Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Colloids Surf B Biointerfaces. 2021 Feb;198:111462. doi: 10.1016/j.colsurfb.2020.111462. Epub 2020 Nov 19.
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.
骨缺损的重建是医学领域的一个重大挑战。目前的治疗方法——骨移植存在固有局限性；因此，近几十年来，骨组织工程作为一种替代治疗方法已经被考虑。骨组织工程旨在通过模拟自然再生过程来替代丢失的组织并恢复其功能。生物相容性材料、成骨前体细胞/干细胞和生物活性因子的协同参与和结合，可紧密模拟骨微环境。生物活性因子通过激活特定的信号级联反应来调节细胞行为，并诱导干细胞向成骨细胞分化。生长因子（GFs）是最重要的生物活性分子和天然骨修复过程的介质。尽管这些可溶性因子已在骨再生中得到应用，但由于其不稳定性、高剂量要求和严重的副作用等限制，其临床应用受到了限制。作为替代方案，具有成骨特性的新一代生物活性分子被使用。这些非肽有机或无机分子由于其体积小，具有生理稳定性和非免疫原性。其中许多来自天然资源，有些是通过化学方法合成的。因此，这些分子已被作为具有成本效益的成骨剂引入到骨组织再生中。在本文中，我们研究了包括有机小分子、矿物质和金属纳米粒子在内的三组生物活性物质，考虑了它们在加速骨再生中的作用。我们综述了最近的体外和体内研究，这些研究利用成骨分子来促进支架基骨组织工程系统中的骨形成。
