Oxygen releasing materials: Towards addressing the hypoxia-related issues in tissue engineering

Manufacturing macroscale cell-laden architectures is one of the biggest challenges faced nowadays in the domain of tissue engineering. Such living constructs, in fact, pose strict requirements for nutrients and oxygen supply that can hardly be addressed through simple diffusion in vitro or without a functional vasculature in vivo. In this context, in the last two decades, a substantial amount of work has been carried out to develop smart materials that could actively provide oxygen-release to contrast local hypoxia in large-size constructs. This review provides an overview of the currently available oxygen-releasing materials and their synthesis and mechanism of action, highlighting their capacities under in vitro tissue cultures and in vivo contexts. Additionally, we also showcase an emerging concept, herein termed as "living materials as releasing systems", which relies on the combination of biomaterials with photosynthetic microorganisms, namely algae, in an "unconventional" attempt to supply the damaged or re-growing tissue with the necessary supply of oxygen. We envision that future advances focusing on tissue microenvironment regulated oxygen-supplying materials would unlock an untapped potential for generating a repertoire of anatomic scale, living constructs with improved cell survival, guided differentiation, and tissue-specific biofunctionality.