Abstract：
Tumor recurrence and massive bone defects are two critical challenges for postoperative treatment of oral and maxillofacial tumor, posing serious threats to the health of patients. Herein, in order to eliminate residual tumor cells and promote osteogenesis simultaneously, the hydrogen peroxide (H2O2) self-sufficient TCP-PDA-CaO2-CeO2 (TPCC) scaffolds are designed by preparing CaO2 or/and CeO2 nanoparticles (NPs)/chitosan solution and modifying the NPs into polydopamine (PDA)-modified 3D printed TCP scaffolds by rotary coating method. CaO2 NPs loaded on the scaffolds can release Ca2+ and sufficient H2O2 in the acidic tumor microenvironment (TME). The generated H2O2 can further produce hydroxyl radicals (·OH) under catalysis effect by peroxidase (POD) activity of CeO2 NPs, in which the photothermal effect of the PDA coating enhances its POD catalytic effect. Overall, NPs loaded on the scaffold chemically achieve a cascade reaction of H2O2 self-sufficiency and ·OH production, while functionally achieving synergistic effects on anti-tumor and bone promotion. In vitro and in vivo studies show that the scaffolds exhibit effective osteo-inductivity, induced osteoblast differentiation and promote osseointegration. Therefore, the multifunctional composite scaffolds not only validate the concept of chemo-dynamic therapy (CDT) cascade therapy, but also provide a promising clinical strategy for postoperative treatment of oral and maxillofacial tumor.
摘要：
肿瘤复发和大量骨缺损是口腔颌面部肿瘤术后治疗的两大挑战,对患者的健康构成严重威胁。在这里，为了消除残留的肿瘤细胞，同时促进成骨，通过制备CaO2或/和CeO2纳米颗粒（NPs）/壳聚糖溶液并将NPs改性为聚多巴胺（PDA）改性的3D打印TCP支架，设计了过氧化氢（H2O2）自给自足的TCP-PDA-CaO2-CeO2（TPCC）支架。负载在支架上的CaO2NPs可以在酸性肿瘤微环境中释放Ca2和足够的H2O2。在CeO2NP的过氧化物酶（POD）的催化作用下，生成的H2O2可以进一步产生羟基自由基（·OH），其中PDA涂层的光热效应增强了其POD催化效应。总的来说,负载在支架上的NP化学实现H2O2自给自足和·OH产生的级联反应，同时在功能上实现抗肿瘤和骨促进的协同作用。体外和体内研究表明，支架表现出有效的骨诱导作用，诱导成骨细胞分化，促进骨整合。因此,多功能复合支架不仅验证了化学动力疗法(CDT)级联疗法的概念，同时也为口腔颌面部肿瘤的术后治疗提供了一种有前景的临床策略。本文受版权保护。保留所有权利。
