Taixing Zhang, Ke Ma, Kangqing Zuo, Pandong Lin, Tailong Zhang, Rongliang Ding, Linbo Zhang, Aonan Li, Yinchuan Wang, Yanling Huang, Jichao Feng, Guiyong Xiao, Yupeng Lu, Bing Han, Zhiqiang Wang, Ningbo Li
Current load-bearing bone implants primarily serve as static structural supports, still fall short of replicating the dynamic, spatiotemporal, and multifunctional coordination inherent in natural bone regeneration. Herein, we first develop a biomimetic force-electric responsive tantalum (Ta) implant with surface-nanostructured LiTaO3 (n- LiTaO3) via combining laser nanofabrication and Li+-induced in situ reaction, achieving favorable immunomodulation-mediated vascularized osseointegration under low-intensity pulsed ultrasound stimulation. The piezoelectric LiTaO3 nanotentacles convert ultrasound vibration into localized electrical signals, triggering Ca2 + influx, accelerating mitochondrial ATP production, and activating PI3K-AKT signaling pathway in BMSCs to promote osteogenesis. It also orchestrates a pro-osteoregenerative immune microenvironment through M2 macrophage polarization and immune-osteogenic crosstalk mediated by ECM-integrin-FAK axis. The force-electric response implant yet promotes angiogenesis mainly via enhancing intracellular Ca2 +-dependent eNOS/NO cue and cellular metabolism, reduces the inflammatory response in the dorsal subcutaneous tissue of rats, and further promotes vascularization and bone integration in femoral defects. The novel force-electric response Ta implant endows real-time controllable regulation of multifunctional tissue regeneration for using as patient-personalized load-bearing osteoarticular prostheses.