Tissue engineering

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The underlying theme of my research program is that biomaterials and the devices based on these materials (e.g., tissue-engineered constructs) are agonists of a biological response. Over the years this theme has manifested itself primarily in the problem of blood compatibility of cardiovascular biomaterials and in the microencapsulation of mammalian cells for the purpose of cell transplantation. Now our efforts are directed towards (1) vascularisation of tissue engineering constructs to circumvent the size limits imposed by Fick's law of diffusion and (2) understanding and controlling the host response to biomaterials. Much of the effort is centered on modular tissue engineering, a novel approach to tissue engineering that results in uniform, scaleable and vascularised constructs. It is based on small (currently cylindrical) modules made from collagen gel or a collagen-poloxamine interpenetrating network, containing embedded cells (e.g., liver cells or pancreatic islets). The modules are then covered with endothelial cells. When filling a space (e.g., a tube or a tissue cavity, in vivo) a packed bed bioreactor is created, in which the endothelial cells enable blood (and hence nutrients) to be perfused. We are currently (i) exploiting the utility of this approach to create fat tissue for post-cancer reconstruction or uniformly contracting sheets of heart muscle cells for the treatment of heart failure or to augment the engraftment of transplanted pancreatic islets and (ii) understanding and controlling the remodelling that occurs when endothelialized modules are implanted in a tissue cavity and subject to the host response The proposed efforts are directed to several of the challenges associated with advancing this concept: for example, (a) further delineation and validation of the design rules (involving Ergun equation; Thiele modulus and Biot number) that underpin the scaleability of the modular approach and (b) evaluation of the phenotype of the endothelial cells in the complex flow arrangements implicit to a packed bed. NSERC support is used to provide the fundamental engineering infrastructure to enable the applied or biomedical studies or as seed money to begin new projects.