Tissue Patterning Approaches

Recapitulating the architecture of native tissue is currently a significant challenge impeding the development of physiologically relevant in vitro mimetic systems. Instructing appropriate organization is especially challenging for tissues that feature organization of multiple cellular components into complex structural units. Traditionally, tissue engineers have directed cells into a specific tissue organization by presenting instructive biochemical and biophysical cues, often in the context of a biomaterial scaffold. This approach provides control over tissue organization but requires knowledge of the target tissue structure. This approach is especially challenging when constructing tissues containing multiple cell types, and, once created, structural stability of the tissue can be an issue. More recently tissue assembly strategies have emerged that more closely mimic the morphogenetic processes that self-organize tissues in the developing embryo, such as chemically induced self-assembling organoid systems, in which tissue assembly and cell fate specification occur in parallel. These approaches have enabled the generation of more complex tissue structures; however, the assembly process is uncontrolled, and the resulting structures do not fully replicate native tissues.   Of these two strategies (traditional externally directed assembly versus self-directed assembly), externally directed approaches are practically useful to generate tissue mimetic systems in the short term. To further improve physiological relevance in the future however, it is important to also understand the rules governing self-directed tissue organization. Understanding these rules will provide opportunities for hybrid approaches whereby self-directed assembly can be precisely controlled and manipulated. My lab therefore explores both i) artificial approaches to direct tissue organization for development of current generation and ii) the rules contributing to self-directed assembly, which will provide an important basis for the next generation of tissue mimetic systems. For example, we have developed a number of micropatterning and cell printing techniques to generate multi-cell type tissues with controlled configurations and organization. We are also interested in the rules that govern how cells collectively organize into tissues and maintain the boundaries between different cellular domains within multi-cell type tissues.

Pattered MDCK ZO1 staining

Tools for micropatterning epithelial cells into microcolonies on transwell filter substrates.Paz AC, Javaherian S, McGuigan AP., Lab Chip. 2011 Oct 21;11(20):3440-8.

Migration Tracks ARPE19

Design principles for generating robust gene expression patterns in dynamic engineered tissues.Javaherian S, Anesiadis N, Mahadevan R, McGuigan AP., Integr Biol (Camb). 2013 Mar;5(3):578-89.

Boundary Formation on Perpendicular Grooves

An in vitro model of tissue boundary formation for dissecting the contribution of different boundary forming mechanisms.Javaherian S, D’Arcangelo E, Slater B, Zulueta-Coarasa T, Fernandez-Gonzalez R, McGuigan AP., Integr Biol (Camb). 2015 Mar;7(3):298-312.