Electrocatalytic on-site oxygenation for transplanted cell-based-therapies

Lee, I.; Surendran, A.; Fleury, S.; Gimino, I.; Curtiss, A.; Fell, C.; Shiwarski, D.; El-Refy, O.; Rothrock, B.; Jo, S.; Schwartzkopff, T.; Singh Mehta, A.; John, S.; Ji, X.; Nikiforidis, G.; Hester, J.; Weber, D. J.; Veiseh, O.; Feinberg, A.; Rivnay, J.; Cohen-Karni, T.

doi:10.1101/2023.06.05.543794

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bioRxiv · 10.1101/2023.06.05.543794

Electrocatalytic on-site oxygenation for transplanted cell-based-therapies

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Abstract

Implantable cell therapies and tissue transplants require sufficient oxygen supply to function and are limited by a delay or lack of vascularization from the transplant host1, 2. Exogenous oxygen production can support cells and tissues, such as pancreatic islets and engineered therapeutic cells. Previous oxygenation strategies have targeted gas circulation or decomposition of solid peroxides. These strategies however require bulky implants, transcutaneous supply lines, and are limited in their total oxygen production or regulation3, 4. Readily integrated and controlled production of oxygen has eluded cell therapy devices. Here, we show an electrocatalytic approach that enables bioelectronic control of oxygen generation in complex cellular environments to sustain engineered cell viability and therapy production under hypoxic stress and at high cell densities. Nanostructured sputtered iridium oxide serves as an ideal catalyst for oxygen evolution reaction (OER) at neutral pH. It enables a lower OER onset and shows selective oxygen production without evolution of toxic side products over a 300 mV window of operation. This electrocatalytic on site oxygenator (ecO2) can sustain high cell loadings (>60k cells/mm3) in hypoxic conditions in vitro and in vivo. Our results demonstrate that exogenous oxygen production devices can be readily integrated into bioelectronic platforms and enable high cell loadings in smaller device footprints with broad applicability.

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Lee, I., Surendran, A., Fleury, S., Gimino, I., Curtiss, A., Fell, C., Shiwarski, D., El-Refy, O., Rothrock, B., Jo, S., Schwartzkopff, T., Singh Mehta, A., John, S., Ji, X., Nikiforidis, G., Hester, J., Weber, D. J., Veiseh, O., Feinberg, A., Rivnay, J., Cohen-Karni, T.. 2023-06-07. Electrocatalytic on-site oxygenation for transplanted cell-based-therapies. https://doi.org/10.1101/2023.06.05.543794

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