Development of a minimally-invasive implanted device for electrical stimulation of pancreatic parenchyma

Abstract

Diabetes is a state of hyperglycemia, which worldwide currently 537 million adults are living with. In 2021 diabetes caused 6.7 million deaths and health expenses of USD 996 billion. 90% of all cases are type 2 diabetes mellitus (T2DM) cases in which insulin resistance as well as impaired insulin secretion lead to hyperglycemia and vascular complications. Current type 2 diabetes mellitus treatments are limited, yield varying side effects and reveal drawbacks. Electrical stimulation of the vagus nerve in order to influence the regulation of glucose homeostasis showed inconclusive results due to off target effects. The rich innervation of the pancreatic parenchyma suggests that local electrical stimulation could be effective. This study proposes a minimally invasive, impedance-guided electrical stimulation device that can be endoscopically implanted and consists of a) a needle-based implant with b) conductive electrical contacts (for impedance measurement and stimulation), c) a gastric anchoring system and d) a wireless chargeable control device. A mosquito inspired needle design was fabricated, tested and optimized ex and in vivo with the aim to provide long-term residency in the pancreatic parenchyma. To measure electrical impedance of biological tissue, a bipolar impedance measurement setup was constructed. Electrical stimulation was performed on porcine animal model due to its anatomical similarity to the human gastrointestinal tract. Penetration and pull-out force for delivery and retrieval of the device was reduced by 54% (compared to control, p<0.01) to 2.736 N and increased by 2,683% (compared to control, p<0.01) to 6.923 N ex vivo by the mosquito inspired needle. In vivo the results were confirmed, but long-term study for validation is required. The electrical impedance at 100kHz of mucosa, muscle, pancreas, and intraperitoneum amount to 180 Ω, 156 Ω, 378 Ω, and 353 Ω and are significantly different (p<0.01) from each other. The range of impedance magnitudes overlap each other, but multiple measurements during incision could enable impedance guided delivery of the stimulation device. Preliminary data demands further optimization of stimulation parameters to enable validation of this methodology. Additionally, glucose clamping experiments could elaborate the effectiveness of the stimulation setup. Moreover, a long-term survival experiment tracking food intake and activity would be of great help for answering fundamental research questions and translation challenges.