Shi Yiwan, Wang Zhaozhen, Zhou Xinting, Lin Chengxiong, Chen Chao, Gao Botao, Xu Weikang, Zheng Xiaofei, Wu Tingting, Wang Huajun
Department of Bone and Joint Surgery and Sports Medicine Center, The First Affiliated Hospital, Jinan University, Guangzhou, China.
National Engineering Research Center for Healthcare Devices, Guangdong Key Lab of Medical Electronic Instruments and Polymer Material Products, Institute of Biological And Medical Engineering, Guangdong Academy of Sciences, Guangzhou, China.
Front Bioeng Biotechnol. 2023 Mar 2;11:1132192. doi: 10.3389/fbioe.2023.1132192. eCollection 2023.
Osteosarcoma remains a worldwide concern due to the poor effectiveness of available therapies in the clinic. Therefore, it is necessary to find a safe and effective therapy to realize the complete resection of osteosarcoma and reconstruction of the bone defect. Magnetic hyperthermia based on magnetic nanoparticles can kill tumor cells by raising the temperature without causing the side effects of conventional cancer treatments. This research aims to design a high-performance magnetic hydrogel composed of gelatin methacrylate and highly magnetic cobalt ferrite (CFO) nanoparticles for osteosarcoma treatment. Specifically, CFO is surface functionalized with methacrylate groups (MeCFO). The surface modified CFO has good biocompatibility and stable solution dispersion ability. Afterward, MeCFO nanoparticles are incorporated into GelMA to fabricate a three-dimensional (3D) printable MeCFO/GelMA magnetic hydrogel and then photocross-linked by UV radiation. MeCFO/GelMA hydrogel has high porosity and swelling ability, indicating that the hydrogel possesses more space and good hydrophily for cell survival. The rheological results showed that the hydrogel has shear thinning property, which is suitable as a bioprinting ink to produce desired structures by a 3D printer. Furthermore, 50 μg/mL MeCFO not only decreases the cell activity of osteosarcoma cells but also promotes the osteogenic differentiation of mBMSCs. The results of the CCK-8 assay and live/dead staining showed that MeCFO/GelMA hydrogel had good cytocompatibility. These results indicated that MeCFO/GelMA hydrogel with potential antitumor and bone reconstruction functions is a promising therapeutic strategy after osteosarcoma resection.
由于临床上现有治疗方法效果不佳,骨肉瘤仍然是一个全球性的问题。因此,有必要找到一种安全有效的治疗方法,以实现骨肉瘤的完全切除和骨缺损的修复。基于磁性纳米粒子的磁热疗可以通过升高温度杀死肿瘤细胞,而不会引起传统癌症治疗的副作用。本研究旨在设计一种由甲基丙烯酸明胶和高磁性钴铁氧体(CFO)纳米粒子组成的高性能磁性水凝胶用于骨肉瘤治疗。具体而言,CFO用甲基丙烯酸酯基团进行表面功能化(MeCFO)。表面改性的CFO具有良好的生物相容性和稳定的溶液分散能力。随后,将MeCFO纳米粒子掺入GelMA中,制备三维(3D)可打印的MeCFO/GelMA磁性水凝胶,然后通过紫外线辐射进行光交联。MeCFO/GelMA水凝胶具有高孔隙率和溶胀能力,表明该水凝胶具有更多的空间和良好的亲水性以利于细胞存活。流变学结果表明,该水凝胶具有剪切变稀特性,适合作为生物打印墨水通过3D打印机生产所需结构。此外,50μg/mL的MeCFO不仅降低了骨肉瘤细胞的细胞活性,还促进了间充质骨干细胞的成骨分化。CCK-8测定和活/死染色结果表明,MeCFO/GelMA水凝胶具有良好的细胞相容性。这些结果表明,具有潜在抗肿瘤和骨修复功能的MeCFO/GelMA水凝胶是骨肉瘤切除术后一种有前景的治疗策略。