Materials can be engineered to deliver specific biological cues that control stem cell growth and differentiation. However, current materials are still limited for stem cell engineering as stem cells are regulated by a complex biological milieu that requires spatiotemporal control. Here a new approach of using materials that incorporate designed bacteria as units that can be engineered to control human mesenchymal stem cells (hMSCs), in a highly dynamic-temporal manner, is presented. Engineered Lactococcus lactis spontaneously colonizes a variety of material surfaces (e.g., polymers, metals, and ceramics) and is able to maintain growth and induce differentiation of hMSCs in 2D/3D surfaces and hydrogels. Controlled, dynamic, expression of fibronectin fragments supports stem cell growth, whereas inducible-temporal regulation of secreted bone morphogenetic protein-2 drives osteogenesis in an on-demand manner. This approach enables stem cell technologies using material systems that host symbiotic interactions between eukaryotic and prokaryotic cells.
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