| AVS 54th International Symposium | |
| Biomaterial Interfaces | Tuesday Sessions |
| Session BI-TuA |
| Session: | Engineered Cellular Interfaces |
| Presenter: | K.D. Hauch, University of Washington |
| Authors: | K.D. Hauch, University of Washington D.J. Mortisen, University of Washington M.A. Laflamme, University of Washington C.E. Murry, University of Washington B.D. Ratner, University of Washington |
| Correspondent: | Click to Email |
Tissue engineering strives to combine parenchymal and other cells with porous biomaterial scaffolds; to grow tissue like constructs that can be used to repair diseased or damaged tissues and organs. The natural course of development, as well as some (but not all) processes of wound repair and regeneration, depend upon complex parameters including: the changing composition and capabilities of the cells that populate the tissue; molecular cues from the interface between cell and its environs; the structural space wherein the cells reside; and mechanical forces. All these and more act to guide the processes that results in a hierarchical living tissue with appropriate structure and function. Here we explore these issues in the context of cardiac tissue engineering. Adult cardiomyocytes demonstrate little if any proliferative potential. However, using an appropriate schema of soluble cues, large quantities of proliferating cardiomyocytes as well endothelial cells can be derived from cultures of human embryonic stem cells, to be used for tissue engineering. Postulating the importance of scaffold geometry, novel scaffolds were constructed with appropriately sized spaces and shapes, providing an engineered support structure that mimics aspects of native muscle architecture. Molecular cues are provided by immobilizing adhesion proteins on the scaffold and delivering other soluble factors to stimulate cell survival, proliferation, and ultimately vascularization. huESC-derived cardiomyocytes populate these scaffolds and survive at high cell densities in culture. Finally, the application of cyclical mechanical stress during in vitro culture is seen to enhance cardiomyocyte size, survival and functional organization. The analysis of these engineered tissues depends on both standard immunohistochemical observations, as well as newer visualization tools, including Digital Volumetric Imaging, a microscopic 3D serial sectioning and reconstruction technique. Together, the appropriate application of proliferative cardiomyocytes to carefully engineered scaffolds featuring spaces of appropriate size and shape, in conjunction with soluble and mechanical cues can lead to the development of a robust functional unit of cardiac muscle.