Osteogenic effects of the bioactive small molecules and minerals in the scaffold-based bone tissue engineering

Reconstruction of the damaged bone is a striking challenge in the medical field. The bone grafts as a current treatment is associated with inherent limitations; hence, the bone tissue engineering as an alternative therapeutic approach has been considered in the recent decades. Bone tissue engineering aims at replacing the lost tissue and restoring its function by recapitulating the natural regeneration process. Concerted participation and combination of the biocompatible materials, osteoprogenitor/ stem cells and bioactive factors closely mimic the bone microenvironment. The bioactive factors regulate the cell behavior and they induce the stem cells to osteogenic differentiation by activating specific signaling cascades. Growth factors (GFs) are the most important bioactive molecules and mediators of the natural bone repair process. Although these soluble factors have approved applications in the bone regeneration, however, there are several limitations such as the instability, high dose requirements, and serious side effects which could restrict their clinical usage. Alternatively, a new generation of bioactive molecules with the osteogenic properties are used. The non-peptide organic or inorganic molecules are physiologically stable and non-immunogenic due to their small size. Many of them are obtained from the natural resources and some are synthesized through the chemical methods. As a result, these molecules have been introduced as the cost-effective osteogenic agents in the bone tissue regeneration. In this paper, three groups of these bioactive agents including the organic small molecules, minerals and metallic nanoparticles have been investigated, considering their function in accelerating the bone regeneration. We review the recent in vitro and in vivo studies that utilized the osteogenic molecules to promote the bone formation in the scaffold-based bone tissue engineering systems.