title: Hypoxia-inducible hydrogels.
abstract: Oxygen is vital for the existence of all multicellular organisms, acting as a signalling molecule regulating cellular activities. Specifically, hypoxia, which occurs when the partial pressure of oxygen falls below 5%, plays a pivotal role during development, regeneration and cancer. Here we report a novel hypoxia-inducible (HI) hydrogel composed of gelatin and ferulic acid that can form hydrogel networks via oxygen consumption in a laccase-mediated reaction. Oxygen levels and gradients within the hydrogels can be accurately controlled and precisely predicted. We demonstrate that HI hydrogels guide vascular morphogenesis in vitro via hypoxia-inducible factors activation of matrix metalloproteinases and promote rapid neovascularization from the host tissue during subcutaneous wound healing. The HI hydrogel is a new class of biomaterials that may prove useful in many applications, ranging from fundamental studies of developmental, regenerative and disease processes through the engineering of healthy and diseased tissue models towards the treatment of hypoxia-regulated disorders.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences-Oncology Center, and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Park
authors.affiliation: 1] Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences-Oncology Center, and the Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, USA [2] Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Gerecht
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001672:Biocompatible Materials; D060833:Cellular Microenvironment; D003198:Computer Simulation; D003373:Coumaric Acids; D042783:Endothelial Cells / Q000378:metabolism*; D005780:Gelatin / Q000737:chemistry; D020869:Gene Expression Profiling; D006801:Humans; D020100:Hydrogels / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D042845:Laccase; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D042683:Angiopoietin-1; D051792:Basic Helix-Loop-Helix Proteins; D001672:Biocompatible Materials; D003373:Coumaric Acids; D005780:Gelatin; D020100:Hydrogels; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042845:Laccase; D020782:Matrix Metalloproteinases; D010100:Oxygen; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099162:Endothelial PAS Domain-Containing Protein 1; C467630:ANGPT1 protein, human; C497442:HIF1A protein, human; C467484:VEGFA protein, human; C004999:ferulic acid; C000588866:KDR protein, human