Solving the oxygen problem in cell-based drug delivery

The Hybrid Oxygenation Bioelectronics system for Implanted Therapy, or HOBIT
Photos Credit: Jared Jones/Rice University

Scientific Frontline: Extended "At a Glance" Summary: Hybrid Oxygenation Bioelectronics system for Implanted Therapy (HOBIT)

The Core Concept: HOBIT is a fully integrated, wireless implantable device that houses engineered, drug-producing cells and sustains them by actively generating local oxygen. It solves the critical challenge of keeping dense clusters of therapeutic cells alive in poorly oxygenated areas of the body, such as under the skin.

Key Distinction/Mechanism: Unlike conventional unoxygenated cell encapsulation methods that suffer from rapid cell death due to resource competition, HOBIT utilizes a miniaturized electrocatalytic oxygenator. Powered by an onboard battery, an iridium oxide-based surface splits water from the surrounding tissue to generate oxygen directly without harmful byproducts. This active oxygenation safely supports cell densities roughly six times higher than traditional approaches.

Major Frameworks/Components:

• Electrocatalytic Oxygenator: A miniaturized system utilizing an iridium oxide surface to safely split tissue water into oxygen.
• Wireless Bioelectronics: An integrated, battery-powered electronic system allowing for the remote modulation of oxygen production.
• Two-Stage Encapsulation: Engineered cells are shielded from the host immune system by being microencapsulated in alginate hydrogel beads, which are then loaded into a larger semipermeable membrane chamber that allows nutrient and drug flow.
• Multiplexed Biologic Production: The system is proven to support cells engineered to simultaneously and continuously produce multiple therapeutic molecules of varying half-lives (e.g., an antibody, a hormone, and a GLP-1-like molecule).

Branch of Science: Bioengineering, Biomedical Engineering, Materials Science Engineering, and Bioelectronics.

Future Application: The technology paves the way for single-implant, long-term therapies for chronic conditions. A primary future application includes the treatment of diabetes via transplanted pancreatic islets, effectively replacing intensive, multi-dose drug regimens with continuous, autonomous in-body biologic production.

Why It Matters: By successfully integrating immune protection, high cell density housing, and active local oxygenation into a single, minimally invasive device, HOBIT overcomes the primary hurdles of cell-based therapies. It significantly advances the clinical viability of utilizing living cells as continuous, long-term drug factories within the human body.

The Hybrid Oxygenation Bioelectronics system for Implanted Therapy, or HOBIT, shields a sufficient number of cells from the host immune system in a comfortably small volume while also providing access to oxygen and nutrients.
Photos Credit: Jared Jones/Rice University

Implanting living cells as long-term drug producers could transform treatment for numerous diseases, but it is difficult to house the tiny workers in quantities high enough to ensure dosage needs are met while also keeping the cells alive and thriving.

Researchers at Rice University and collaborators at Carnegie Mellon University and Northwestern University have now successfully integrated solutions to several persistent challenges to implantable drug factories into a single device. According to a new study, the Hybrid Oxygenation Bioelectronics system for Implanted Therapy, or HOBIT, shields a sufficient number of cells from the host immune system in a comfortably small volume while also providing access to oxygen and nutrients.

HOBIT is designed to be placed under the skin ⎯ an area that can be accessed via minimally-invasive surgery and is relatively low risk, but which tends to be poorly oxygenated compared to more vascularized tissues.

“When they are packed into dense clusters, cells compete with each other for oxygen,” said Chris Wright, a Rice Ph.D. student who is a first author on a study reporting the findings published in the journal Device. “Under the skin, there simply is not enough local supply to support the number of cells you would need for a clinically meaningful dose.”

To address this, HOBIT incorporates a miniaturized electrocatalytic oxygenator, i.e. an oxygen-making machine that uses an iridium oxide-based surface that uses electricity supplied by an on-board battery to split water present in surrounding tissue to generate oxygen locally, without producing harmful byproducts.

“Our collaborative efforts are highly unique, a combination of energy research, with bioengineering - toward efficiently providing oxygen to the cell factories,” said Tzahi Cohen-Karni, a professor of materials science engineering and biomedical engineering at Carnegie Mellon University.

Omid Veiseh and Chris Wright
Photo Credit: Jared Jones/Rice University

Earlier versions of the oxygen-generating chip required external wiring. In the current study, the oxygenator, battery and electronics are fully integrated into a wireless, implantable system that can be remotely adjusted to modulate oxygen production.

“We are producing oxygen directly where the cells need it,” said Jonathan Rivnay, the Jerome B. Cohen Professor in Engineering at Northwestern University. “That allows us to support much higher cell densities in a much smaller space: Cell densities in HOBIT were roughly six times higher than conventional unoxygenated encapsulation approaches.”

The compact device roughly the size of a folded stock of gum also houses a cell chamber designed to protect the cells from the host immune system while also allowing for nutrients and secreted biologics to flow unimpeded. HOBIT achieves this with a two-stage encapsulation approach: Engineered cells are first microencapsulated in alginate hydrogel beads and then the microcapsules are loaded into a larger chamber consisting of a semipermeable membrane.

The encapsulated cells were engineered to continuously produce three biologic molecules representing different therapeutic classes and half-lives: an antibody, a hormone and an exenatide, which is a GLP-1-like molecule.

“In addition to solving the oxygenation and cell density problem, the HOBIT platform is also proof of concept that cell factories can be engineered to produce multiple biologic molecules simultaneously,” said Omid Veiseh, a professor of bioengineering at Rice who is a corresponding author on the study.

Veiseh is also a Cancer Prevention and Research institute of Texas Scholar and serves as director of the Rice Biotech Launch Pad, an accelerator focused on expediting the translation of the university’s health and medical technology discoveries into cures. Together with collaborators, Veiseh has been working to make implantable cell factories a clinical reality across several different projects.

“The results are very encouraging ⎯ HOBIT brings us significantly closer to clinically viable platform,” Veiseh said. “If you can compact cells and keep them alive, you open the door to more sophisticated therapies ⎯ multiple cell types, regulated secretion, integration with sensing electronics ⎯ all within a retrievable device.”

To evaluate performance, the team implanted oxygenated and non-oxygenated control devices in rats for 30 days. Blood measurements showed sustained levels of all three biologics throughout the study period in animals receiving oxygenated implants. In contrast, short-half-life biologics became undetectable by day seven in animals implanted with the control devices, while longer-half-life molecules declined steadily over time.

At the end of the testing period, roughly 65% of the cells in the oxygenated devices had remained viable compared to roughly 20% in control devices.

Next, the team plans to pursue larger-animal studies and disease-specific applications, including for diabetes, where transplanted pancreatic islets have high yet variable oxygen demands.

“Many groups are working to make drugs last longer or require less intensive dosing regimens,” Veiseh said. “Cell therapy offers a different approach, with a single implant that continuously produces the biologic. Our goal is to provide the engineering framework that makes that feasible.”

Disclaimer: The content in this press release is solely the responsibility of the authors and does not necessarily represent the official views of funding entities.

Funding: The research was supported by Breakthrough T1D (3-SRA-2024-1564-S-B), the U.S. Defense Advanced Research Projects Agency (FA8650-21-2-7119), the Carnegie Mellon University Department of Materials Science and Engineering Materials Characterization Facility (MCF-677785) and the Claire and John Bertucci Nanotechnology Laboratory. 

Published in journal: Device

Title: Design of a wireless, fully implantable platform for in-situ oxygenation of encapsulated cell therapies

Authors: Chris Wright, Abhijith Surendran, Inkyu Lee, Juan E. Villacres, Alex Ezerins, Alexander Curtiss, Nathan Brown, Junyi Liu, Blaine Rothrock, Peter Rios, Daisy Lopez, Ira Joshi, Hafsa Nasir, Han Wang, Cody Fell, Anthony Davis, Jose Oberholzer, Josiah Hester, Tzahi Cohen-Karni, Jonathan Rivnay, and Omid Veiseh

Source/Credit: Rice University | Silvia Cernea Clark

Reference Number: beng032726_01

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