Titanium alloys for orthopedic applications: A review on the osteointegration induced by physicomechanical stimuli

Titanium (Ti) alloys have been widely applied clinically due to their good biocompatibility, corrosion resistance and mechanical stability. However, how to improve the weak osteointegration caused by their intrinsic bio-inertness has been a long-standing puzzle. Osteogenic-related cells, endothelial cells (ECs) and macrophages are the main cells involved in osteointegration. In recent years, surface topography based on Ti alloys, which mimics the topographical cues of the extracellular matrix (ECM), has been confirmed to precisely regulate these cells' fate to improve osteointegration. More importantly, while serving as a physicomechanical stimuli, topographic surface modification is considered more biosafe and stable than biochemical cues. Nevertheless, how different topographic modifications affect cell behavior and the specific mechanisms involved remain elusive. In this review, we highlight the regulation of surface topography based on Ti alloys on the behaviors of bone repair-related cells, such as osteogenic-related cells, ECs and macrophages, and summarize the activated intracellular mechanotransduction pathways, which aims to provide basis and support for further research on osteointegration of Ti alloys.