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In response to the core issue of insufficient angiogenesis in the repair of ischemic bone defects, this study constructed a 3D-printed magnesium alloy porous scaffold loaded with neural filamin-1 liposomes. Through a composite coating, the magnesium ions were controlled-release and functional factors were anchored, synergistically regulating the magnesium ion signal transduction and the angiogenesis process mediated by neural filamin-1, successfully establishing a coupling regulatory axis for bone formation and angiogenesis, providing a new theoretical and experimental basis for bone regeneration and repair in ischemic microenvironments. This review addresses the regeneration and repair dilemma caused by the heterogeneity of bone-cartilage tissue, with the tissue engineering system combining mesenchymal stem cells and biomaterial scaffolds as the core, clarifying the regulatory mechanism of biological physical signals on the fate of stem cells, systematically summarizing the progress in the design of biomimetic microenvironment scaffolds under mechanical biology guidance, achieving precise regulation of the lineage-specific differentiation of mesenchymal stem cells, and providing theoretical support and design references for layered bone-cartilage regeneration, especially the regeneration of subchondral bone. 01 Research Background
Ischemic bone defects are a key challenge in the field of bone tissue engineering. The local blood supply in the lesion area is severely damaged, directly leading to the failure of normal initiation of the angiogenesis process, unable to provide sufficient nutrition and microenvironment support for bone regeneration, thereby hindering the process of bone formation and bone integration. Existing bone repair scaffolds often fail to balance mechanical support, material degradation regulation, and the synergistic regeneration function of bone and blood vessels, lacking precise functional design for the ischemic microenvironment. Therefore, it is urgent to develop a new functionalized scaffold system that can coordinate angiogenesis and bone formation. The tendon-bone transitional tissue has a highly specialized extracellular matrix structure, with the core feature being the hierarchical arrangement of collagen and the gradient composition of minerals. This structure system can achieve stable force transmission and directional guidance of cell phenotype in spatial organization. Currently, it is impossible to precisely reproduce the complex multi-scale structure and composition gradient at the tendon-bone interface, becoming a key bottleneck in the integration and regeneration of soft and hard tissues. It is urgently needed to develop a biomimetic matrix construction scheme that conforms to the natural structure characteristics. 02 Main Content
This study developed a new bioactive bone repair implant, integrating the neural filamin-1-laden pre-angiogenic liposomes with the 3D-printed magnesium alloy porous scaffold; through the surface composite coating, the degradation rate of the magnesium alloy was regulated, and the binding sites for the neural filamin-1 liposomes were provided; systematically explored the synergistic effect of magnesium ion signals and the angiogenesis mediated by neural filamin-1, clarifying the intrinsic mechanism of the coupling regulation of bone regeneration by the two; and in the ischemic bone defect model, verified the actual effect of this functional scaffold on the formation of new bone, the increase in bone density, and the integration effect at the interface between bone and scaffold.
03 Research Design
The magnesium alloy porous scaffold was fabricated using 3D printing technology to match the morphology of bone defects, with interconnected micro-porous structures to provide spatial support for bone tissue growth; the neural filamin-1-laden pre-angiogenic liposomes were prepared and fixed on the surface of the scaffold through the composite coating; the degradation behavior of the magnesium alloy was controlled and regulated through the composite coating, while the functional liposomes were stably anchored; an ischemic bone defect model was established and the functional scaffold was implanted, evaluating the actual effects of vascularization, bone formation, and interface bone integration at the tissue level, and analyzing the regulatory mechanisms of magnesium ions and neural filamin-1 on related signaling pathways and bone differentiation at the molecular level.
04 Results
The 3D-printed magnesium alloy scaffold can precisely match the morphology of bone defects, has stable mechanical support performance, and its porous structure can effectively support bone tissue growth and interface integration; the composite coating can effectively regulate the degradation process of the magnesium scaffold and provide sufficient binding sites for the neural filamin-1 liposomes; after implanting the scaffold into the ischemic bone defect model, it can significantly increase the level of local vascularization, improve bone formation density, and optimize the integration effect at the interface between bone and scaffold; The controlled release of magnesium ions can effectively promote bone formation and differentiation, and simultaneously upregulate the expression of vascular endothelial growth factor A; neuregulin-1 can further enhance the signal transduction of vascular endothelial growth factor A-receptor 2, and enhance the angiogenic effect, ultimately achieving the synergistic coupling of bone formation and angiogenesis.
05 Extension of the idea
This study clearly defines the magnesium ion/neuregulin-1 bone-vascular coupling axis, which can provide a new theoretical direction for the design of functional scaffolds for ischemic bone defect repair; based on this coupling mechanism, different combinations of bioactive metal ions and vascular regulatory factors can be expanded, and the surface functionalization modification strategies of porous scaffolds can be optimized; further exploration of the effect of this regulatory system in different bone defect microenvironments can be conducted to continuously deepen the basic research on the coordinated regulation of bone regeneration and angiogenesis.
Original source:
1. Journal: Bioactive Materials
2. Publication Date: 2026-03-26
3. DOI: 10.1016/j.bioactmat.2026.02.031
4. Authors: Zijie Pei, Haojing Xu, Piqian Zhao, Ya Wen, Ze Zhang, Liangkun Huang, Mengyu Wang, Bo Peng, Liangyuan Wen, Peng Wen, Fengpo Sun
