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β-蜕皮激素/聚乳酸-羟基乙酸共聚物复合支架促进糖尿病大鼠颅骨缺损愈合

β-ecdysone/PLGA composite scaffolds promote skull defect healing in diabetic rat.

作者信息

Luo Yicai, Wu Ziwei, Zhang Yingjuan, Qiao Yang, Wei Yinge, Yan Xuan, Ma Xiangyu, Huang Xianxian, Zhong Xiaoxia, Ye Zhimao, Lu Xinping, Liao Hongbing

机构信息

Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction, College and Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi, China.

出版信息

Front Bioeng Biotechnol. 2025 Jan 13;12:1536102. doi: 10.3389/fbioe.2024.1536102. eCollection 2024.

Abstract

INTRODUCTION

Diabetes mellitus often leads to bone metabolism disorders, hindering bone regeneration and delaying the healing of bone defects. β-Ecdysone, a plant-derived hormone known for its wide range of physiological activities, possesses hypoglycemic effects and promotes osteogenic differentiation. This study developed a composite PLGA slow-release scaffold loaded with β-ecdysone to enhance its bioavailability through topical administration and to investigate its potential to heal diabetic bone defects.

METHODS

The composite scaffolds were fabricated using solution casting/particle leaching and freeze-drying techniques. Then a series of characterizations were subjected to test the performance of composite scaffolds, and safety of the composite scaffolds was tested by CCK8 assay and live/dead cell staining. Further, micro-CT and histology to evaluate the effect of β-E/PLGA composite scaffolds on healing of skull defects in diabetic rats at 4 and 8 weeks after implantation. Simultaneously, the safety of the scaffolds was also evaluated.

RESULTS

The material characterization results indicated that, in comparison to the single-pore size scaffold, the composite scaffold exhibited superior porosity, swelling ratio, drug loading capacity, and mechanical properties. Additionally, the composite scaffolds showed appropriate degradation performance and sustained drug release profiles. The CCK8 cytotoxicity assay and live/dead cell staining demonstrated that BMSCs survived and proliferated on the composite scaffold under both low-glucose and high-glucose conditions. Micro-CT and histological investigation demonstrated that β-E/PLGA composite scaffolds promoted new bone growth in the skull defect region of diabetic rats.

CONCLUSION

Overall, these findings suggest that the β-E/PLGA composite scaffolds promote the healing of bone defects in diabetic rats. The combination of β-ecdysone and tissue-engineered scaffolds presents a promising approach for treating diabetes-related bone defects.

摘要

引言

糖尿病常导致骨代谢紊乱,阻碍骨再生并延缓骨缺损愈合。β-蜕皮激素是一种具有广泛生理活性的植物源激素,具有降血糖作用并促进成骨分化。本研究开发了一种负载β-蜕皮激素的聚乳酸-羟基乙酸共聚物(PLGA)复合缓释支架,通过局部给药提高其生物利用度,并研究其治愈糖尿病性骨缺损的潜力。

方法

采用溶液浇铸/粒子沥滤和冷冻干燥技术制备复合支架。然后进行一系列表征以测试复合支架的性能,并通过CCK8测定法和活/死细胞染色测试复合支架的安全性。此外,通过显微CT和组织学评估β-E/PLGA复合支架在植入后4周和8周对糖尿病大鼠颅骨缺损愈合的影响。同时,还评估了支架的安全性。

结果

材料表征结果表明,与单孔径支架相比,复合支架具有更高的孔隙率、溶胀率、载药能力和机械性能。此外,复合支架表现出适当的降解性能和持续的药物释放曲线。CCK8细胞毒性测定和活/死细胞染色表明,在低糖和高糖条件下,骨髓间充质干细胞(BMSCs)在复合支架上存活并增殖。显微CT和组织学研究表明,β-E/PLGA复合支架促进了糖尿病大鼠颅骨缺损区域的新骨生长。

结论

总体而言,这些发现表明β-E/PLGA复合支架促进了糖尿病大鼠骨缺损的愈合。β-蜕皮激素与组织工程支架的结合为治疗糖尿病相关骨缺损提供了一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b5/11770018/1535c5f8f8dc/fbioe-12-1536102-g001.jpg

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