Grant: Strategic Projects - Group

During embryonic development, cells secrete an extracellular matrix (ECM) around themselves that is turn provides cues to the cells to direct organ development. The same ECM componants would therefore also be likely to direct repair and regeneration of these organs. Our goal, therefore, is to develop biomimetic materials that are ECM analogs, capable of sustaining a native-like ECM environment and interacting with host tissues and stem cells to effect regeneration. As particular requirements vary from patient to patient, a combinatorial approach to these biomaterials, in which modular elements would be incorporated into a customizable platform, would be very desirable. Specifically, we will be focus on epithelial tissues, i.e. tissues with an epithelium and underlying ECM containing fibroblastic cells such as the cornea and skin. Our patient population will include elderly individuals with limited stem cell reserves and therefore, regeneration capability. These include diabetic patients with loss of innervation that have resulted in chronic foot ulcerations (diabetic foot) and patients with corneal blindness due to nerve loss and surface ulcerations. Our research plan therefore is to develop  a series of artificial proteins and sugar chains as building blocks for assembly into ECM analogs with tailored specific bioactivities, specifically for modulating stem cell activity. We would then assemble these into simple 3-D ECM analogs and will test them for properties such as optical clarity, mechanical strength and biocompatobility. Materials that show desirable properties will then be further engineered into more complex cornea and then skin constructs, after which we will test their ability to control cell behavior. Our aim is to control stem cell behavior in these engineered tissues and well as in-growth of nerve and blood vessels into these constructs.