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

Author:

Lee Inkyu,Surendran Abhijith,Fleury Samantha,Gimino Ian,Curtiss Alexander,Fell Cody,Shiwarski Daniel,El-Refy Omar,Rothrock Blaine,Jo Seonghan,Schwartzkopff Tim,Mehta Abijeet Singh,John Sharon,Ji Xudong,Nikiforidis Georgios,Feinberg Adam,Hester Josiah,Weber Douglas J.,Veiseh Omid,Rivnay Jonathan,Karni Tzahi Cohen-

Abstract

AbstractImplantable 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.

Publisher

Cold Spring Harbor Laboratory

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