Successful materials design for bone-tissue engineering requires an understanding of the composition and structure of native bone tissue, as well as appropriate selection of biomimetic natural or tunable synthetic materials (biomaterials), such as polymers, bioceramics, metals and composites. Scalable fabrication technologies that enable control over construct architecture at multiple length scales, including three-dimensional printing and electric-field-assisted techniques, can then be employed to process these biomaterials into suitable forms for bone-tissue engineering. In this Review, we provide an overview of materials-design considerations for bone-tissue-engineering applications in both disease modelling and treatment of injuries and disease in humans. We outline the materials-design pathway from implementation strategy through selection of materials and fabrication methods to evaluation. Finally, we discuss unmet needs and current challenges in the development of ideal materials for bone-tissue regeneration and highlight emerging strategies in the field. Design of bone-tissue-engineering materials involves consideration of multiple, often conflicting, requirements. This Review discusses these considerations and highlights scalable technologies that can fabricate natural and synthetic biomaterials (polymers, bioceramics, metals and composites) into forms suitable for bone-tissue-engineering applications in human therapies and disease models.