April 22 - 26, 2024
Seattle, Washington
May 7 - 9, 2024 (Virtual)

Event Supporters

2024 MRS Spring Meeting
SB05.06.03

Wireless, Battery-Free Bioelectronics for Fully Implantable, Living Medical Devices

When and Where

Apr 24, 2024
11:15am - 11:45am
Room 434, Level 4, Summit

Presenter(s)

Co-Author(s)

Siddharth Krishnan1,Matthew Bochenek1,Suman Bose1,Claudia Liu1,Amanda Facklam1,Nima Khatib1,Ben Walters1,Derin Gumustop1,Laura O'Keeffe1,Robert Langer1,Daniel Anderson1

MIT1

Abstract

Siddharth Krishnan1,Matthew Bochenek1,Suman Bose1,Claudia Liu1,Amanda Facklam1,Nima Khatib1,Ben Walters1,Derin Gumustop1,Laura O'Keeffe1,Robert Langer1,Daniel Anderson1

MIT1
Living cells are a novel class of therapeutics that offer possibilities in long-term protein replacement. Primary cells such as pancreatic islets can offer functional cures for Type I Diabetes via responsive insulin secretion, as can stem-cell derived products<sup>1</sup>. Immortalized cell lines can be engineered or transfected to secrete nearly any protein of choice, to address a broad range of conditions from blood-borne disorders to degenerative neural disease and cancer<sup>2,3</sup>. Two core challenges limit the clinical translation of these types of cell therapies: first, the potential for recognition and attack by the host immune system necessitates the use of chronic immunosuppressants to maintain graft viability, with mixed success. Second, the formation of fibrotic capsules around transplanted cells isolates them from native vasculature, resulting in hypoxia<sup>1</sup>.<br/><br/>In this work, we demonstrate a wireless battery-free device system capable of housing and supporting therapeutic cells in vivo by providing both immune-isolation and oxygen supply<sup>4</sup>. Transplanted cells are separated from host tissue by nanoporous membranes that prevent infiltration and attack by immune cells, obviating the need for immune suppression. A multilayer materials system comprising a proton-exchange membrane electrolyzer and an elastomeric encapsulation allows for direct splitting of molecular water into oxygen and hydrogen. Oxygen is stored in an elastomeric chamber that diffuses directly into regions containing transplanted cells. The entire reaction is sustained by a wireless power harvesting circuit based on resonant inductive coupling, at a frequency (13.56 MHz) chosen for its low specific absorption rate in biological tissue and compatibility with existing commercial infrastructure for two-way data and power transfer.<br/>Systematic numerical modeling, benchtop testing, and in vitro experimentation highlight key aspects of device and materials performance.<br/><br/>In vivo studies demonstrate high levels of performance. HEK293T cells engineered to secrete a model protein system (erythropoietin, EPO), demonstrate sustained, significantly elevated levels of protein production when transplanted in O<sub>2</sub>-Macrodevices relative to cells encapsulated in non-oxygenated control devices over several weeks. Xenogeneic rat islets transplanted into immune competent, diabetic C57BL/6J mice resulted in complete diabetic reversal for several weeks, with explantation studies revealing viable, glucose response islets. Notably, all of these studies involved transplantation into minimally invasive subcutaneous sites, that are clinically attractive owing to their easy accessibility for implantation and explantation procedures.<br/><br/>Taken together, these results combine advances in materials, electrochemistry, wireless power transfer and bioengineering to support xenogeneic and allogeneic therapeutic cells in vivo without the need for immune suppression, in minimally invasive sites. These hybrid “living” medical devices, combining cellular and inorganic device materials, could provide pathways for functional cures for a broad range of organ-specific diseases.<br/><br/><br/><br/>References<br/>1 Thanos, C. G., Gaglia, J. L. & Pagliuca, F. W. Considerations for successful encapsulated β-cell therapy. <i>Cell therapy: Current status and future directions</i>, 19-52 (2017).<br/>2 Fomin, M. E., Togarrati, P. P. & Muench, M.O. <i>Journal of Thrombosis and Haemostasis</i> (2014).<br/>3 Emerich, D. F., Orive, G., Thanos, C., Tornoe, J. & Wahlberg, L. U. Encapsulated cell therapy for neurodegenerative diseases: from promise to product. <i>Advanced drug delivery reviews</i> <b>67</b>, 131-141 (2014).<br/>4 Krishnan, S. R.<i> et al.</i> A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo. <i>Proceedings of the National Academy of Sciences</i> <b>120</b>, e2311707120 (2023).

Symposium Organizers

Eric Glowacki, Central European Institute of Technology
Philipp Gutruf, University of Arizona
John Ho, National University of Singapore
Flavia Vitale, University of Pennsylvania

Symposium Support

Bronze
Diener Electronic GmbH + Co. KG

Session Chairs

Philipp Gutruf
Flavia Vitale

In this Session