Bioengineering glucose-responsive cannulas for electronics-free, automated insulin delivery

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Blood sugar is maintained by ß cells of healthy individuals within the pancreatic islets of Langerhans that secrete insulin in response to fluctuations in blood glucose. Type 1 diabetes (T1D) is an immune-mediated disease where the ß cells of a patient are destroyed. Consistent blood glucose control is therefore achieved via lifelong administration of exogenous insulin. However, insulin therapies do not prevent glycemic variability, and improper dosing of insulin can lead to severe complications. Moreover, these conventional therapies are “open-loop” given they require patients monitoring their blood glucose to determine the corresponding insulin dosages. Consequently, sustaining normoglycemia for T1D patients is very difficult and imposes a high burden of diabetes self-care. As such, there is a great interest in “closed-loop” therapies capable of mimicking dynamic ß cell function by precisely releasing insulin in response to fluctuating glucose levels in real-time with minimal burden to the patient. To address limitations of closed-loop therapies, an electronics-free method of glucose sensing and insulin infusion was engineered using biocompatible biomaterials. First, a novel one-pot solvent exchange protocol was developed to combine elastomers and hydrogels at a molecular level. The final hybrid interpenetrating network biomaterial showed robust mechanical strength and tunable permeability that can be exploited to form robust, retrievable, and implantable devices for therapeutic applications such as cell encapsulation and drug delivery. Then, the functionalization of the hybrid biomaterial with glucose-responsive properties was explored demonstrating that the material supports robust insulin delivery under physiologically relevant glucose environments in vitro. Furthermore, when implanted subcutaneously in T1D murine models both as a fully implantable ends-sealed device or as an externally refillable, transcutaneous device, the newly developed technology consistently maintained glucose levels in mice within the normal range for ~72 hours. Finally, to demonstrate the feasibility of using this biomaterial for non-invasive insulin delivery, the potential of the hybrid material as a core-shell cannula for basal and bolus insulin infusion was investigated. Collectively, this research provides a novel insulin delivery platform to improve glycemic management in a minimalistic and user-centric fashion.

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223 pages


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Ma, Minglin

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Putnam, David
Wang, Yadong

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Biological and Environmental Engineering

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Ph. D., Biological and Environmental Engineering

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Doctor of Philosophy

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