Lineage specific differentiation of mesenchymal stem cells on biomimetic 3D scaffolds

Lineage specific differentiation of stem cells is the governing factor behind the success of tissue engineering approaches. Current philosophy is to use growth factors to guide the differentiation of stem cells. However, complex growth factor delivery systems, timing and dosage of growth factor delivery severely hamper the translational potential of tissue engineering approaches. We have developed a three dimensional biomimetic system that contains the intact extracellular matrix (ECM) of the target cell phenotype. These scaffolds contain all the ECM components including structural and functional proteins of a specific target cell type. Our results show that it is possible to achieve lineage specific differentiation of mesenchymal stem cells by varying their environment alone without the need for complex growth factor delivery systems. In this manuscript we have shown the differentiation of human marrow stromal cells (HMSCs) into an osteogenic (bone forming), chondrogenic (cartilage forming) and odontogenic (dentin forming) phenotype by varying only their biomimetic environment. With these scaffolds being mass-producible, we hypothesize that they have the potential for easy and early clinical translation.