Remotely controlled self-powering electrical stimulators for osteogenic differentiation using bone inspired bioactive piezoelectric whitlockite nanoparticles

Endogenous electric fields naturally exist in our body and plays a vital role especially in the development and regeneration of bones. Therefore, piezoelectric bone implants are gaining ample attention due to its inherent electrical signal generation, but generally they lack bioactivity, resorption, and ECM like composition. To address this, we evoke ‘piezoelectricity’ in whitlockite (Ca18Mg2(HPO4)2(PO4)12) nanoparticles (WH NPs) for the first time in literature. WH NPs are the second most-abundant inorganic bone mineral and reported for intermediate resorption compared to hydroxyapatite and tricalcium phosphate. Systematic electrical studies reveal that WH NPs annealed at 750 °C (PWH-750) exhibit superior ferroelectric and dielectric characteristics and produce electrical signals analogous to native tissues when triggered using FDA approved low-intensity pulsed ultrasound (LIPUS) noninvasively. The energy generation performance of Piezoelectric WH based self powered nanogenerators are analyzed and demonstrated to power the commercial LED upon LIPUS stimulation. The in vitro studies with pre-osteoblast MC3T3-E1 cells co-cultured with piezoelectric WH NPs exhibit increased ALP activity, calcium mineralization, and osteogenic gene expression along with significant upregulation of Piezo1, and TRPV4 expressions. This confirms the enhanced osteogenic differentiation compared to the control WH nanoparticles due to the remotely activated self powering capacity of piezoelectric WH NPs and thereby produce bioelectric signals analogous to native tissues. Thus, the study evidences the development of a potential bioactive piezoelectric ceramic with extensive applicability for future clinical translation.