Objective
We aim to translate a next generation bioelectronic macrodevice platform for islet transplantation as a functional cure for type I diabetes. The platform consists of a wirelessly powered device that generates oxygen from water vapor in the body to improve islet cell survival contained within the device. This device can be transplanted just under the skin where the supplemental oxygen generated by the device supports insulin secretion by the islet cells to control blood sugar levels. This would reduce or remove the need for exogenous insulin injections. In this proposal, we will continue testing the device in large animals and engineer the oxygen device to be compliant with FDA regulations for safety and efficacy to begin testing in human patients with TID.
Background Rationale
Transplantation of pancreatic beta cells encapsulated within devices has tremendous potential as a long-term treatment for type 1 diabetes. A single macrodevice that can contain all the insulin producing cells necessary to control blood glucose levels, be transplanted just under the skin as a minimally invasive transplantation procedure, and allow for easy removal and replacement of the implant at the end of its functional life-cycle, is an attractive therapeutic intervention. Despite the advantages of a macrodevice, several challenges need to be addressed for realizing a device that would work in humans. Two main hurdles in the translation of macrodevice technology are the poor biocompatibility of the device material and the insufficient nutrient/oxygen supply to the implanted beta cells. Our goal is to address these two key roadblocks and develop a macrodevice which can work in humans. We have extensive expertise in developing materials and coatings which can cloak implanted materials from the body's immune system. We also have developed advanced bioelectronic technology to create an implant that can be wirelessly powered through the skin to provide supplemental oxygen for the implanted beta cells. Oxygen is the most essential nutrient islets need to secrete insulin at sufficient levels that can regulate blood sugar levels. We will pursue engineering efforts and work with regulatory agencies to bring this bioelectronic oxygen device to the clinic and suitable for implantation in humans.
Description of Project
Type 1 diabetes (T1D) affects millions of people worldwide, requiring them to monitor their blood sugar levels and administer insulin daily. While these treatments are life-saving, they do not replicate the body’s natural ability to regulate blood sugar levels. This results in a constant struggle to maintain balance, increasing the risk of complications like heart disease, kidney failure, and nerve damage. Our research aims to improve this by developing a “functional cure” for TID that can restore the body’s ability to produce insulin naturally, eliminating the need for daily injections. The focus of our work is to create a small, implantable device that houses insulin-producing cells. These cells could be grown in the lab from stem cells or harvested from deceased organ donors to isolate the insulin producing beta cells from a healthy pancreas. Importantly, these cells would then sense high blood sugar levels and release insulin if needed. A critical challenge for this approach has been keeping the cells alive and functioning after transplantation. Without enough nutrients for survival or protection from the immune system, these cells often die, making the therapy ineffective.
Our solution is to engineer a device that combines several innovative technologies to protect the cells from the immune system and provide enough nutrients to keep the cells alive and secreting insulin. 1) Immune protection: The device shields the cells from the immune system by a semi-permeable barrier, removing the need for immunosuppressive drugs, which can have serious side effects such as infections and cancers. 2) Wirelessly powered oxygen generation: The device incorporates electronics to generate supplemental oxygen for the cells by splitting water in the body into oxygen gas. Oxygen is an essential nutrient beta cells need to survive and secrete insulin. The device harvests power through the skin similar to placing a smart phone on a remote charger. Remote powering of the device then creates important oxygen the cells need for survival and to secrete insulin. 3) Retrievability: The device is designed to be easily removed and replaced if necessary, providing a safety net for patients.
We have shown the oxygen device can control blood sugar levels of diabetic mice and rats for up to 3 months. In the next funding period, we propose to further the clinical development of this device by testing in large animals that are more similar to humans. Lastly, we will work to build the device in a manner that is compliant with all safety and manufacturing standards needed by the FDA to begin testing in humans.
Anticipated Outcome
This project will develop a next generation oxygen generating macrodevice with improved biocompatibility, nutrient and oxygen transport, and scale-up potential to allow for clinical application.
Relevance to T1D
Diabetes is a global epidemic afflicting over 400 million people. While a rigorous regimen of blood glucose monitoring coupled with daily injections of recombinant human or animal sources of insulin remains the leading treatment, patients with diabetes still suffer ill effects due to the challenges associated with daily compliance. In addition, the regulation of insulin secretion by the beta cells of the pancreatic islets in response to blood glucose level is a highly dynamic process, which is imperfectly simulated by periodic insulin injections. Beta cell transplantation has tremendous potential, but serious technological limitations remain. The poor biocompatibility of biomaterials used for beta cell replacement therapies is one of the major barriers to clinical application. Materials used to date are immunogenic, lead to scar tissue capsule formation around the device, and eventually, failure. A fundamental challenge to successful islet transplantation is the lack of adequately biocompatible biomaterials that do not cause scar tissue formation. For this reason, the development of non-immunogenic biomaterials and drug delivery systems for use in beta cell transplantation has been a central focus of our efforts. Building on these non-inflammatory materials, we are now incorporating electronic systems to enhance the function of the beta cells within biocompatible implantable devices. We have created a bioelectronic macrodevice that can be charged through the skin and generates oxygen as the most important nutrient the beta cells need to secrete insulin. This bioelectronic oxygen generating device can be placed just under the skin as a minimally invasive implant and easily removed if needed. We have shown the oxygen device can control blood glucose levels of diabetic rodents for up to 3 months. In the next funding period, we propose to further the clinical development of this device by testing in large animal models and build a version of the device that will be compliant with regulatory agencies such as the FDA to begin testing in humans.