Grant: Foundation Grant

Our goal is to create new medical devices to address unmet needs in medicine. The materials that are used to build current devices provoke a scar which prevents their integration with the host. This is a fundamental challenge to tissue engineering in which tissue constructs are created to act as "spare body parts" to replace diseased tissues and organs. Such constructs require blood vessels in order to supply the tissue with oxygen and enable tissue survival and integration. We have pioneered two approaches to forming the needed blood vessels. In one method ("modular tissue engineering") collagen gel pieces are coated with endothelial cells, the cells that line blood vessels. However, vessel formation is slow and the resulting vessels are imperfect. Here we address the barriers (low oxygen, inflammation) to successful vessel formation in order to accelerate this process. We are using this approach to enable under the skin delivery of pancreatic islets to resolve the issues with this promising treatment for the 1% of Canadians who live with insulin dependent (type 1) diabetes. We have also discovered that materials that incorporate methacrylic acid cause blood vessels to grow once the material is implanted. This vascular regenerating effect is unique among biomaterials. Unfortunately we don't understand why we are getting blood vessels (instead of the conventional "scar" response), although we have some clues as to the origins of this seemingly "magical" effect. We propose to deepen our understanding of the magic by using a method that analyses the critical means by which cells respond to changes in their environment (here our unique biomaterial). We expect these results will help us design better materials and better devices for use in diabetes (e.g., better glucose sensors) and in other situations which are as yet precluded by the limitations of existing materials.