Bio-HhOST will build bio-hybrid materials that comprise living & artificial cells, in dynamic communication, such that artificial cells may influence the proliferation, differentiation and function of living cells. This will be accomplished by producing precision engineered, microscale, liquid and lipid bilayer-based, chemically compartmentalised artificial cells, co-localised with live cells. This will be done by an interdisciplinary team of biologists, engineers, mathematicians and entrepreneurs. The artificial cells will contain functional metabolisms, and the ability to respond to chemical stimuli in the environment to release signaling molecules, on demand, to regulate the neighboring living cells, as found in complex biological tissues. These new chemically programmable organoid-synthetic tissues will enable a paradigm shift, in both ability to elucidate and control the complexity of physio-chemical interactions within 3D tissues, and reduce animal use in pharmaceutical R&D. To achieve these ambitions we have designed an integrated multistage workplan driving towards the following overarching aims:- Aim 1. Create 3D tissues where spatial regulation of living cell differentiation is determined by co-located (chemically programmable) artificial cells. Aim 2. Regulate and maintain such 3D tissues by dynamic communication between live and artificial cells. Aim 3. Develop multi-level, multi-approach models of organoid-synthetic tissues behavior. These will be applied to target applications; Aim4. Evaluating drug delivery vectors for next generation biological therapeutics. And Aim5. generation of complex tissues formed of distinct different regions, not achievable with current organoid protocols. These exemplify our wider ambitions for the Bio-HhOST approach including to, i) understand cell behavior in increasingly realistic 3D tissue models, ii) elucidate targets for the treatment of disease, and iii) enable the reduction of animal use in pharmacuetical research.