Project Summary: Osteoporosis, a skeletal disorder characterized by bone mass loss and increased fracture risk, is one of the most common bone-related disease around the world. By the year of 2030, the total number of osteoporosis patients in US is projected to be 11.9 million. Traditional clinical treatments relying on exogenous biochemical stimuli, such as grow factors and hormones, are challenging due to the difficulties in dose control and off-target delivery. As an alternative to biochemical stimuli, low intensity vibration (LIV) arising from the dynamics of muscle contraction is a non-pharmacologic alternative to enhance anabolic activities in bones. Despite its merits in bone biology, LIV is currently limited in bioreactor systems due to the lack of osteo-inductive scaffolds. Therefore, there is an immediate need to devise wirelessly-driven and mechano-active scaffolds that can generate controllable and localized LIV for bone repair and regeneration while minimizing the potential damages to nearby physiologic systems. Magnetostrictive material (MsM) exhibits a deformation (up to 1400 ??) while maintaining high stiffness when driven wirelessly by a magnetic field [8]. The deformation amplitude is linearly related to the applied field strength. While we have additively manufactured and theoretically modeled MsM devices, the viability of MsM in tissue engineering is still undetermined. Electrical stimuli are another type of non-pharmacologic alternative. Most studies incorporated scaffolds with piezoelectric materials, which produce bioelectrical signals similar to the natural extracellular matrix (ECM). By combining MsM and piezoelectric materials, recent studies have fabricated magnetoelectric (MeM) scaffolds generating mechanical and electrical stimuli simultaneously via magnetic excitations. However, 3-dimensional (3D) MeM structures mimicking the actual bone morphology are unavailable due to manufacturing difficulties. With a long-term vision of advancing fundamental knowledge in bone biology, understanding the basic mechanism of osteoporosis, and developing reliable therapies for bone mass loss, in this project, we propose a multidisciplinary research targeting the first creation of additively-manufactured and magnetically-driven 3D scaffolds for bone tissue engineering. To fill the gaps between materials science and ECM biology, we will: (1) print magnetostrictive scaffolds to mimic the mechanical stimuli associated with muscle contraction, (2) print magnetoelectric scaffolds to mimic the mechanical and electrical environment in bone ECM, and (3) test in vitro if printed magneto-active scaffolds improve progenitor MSC osteogenesis. We hypothesize that the magnetically-driven scaffold would replicate the physical factors in bone ECM and result in improvement in bone progenitor osteogenesis compared to non-stimulated groups. If successful, the physicochemical and bioactive characteristics of the printed scaffold would reduce cell culture time, improve tissue functionality, and facilitate future therapeutic applications and fundamental ECM studies.