Engineering a macroporous oxygen-generating scaffold for enhancing islet cell transplantation within an extrahepatic site

• Published in: Acta biomaterialia 2021-08, Vol.130, p.268-280
• Main Authors: Liang, Jia-Pu, Accolla, Robert P., Soundirarajan, Madhuvanthi, Emerson, Amy, Coronel, Maria M., Stabler, Cherie L.
• Format: Article
• Language: English
• Subjects: Biomedical materials; Calcium; Cell death; cellular transplantation; Diabetes; Diabetes mellitus; Grafting; Hypoxia; Implants; Intermediates; Islet cells; Islets; Microspheres; Nanoparticles; Oxygen; Oxygen demand; Oxygen-generating microbead; Oxygenation; Pancreas transplantation; Pancreatic islet transplantation; Peroxide; Polydimethylsiloxane; Purity; Scaffolds; Supplements; Syngeneic grafts; Transplantation; Transplants & implants; Vascularization
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2021.05.028

Insufficient oxygenation is a serious issue arising within cell-based implants, as the hypoxic period between implantation and vascularization of the graft is largely unavoidable. In situ oxygen supplementation at the implant site should significantly mitigate hypoxia-induced cell death and dysfunction, as well as improve transplant efficacy, particularly for highly metabolically active cells such as pancreatic islets. One promising approach is the use of an oxygen generating material created through the encapsulation of calcium peroxide within polydimethylsiloxane (PDMS), termed OxySite. In this study, OxySite microbeads were incorporated within a macroporous PDMS scaffold to create a single, streamlined, oxygen generating macroporous scaffold. The resulting OxySite scaffold generated sufficient local oxygenation for up to 20 days, with nontoxic levels of reaction intermediates or by-products. The benefit of local oxygen release on transplant efficacy was investigated in a diabetic Lewis rat syngeneic transplantation model using a clinically relevant islet dosage (10,000 IEQ/kg BW) with different isolation purities (80%, 90%, and 99%). Impure islet preparations containing pancreatic non-islet cells, which are common in the clinical setting, permit examination of the effect of increased overall oxygen demand. Our transplantation outcomes showed that elevating the oxygen demand of the graft with decreasing isolation purity resulted in decreased graft efficacy for control implants, while the integration of OxySite significantly mitigated this impact and resulted in improved graft outcomes. Results highlight the superior clinical translational potential of these off-the-shelf OxySite scaffolds, where islet purity and the overall oxygen demands of implants are increased and highly variable. The oxygen-generating porous scaffold further provides a broad platform for enhancing the survival and efficacy of cellular implants for numerous other applications. Hypoxia is a serious issue within tissue engineered implants. To address this challenge, we developed a distinct macroporous scaffold platform containing oxygen-generating microbeads. This oxygen-generating scaffold showed the potential to support clinically relevant cell dosages for islet transplantation, leading to improved treatment efficacy. This platform can also be used to mitigate hypoxia for other biomedical applications. [Display omitted]