Research Overview

Since the experiments by Harrison (1911) and Weiss (1945), it has been long recognized that mammalian cells are sensitive to the composition of their microenvironment. Surface chemistry and topography have been observed to influence many cellular processes such as adhesion, spreading, morphology, cytoskeletal organization, proliferation, migration, and gene expression. As methods of material fabrication and characterization have evolved, it has become possible to identify the limits of cell sensing and how topographical and chemical cues can influence tissue integration around implanted materials, as well as in vitro tissue development. We are developing new model systems, in conjunction with Dr. Silvia Mittler to evaluate cell response to biomaterial surface characteristics, using state of the art microscopy and proteomic techniques.

Chronic wounds represent a significant burden to health care across world and one of the most devastating complications of diabetes is the occurrence of ulcers and chronic wounds.  Approximately 15% of 2.3 million Canadians who live with diabetes today will develop a non-healing foot ulcer in their lifetime.  A non-healing foot ulcer results in amputations of limb and an estimated 1500 Ontarians with diabetes had a limb amputated in 2008. Non-healing wounds are characterized by increased inflammation, a loss of extracellular matrix (ECM, support scaffold in normal skin) and dermal fibroblasts (which make the ECM). As a result the wounds do not contract and remain open, causing patients considerable pain, disability and putting them at risk for systemic infection. We have developed an artificial scaffold containing proteins required for normal skin repair. The purpose of these scaffolds is to essentially create an artificial extracellular matrix that would normally be present as wounds repair, but is absent in non-healing wounds.

To date, the development of biomaterials has often been driven on an empirical basis, rather than on advances made in the understanding of cell and tissue biology/pathophysiology. Our philosophy on biomaterials development is to use biological data from in vitro and in vivo models to re-design materials that will further promote desired cell behaviour, and advantageous gene and protein expression. Through characterization of the material chemistry and topography, as well as the cellular response, materials can be furthered adapted where applicable, through the incorporation of biologically active molecules on the surfaces. We are developing a rigorous screening system for gene and protein changes in newly implanted, as well as end stage failure biomaterials. Furthermore, such an approach could be used to identify gene changes in pathologies prior to the onset of implant or biomaterial failure. 

In vitro analyses of the effects of topographical and chemical cues on mammalian cell behaviours have correlated relatively well with in vivo observations. Exactly how substratum topography regulates bone and connective tissue formation at the molecular level remains unknown. Does short-term protein activation and translation influence long-term tissue development? Our approach to address these questions involves the use of gene knockout mice and cell lines in collaboration with as well as state of the art proteomics and genomic techniques. Such an approach could lead to the identification of novel diagnostic markers and therapeutic targets that can be applied to other bone and connective tissue diseases.