Deferoxamine and Mesenchymal Cells Along With Acellular Bone Graft Improved Vascularization Marker and Bone Regeneration in Radius Critical-Size Defect of Rat Publisher



Oskouie IM ; Metanat S ; Rahimdoost N ; Saravi MN ; Mohseni M ; Esmaeil Pour R ; Zolbin MM
Source: Regenerative Engineering and Translational Medicine Published:2026

Abstract

Background: Critical-sized bone defects do not heal spontaneously and remain a major clinical challenge. Strategies that simultaneously enhance angiogenesis and osteogenesis may improve graft integration and bone regeneration. This study investigated the combined effect of deferoxamine (DFO)-coated acellular bone grafts (ABG) and mesenchymal stem cell (MSC) injections on vascularization and bone regeneration in a rat critical-sized radius defect model. Methods: Sixteen male Sprague–Dawley rats with 5-mm mid-diaphyseal radius critical-sized defects were randomly assigned to four groups (n = 4/group): untreated control, ABG, DFO-coated ABG (ABG + DFO), and DFO-coated ABG combined with MSC injection (ABG + DFO+MSC). After 4 weeks, bone regeneration was assessed using micro-computed tomography (µCT), and angiogenesis was evaluated by CD31 immunohistochemistry. Results: The ABG + DFO+MSC group demonstrated significantly enhanced vascularization, with the highest percentage of CD31-positive cells (34 ± 4.6%), compared with the ABG + DFO group (14.5 ± 2.2%; p < 0.0001), ABG group (3.1 ± 0.4%; p < 0.0001), and control group (2.5 ± 0.6%; p < 0.0001). µCT analysis revealed significantly greater callus volume in the ABG + DFO+MSC group compared to all other groups (p < 0.05), with near-complete bridging of the defect, whereas persistent fracture gaps were observed in control and ABG groups. Conclusion: The combination of DFO-coated acellular bone grafts and MSC injection synergistically enhances angiogenesis and bone regeneration in critical-sized radius defects in rats. This dual angiogenic–osteogenic strategy shows promise as a translational approach for improving outcomes in large bone defects. Lay Summary: Large bone defects often fail to heal on their own, creating a major clinical challenge. In this study, we tested a new approach that combines a treated bone graft with injections of stem cells to improve blood vessel formation and bone repair. Using a rat model, we found that grafts coated with the drug deferoxamine (DFO) became much more effective when paired with mesenchymal stem cells. This combination produced the highest levels of new blood vessels and new bone tissue. Our findings suggest that this dual treatment strategy could offer a promising future option for patients with severe bone injuries. Future Works: Future studies should evaluate this dual DFO-coated graft and stem-cell strategy in larger animal models, optimize dosing and timing, and investigate long-term mechanical strength. Translational work should also assess safety, scalability, and regulatory considerations to support potential clinical application in complex human bone defects. © The Author(s), under exclusive licence to The Regenerative Engineering Society 2026.