Abstract
Bone regeneration presents an enduring clinical barrier, particularly with the projected rise in osteoporotic fractures exceeding 6 million annually by 2050. Autografts, allografts, and xenografts remain foundational in bone repair due to their inherent osteogenic, osteoconductive, and osteoinductive capacities. However, issues such as donor site morbidity, immunogenicity, limited graft availability, and pathogen transmission risks limit their applicability. In response, recent developments in biomaterials, including ion-doped bioceramics, bioactive glass-polymer composites, and stem cell-functionalized hydrogels, aim to replicate the hierarchical structure and biochemical microenvironment of native bone. This review surveys advancements in scaffold materials over the past five years, evaluating their physicochemical properties, immune modulation potential, and clinical readiness within the context of bone tissue engineering (BTE). Specific attention is given to strategies for selecting appropriate biomaterials based on clinical needs, considering their physical and biological properties, as well as their respective advantages and limitations. Despite this progress, clinical translation remains limited; only a few engineered scaffolds have achieved regulatory approval for routine use. To accelerate adoption, efforts must focus on scalable fabrication, quantitative immune profiling, and scaffold degradation monitoring to bridge preclinical performance with clinical efficacy.