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.

在医学领域中，重建受损的骨骼是一项严峻的挑战。作为当前治疗方法的骨移植物具有固有的局限性。因此，近几十年来已经考虑将骨组织工程作为替代治疗方法。骨组织工程旨在通过概括自然再生过程来替换丢失的组织并恢复其功能。生物相容性材料，骨祖细胞/干细胞和生物活性因子的共同参与和结合紧密地模仿了骨骼的微环境。生物活性因子调节细胞行为，并通过激活特定的信号级联反应诱导干细胞向成骨细胞分化。生长因子（GFs）是天然骨修复过程中最重要的生物活性分子和介体。尽管这些可溶性因子已经在骨再生中得到了批准，但是存在一些局限性，例如不稳定，高剂量要求以及严重的副作用，这些都可能限制其临床应用。或者，使用具有成骨特性的新一代生物活性分子。非肽有机或无机分子由于其尺寸小而在生理上是稳定的并且是非免疫原性的。其中许多是从自然资源中获得的，有些是通过化学方法合成的。结果，这些分子作为骨组织再生中的成本有效的成骨剂被引入。本文研究了三类生物活性剂，包括有机小分子，矿物质和金属纳米颗粒，考虑它们在加速骨骼再生中的作用。我们回顾了最近在基于支架的骨组织工程系统中利用成骨分子促进骨形成的体外和体内研究。