Coupling synthetic biology and programmable materials to construct complex tissue ecosystems

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ynthetic Biology Prospective

Coupling synthetic biology and programmable materials to construct complex tissue ecosystems Catherine S. Millar-Haskell, Departments of Biomedical Engineering, University of Delaware, Newark, DE 19716, USA Allyson M. Dang, Departments of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA Jason P. Gleghorn, Departments of Biomedical Engineering, University of Delaware, Newark, DE 19716, USA Address all correspondence to Jason P. Gleghorn at [email protected] (Received 4 February 2019; accepted 15 May 2019)

Abstract Synthetic biology combines engineering and biology to produce artificial systems with programmable features. Specifically, engineered microenvironments have advanced immensely over the past few decades, owing in part to the merging of materials with biologic mimetic structures. In this review, the authors adapt a traditional definition of community ecology to describe “cellular ecology,” or the study of the distribution of cell populations and interactions within their microenvironment. The authors discuss two exemplar hydrogel platforms: (1) self-assembling peptide hydrogels and (2) poly(ethylene) glycol hydrogels and describe future opportunities for merging smart material design and synthetic biology within the scope of multicellular platforms.

Introduction Synthetic biology is a growing and ever-changing field that utilizes biologic components to engineer synthetic or artificial systems. Over the past few decades, researchers have continually revised the definition of synthetic biology to broaden the scope as new technologies develop.[1] In general, the field of synthetic biology involves the creation of artificial biologic systems or the redesign of existing natural biologic systems to achieve a functional output.[2] Some intriguing and very practical tools have emerged from synthetic biology: some examples include programming Escherichia coli to express recombinant proteins,[3] generating induced pluripotent stem cells via genetic manipulation,[4] and repurposing the CRISPR/Cas9 machinery for targeted genome editing.[5] Many tools in synthetic biology focus on reprogramming the internal environment of the cell, while little attention has been given to the extracellular matrix (ECM). We believe the scope of synthetic biology should be broadened to include engineered cellular microenvironments. In fact, others have already suggested that synthetic biology should have its own niche in tissue engineering,[6] especially as synthetic materials are now being combined with biologically-derived moieties to control cellular behavior. Finally, we propose that synthetic biology and materials research both have a vital role to play in recreating fundamental aspects of cellular ecology within in vitro cell culture models. For many types of research, it is no longer enough to use a generic hydrogel scaffold, such as PEG-RGD or collagen, to model specific cellular environments. These scaffolds contain an incomplete picture of the spatiotemporal chemical and

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