Fellow (Grant No.353146), Research Project (347897), Solution for Health Profile (336355), InFLAMES Flagship (337531) grants and Printed Intelligence Infrastructure" (PII-FIRI) from Research Council of Finland. This study is part of the activities of the Åbo Akademi University Foundation (SÅA) funded Center of Excellence in Research "Materials-driven solutions for combating antimicrobial resistance (MADNESS)" at ÅAU.
