Fani Nesa, Farokhi Mehdi, Azami Mahmoud, Kamali Amir, Bakhshaiesh Nasrin Lotfi, Ebrahimi-Barough Somayeh, Ai Jafar, Eslaminejad Mohamadreza Baghaban
Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, 1417755469 Tehran, Iran.
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, 1665659911, ACECR, Tehran, Iran.
ACS Biomater Sci Eng. 2019 May 13;5(5):2134-2146. doi: 10.1021/acsbiomaterials.8b01372. Epub 2019 Apr 22.
A major problem in the treatment of large bone defects is the inability to provide an adequate blood supply to the implantation site. Therefore, a bone regeneration strategy that provides an adequate supply of vessels would address this need. Cobalt (Co), because of its ability to induce hypoxia, has been used to accelerate new vessel formation. In this study, we used a freeze-drying technique to fabricate a scaffold that consisted of Co-doped calcium phosphate (CaP) [e.g., hydroxyapatite (HA)] and natural silk fiber through an optimized alternate mineralization process. The composition and structure of the scaffold were confirmed by X-ray diffraction (XRD), Fourier transform infrared (FTIR), inductively coupled plasma (ICP), and scanning electron microscope (SEM). The data showed that the scaffolds promoted differentiation of adipose-derived mesenchymal stem cells (ADSCs) toward endothelial and osteoblast linages. We observed improved angiogenesis and bone formation with the fabricated scaffolds compared with the control groups. Computed tomography (CT) scans and radiographic imaging, in addition to histology and immunohistochemical analyses, showed the presence of angiogenesis and bone regeneration after implantation of the ADSC-seeded scaffolds in a critical size calavarial bone defect in a Wistar rat model. We obtained the best in vitro and in vivo results by doping 2% Co in HA. Taken together, we propose that the Co-doped HA/silk fibroin (SF) scaffold would be a good candidate to induce angiogenesis and bone formation both in vitro and in vivo.
大骨缺损治疗中的一个主要问题是无法为植入部位提供充足的血液供应。因此，一种能提供充足血管供应的骨再生策略将满足这一需求。钴（Co）因其诱导缺氧的能力，已被用于加速新血管形成。在本研究中，我们采用冷冻干燥技术，通过优化的交替矿化工艺制备了一种由钴掺杂磷酸钙（CaP）[如羟基磷灰石（HA）]和天然丝纤维组成的支架。通过X射线衍射（XRD）、傅里叶变换红外光谱（FTIR）、电感耦合等离子体（ICP）和扫描电子显微镜（SEM）对支架的组成和结构进行了确认。数据表明，该支架促进脂肪来源间充质干细胞（ADSCs）向内皮细胞和成骨细胞谱系分化。与对照组相比，我们观察到所制备的支架能改善血管生成和骨形成。在Wistar大鼠模型的临界尺寸颅骨骨缺损中植入接种了ADSCs的支架后，计算机断层扫描（CT）和放射成像，以及组织学和免疫组织化学分析均显示存在血管生成和骨再生。我们通过在HA中掺杂2%的Co获得了最佳的体外和体内结果。综上所述，我们认为钴掺杂的HA/丝素蛋白（SF）支架将是在体外和体内诱导血管生成和骨形成的良好候选材料。
