Synergistic dual chemophysical FeCu-MOF scaffold with PEMF stimulation drives angiogenic-osteogenic coupling for bone regeneration

再生(生物学) 生物相容性 脚手架 刺激 间充质干细胞 化学 联轴节(管道) 骨愈合 骨组织 骨形成 骨髓 细胞生物学 生物医学工程 间质细胞 干细胞 纳米技术 生物物理学 控制释放 细胞 骨细胞 药物输送 血管生成
作者
Dongdong Guo,Wenjie Wang,Dongyang Zhao,Tianyu Chen,Xingyu Ma,Yixiao Li,Xiaojun Zhang
出处
期刊:Materials today bio [Elsevier BV]
卷期号:35: 102324-102324 被引量:1
标识
DOI:10.1016/j.mtbio.2025.102324
摘要

Repairing large bone defects effectively requires concurrent osteogenesis and angiogenesis, a significant challenge for conventional biomaterials often limited by suboptimal structural design and an inability to provide spatiotemporally controlled bioactive cues. Here, we report a novel chemophysical dual-responsive system rationally designed to address this osteogenic-angiogenic coupling challenge. This system integrates a structurally engineered bimetallic FeCu-metal-organic framework (FeCu-MOF) within a poly(lactic acid)/hydroxyapatite (PLA/HA) scaffold. The engineered FeCu-MOF architecture enables the programmed and sustained co-release of Fe3+ and Cu2+ ions, providing tailored chemical signals. Synergistic pulsed electromagnetic field (PEMF) stimulation was introduced as a physical cue to further enhance the scaffold's bioactivity. The composite scaffolds, featuring interconnected hierarchical porosity and enhanced hydrophilicity due to FeCu-MOF incorporation, demonstrated distinct Fe3+/Cu2+ release profiles. In vitro, these scaffolds exhibited excellent biocompatibility and significantly promoted bone marrow mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation. Notably, this structure-derived dual-ion release also indicated pro-angiogenic potential. Crucially, daily PEMF treatment synergistically amplified these cellular responses. In vivo evaluation in a rat cranial defect model confirmed the system's efficacy. While FeCu-MOF/PLA/HA scaffolds alone enhanced bone regeneration, their combination with PEMF yielded the most robust outcomes, characterized by markedly superior vascularized bone formation. Comprehensive analysis, including micro-CT, histology, and immunohistochemistry, confirmed these findings by demonstrating improved bone volume, density, and architecture, mature integrated tissue, and enhanced coupled expression of CD31 and osteogenic markers. In summary, the study validates a powerful synergistic strategy for enhanced bone regeneration. This strategy, integrating programmable, structure-derived bimetallic ion release with PEMF stimulation, successfully achieved synergistic angiogenic-osteogenic coupling, offering a promising approach for complex defect scenarios.
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