Chris Highley — 2009-10 Fellow
Advances in tissue engineering will depend on approaches to the three factors central to the field: cells, scaffolding, or signaling molecules. Combinations of these factors comprise tissue engineering constructs, and the way the combination is designed largely determines how the fates of cells, which may be part of the construct and/or native to a patient, are directed towards tissue formation. No construct is without strengths and weaknesses, and despite successes within the field, further work in fields ranging from biology to materials science and engineering is needed before routinely engineering fully functional complex tissue becomes a reality. While tissue engineering approaches vary, issues that a construct design must address with respect to its final application include:
- how the material(s) and signaling molecules used in the construct are chosen and arranged to influence cell fate and how they will interact with developing tissue over the life of the construct,
- whether a construct includes cells and if so, what cell types are used and where/how will they be placed within the material environment,
- how, in the case of cell-containing constructs, the physical stability of a construct will be established—materials used in such constructs are generally polymers which are crosslinked to form gels around the cells, so the method of crosslinking should seek to avoid damage to cells,
- and how nutrients, waste, and cellular signaling molecules are transported within a construct.
Approaches in recent years have focused on control of construct composition and geometry at scales from hundreds to single microns. These include modular approaches, which offer the potential to control cellular composition and location during construct creation. In the ideal modular construct, an engineer might be able to design a construct whose material and cellular composition can be planned and controlled at every point. With this goal in mind, this work will develop microfluidic technologies capable of creating cell-containing units, which are biocompatible and cell-instructive and aim to reproduce microenvironments experienced by cells in vivo. Furthermore, this fellowship will support the development of microfluidics technology which is designed to enable the arrangement of these units into ordered tissue-scale structures whose cellular and chemical composition can be controlled at resolutions approaching that of the cellular microenvironment.