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To meet the demand for the coordinated bone generation and vascularization in large bone defect repair, this study constructed a FeCu-MOF/PLA/HA composite scaffold, integrating the chemical signals of programmed release of dual metal ions and the physical signals of PEMF stimulation, to form a chemical-physical dual-responsive system. This system can promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells in vitro, and has the potential to promote angiogenesis. In vivo experiments, when used in combination with PEMF, it can significantly enhance the formation of vascularized bone, achieving the coupled regulation of bone generation and vascularization.
Effective repair of large bone defects relies on the synchronous occurrence of bone formation and angiogenesis. Traditional biomaterials are often limited by structural design flaws and the inability to release bioactive signals in a spatiotemporal controlled manner, making it difficult to meet the requirements for the coordinated repair. This has become a core challenge in this field.
This study focuses on the coupling repair problem of bone formation and angiogenesis, and designs a chemo-physical dual-responsive system. The structurally engineered bimetallic FeCu-MOF is embedded in the PLA/HA scaffold, enabling it to have the programmed continuous co-release capability of Fe³⁺ and Cu²⁺. Additionally, pulsed electromagnetic fields (PEMF) are introduced as a synergistic physical stimulus. Through in vitro experiments, the biocompatibility of the scaffold and its effects on the biological behavior of stem cells are investigated. Combined with an in vivo rat skull defect model, the effect of this composite system in regulating bone regeneration and angiogenesis coupling is systematically verified.
Firstly, FeCu-MOF/PLA/HA composite scaffolds were prepared, and their pore structure, hydrophilicity, and ion release characteristics were characterized. At the in vitro level, the effects of the scaffolds on the proliferation and differentiation of bone marrow mesenchymal stem cells, as well as the potential of dual-ion release for promoting angiogenesis, were evaluated. The synergistic effect of PEMF stimulation was also investigated. At the in vivo level, a rat skull defect model was constructed, and the regulatory effects of the scaffolds alone and combined with PEMF stimulation on bone regeneration and vascularization were compared using micro-CT, histology, and immunohistochemistry techniques.
The FeCu-MOF/PLA/HA composite scaffold has interconnected hierarchical pore structures, with enhanced hydrophilicity due to the incorporation of FeCu-MOF, enabling the programmed continuous co-release of Fe³⁺ and Cu²⁺. In vitro experiments confirmed the excellent biocompatibility of the scaffold, which promotes the proliferation and differentiation of bone marrow mesenchymal stem cells and exhibits the potential for promoting angiogenesis. PEMF stimulation can synergistically amplify these cellular responses. In vivo evaluation showed that the FeCu-MOF/PLA/HA scaffold alone can enhance bone regeneration, and when combined with PEMF, the effect is more significant, presenting better vascularized bone formation, improved bone volume, density, and structure, and mature tissue integration, with enhanced expression of CD31 and bone formation markers.
Further optimization of the structural parameters and composition ratio of FeCu-MOF can precisely control the rate and timing of dual-ion release to adapt to the needs of different stages of bone regeneration. In-depth exploration of the specific parameters (strength, frequency, etc.) of PEMF stimulation on the biological activity of the scaffold can provide regulatory laws. Clarifying the molecular mechanism of Fe³⁺, Cu²⁺, and PEMF synergistically regulating angiogenesis and bone formation coupling can provide theoretical support for the performance optimization of this type of dual-responsive scaffold.
Original source: Journal: Materials Today Bio (Impact Factor 10.2) Publication Date: September 18, 2025 DOI: 10.1016/j.mtbio.2025.102324 Authors: Dongdong Guo, Wenjie Wang, Dongyang Zhao, et al.
