Hypoxia-induced angiogenesis is increased by the controlled release of deferoxiamine from gelatin hydrogels

Saito, Takashi; Tabata, Yasuhiko

doi:10.1016/j.actbio.2014.04.021

Cited by 36 publications

(28 citation statements)

References 48 publications

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“…The mild VEGF producing ability of HUVECs was possibly due to the inappropriate oxygen level according to a recent report on DFO. 20 Interactions between HUVECs and hMSCs greatly contribute to both angiogenesis and osteogenesis from both in vitro and in vivo studies. 35–38 Therefore, our data from two cell types will provide more related information on cell response studies of DFO-decorated scaffold for bone regeneration compared to data using just one cell type.…”

Section: Discussionmentioning

confidence: 99%

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Hypoxia-Mimicking Nanofibrous Scaffolds Promote Endogenous Bone Regeneration

Yao

Liu

Tao

et al. 2016

ACS Appl. Mater. Interfaces

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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.

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Section: Discussionmentioning

confidence: 99%

“…19 Thus, DFO can activate HIF-1 α and subsequently angiogenesis. 19,20 Whether locally or systemically injected, DFO has shown promise in promoting bone regeneration. 5,12,19,21,22 However, its further application is significantly impeded by a short plasma half-life (~5.5 min) and high drug toxicity.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Mimicking Nanofibrous Scaffolds Promote Endogenous Bone Regeneration

Yao

Liu

Tao

et al. 2016

ACS Appl. Mater. Interfaces

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“…These results are consistent with the above MTT assay. The cytotoxicity of DFO may be result from the ability of DFO to diffuse into cells and chelate intracellular iron stores (Saito & Tabata, 2014). The viability of the cell is thus adversely affected because of lack of this essential trace metal.…”

Section: Cytotoxicitymentioning

confidence: 99%

Synthesis and evaluation of oxidation-responsive alginate-deferoxamine conjugates with increased stability and low toxicity

Tian

Chen

et al. 2016

Carbohydrate Polymers

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“…These scaffolds and hydrogels can often be engineered with modified microenvironmental features to enhance the proliferation and self-organization of vascular cells embedded within. For example, locally hypoxic conditions are a particularly attractive feature that investigators have attempted to precisely modulate [31–34] because of the demonstrated ability of controlled hypoxia to enhance vessel formation in 3D tissue-engineered structures in vitro [35] and the relevance to the tumor microenvironment in cancer biology.…”

Section: Advances In Stem Cell-derived Vascular Modelsmentioning

confidence: 99%

Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering

Lowenthal

Gerecht

2016

Biochemical and Biophysical Research Communications

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Proper blood vessel networks are necessary for constructing and re-constructing tissues, promoting wound healing, and delivering metabolic necessities throughout the body. Conversely, an understanding of vascular dysfunction has provided insight into the pathogenesis and progression of diseases both common and rare. Recent advances in stem cell-based regenerative medicine – including advances in stem cell technologies and related progress in bioscaffold design and complex tissue engineering – have allowed rapid advances in the field of vascular biology, leading in turn to more advanced modeling of vascular pathophysiology and improved engineering of vascularized tissue constructs. In this review we examine recent advances in the field of stem cell-derived vasculature, providing an overview of stem cell technologies as a source for vascular cell types and then focusing on their use in three primary areas: studies of vascular development and angiogenesis, improved disease modeling, and the engineering of vascularized constructs for tissue-level modeling and cell-based therapies.

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Hypoxia-induced angiogenesis is increased by the controlled release of deferoxiamine from gelatin hydrogels

Cited by 36 publications

References 48 publications

Hypoxia-Mimicking Nanofibrous Scaffolds Promote Endogenous Bone Regeneration

Hypoxia-Mimicking Nanofibrous Scaffolds Promote Endogenous Bone Regeneration

Synthesis and evaluation of oxidation-responsive alginate-deferoxamine conjugates with increased stability and low toxicity

Stem cell-derived vasculature: A potent and multidimensional technology for basic research, disease modeling, and tissue engineering

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