Scientific advancements in bottom-up synthetic biology have led to the development of numerous models of synthetic cells, or protocells. To date, research has mainly focused on increasing the (bio)chemical complexity of these bioinspired micro-compartmentalized systems, yet the successful integration of protocells with living cells remains one of the major challenges in bottom-up synthetic biology. In this review, we aim to summarize the current state of the art in hybrid protocell/living cell and prototissue/living cell systems. Inspired by recent breakthroughs in tissue engineering, we review the chemical, bio-chemical, and mechano-chemical aspects that hold promise for achieving an effective integration of non-living and living matter. The future production of fully integrated protocell/living cell systems and increasingly complex prototissue/living tissue systems not only has the potential to revolutionize the field of tissue engineering, but also paves the way for new technologies in (bio)sensing, personalized therapy, and drug delivery.
