This review article, authored by Wenhao Wang and Kelvin W.K. Yeung, discusses the current state and advancements in bone grafts and biomaterials for treating bone defects. The authors highlight the limitations of traditional autologous bone grafts, such as donor site complications and limited availability, and explore the emergence of synthetic bone substitutes and biological factors to address these issues. Key topics include: 1. **Natural Bone Grafts**: Autologous and allogeneic bone grafts are discussed, with autologous bone grafts considered the gold standard due to their osteoconductive, osteoinductive, and osteogenic properties. Allogeneic bone grafts, while less immunogenic, face challenges such as immune responses and viral transmission. 2. **Synthetic Bone Substitutes**: Calcium sulfate, calcium phosphate ceramics, calcium phosphate cements, bioactive glass, and poly(methyl methacrylate) (PMMA) are reviewed for their mechanical properties, osteoconductive abilities, and potential for bone regeneration. 3. **Biological Factors**: The role of growth factors like bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGFs), and platelet-rich plasma (PRP) in enhancing bone healing is examined. BMPs, particularly BMP-2 and BMP-7, have shown promise in clinical trials for treating skeletal defects, but their off-label use and potential complications are noted. 4. **Bioinorganic Ions**: Magnesium, strontium, and zinc are highlighted as alternative osteogenic factors, offering potential benefits over biological factors due to their lower cost and fewer side effects. The article emphasizes the importance of enhancing osteointegration and the need for further research to optimize the use of bone grafts and substitutes in clinical practice.This review article, authored by Wenhao Wang and Kelvin W.K. Yeung, discusses the current state and advancements in bone grafts and biomaterials for treating bone defects. The authors highlight the limitations of traditional autologous bone grafts, such as donor site complications and limited availability, and explore the emergence of synthetic bone substitutes and biological factors to address these issues. Key topics include: 1. **Natural Bone Grafts**: Autologous and allogeneic bone grafts are discussed, with autologous bone grafts considered the gold standard due to their osteoconductive, osteoinductive, and osteogenic properties. Allogeneic bone grafts, while less immunogenic, face challenges such as immune responses and viral transmission. 2. **Synthetic Bone Substitutes**: Calcium sulfate, calcium phosphate ceramics, calcium phosphate cements, bioactive glass, and poly(methyl methacrylate) (PMMA) are reviewed for their mechanical properties, osteoconductive abilities, and potential for bone regeneration. 3. **Biological Factors**: The role of growth factors like bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGFs), and platelet-rich plasma (PRP) in enhancing bone healing is examined. BMPs, particularly BMP-2 and BMP-7, have shown promise in clinical trials for treating skeletal defects, but their off-label use and potential complications are noted. 4. **Bioinorganic Ions**: Magnesium, strontium, and zinc are highlighted as alternative osteogenic factors, offering potential benefits over biological factors due to their lower cost and fewer side effects. The article emphasizes the importance of enhancing osteointegration and the need for further research to optimize the use of bone grafts and substitutes in clinical practice.