Advances in nanoscopic mechanobiological structure-property relationship in human bones for tailored fragility prevention

It is well documented that fragility fractures represent an enormous health, economic and psycho-social burden, leading to severe pain, loss of mobility, and even death. While clinical approaches focusing on macro down to micro-scale damage in bones are often ineffective to diagnose early fracture occurrence, nano-scale investigations are opening new frontiers for targeted fragility prevention. This review highlights a novel triad that merges advanced nano-imaging techniques, nano-mechanical characterization and finite element/molecular dynamics-based computational models to elucidate the structure-property relationship that leads to bone fractures. Techniques such as atomic force microscopy and high-resolution electron microscopy enable the evaluation of mechanobiological mechanisms and damage occurrence at the sub-micro scale, providing visualization of bone ultrastructure. Simultaneously, nanoindentation and micropillar compression offer precise measurements of mechanical properties, unraveling how bone responds to diverse forces. Pertaining computational tools, nano-scale modeling simulations explore the behavior of bone components under varying conditions, yielding crucial insights into fracture mechanisms. This holistic triad unveils interactions between mineralized collagen fibrils, cross-links, and bone structures, leading to targeted prevention and personalized treatment of bone fragility, by addressing their root causes at the nano-scale, potentially lowering their incidence and severity.