Protein nanosheet-stabilised emulsions for next generation biomanufacturing
The large scale expansion of adherent cells, which underpins the production of stem cells for regenerative medicine and the manufacturing of complex biotherapeutics (e.g. exosomes and vaccines) remains challenging and a key hurdle to the accessibility of associated therapies. Indeed, the expansion of adherent stem cells and adherent cell lines for bioproduction relies on culture on solid microcarriers that remain difficult to process and significantly add to costs. Cell adhesion to solid substrates and associated mechanotransduction is thought to be essential to mediate key processes regulating the production of biotherapeutics, such as exosome secretion and protein glycosylation. However, we recently demonstrated that liquid substrates, such as emulsion microdroplets, can support cell adhesion and promote the retention of a normal adherent phenotype. We showed that this process is mediated by the self-assembly of mechanically strong protein nanosheets at corresponding liquid-liquid interfaces. This project will demonstrate the scale up of emulsion-based biomanufacturing platforms. We will scale up (L scale) bio-emulsions based on protein nanosheets that promote cell adhesion and display suitable interfacial mechanics, from affordable protein sources. We will demonstrate the compatibility of such systems with bioreactors routinely used in the field, for the scale up of adherent stem cells production, and that of adherent cell lines for biotherapeutics production (exosomes and vaccines). We will establish further IP and a commercialisation strategy with identified partners to translate our technology in the field of biomanufacturing. We propose that bio-emulsions for the culture of adherent cells will bring a step change to the field of biomanufacturing, enabling to borrow concepts and processes from the field of chemical engineering, in which biphasic liquid-liquid systems and emulsions have revolutionised the production of fine chemicals, drugs and nanomaterials.