Therapeutic Implants: Mechanobiologic Enhancement of Osteogenic, Angiogenic, and Myogenic Responses in Human Mesenchymal Stem Cells on 3D‐Printed Titanium Truss

This study investigates the effect of mechanotransduction on human mesenchymal stem cells (hMSCs) attached to structural elements of an implant, specifically a titanium truss element. It is found that surface features generated by 3D printing technology promote osteogenic activity, comparable to conventional treatments such as acid etching. Cell morphology and differentiation are evaluated using test coupons with either smooth or rough surface features. hMSCs on smooth titanium surfaces exhibit a flat, spread morphology consistent with fibrous tissue formation. In contrast, cells on 3D printed hierarchical surfaces cluster within surface asperities, resembling a trabecular bone-like orientation, and exhibited enhanced osteogenic gene expression. Building on this static surface-induced osteogenesis, we further investigated the effect of load-induced strain on hMSCs attached to the rough surface. Upon applying dynamic mechanical loading, RNA-sequencing analysis reveals that strain not only amplified osteogenic gene expression but also significantly upregulated angiogenic and myogenic pathways compared with static conditions. These findings demonstrate a synergistic effect between surface topography and mechanical strain in promoting osteogenesis. This study highlights the potential of utilizing mechanical strain through an implant's structural design to enhance osteogenic responses, offering valuable insights for the development of next-generation therapeutic implants.