This review focuses on the design of advanced biomaterials to address the challenges of bone regeneration in aged individuals, particularly in the context of China's aging population. It highlights the decline in bone regeneration capacity due to cellular dysfunction and inflammation, and explores various strategies to restore tissue integrity. The review covers several key areas: 1. **Stem Cell Manipulation**: Techniques to regulate and activate stem cells, such as mesenchymal stromal cells (MSCs), to enhance their migration, proliferation, and self-renewal capacities. 2. **Inflammatory Microenvironment Regulation**: Strategies to modulate the inflammatory microenvironment, including the use of biomaterials to control the phenotype and number of inflammatory cells. 3. **Blood Vessel Regeneration**: Approaches to promote angiogenesis and improve blood supply, such as incorporating pro-angiogenic factors or biomimetic structures into biomaterials. 4. **Bone Anabolism and Catabolism Intervention**: Methods to balance bone resorption and formation, including the use of bisphosphonates and osteoinductive proteins. 5. **Nerve Regulation**: Techniques to enhance neural innervation, which is crucial for maintaining the balance between osteogenesis and adipogenesis in bone marrow stromal cells. The review also discusses the development of a database-driven design process for future biomaterial development, emphasizing the importance of high-throughput fabrication and evaluation systems, artificial intelligence, and multi-omics approaches. The ultimate goal is to accelerate the pace of material development and clinical translation, contributing to the pursuit of "healthy aging" by addressing age-related bone diseases.This review focuses on the design of advanced biomaterials to address the challenges of bone regeneration in aged individuals, particularly in the context of China's aging population. It highlights the decline in bone regeneration capacity due to cellular dysfunction and inflammation, and explores various strategies to restore tissue integrity. The review covers several key areas: 1. **Stem Cell Manipulation**: Techniques to regulate and activate stem cells, such as mesenchymal stromal cells (MSCs), to enhance their migration, proliferation, and self-renewal capacities. 2. **Inflammatory Microenvironment Regulation**: Strategies to modulate the inflammatory microenvironment, including the use of biomaterials to control the phenotype and number of inflammatory cells. 3. **Blood Vessel Regeneration**: Approaches to promote angiogenesis and improve blood supply, such as incorporating pro-angiogenic factors or biomimetic structures into biomaterials. 4. **Bone Anabolism and Catabolism Intervention**: Methods to balance bone resorption and formation, including the use of bisphosphonates and osteoinductive proteins. 5. **Nerve Regulation**: Techniques to enhance neural innervation, which is crucial for maintaining the balance between osteogenesis and adipogenesis in bone marrow stromal cells. The review also discusses the development of a database-driven design process for future biomaterial development, emphasizing the importance of high-throughput fabrication and evaluation systems, artificial intelligence, and multi-omics approaches. The ultimate goal is to accelerate the pace of material development and clinical translation, contributing to the pursuit of "healthy aging" by addressing age-related bone diseases.