Hypoxia-Mimicking Nanofibrous Scaffolds Promote Endogenous Bone Regeneration.
Utilizing biomimetic materials to potentiate endogenous cell growth or signaling is superior to relying on exogenous cells or signals for bone formation. Desferoxamine (DFO), which is a hypoxia-mimetic agent that chelates iron (Fe3+), mimics hypoxia to encourage bone healing. However, high cytotoxicity, off-target effects, and the short half-life of DFO have significantly impeded its further applications. We mitigated these side effects by locally immobilizing DFO onto a gelatin nanofibrous (GF) scaffold that retained DFO's ability to chelate Fe3+. Moreover, DFO-functionalized GF (GF-DFO) scaffolds, which have similar micro/macrostructures to GF scaffolds, not only demonstrated decreased cytotoxicity on both human umbilical vein endothelial cells and human mesenchymal stem cells but also significantly increased vascular endothelial growth factor (VEGF) expression in vitro. Most importantly, in our in vivo experiments on a critical-sized cranial bone defect mouse model, a significant amount of bone was formed in most of the GF-DFO scaffolds after six weeks, while very little new bone was observed in the GF scaffolds. These data suggest that use of a hypoxia-mimicking nanofibrous scaffold is a promising strategy for promoting endogenous bone formation.
Department of Biomedical Engineering, University of South Dakota , Sioux Falls, South Dakota 57107, United States.|BioSNTR , Sioux Falls, South Dakota 57107, United States.
Qingqing
Q
Yao
Department of Biomedical Engineering, University of South Dakota , Sioux Falls, South Dakota 57107, United States.|BioSNTR , Sioux Falls, South Dakota 57107, United States.
Yangxi
Y
Liu
Children's Health Research Center at Sanford Research , Sioux Falls, South Dakota 57104, United States.
Jianning
J
Tao
Orthopedic Institute , Sioux Falls, South Dakota 57105, United States.
Keith M
KM
Baumgarten
Department of Biomedical Engineering, University of South Dakota , Sioux Falls, South Dakota 57107, United States.|BioSNTR , Sioux Falls, South Dakota 57107, United States.
Hongli
H
Sun
D000818:Animals; D001861:Bone Regeneration; D015687:Cell Hypoxia; D006801:Humans; D059630:Mesenchymal Stem Cells; D051379:Mice; D057139:Nanofibers; D010012:Osteogenesis; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A
D042461:Vascular Endothelial Growth Factor A
angiogenesis; desferoxamine; endogenous bone regeneration; hypoxia; nanofibrous scaffold