Virtual Twin-Powered Rapid Development of Bioactive Multifunctional Dental Restoratives - Summary There is a global need to prioritize the development of a novel dental restoration that meets the criteria of being long-lasting, easy to use, and accessible without complicated equipment. We aim to revolutionize dental care by developing a cutting-edge platform for the rapid and precise creation of dental restoration materials. Our vision is to tailor these materials to individual needs, adapting to the unique conditions of patients' oral environments. Our innovative restorative system will include self-strengthening adhesives, bioactive fillers that respond to biological signals, durable resins, and additives that provide new functions. Designed to be adaptable, this new class of dental materials will be able to repair microcracks autonomously and prevent cariogenic biofilm. Moreover, the easily applicable and durable restorative system will advance digital dentistry to a new level. Our new approach integrates a physics-based model of testing and data-based simulations into the workflow of material design and evaluation, this will drastically expedite the traditionally slow and costly route of material development. Our ultimate goal is to introduce a novel operational platform in restorative dentistry, along with a suite of multifunctional materials tailored for various dental treatments. Our diverse team, with expertise spanning materials science, engineering, dentistry, and computational modeling, is committed to achieving this through a three-pronged strategic approach. Aim 1 is to create a self-improving dental adhesive that enhances its bond with the tooth substrate by facilitating mineralization at the interface. This auto-enhancing universal dental adhesive (AUDA) will fill gaps between the tooth and adhesive, offering better adhesion than current products. We will expedite AUDA development using hybrid modeling and simulation approaches (HMSA), which incorporate data-driven multi-physics simulation techniques and create a virtual twin of the physical testing environment. The performance of AUDA will undergo rigorous validation, including tests for bond strength to extracted human teeth and durability under various challenges simulating human oral environments. Aim 2 focuses on crafting bioactive dental composites with self-healing and antimicrobial properties, achieved by integrating innovative nanofillers. These composites that are designed to be compatible with existing dental adhesives and AUDA will be validated for mechanical strength, bacterial inhibition, healing efficiency, and fatigue life improvement. Aim 3 is to produce CAD/CAM restoratives optimized for digital dentistry, offering robust, biocompatible materials with excellent aesthetics and bonding strength to teeth. Ultimately, our integration of artificial intelligence and a virtual lab with the material development process in the physical lab will revolutionize and individualize dental care. This platform will provide materials precisely tailored to meet diverse patient needs. Successful completion of these Aims will generate a battery of novel bioactive multifunctional restorative materials for precision placement and patients' needs. Its success will redefine dental restorative materials, ushering in an era of personalized caries treatment.