초록 |
Hypoxia is recognized as a key regulator that promotes vascular development in various biological processes. Here we report a hypoxia-inducible (HI) hydrogels that can form hydrogel networks via oxygen (O2) consumption in a laccase-mediated reaction. O2 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 (HIFs) activation. In addition, we utilize the HI hydrogels as artificial tumor microenvironments to study the effect of O2 gradients on tumor motility, demonstrating hypoxic gradients guided tumor motility and matrix remodeling via HIF-1α activation. In sum, the HI hydrogel have a great potential 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. |