Hypoxia-induced angiogenesis is increased by the controlled release of deferoxiamine from gelatin hydrogels.
The objective of this study is to design biodegradable hydrogels for the controlled release of deferoxiamine (DFO) and evaluate their biological activity. When the DFO was added to human umbilical vein endothelial cells cultured in 5.0% O2, the level of hypoxia-inducible factor-1α and vascular endothelial growth factor significantly increased compared with that without DFO. The expression of angiogenesis-related genes was accordingly increased by the DFO addition. An aqueous solution of mixed gelatin and DFO was freeze-dried, and dehydrothermally treated at 140°C for 24h to prepare a gelatin hydrogel incorporating DFO. In the release test with phosphate-buffered saline solution (PBS) at 37°C, an initial DFO release of 60% was observed, followed by no release. When placed in PBS containing collagenase, the hydrogel was enzymatically degraded with time, and consequently released DFO in a degradation-dependent manner. After the hydrogel incorporating DFO was injected intramuscularly into a mouse model of hind limb ischemia, the number of new blood vessels formed was significantly higher than that with free DFO and DFO-free hydrogel. It is concluded that the DFO-containing hydrogel shows promising for inducing angiogenesis locally.
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Takashi
T
Saito
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: yasuhiko@frontier.kyoto-u.ac.jp.
Yasuhiko
Y
Tabata
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003676:Deferoxamine / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D007866:Leg / Q000098:blood supply; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D017262:Siderophores / Q000008:administration & dosage / Q000737:chemistry; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D020100:Hydrogels; D017262:Siderophores; D005780:Gelatin; D003676:Deferoxamine
Angiogenesis; Controlled release; Deferoxiamine; Gelatin hydrogel; Hypoxia