Developmentally inspired synthetic kidney engineering

Developmentally inspired kidney tissues derived from stem cells hold promise for future renal replacement tissue, but clinical translation is limited by variability in outcomes, absence of cell types, lack of functional maturity and implausible scalability. Overcoming these may benefit from tissue engineering strategies that leverage processes for tissue construction that the embryonic kidney uses to achieve its diverse and parallelized functions. We present a ‘developmental engineering’ strategy in which spatial and temporal cues inspired by in vivo development guide multiscale structure formation in vitro. We highlight emerging tools in synthetic biology, spatial patterning and control over tissue microenvironments that can set initial and boundary conditions to instigate and guide the development of a desired ‘motif’. We then present a vision for scalable developmental engineering by guiding and daisy-chaining tissue motifs, bridging discontinuities in self-organization via direct assembly. Although we articulate a blueprint for developmental engineering of translationally viable renal replacement tissues, the strategy is also applicable to other solid organs.