| Summary: | Osteocytes function as the master orchestrator of bone remodeling activity in the telophase of osseointegration. However, most contemporary studies focus on the manipulation of osteoblast and/or osteoclast functionality via implant surface engineering, which neglects the pivotal role of osteocytes in de novo bone formation. It is confirmative that osteocyte processes extend directly to the implant surface, but whether the surface physicochemical properties can affect the functionality of osteocytes and determine the fate of the osseointegration in the final remodeling stage remains to be determined. Titania nanotube arrays (NTAs) with distinct diameters were fabricated to investigate the relationship between the nanoscale topography and the functionality of osteocytes. In vitro results pinpointed that NTA with a diameter of 15 nm (NTA-15) significantly promote osteogenesis of osteocytes via the enhancement of spreading, proliferation, and mineralization. The osteocyte transcriptome of each group further revealed that the TGF-β signaling pathway plays a pivotal role in osteocyte-mediated osteogenesis. The in vivo study definitely mirrored the aforementioned results, that NTA-15 significantly promotes bone formation around the implant. Consequently, nanoscaled topography-induced osteocyte functionality is important in late osseointegration. This suggests that surface designs targeting osteocytes may, therefore, be a potential approach to solving the aseptic loosening of the implant, and thus strengthen osseointegration. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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