Enhancement of implantable glucose sensor function in vivo using gene transfer-induced neovascularization

Abstract

The in vivo failure of implantable glucose sensors is thought to be largely the result of inflammation and fibrosis-induced vessel regression at sites of sensor implantation. To determine whether increased vessel density at sites of sensor implantation would enhance sensor function, cells genetically engineered to over-express the angiogenic factor (AF) vascular endothelial cell growth factor (VEGF) were incorporated into an ex ova chicken embryo chorioallantoic membrane (CAM)-glucose sensor model. The VEGF-producing cells were delivered to sites of glucose sensor implantation on the CAM using a tissue-interactive fibrin bio-hydrogel as a cell support and activation matrix. This VEGF-cell-fibrin system induced significant neovascularization surrounding the implanted sensor, and significantly enhanced the glucose sensor function in vivo. This model system, for the first time, provides the "proof of principle" that increasing vessel density at the sites of implantation can enhance glucose sensor function in vivo, and demonstrates the potential of gene transfer and tissue interactive fibrin bio-hydrogels in the development of successful implants.