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MgFe-Layered Double Hydroxide-Reinforced Injectable GelMA Hydrogels Promote Calvarial Bone Regeneration with
Jiajie Zheng1, Kang Wang2, Hao Xu1
1Department of Neurosurgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People's Republic of China.
International Journal of Nanomedicine
|August 11, 2026
Summary
Injectable hydrogels with iron and magnesium layered double hydroxide (MgFe-LDH) nanoparticles significantly enhance calvarial bone regeneration by modulating immune responses and promoting osteogenesis. This biomaterial shows promise for treating critical-sized bone defects.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Immunology
Background:
- Critical-sized calvarial defects pose significant challenges due to limitations in current grafting strategies.
- Existing methods struggle with irregular defect geometries and inadequate regulation of the immune-osteogenic microenvironment.
Purpose of the Study:
- To develop and evaluate an injectable hydrogel system for enhanced calvarial bone regeneration.
- To investigate the influence of layered double hydroxide (LDH) cation composition (MgFe-LDH vs. MgAl-LDH) on bone repair.
Main Methods:
- Synthesized MgFe-LDH and MgAl-LDH nanoplatelets and incorporated them into gelatin methacryloyl (GelMA) hydrogels.
- Assessed nanoparticle characteristics, cellular interactions, and in vitro osteogenic differentiation of bone marrow stromal cells (BMSCs).
- Evaluated regenerative efficacy in a murine critical-sized calvarial defect model over 12 weeks using micro-CT, histology, and molecular analyses.
Main Results:
- MgFe-LDH hydrogels demonstrated favorable cytocompatibility and efficient cellular uptake.
- MgFe-LDH significantly modulated macrophage responses, reducing pro-inflammatory cytokines (TNF-α, IL-1β) and increasing anti-inflammatory cytokines (IL-10, TGF-β).
- MgFe-LDH enhanced BMSC osteogenic differentiation and promoted superior bone defect bridging and mineralized tissue formation in vivo.
Conclusions:
- Injectable GelMA-MgFe-LDH hydrogels effectively promote calvarial bone regeneration.
- The observed bone repair is linked to pro-resolving immune responses and osteogenic remodeling, potentially involving IL-10RA-JAK1-STAT3 signaling.
- Cation-engineered LDH hydrogels represent promising injectable biomaterials for bone regeneration, warranting further mechanistic and safety studies.
