Engineering Modular, Oxygen-Generating Microbeads for the in situ Mitigation of Cellular Hypoxia.

Insufficient oxygenation is a key obstacle in the design of clinically scalable tissue-engineered grafts. In this work, an oxygen-generating composite material, termed OxySite, was created through the encapsulation of calcium peroxide (CaO 2 ) within polydimethylsiloxane and formulated into microbeads for ease in tissue integration. Key material parameters of reactant loading, porogen addition, microbead size, and an outer rate-limiting layer were modulated to characterize oxygen generation kinetics and their suitability for cellular applications. In silico models were developed to predict the local impact of different OxySite microbead formulations on oxygen availability within an idealized cellular implant. Promising OxySite microbead variants were subsequently co-encapsulated with murine β-cells within macroencapsulation devices, resulting in improved cellular metabolic activity and function under hypoxic conditions when compared to controls. Additionally, the co-injection of optimized OxySite microbeads with murine pancreatic islets within a confined transplant site demonstrated ease of integration and improved primary cell function. These works highlight the broad translatability delivered by this new oxygen-generating biomaterial format, whereby the modularity of the material provides customization of the oxygen source to the specific needs of the cellular implant. This article is protected by copyright. All rights reserved.