Enhancing sensor function in vivo using gene transfer and bio-hydrogel systems

Date of Completion

January 2003

Keywords

Engineering, Biomedical|Health Sciences, Public Health

Degree

Ph.D.

Abstract

Diabetes has reached epidemic proportions in the US, currently affecting 17 million people, with an estimated increase of 2,200 patients daily. Currently, the successful management of diabetes requires monitoring of blood glucose levels by repeatedly obtaining a blood sample from the capillary vasculature (“finger sticks”), which is painful and as such results in poor patient compliance. Ultimately inadequate blood glucose monitoring and management, results in wide swings in blood glucose levels, which leads to a compromised quality of life, as well as debilitating and life-threatening complications and premature death. Clearly, there is a pressing need for a better approach to monitor blood glucose levels in diabetics, e.g. implantable glucose sensors. Despite the increasing efforts over the last 3 decades to develop an implantable subcutaneous sensor, a reliable long-term continuous monitoring is yet to be achieved. ^ The in vivo failure of implantable glucose sensors for diabetics is thought to be a result of fibrosis induced vessel regression surrounding the sensor. It was hypothesized that neovascularization of local sites of sensor implantation would enhance sensor function in vivo. To test this hypothesis we utilized an in vivo gene delivery system composed of cells genetically engineered to express the angiogenic factor vascular endothelial cell growth factor (VEGF) and VEGF:viral vectors, supported in naturally occurring tissue interactive bio-hydrogels (i.e. fibrin matrix). Both a chemical (acetaminophen) and a biosensor (electrochemical glucose sensor) were used for the in vivo studies. Chick embryos grown in petri-dishes (Ex Ova) served as our in vivo model to test gene transfer and sensor function in vivo. The results of our studies demonstrated that our in vivo gene delivery systems not only induced neovascularization around both sensor types in the chick embryo model, but dramatically enhanced both chemical (acetaminophen) and biosensor (glucose sensor) function in vivo. These results support our hypothesis by providing “proof of principle” that enhancing vessel density around an implanted sensor enhances sensor function in vivo. These studies also demonstrate the usefulness of the Ex Ova model for the rapid development and evaluation of in vivo strategies for enhancing biocompatibility of implants in vivo. ^

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