Engineering Modular, Oxygen‐Generating Microbeads for the In Situ Mitigation of Cellular Hypoxia

• Published in: Advanced healthcare materials 2023-07, Vol.12 (19), p.e2300239-n/a
• Main Authors: Accolla, Robert P., Liang, Jia‐Pu, Lansberry, Taylor R., Miravet, Irayme Labrada, Loaisiga, Marlon, Sardi, Baltasar Lopez, Stabler, Cherie L.
• Format: Article
• Language: English
• Subjects: Animals; Biomaterials; Biomedical materials; Cell Hypoxia; cell‐based materials; Composite materials; Hypoxia; Islets of Langerhans - metabolism; Mice; Microspheres; Modular engineering; Modularity; Nanoparticles; Oxygen; Oxygen - metabolism; Oxygenation; Polydimethylsiloxane; Surgical implants; therapeutics; Tissue engineering; Tissue Engineering - methods; Transplants & implants
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202300239

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, is created through the encapsulation of calcium peroxide (CaO2) 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 are modulated to characterize oxygen generation kinetics and their suitability for cellular applications. In silico models are developed to predict the local impact of different OxySite microbead formulations on oxygen availability within an idealized cellular implant. Promising OxySite microbead variants are subsequently coencapsulated with murine β‐cells within macroencapsulation devices, resulting in improved cellular metabolic activity and function under hypoxic conditions when compared to controls. Additionally, the coinjection of optimized OxySite microbeads with murine pancreatic islets within a confined transplant site demonstrates 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. An oxygen‐generating biomaterial with customizable oxygen kinetics, termed OxySite, is fabricated into a microbead format. Via discreet manipulation of material parameters, including reactant (CaO2) dosage, porogen inclusion, modulation of microbead size, and the addition of an outer, rate‐limiting PDMS layer, resulting OxySite microbeads are capable of delivering oxygen to support the nutritional cellular needs of different devices and tissues.