850-P: Continued Monitoring of the Foreign-Body Response to Improve Long-Term Success of Macroencapsulation Devices for Type 1 Diabetes: A Proof-of-Concept Study

Over 463 million people are living with diabetes mellitus (DM). Type 1 DM results from an autoimmune destruction of pancreatic β-cells and accounts for 5-10% of cases. Macroencapsulation devices are a promising therapy for the treatment of T1DM as they improve insulin producing cell retention and viability. However they have had limited success due to a complex cascade of events, causing fibrous encapsulation and ultimately device failure (the foreign body response (FBR)). The FBR is a critical hurdle associated with the success of implantable devices. Here, we aim to develop a biosensing membrane that monitors the FBR in real time; ensuring steps can be taken to modulate the host’s response to the implant. A biosensing membrane was developed consisting of a conductive layer of nonmetallic, highly conductive acrylic adhesive sandwiched between two layers of 0.08 mm thermoplastic polyurethane (TPU). Thereafter the membrane was incorporated into a refillable macroencapsulation device with soft robotic capabilities. In vitro experiments were carried out using electrical impedance spectroscopy. Baseline impedance measurement were taken for porous and non-porous devices using a buffered saline (PBS). Various concentrations of Matrigel (30%, 40%, 50% and 60%) were left to solidify on the membrane, as it contains extracellular matrix proteins, making it analogous to fibrotic tissue components. A significant increase of impedance was seen across the Matrigel groups when compared to PBS alone (p<0.001). A significant difference was also evident between the varying concentrations of Matrigel along the spectra, an example of which is 30% vs. 50% Matrigel at 1.2649 Hz (p<0.001). We have developed a novel approach to measure the membrane permeability in vitro. Monitoring the FBR in vivo, will provide feedback on the functionality of implanted devices, to improve their longevity for the delivery of insulin producing cells.