Programmed Assembly of Bespoke Prototissue Spheroids on a Microfluidic Platform

The precise assembly of protocell building blocks into prototissues that are stable in water, capable of sensing the external environment and which display collective behaviours remains a considerable challenge in prototissue engineering. In this work we explore the use of microfluidic technologies for the programmed assembly of bio-orthogonally reactive protein-polymer protocells into prototissue spheroids of precise size, composition and with unique Janus configurations. We then show that by controlling the number and phenotype of the protocells that compose the prototissue spheroids it is possible to modulate both the amplitude of the thermally induced contractions of the biomaterial and its collective endogenous biochemical reactivity. Overall, our results show that microfluidic technologies enable a new route to the precise and high-throughput fabrication of tissue-like materials with programmable collective properties that can be tuned through a careful assembly of protocell building blocks of different phenotypes. We anticipate that our bespoke prototissues will be a starting point for the development of more sophisticated artificial tissues for use in medicine, soft robotics and environmentally beneficial bioreactor technologies.