Proto-bone: an integrated protocell/matrix paradigm for prototissue calcification

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Protocells are cytomimetic architectures that are integrated with cell-like active traits, such as supramolecular compartmentalizationand signal communication. Assembly of three-dimensional protocellular consortia into emergent prototissues provides anopportunity to mimic the complexity and structural integrity of higher-order living systems and promotes the development ofanimate materials. Although dynamic interactive processes between cells and their localized extracellular matrix environments play akey role in diverse biological activities such as bone tissue biomineralization, artificial tissue-like systems that concurrently mimic cell/matrix interactivity have not yet been achieved. The aim of the proposed project is to develop a prototissue model capable of extraprotocellularcalcification and the formation of a calcified synthetic tissue - proto-bone. To achieve this, a new prototissue modelbased on the structural and functional integration of interconnected synthetic protocells within an extra-protocellular matrix (EPM)will be developed. Implementation of the project will provide a new mode of prototissue construction, demonstrate the first exampleof protocell-mediated EPM remodeling, and develop a route to the fabrication of new tissue-like mineral/matrix composites. The newmethodology for constructing prototissues with integrated protocell/matrix organization will provide new opportunities forconstructing protoliving models in synthetic biology, as well as developing new biomimetic platforms and routes to animatematerials capable of autonomous self-formation and degeneration. Outcomes from the proposed project will contribute to thedevelopment of materials-based bioengineering within the European community, and could have long-term applications inregenerative medicine (tissue repair, proto-bone implants etc).