Shen Guangxin, Gao Botao, Guo Jiayi, Xu Weikang, Chen Guangfu, Huang Shuai, Zeng Zhiwen, Zhao Xiaodong
Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Guangdong Province, Foshan 528031, China; Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510316, China.
Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510316, China; National Engineering Research Center for Healthcare Devices, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510316, China; Guangdong Provincial Key Laboratory of Medical Electronic Instruments and Materials, Guangdong Academy of Sciences, Guangzhou 510316, China.
Int J Biol Macromol. 2025 Apr;298:139906. doi: 10.1016/j.ijbiomac.2025.139906. Epub 2025 Jan 17.
Due to the limited ability to self-repair, the regeneration of bone critical-sized defects (CSD) is a significant challenge. Bone tissue engineering scaffolds are considered promising candidates for CSD repair, but low cell infiltration efficiency and a lack of nutrients greatly restrict bone regeneration abilities. Herein, we developed a dynamic culturing of large biomimetic bone scaffolds, PCL/GelMA@cells that combining 3D printed polycaprolactone (PCL) multi-channel cylinder with gelatin methacryloyl (GelMA) encapsulated with bone marrow mesenchymal stem cells (BMSCs) and rat aortic endothelial cells (RAECs). A cell dynamic culture system was fabricated to simulate the dynamic microenvironment. Compared to static culturing, dynamic culturing proved to enhance the nutrient exchange within the large scaffold to promote the cells infiltration, growth, proliferation and induce osteogenic and angiogenic differentiation. Furthermore, a rat cranial CSD (D = 10 mm) repair model verified the accelerated vascular ingrowth and new bone formation with the implantation of dynamic culturing of PCL/GelMA@cells scaffold (∼10 times higher than Blank group), indicating the great potential of dynamical culturing of scaffolds for bone repair. In summary, the results highlight the significant advantages of the dynamical culturing of cell-loaded scaffolds for bone regeneration, offering a promising strategy for addressing critical size bone defects.
由于自我修复能力有限，骨临界尺寸缺损（CSD）的再生是一项重大挑战。骨组织工程支架被认为是修复CSD的有前途的候选者，但细胞浸润效率低和缺乏营养物质极大地限制了骨再生能力。在此，我们开发了一种大型仿生骨支架的动态培养方法，即PCL/GelMA@细胞，它将3D打印的聚己内酯（PCL）多通道圆柱体与包裹有骨髓间充质干细胞（BMSCs）和大鼠主动脉内皮细胞（RAECs）的甲基丙烯酸明胶（GelMA）相结合。构建了一个细胞动态培养系统来模拟动态微环境。与静态培养相比，动态培养被证明可以增强大型支架内的营养物质交换，以促进细胞浸润、生长、增殖，并诱导成骨和血管生成分化。此外，大鼠颅骨CSD（D = 10 mm）修复模型验证了植入PCL/GelMA@细胞支架动态培养物可加速血管长入和新骨形成（比空白组高约10倍），表明支架动态培养在骨修复方面具有巨大潜力。总之，结果突出了负载细胞的支架动态培养在骨再生方面的显著优势，为解决临界尺寸骨缺损提供了一种有前途的策略。
