Hypoxia-inducible Hydrogels

Hypoxia, low oxygen tension, plays a pivotal role during development, regeneration, and cancer. However, nobody has stimulated hypoxia in a 3D microenvironment. Here, we developed a fundamental technology to create hydrogel materials that can serve as 3D hypoxic microenvironments. The HI hydrogels are formed via oxygen consumption in a laccase-mediated crosslinking reaction with biodegradability, cytocompatibility, and tunable mechanical properties. Oxygen levels and gradients within the HI hydrogels can be accurately controlled and precisely predicted. We demonstrate that HI hydrogels guide vascular morphogenesis in vitro by activating hypoxia-inducible factors (HIFs) and promote rapid neovascularization from the host tissue when transplanted subcutaneously. The HI hydrogel is a new class of biomaterials that may prove useful in many applications, ranging from the engineering of de novo tissues and disease models to the treatment of vascular disorders.

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