Stem Cell–Biomaterial Interactions in Bone Tissue Engineering: From Molecular Mechanisms to Translational Challenges

The growing incidence of trauma-induced bone defects, tumors, malformations, and age-related degenerative conditions presents a substantial clinical and socioeconomic challenge. Traditional treatments, such as autografts and implants, have significant limitations, including donor-site morbidity and immune rejection. Emerging bone tissue engineering (BTE) leverages mesenchymal stem cells (MSCs) and induced pluripotent stem cell (iPSC)-derived osteoprogenitors to create a regenerative microenvironment. Advances in biomaterials, including osteoconductive ceramics and bioresorbable polymers, enhance scaffold design, enabling the creation of hierarchical architectures that mimic the natural properties of bone. Innovations like smart scaffolds are poised to improve regeneration through controlled release of growth factors and responsiveness to external cues. However, the transition from promising preclinical results to routine clinical application faces challenges, including variability in stem cell sources, scalability issues in scaffold production, and regulatory hurdles. This review synthesizes research on stem cell-biomaterial interactions, which are vital for bone regeneration, focusing on molecular processes, scaffold design principles, osteogenic promotion strategies, and existing preclinical and clinical evidence. The findings aim to guide researchers and clinicians in developing effective bone-regenerative therapies.