Tan Wei, Gao Chengde, Feng Pei, Liu Qing, Liu Congcong, Wang Zhenting, Deng Youwen, Shuai Cijun
Department of Spine Surgery, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Changsha, Hunan 410013, People's Republic of China; Department of Spinal Orthopedics, Huizhou Third People's Hospital, Guangzhou Medical University, No.1, Xuebei Road, Huizhou, Guangdong 516002, People's Republic of China.
State Key Laboratory of High Performance Complex Manufacturing, College of Mechanical and Electrical Engineering, Central South University, Changsha, Hunan, People's Republic of China.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;120:111592. doi: 10.1016/j.msec.2020.111592. Epub 2020 Nov 12.
Bone defects caused by tumors are difficult to repair clinically because of their poor morphology and residual tumor cell-induced recurrence. Scaffolds with the dual function of bone repair and bone tumor treatment are urgently needed to resolve this problem. In this study, a poly(L-lactic acid) (PLLA)/nanoscale hydroxyapatite (nHA)/metformin (MET) nanocomposite scaffold was constructed via selective laser sintering. The scaffolds were expected to combine the excellent mechanical strength and biodegradability of PLLA, the good bioactivity of nHA, and the water solubility and antitumor properties of MET. The PLLA/nHA/MET scaffolds showed improved cell adhesion, appropriate porosity, good biocompatibility and osteogenic-induced ability in vitro because metformin improves water solubility and promotes the osteogenic differentiation of cells within the scaffold. The PLLA/nHA/MET scaffold had an extended drug release time because the MET particles were wrapped in the biodegradable polymer PLLA and the wrapped MET particles were slowly released into body fluids as the PLLA was degraded. Moreover, the scaffold induced osteosarcoma (OS) cell apoptosis by upregulating apoptosis-related gene expression and showed excellent tumor inhibition characteristics in vitro. In addition, the scaffold induced osteogenic differentiation of bone marrow mesenchymal cells (BMSCs) by promoting osteogenic gene expression. The results suggest that the PLLA/nHA/MET composite scaffold has the dual function of tumor inhibition and bone repair and therefore it provides a promising new approach for the treatment of tumor-induced bone defects.
由于肿瘤导致的骨缺损形态不佳且残留肿瘤细胞易引发复发，临床上难以修复。迫切需要具有骨修复和骨肿瘤治疗双重功能的支架来解决这一问题。在本研究中，通过选择性激光烧结构建了聚（L-乳酸）（PLLA）/纳米级羟基磷灰石（nHA）/二甲双胍（MET）纳米复合支架。预期该支架能兼具PLLA优异的机械强度和生物降解性、nHA良好的生物活性以及MET的水溶性和抗肿瘤特性。PLLA/nHA/MET支架在体外表现出改善的细胞黏附、适宜的孔隙率、良好的生物相容性和成骨诱导能力，因为二甲双胍提高了水溶性并促进了支架内细胞的成骨分化。PLLA/nHA/MET支架具有延长的药物释放时间，这是因为MET颗粒被包裹在可生物降解聚合物PLLA中，随着PLLA降解，被包裹的MET颗粒缓慢释放到体液中。此外，该支架通过上调凋亡相关基因表达诱导骨肉瘤（OS）细胞凋亡，在体外表现出优异的肿瘤抑制特性。另外，该支架通过促进成骨基因表达诱导骨髓间充质细胞（BMSCs）成骨分化。结果表明，PLLA/nHA/MET复合支架具有肿瘤抑制和骨修复双重功能，因此为治疗肿瘤诱导性骨缺损提供了一种有前景的新方法。
