ArticlePolymers2025
An Electrospun DFO-Loaded Microsphere/SAIB System Orchestrates Angiogenesis-Osteogenesis Coupling via HIF-1α Activation for Vascularized Bone Regeneration.
Article in Polymers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Metabolism-Regulating Microspheres: Design Principles, Therapeutic Applications Across Multisystem Diseases, and Future Perspectives.Research (Washington, D.C.) · 2026Review
- HIF-1α at the intersection of hypoxia, ferroptosis-associated stress, and cell death crosstalk in osteomyelitis.Frontiers in cell and developmental biology · 2026Review
- Sequential drug release from dual-responsive scaffold with ultrasound-enhanced efficacy for infectious oral ulcer therapy.Regenerative biomaterials · 2026Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study developed electrosprayed deferoxamine (DFO)-loaded poly(lactic-co-glycolic acid) microspheres (DFO-MS) combined with a sucrose acetate isobutyrate (SAIB) depot (DFO-MS@SAIB) for bone-defect repair, targeting the coordinated regulation of angiogenesis and osteogenesis in vascularized bone regeneration-where new blood vessels support functional bone integration. In vitro/in vivo evaluations confirmed its dual pro-angiogenic and pro-osteogenic effects via HIF-1α pathway activation. BACKGROUND/
objectivesEmerging evidence underscores the indispensability of vascularization in bone-defect repair, a clinical challenge exacerbated by limited intrinsic healing capacity. While autologous grafts and growth-factor-based strategies remain mainstream, their utility is constrained by donor-site morbidity, transient bioactivity, and poor spatiotemporal control over angiogenic-osteogenic coupling. Here, we leveraged DFO, a hypoxia-mimetic HIF-1α stabilizer with angiogenic potential, to engineer an injectable DFO-MS@SAIB depot. This system was designed to achieve sustained DFO release, thereby synchronizing vascular network formation with mineralized tissue regeneration in critical-sized defects.
methodsDFO-MS were fabricated via electrospraying and combined with SAIB (DFO-MS@S) to form an injectable sustained-release depot. Their physicochemical properties, including morphology, encapsulation efficiency, degradation, release kinetics, and rheology, were systematically characterized. In vitro, the angiogenic capacity of HUVECs co-cultured with DFO-MS was evaluated; conditioned HUVECs were then co-cultured with BMSCs to assess the BMSCs' cytocompatibility and osteogenic differentiation. In vivo bone regeneration in a rat calvarial defect model was evaluated using micro-CT, histology, and immunohistochemistry.
resultsThe DFO-MS@SAIB system achieved sustained DFO release, stimulating HUVEC proliferation, migration, and tubulogenesis. In a Transwell co-culture model, pretreated HUVECs promoted BMSC migration and osteogenic differentiation via paracrine signaling involving endothelial-secreted factors (e.g., VEGF). HIF-1α pathway activation upregulated osteogenic markers (ALP, Col1a1, OCN), while in vivo experiments demonstrated enhanced vascularized bone regeneration, with significantly increased bone volume/total volume (BV/TV) and new bone area compared with controls.
conclusionThe DFO-MS@SAIB system promotes bone regeneration via sustained deferoxamine release and HIF-1α-mediated signaling. Its angiogenesis-osteogenesis coupling effect facilitates vascularized bone regeneration, thereby offering a translatable strategy for critical-sized bone-defect repair.
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