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将聚多巴胺包裹在载阿霉素的层状羟基磷灰石/聚(乳酸-羟基乙酸)复合纤维上,以抑制骨肿瘤复发和增强骨再生。

Enwrapping Polydopamine on Doxorubicin-Loaded Lamellar Hydroxyapatite/Poly(lactic--glycolic acid) Composite Fibers for Inhibiting Bone Tumor Recurrence and Enhancing Bone Regeneration.

机构信息

Jiangxi Key Laboratory of Nanobiomaterials, Institute of Advanced Materials, East China Jiaotong University, Nanchang 330013, China.

School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China.

出版信息

ACS Appl Bio Mater. 2021 Aug 16;4(8):6036-6045. doi: 10.1021/acsabm.1c00297. Epub 2021 Jul 14.

Abstract

Simultaneous prevention of bone tumor recurrence and promotion of repairing bone defects resulting from tumorectomy remain a challenge. Herein, we report a polydopamine (PDA)-coated composite scaffold consisting of doxorubicin (DOX)-loaded lamellar hydroxyapatite (LHAp) and poly(lactic--glycolic acid) (PLGA) in an attempt to reach dual functions of tumor inhibition and bone repair. The DOX was intercalated into LHAp, and the DOX-loaded LHAp was incorporated into PLGA solution to prepare a DOX-intercalated LHAp/PLGA (labeled as DH/PLGA) scaffold that was coated with PDA to obtain a PDA@DH/PLGA scaffold. The morphology, structure, wettability, mechanical properties, drug release, biocompatibility, and and bioactivities of the PDA@DH/PLGA scaffold were evaluated. It is found that PDA coating not only improves hydrophilicity and mechanical properties, but also leads to more sustainable drug release. More importantly, the PDA@DH/PLGA scaffold shows significantly inhibited growth of tumor cells initially and subsequent improved adhesion and proliferation of osteoblasts. In addition, the PDA coating improves the bioactivity of the DH/PLGA scaffold as suggested by the biomineralization. Further study demonstrates the improved bone growth around PDA@DH/PLGA over DH/PLGA after 20 days of drug release. The dual functional PDA@DH/PLGA scaffold shows great promise in the treatment of bone tumor.

摘要

同时预防肿瘤切除后肿瘤复发和促进骨缺损修复仍然是一个挑战。在此,我们报告了一种由载多柔比星(DOX)的层状羟基磷灰石(LHAp)和聚(乳酸-乙醇酸)(PLGA)组成的聚多巴胺(PDA)涂层复合支架,试图达到肿瘤抑制和骨修复的双重功能。将 DOX 插入 LHAp 中,并将载 DOX 的 LHAp 掺入 PLGA 溶液中,制备 DOX 插层 LHAp/PLGA(标记为 DH/PLGA)支架,然后用 PDA 对其进行涂层,得到 PDA@DH/PLGA 支架。对 PDA@DH/PLGA 支架的形态、结构、润湿性、机械性能、药物释放、生物相容性和生物活性进行了评估。结果发现,PDA 涂层不仅提高了亲水性和机械性能,而且还导致了更可持续的药物释放。更重要的是,PDA@DH/PLGA 支架最初显示出明显抑制肿瘤细胞生长,随后促进成骨细胞的黏附和增殖。此外,PDA 涂层提高了 DH/PLGA 支架的生物活性,如生物矿化所表明的那样。进一步的研究表明,在释放药物 20 天后,PDA@DH/PLGA 周围的骨生长明显优于 DH/PLGA。具有双重功能的 PDA@DH/PLGA 支架在骨肿瘤的治疗中具有很大的应用前景。

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