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一种新型的聚(3-羟基丁酸酯-3-羟基戊酸酯)(PHBV)-聚乙二醇-褪黑素复合支架在抑制骨肿瘤复发和促进骨再生方面具有增强作用。

A novel poly(3-hydroxybutyrate--3-hydroxyvalerate) (PHBV)-PEG-melatonin composite scaffold enhances for inhibiting bone tumor recurrence and enhancing bone regeneration.

作者信息

Zhang Wei-Lin, Dai Zhi-Wen, Chen Si-Yuan, Guo Wei-Xiong, Wang Zhong-Wei, Wei Jin-Song

机构信息

Department of Spinal Degeneration and Deformity Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

出版信息

Front Pharmacol. 2023 Aug 17;14:1246783. doi: 10.3389/fphar.2023.1246783. eCollection 2023.

Abstract

Postoperative comprehensive treatment has become increasingly important in recent years. This study was to repair tissue defects resulting from the removal of diseased tissue and to eliminate or inhibit the recurrence and metastasis of residual tumors under the condition of reducing the systemic side effects of chemotherapeutic drugs. To address these challenges, multifunctional scaffolds based local drug delivery systems will be a promising solution. An optimal drug-loaded scaffold material PHBV-mPEG5k (PP5) was prepared, which is biocompatible, hydrophilic and biodegradable. Furthermore, this material showed to promote bone healing, and could be conveniently prepared into porous scaffold by freeze-drying the solution. By means of introducing melatonin (MT) into the porous surfaces, the MT loaded PP5 scaffold with desirable sustained release ability was successfully prepared. The effectiveness of the MT loaded PP5 scaffold in promoting bone repair and anti-tumor properties was evaluated through both and experiments. The MT loaded PP5 scaffold is able to achieve the desired outcome of bone tissue repair and anti-bone tumor properties. Furthermore, our study demonstrates that the PP5 scaffold was able to enhance the anti-tumor effect of melatonin by improving cellular autophagy, which provided a therapeutic strategy for the comprehensive postoperative treatment of osteosarcoma.

摘要

近年来,术后综合治疗变得越来越重要。本研究旨在修复因切除病变组织而导致的组织缺损,并在降低化疗药物全身副作用的情况下消除或抑制残留肿瘤的复发和转移。为应对这些挑战,基于多功能支架的局部给药系统将是一个有前景的解决方案。制备了一种最佳的载药支架材料PHBV-mPEG5k(PP5),它具有生物相容性、亲水性和可生物降解性。此外,这种材料显示出促进骨愈合的作用,并且可以通过将溶液冷冻干燥方便地制备成多孔支架。通过将褪黑素(MT)引入多孔表面,成功制备了具有理想缓释能力的载MT的PP5支架。通过 和 实验评估了载MT的PP5支架在促进骨修复和抗肿瘤特性方面的有效性。载MT的PP5支架能够实现骨组织修复和抗骨肿瘤特性的预期效果。此外,我们的研究表明,PP5支架能够通过改善细胞自噬来增强褪黑素的抗肿瘤作用,这为骨肉瘤的术后综合治疗提供了一种治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7ab/10469957/4c76223015a7/fphar-14-1246783-g001.jpg

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