Bone provides structural support and protects vital organs in our bodies. Its structure, composition, and functionality vary across development and aging as well as across sex. In this chapter, we discuss sex-based differences in bone during different stages of development, injury, and aging and we highlight sex-based considerations one should take when designing an experiment and choosing materials and reagents. First, we provide an overview of key mediators of bone homeostasis and sex-based differences that result in changes to the composition, structure, or function of healthy, injured, and aging bone. We then summarize biomaterial design strategies to develop bone-mimetic biomaterials that recapitulate the mechanical properties and heterogeneous composition of bone. Finally, we introduce biomaterials approaches to evaluate sex-based differences in bone-mimetic microenvironments in vitro, in vivo, and ex vivo.