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Regulation of metabolic microenvironment with a nanocomposite hydrogel for improved bone fracture healing
- Source :
- Bioactive Materials, Vol 37, Iss , Pp 424-438 (2024)
- Publication Year :
- 2024
- Publisher :
- KeAi Communications Co., Ltd., 2024.
-
Abstract
- Bone nonunion poses an urgent clinical challenge that needs to be addressed. Recent studies have revealed that the metabolic microenvironment plays a vital role in fracture healing. Macrophages and bone marrow-derived mesenchymal stromal cells (BMSCs) are important targets for therapeutic interventions in bone fractures. Itaconate is a TCA cycle metabolite that has emerged as a potent macrophage immunomodulator that limits the inflammatory response. During osteogenic differentiation, BMSCs tend to undergo aerobic glycolysis and metabolize glucose to lactate. Copper ion (Cu2+) is an essential trace element that participates in glucose metabolism and may stimulate glycolysis in BMSCs and promote osteogenesis. In this study, we develop a 4-octyl itaconate (4-OI)@Cu@Gel nanocomposite hydrogel that can effectively deliver and release 4-OI and Cu2+ to modulate the metabolic microenvironment and improve the functions of cells involved in the fracture healing process. The findings reveal that burst release of 4-OI reduces the inflammatory response, promotes M2 macrophage polarization, and alleviates oxidative stress, while sustained release of Cu2+ stimulates BMSC glycolysis and osteogenic differentiation and enhances endothelial cell angiogenesis. Consequently, the 4-OI@Cu@Gel system achieves rapid fracture healing in mice. Thus, this study proposes a promising regenerative strategy to expedite bone fracture healing through metabolic reprogramming of macrophages and BMSCs.
Details
- Language :
- English
- ISSN :
- 2452199X
- Volume :
- 37
- Issue :
- 424-438
- Database :
- Directory of Open Access Journals
- Journal :
- Bioactive Materials
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.83d4cbc01a48fc8c9392ee749974cf
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.bioactmat.2024.03.025