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Deferoxamine released from poly(lactic‐co‐glycolic acid) promotes healing of osteoporotic bone defect via enhanced angiogenesis and osteogenesis
Author(s) -
Jia Peng,
Chen Hao,
Kang Hui,
Qi Jin,
Zhao Peng,
Jiang Min,
Guo Lei,
Zhou Qi,
Qian Nian Dong,
Zhou Han Bing,
Xu You Jia,
Fan Yongqian,
Deng Lian Fu
Publication year - 2016
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.35793
Subject(s) - angiogenesis , deferoxamine , plga , bone healing , mesenchymal stem cell , vascular endothelial growth factor , wound healing , growth factor , cancer research , pharmacology , materials science , medicine , chemistry , pathology , immunology , in vitro , surgery , biochemistry , receptor , vegf receptors
The regeneration capacity of osteoporotic bones is generally lower than that of normal bones. Current methods of osteoporotic bone defect treatment are not always satisfactory. Recent studies demonstrate that activation of the hypoxia inducible factor‐1α (HIF‐1α) pathway, by genetic methods or hypoxia‐mimicking agents, could accelerate bone regeneration. However, little is known as to whether modulating the HIF‐1α pathway promotes osteoporotic defect healing. To address this problem in the present study, we first demonstrated that HIF‐1α and vascular endothelial growth factor expression levels are lower in osteoporotic bones than in normal bones. Second, we loaded poly(Lactic‐co‐glycolic acid) (PLGA) with the hypoxia‐mimetic agent deferoxamine (DFO). DFO released from PLGA had no significant effect on the proliferation of mesenchymal stem cells (MSCs); however, DFO did enhance the osteogenic differentiation of MSCs. In addition, DFO upregulated the mRNA expression levels of angiogenic factors in MSCs. Endothelial tubule formation assays demonstrate that DFO promoted angiogenesis in human umbilical vein endothelial cells. Third, untreated PLGA scaffolds (PLGA group) or DFO‐containing PLGA (PLGA + DFO group) were implanted into critically sized osteoporotic femur defects in ovariectomized rats. After treatment periods of 14 or 28 days, micro‐CT, histological, CD31 immunohistochemical, and dynamic bone histomorphometric analyses showed that DFO dramatically stimulated bone formation and angiogenesis in a critically sized osteoporotic femur defect model. Our in vitro and in vivo results demonstrate that DFO may promote the healing of osteoporotic bone defects due to enhanced angiogenesis and osteogenesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2515–2527, 2016.