This review discusses the design of biomaterials for regenerating aged bone, focusing on materiobiological advances and paradigm shifts. With China's aging population, bone regeneration capacity declines due to cellular dysfunction and inflammation, making advanced biomaterials essential for effective treatment. The review synthesizes materiobiology principles, targeting specific biological functions to restore tissue integrity. It covers strategies for stem cell manipulation, regulation of the inflammatory microenvironment, blood vessel regeneration, intervention in bone anabolism and catabolism, and nerve regulation. The review also explores molecular and cellular mechanisms underlying aged bone regeneration and proposes a database-driven design process for future biomaterial development. These insights may guide therapies for other age-related conditions, contributing to the pursuit of 'healthy aging'. Materiobiology is a recently proposed scientific discipline for biomaterials design. In aged bone repair, materiobiology focuses on the precise regulation and recovery of biological functions at the cellular, tissue, organ, and whole organism levels using functionalized biomaterials via the systematic combination of 'elements' from the biomaterial 'toolbox'. The biomaterial 'toolbox' includes biochemical factors (e.g., growth factors, polypeptides, chemical and biological drugs, and genes) and customized biophysical effects (composition, mechanical properties, two-dimensional topography, three-dimensional geometry, as well as adequate delivery and fabrication technology). The review highlights material design strategies targeting stem cell function, inflammatory microenvironment regulation, blood vessel regeneration, bone anabolism and catabolism intervention, and nerve regulation. These strategies aim to enhance bone regeneration in aged individuals by modulating biological functions through the integration of 'elements' from the biomaterial 'toolbox'. The review also discusses the role of senescent cells in aged bone regeneration and the potential of precision medicine in developing novel therapeutic methods. Additionally, the review emphasizes the importance of high-throughput in vitro platforms, such as organoids, in assessing the regulatory effects of biomaterial 'elements' on specific biological functions. The development of an aged bone repair-associated database is proposed to enhance the matching between designed biomaterials and their therapeutic effects on diseases, significantly accelerating the speed of clinical translation. The review concludes that an ideal biomaterial design process for aged bone regeneration involves identifying scientific inquiries, retrieving specific biological functions, locating matched biomaterial 'elements' within a biomaterials database, selecting candidate material combinations through a high-throughput fabricating and screening system, validating the efficacy of biomaterials via in vivo experiments, and ultimately achieving clinical application following clinical trials. Materiobiology, as an interdisciplinary field, directs biological function-targeted material design strategies that require collaboration from multidisciplinary researchers to further enrich its research content and methods. The review seeks to drive a paradigm shift in the research approach to material design for bone aging-related diseases and to inspire a similar shift in the research paradigm for other aging-related diseases.This review discusses the design of biomaterials for regenerating aged bone, focusing on materiobiological advances and paradigm shifts. With China's aging population, bone regeneration capacity declines due to cellular dysfunction and inflammation, making advanced biomaterials essential for effective treatment. The review synthesizes materiobiology principles, targeting specific biological functions to restore tissue integrity. It covers strategies for stem cell manipulation, regulation of the inflammatory microenvironment, blood vessel regeneration, intervention in bone anabolism and catabolism, and nerve regulation. The review also explores molecular and cellular mechanisms underlying aged bone regeneration and proposes a database-driven design process for future biomaterial development. These insights may guide therapies for other age-related conditions, contributing to the pursuit of 'healthy aging'. Materiobiology is a recently proposed scientific discipline for biomaterials design. In aged bone repair, materiobiology focuses on the precise regulation and recovery of biological functions at the cellular, tissue, organ, and whole organism levels using functionalized biomaterials via the systematic combination of 'elements' from the biomaterial 'toolbox'. The biomaterial 'toolbox' includes biochemical factors (e.g., growth factors, polypeptides, chemical and biological drugs, and genes) and customized biophysical effects (composition, mechanical properties, two-dimensional topography, three-dimensional geometry, as well as adequate delivery and fabrication technology). The review highlights material design strategies targeting stem cell function, inflammatory microenvironment regulation, blood vessel regeneration, bone anabolism and catabolism intervention, and nerve regulation. These strategies aim to enhance bone regeneration in aged individuals by modulating biological functions through the integration of 'elements' from the biomaterial 'toolbox'. The review also discusses the role of senescent cells in aged bone regeneration and the potential of precision medicine in developing novel therapeutic methods. Additionally, the review emphasizes the importance of high-throughput in vitro platforms, such as organoids, in assessing the regulatory effects of biomaterial 'elements' on specific biological functions. The development of an aged bone repair-associated database is proposed to enhance the matching between designed biomaterials and their therapeutic effects on diseases, significantly accelerating the speed of clinical translation. The review concludes that an ideal biomaterial design process for aged bone regeneration involves identifying scientific inquiries, retrieving specific biological functions, locating matched biomaterial 'elements' within a biomaterials database, selecting candidate material combinations through a high-throughput fabricating and screening system, validating the efficacy of biomaterials via in vivo experiments, and ultimately achieving clinical application following clinical trials. Materiobiology, as an interdisciplinary field, directs biological function-targeted material design strategies that require collaboration from multidisciplinary researchers to further enrich its research content and methods. The review seeks to drive a paradigm shift in the research approach to material design for bone aging-related diseases and to inspire a similar shift in the research paradigm for other aging-related diseases.