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.

Engineering multicellular systems: Using synthetic biology to control tissue self-organization

“…Simple rules of communication along with their subsequent activation of functional genes provide the basic routine for emergence of more complex behaviors. It was speculated that manipulation of those rules with the introduction of synthetic input-output circuits should be able to generate developmental phenomena even in natively non-developmental systems [8,9,18]. …”

Controlling spatiotemporal pattern formation in a concentration gradient with a synthetic toggle switch

“…The rise of synthetic biology has successfully allowed to build synthetic systems able to explore core patterning principles (reviewed in (Santos-Moreno and Schaerli, 2019b, Luo et al, 2019, Davies, 2017, Ebrahimkhani and Ebisuya, 2019). In addition, synthetic pattern formation is also an attractive technology for the engineering of living materials (Gilbert and Ellis, 2018, Nguyen et al, 2018, Moser et al, 2019, Cao et al, 2017 and tissues (Davies and Cachat, 2016, Healy and Deans, 2019, Webster et al, 2016.…”

Cell-in-the-loop pattern formation with optogenetically emulated cell-to-cell signaling

“…Spatial patterning is crucial for the proper functioning of diverse multicellular biological systems from slime molds [1] to developing embryos. The ability to synthetically engineer multicellular patterning will facilitate advances in designing microbial communities [2] [3] [4], creating synthetic biomaterials [5] [6], and programming tissue and organ growth [7] [8] [9] [10], among other applications [11]. While recent efforts to synthetically engineer multicellular patterning have met with success (see [12], [13], [14] for reviews), relatively few of these efforts [15] [16] have been guided by quantitative mathematical theory beyond numerical simulation.…”

“…Gene expression patterning has received much focus in the theoretical literature [17] [18] [19] [20] [21] [22] [23], and is also of particular interest in regenerative medicine, since it is central to the early stages of embryonic development and eventual cell fate determination [7] [24]. There are a number of challenges associated with engineering spontaneous gene expression patterning into biochemical systems, including how to facilitate interaction among cells [25] and achieve spatial precision in the resulting patterns [26] [27] [28].…”