Synthetic tissue engineering with smart, cytomimetic protocells

Synthetic protocells are rudimentary origin-of-life versions of natural cell counterparts. Protocells are widely engineered to advance efforts and useful accepted outcomes in synthetic biology, soft matter chemistry and bioinspired materials chemistry. Protocells in collective symbiosis generate synthetic proto-tissues that display unprecedented autonomy and yield advanced materials with desirable life-like features for smart multi-drug delivery, micro bioreactors, renewable fuel production, environmental clean-up, and medicine. Current levels of protocell and proto-tissue functionality and adaptivity are just sufficient to apply them in tissue engineering and regenerative medicine, where they animate biomaterials and increase therapeutic cell productivity. As of now, structural biomaterials for tissue engineering lack the properties of living biomaterials such as self-repair, stochasticity, cell synergy and the sequencing of molecular and cellular events. Future protocell-based biomaterials provide these core properties of living organisms, but excluding evolution. Most importantly, protocells are programmable for a broad array of cell functions and behaviors and collectively in consortia are tunable for multivariate functions. Inspired by upcoming designs of smart protocells, we review their developmental background and cover the most recently reported developments in this promising field of synthetic proto-biology. Our emphasis is on manufacturing proto-tissues for tissue engineering of organoids, stem cell niches and reprogramming and tissue formation through stages of embryonic development. We also highlight the exciting reported developments arising from fusing living cells and tissues, in a valuable hybrid symbiosis, with synthetic counterparts to bring about novel functions, and living tissue products for a new synthetic tissue engineering discipline.