通过近红外二区光热-化学动力学协同作用,利用3D打印生物陶瓷支架与二维纳米片相结合的增强型序贯骨肉瘤治疗。
Enhanced sequential osteosarcoma therapy using a 3D-Printed bioceramic scaffold combined with 2D nanosheets via NIR-II photothermal-chemodynamic synergy.
作者信息
Jian Guangyu, Wang Si, Wang Xinlu, Lu Qinyi, Zhu Xingyu, Wan Shucheng, Wang Shan, Li Dize, Wang Chao, He Qingqing, Chen Tao, Song Jinlin
机构信息
The Affiliated Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases, Chongqing Municipal Key aboratory of Oral Biomedical Engineering of Higher Education, Chongqing Municipal Health Commission Key Laboratory of Oral Biomedical Engineering, Chongqing, 401147, PR China.
Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, School of Engineering Medicine, Beihang University, Beijing 100083, PR China.
出版信息
Bioact Mater. 2025 Apr 30;50:540-555. doi: 10.1016/j.bioactmat.2025.04.029. eCollection 2025 Aug.
BACKGROUND
Osteosarcoma (OS) is a malignant tumor originating from primitive mesenchymal cells, characterized by rapid metastasis, high invasiveness, and significant mortality. The primary challenges in OS management include the effective elimination of residual tumor cells to prevent recurrence and the repair of extensive bone defects caused by surgical intervention.
OBJECTIVE
This study aims to develop an innovative biomimetic 3D-printed bioactive glass ceramic (BGC) scaffold modified with two-dimensional nanosheets to address both tumor ablation and bone tissue repair.
MATERIALS AND METHODS
The nanosheets were constructed via ellagic acid (EA) and ruthenium (Ru) coordination, leveraging the non-topological adhesion properties of catechol in EA to deposit the nanosheets onto the BGC scaffold (EARu-BGC). The therapeutic effects of EARu-BGC were evaluated and .
RESULTS
EARu-BGC sequentially responds to the local microenvironment during OS treatment. During the tumor ablation phase, EARu-BGC induced ferroptosis through the synergistic effects of photothermal and chemodynamic therapy, achieving over 90 % tumor cell ablation and significantly inhibiting tumor volume and weight. In the bone tissue repair phase, EARu-BGC exhibited adaptive ROS scavenging and facilitated a pro-healing microenvironment, promoting osteogenic differentiation. The gradual degradation of the BGC scaffold provided essential minerals and space for new bone formation. In vivo experiments demonstrated that EARu-BGC significantly enhanced osteogenesis, increasing the trabecular number to 1.51 ± 0.15/mm and reducing trabecular separation to 1.50 ± 0.04 mm.
CONCLUSION
The EARu-BGC scaffold presents a promising multifunctional platform for OS treatment by effectively balancing antitumor efficacy with bone repair capabilities.
背景
骨肉瘤(OS)是一种起源于原始间充质细胞的恶性肿瘤,具有快速转移、高侵袭性和高死亡率的特点。骨肉瘤治疗的主要挑战包括有效清除残留肿瘤细胞以防止复发,以及修复手术干预导致的广泛骨缺损。
目的
本研究旨在开发一种用二维纳米片修饰的创新型仿生3D打印生物活性玻璃陶瓷(BGC)支架,以解决肿瘤消融和骨组织修复问题。
材料与方法
通过鞣花酸(EA)与钌(Ru)配位构建纳米片,利用EA中儿茶酚的非拓扑粘附特性将纳米片沉积到BGC支架上(EARu-BGC)。评估了EARu-BGC的治疗效果。
结果
EARu-BGC在骨肉瘤治疗过程中依次对局部微环境做出反应。在肿瘤消融阶段,EARu-BGC通过光热疗法和化学动力学疗法的协同作用诱导铁死亡,实现了超过90%的肿瘤细胞消融,并显著抑制了肿瘤体积和重量。在骨组织修复阶段,EARu-BGC表现出适应性活性氧清除能力,促进了有利于愈合的微环境,促进了成骨分化。BGC支架的逐渐降解为新骨形成提供了必需的矿物质和空间。体内实验表明,EARu-BGC显著增强了成骨作用,使骨小梁数量增加到1.51±0.15/mm,骨小梁间距减小到1.50±0.04mm。
结论
EARu-BGC支架通过有效平衡抗肿瘤疗效和骨修复能力,为骨肉瘤治疗提供了一个有前景的多功能平台。