Biological systems and their interactions often take place at nanometer level. However, engineering approaches, and modeling biological systems often is at macro or a global level. Examples include devices that mimic the anatomical joints and/or organs replacing them by utilizing the engineering materials in bio environments and follow them up for their durability. During the course of in vivo use of the devices new pathophysiology emerges, affecting other pathways that were not known before. Osteolysis in the case of total joint replacement arises from debris may also be initiated by metal ions. However, engineering approaches are evolving to reduce the debris from the liners in total joint replacements via new manufacturing routes and cross-linking the polymers as well as kinetics of wear rates of the liners. The presentation will show modeling methods utilized to optimize new total joint replacement models of the ankle, and others, understand the tear of anterior cruciate ligament and other injury mechanisms and develop new probabilistic methods to predict the injury occurrences. An overview of device and bone damage mechanics will be presented, at large scale.