Advances in Hypoxia-Inducible Factor-1α Stabilizer Deferoxamine in Tissue Engineering

Deferoxamine (DFO) is an iron chelator with FDA approval for the clinical treatment of iron excess. As a well-established stabilizer of hypoxia-inducible factor-1α (HIF-1α), DFO can efficiently upregulate HIF-1α and relevant downstream angiogenic factors, leading to accelerated vascularization. Moreover, as increasing studies have focused on DFO as a hypoxia-mimetic agent in recent years, it has been shown that DFO exhibited multiple functions, including stem cell regulation, immunoregulation, provascularization, and pro-osteogenesis. On the contrary, DFO can bind excess iron ions in wounds of chronic inflammation, while serving as an antioxidant with the characteristic of removing reactive oxygen species. Collectively, these characteristics make DFO a potent modulator in tissue engineering for increasing tissue integration of biomaterials in vivo and facilitating wound healing. This review outlines the activity of DFO as a representative hypoxia-mimetic agent in cells as well as the evolution of its application in tissue engineering. It can be concluded that DFO is a medication with tremendous promise and application value in future trends, which can optimize biomaterials and existing tissue engineering techniques for tissue regeneration. This review gives a thorough overview of current developments in several tissue regeneration therapies based on stem cells or biomaterials that have used deferoxamine (DFO). This hypoxia-mimetic agent pretreatment of stem cells resulted in an improvement in their capacity for survival, differentiation, and paracrine activity. It is primarily explained by the fact that DFO prompts cells to initiate hypoxic signaling pathways in normoxia and secrete a range of substances that promote anti-inflammatory, angiogenesis, and osteogenesis. The ability of DFO to bind free iron and act as an antioxidant can also be used to combine it with scaffold materials, which can significantly improve the antibacterial and anti-inflammatory properties of biomaterials used for tissue regeneration as well as the quality of vascularization and osteogenesis.