Synthetic biology meets tissue engineering

Abstract

Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the 'embryological cycle' of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work.

Keywords: development; morphogenesis; self-organization; synthetic biology; synthetic morphology; tissue engineering.

Figure 1. The embryological cycle

Patterning directs differentiation which results in morphogenesis and the cycle repeats to add finer details as the embryo grows.

Figure 2. Synthetic biological modules for patterning in bacteria

(a) Depicts the repressilator of Elowitz and Leibler [19], 2000 that generates oscillations, effectively a pattern in time; (b) depicts a module that interprets a gradient of signal concentration to generate a central ‘stripe’ only in zones of moderate signal concentration.

Figure 3. De novo pattern formation by cadherin-driven phase separation

This is seen in (a) 2D and (b) 3D. Reproduced from [33]: Cachat, E., Liu, W., Martin, K.C., Yuan, X., Yin, H., Hohenstein, P. and Davies J.A. (2016) 2- and 3-dimensional synthetic large-scale de novo patterning by mammalian cells through phase separation. Sci. Rep., doi:10.1038/srep20664.