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Material development and characterisation of a functionalised biomaterial to support pancreatic islet viability.

thesis
posted on 03.12.2020, 16:20 by Liam McDonough

Diabetes mellitus is a chronic disease which affects over 425 million people worldwide (2017), a number which is expected to rise to 629 million people by 2045. Diabetes mellitus occurs when the pancreas does not produce enough insulin to meet the demands of the body, due to the malfunction or immune-mediated destruction of the insulin producing β-cells.

The bio-artificial pancreas approach aims to return endogenous insulin production to the patient, by delivering donor pancreatic islets encapsulated in a supportive biomaterial and protected by a semi-permeable immunoisolating shell. The overall objective of the research in this PhD thesis is to develop a novel functionalised biomaterial suitable for use as the extracellular matrix in a bio-artificial pancreas. This functionalised biomaterial would first be assessed in vitro with a suitable cell model and then undergo process development and scale-up manufacture for use in pre-clinical small and large animal model in vivo testing.

The functionalised biomaterial was formulated as a hydrogel and functionalised with an oxygen carrier. The formulated biomaterial showed rheological characteristics suitable for delivery to a bio-artificial pancreas and improved oxygen storage characteristics compared to non-functionalised hydrogels.

In vitro testing of the biomaterial seemed to show that is was not beneficial to a β-cell line. However it was shown to be biocompatible by an International Organisation for Standardisation (ISO) validated method and also showed biocompatibility with human islets in vitro.

Process development of the biomaterial resulted in the development of a protocol for its preparation that was successfully transferred to facilitate the in vivo testing. In a large animal model the biomaterial was successfully filled into a semi-permeable immunoisolating shell. In the small animal model the biomaterial showed efficacy when used to deliver primary rat islets cells to the rat model, showing improved fasting and post-prandial blood glucose for up to 8 weeks.

Funding

Funding for this project was provided through the DRIVE project, which received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 645991. Additional funding was received for the Erasmus+ placement through the Erasmus Plus Programme of the European Union and the Royal College of Surgeon’s in Ireland.

History

First Supervisor

Doctor Helena Kelly

Second Supervisor

Professor Garry Duffy

Comments

A thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2019.

Published Citation

McDonough L. Material development and characterisation of a functionalised biomaterial to support pancreatic islet viability [PhD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2019.

Degree Name

Doctor of Philosophy (PhD)

Date of award

30/11/2019

Programme

  • Doctor of Philosophy (PhD)

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