Regenerative and cell-based immunotherapies are on track to revolutionize the treatment of many diseases, especially those which have been recalcitrant to treatment such as tissue loss due to disease or injury. While exciting, the emerging field of regenerative medicine faces the critical challenge of how to scale the production of cells therapies so that they can be brought to market at a price that enables broad access. The culture of human cells requires growth factor to promote the healthy expansion of cells and ensure that cells remain in a clinically relevant state (e.g. pluripotent). These growth factors can be incredibly expensive, often over a million dollars a gram, and their natural instability can pose additional expense for biomanufacturing. Here, we propose to use cell-free directed evolution to develop antibodies that mimic the binding of growth factors to cell receptors. This proposal builds on proof-of-concept work by others1, which showed that antibodies could phenocopy growth factors and even provide greater receptor selectivity over natural growth factors. Moreover, antibodies exhibit considerable natural stability, adding to the appeal of this approach. We have been pioneering cell-free technologies for years, including the cell-free expression of complex antibodies that mimic growth factors (Wnt). This positions our group well to develop new antibody mimics for four growth factors that are key to the culture of clinically relevant stem cells and immune cells. In addition to generating potentially high-value growth factor mimics, the project will also establish a cell-free, directed evolution discovery platform that can be reprogrammed. With the platform in-hand, we anticipate the production of other antibodies for cell therapy, high-value reagents for biomanufacturing and, in the longer-term,therapeutics.Conversations with industry have also highlighted a need for antibodies in cell purification and bead-based activation, suggesting there is a deep well of potential application. Seeking to make a meaningful impact on human health, our goal will be to ensure that antibodies generated by this project make it to market, contributing to the health and economy of Canadians.