SUMMARY A set of experiments is proposed to develop a new mineral-based nanoparticle technology for modulating the cellular activity in absence of growth factors for regenerative therapies. Current therapeutic approaches to regulate cellular responses include delivery of a multitude of supraphysiological doses of growth factors that results in a range of complications, including uncontrolled tissue formation, inflammation, and tumorogenesis. These adversely limit the usage of growth factors as a therapeutic agent in the field of regenerative medicine. In this New Innovator Award, I propose to develop new mineral-based nanoparticles to regulate and direct the differentiation of human stem cells in the absence of growth factors. It is our expectation that adequate and efficacious grow-factor free therapeutics can be designed for regenerative medicine by leveraging our knowledge about the molecular signaling induced by minerals. This research proposal is particularly well suited for this unique funding mechanism because it proposes innovative, high-risk, and high-reward research at the interface of bioengineering and stem cells that would have a major impact on repair and regeneration of damaged tissue. We propose to combine principles of high throughput computational genomics, stem cell biology, materials science, microfabrication, and regenerative medicine to design novel strategies based on newly emerging but unexplored concepts of mineral-induces cellular signaling. It is our expectation that a comprehensive understanding of the molecular pathways regulated by the usage of minerals will radically alter the current growth-factor based approach to repair and regenerate damage tissue.