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Biomaterial systems have allowed for the in vitro production of complex,emergent tissue behaviors that were not possible with conventional 2D culturesystems allowing for analysis of the normal development as well as diseaseprocesses. We propose that the path towards developing the design parametersfor biomaterial systems lies with identifying the molecular drivers of emergentbehavior through leveraging technological advances in systems biology,including single cell omics, genetic engineering, and high content imaging.This research focus, which we term systems tissue engineering, can uniquelyinterrogate the mechanisms by which complex tissue behaviors emerge with thepotential to capture the contribution of i) dynamic regulation of tissuedevelopment and dysregulation, ii) single cell heterogeneity and the functionof rare cell types, and iii) the spatial distribution and structure ofindividual cells and cell types within a tissue. Collectively, systems tissueengineering can facilitate the identification of biomaterial design parametersthat will accelerate basic science discovery and translation.

Towards systems tissue engineering: elucidating the dynamics, spatial coordination, and individual cells driving emergent behaviors