Oxygen-Releasing Calcium Peroxide nanoparticles embedded in hydrogels as a strategy for overcoming Hypoxia in large 3D tissue constructs

Hypoxia remains a major barrier to engineering large and complex 3D tissue constructs, as oxygen diffusion limits restricts cell survival in thick scaffolds [1,2]. Hypoxic environments are particularly problematic in chronic wounds and tissue defects, where limited oxygen availability delays healing and contributes to infection and inflammation [3]. Addressing oxygen deprivation is essential to improve tissue viability and regenerative tissue outcomes. Within the last 20 years, calcium peroxide (CaO2) nanoparticles have emerged as effective oxygen-releasing materials (ORMs), capable of sustained oxygen delivery through hydrogen peroxide (H2O2) decomposition within biocompatible hydrogel matrices [4–6]. These nanomaterials have been successfully embedded to enhance cellular vascularization in preclinical models [4,7]. Despite promising in vivo studies and animal data, translating CaO2-based oxygen-releasing biomaterials to clinical applications encounters persistent challenges such as uncontrolled oxygen release and the risk of generating H2O2 [8]. This viewpoint reviews novel advances in CaO2 oxygen-releasing polymers while evaluating efforts to translate these systems into clinical application through scaffold engineering. Consideration of a variety of limitations is examined, emphasizing why targeted research is paramount to refining these engineered systems for therapeutic use.

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