In a new paper, scientists from Northwestern University and their collaborators at Rice University and Carnegie Mellon University report on their progress towards developing so-called implantable “living pharmacies.” These are tiny devices containing engineered cells that continuously produce medicines inside the body. Details of the study, which was done in rats, are published in Device in a paper titled “Design of a wireless, fully implantable platform for in-situ oxygenation of encapsulated cell therapies.”
The device, which is called the hybrid oxygenation bioelectronics system for implanted therapy or HOBIT, is roughly the size of a folded stick of gum. It integrates engineered cells with oxygen-producing bioelectronics and is designed in such a way that the cells are shielded from the body’s immune system while also receiving oxygen and nutrients needed to keep them alive and producing drugs for several weeks. In the future, these devices could be deployed to treat chronic conditions without requiring patients to carry, inject, or remember to take medications.
“This work highlights the broad potential of a fully integrated biohybrid platform for treating disease,” said Jonathan Rivnay, PhD, a professor of biomedical engineering and materials science and engineering at Northwestern and a co-principal investigator of the project. “Traditional biologic drugs often have very different half-lives, so maintaining stable levels of multiple therapies can be challenging. Because our implanted ‘cell factories’ continuously produce these biologics, keeping the cells alive with our oxygenation technology allows us to sustain steady levels [of] multiple different therapeutics at once.”
Solving the oxygenation challenge was critical to the success of HOBIT. When engineered cells are packed together in an implant, they compete for oxygen to live. Without a steady supply, many cells die, which limits how much medicine the implants can produce. In an earlier study, Rivnay and his collaborators demonstrated how a tiny electrochemical device could generate oxygen by splitting nearby water molecules, and showed that supplying oxygen locally dramatically improved the survival of implanted therapeutic cells. The latest iteration of their device integrates that oxygen-generation technology in a fully implantable, wireless system.
Digging into the details of the device, HOBIT contains three primary components: a cell chamber that holds the genetically engineered cells, a miniature oxygen generator, and electronics and a battery to regulate oxygen production and wirelessly communicate with external devices. Because the device produces oxygen directly inside the implant, the cells receive a steady supply even in hypoxic environments. “We are producing oxygen directly where the cells need it,” Rivnay said. “That allows us to support much higher cell densities in a much smaller space.” In fact, “cell densities in HOBIT were roughly six times higher than conventional unoxygenated encapsulation approaches.”
According to the paper, the team engineered the cells to produce three different biologics—an anti-HIV antibody, a GLP-1-like peptide used to treat type 2 diabetes, and leptin, a hormone that regulates appetite and metabolism. They implanted the devices under the skin of rats and monitored drug levels in their bloodstreams for 30 days. Blood measurements of animals with the implanted devices showed sustained levels of all three biologics throughout the study period. In contrast, in animals that were implanted with devices without oxygenation, the biologics that had shorter half-lives were undetectable by the seventh day. Drugs with longer half-lives in these animals also declined steadily over time. At the end of the testing period, roughly 65% of the cells in the oxygenated devices remained viable compared with roughly 20% in control devices.
For their next steps, the scientists intend to test their devices in larger animal models and explore disease-specific applications, including therapies based on transplanted pancreatic cells. “As these technologies continue to develop, devices like this could eventually act as programmable drug factories inside the body—delivering complex therapies in ways that simply aren’t possible today,” Rivnay said.
