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基于聚(3,4-乙烯二氧噻吩):聚苯乙烯磺酸盐导电聚合物支架的生物物理电机械刺激促进干细胞软骨分化。

Biophysical Electrical and Mechanical Stimulations for Promoting Chondrogenesis of Stem Cells on PEDOT:PSS Conductive Polymer Scaffolds.

机构信息

Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan.

Department of Chemical Engineering, College of Engineering, National Taiwan University, Taipei 10617, Taiwan.

出版信息

Biomacromolecules. 2023 Aug 14;24(8):3858-3871. doi: 10.1021/acs.biomac.3c00506. Epub 2023 Jul 31.

DOI:10.1021/acs.biomac.3c00506
PMID:37523499
Abstract

The investigation of the effects of electrical and mechanical stimulations on chondrogenesis in tissue engineering scaffolds is essential for realizing successful cartilage repair and regeneration. The aim of articular cartilage tissue engineering is to enhance the function of damaged or diseased articular cartilage, which has limited regenerative capacity. Studies have shown that electrical stimulation (ES) promotes mesenchymal stem cell (MSC) chondrogenesis, while mechanical stimulation (MS) enhances the chondrogenic differentiation capacity of MSCs. Therefore, understanding the impact of these stimuli on chondrogenesis is crucial for researchers to develop more effective tissue engineering strategies for cartilage repair and regeneration. This study focuses on the preparation of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conductive polymer (CP) scaffolds using the freeze-drying method. The scaffolds were fabricated with varying concentrations (0, 1, 3, and 10 wt %) of (3-glycidyloxypropyl) trimethoxysilane (GOPS) as a crosslinker and an additive to tailor the scaffold properties. To gain a comprehensive understanding of the material characteristics and the phase aggregation phenomenon of PEDOT:PSS scaffolds, the researchers performed theoretical calculations of solubility parameters and surface energies of PSS, PSS-GOPS, and PEDOT polymers, as well as conducted material analyses. Additionally, the study investigated the potential of promoting chondrogenic differentiation of human adipose stem cells by applying external ES or MS on a PEDOT:PSS CP scaffold. Compared to the group without stimulation, the group that underwent stimulation exhibited significantly up-regulated expression levels of chondrogenic characteristic genes, such as SOX9 and COL2A1. Moreover, the immunofluorescence staining images exhibited a more vigorous fluorescence intensity of SOX9 and COL II proteins that was consistent with the trend of the gene expression results. In the MS experiment, the strain excitation exerted on the scaffold was simulated and transformed into stress. The simulated stress response showed that the peak gradually decreased with time and approached a constant value, with the negative value of stress representing the generation of tensile stress. This stress response quantification could aid researchers in determining specific MS conditions for various materials in tissue engineering, and the applied stress conditions could be further optimized. Overall, these findings are significant contributions to future research on cartilage repair and biophysical ES/MS in tissue engineering.

摘要

研究电刺激和机械刺激对组织工程支架中成软骨的影响对于实现成功的软骨修复和再生至关重要。关节软骨组织工程的目的是增强具有有限再生能力的受损或患病关节软骨的功能。研究表明,电刺激(ES)促进间充质干细胞(MSC)的软骨生成,而机械刺激(MS)增强 MSC 的软骨分化能力。因此,了解这些刺激对软骨生成的影响对于研究人员开发更有效的软骨修复和再生组织工程策略至关重要。本研究专注于使用冷冻干燥法制备聚(3,4-亚乙基二氧噻吩)-聚(苯乙烯磺酸盐)(PEDOT:PSS)导电聚合物(CP)支架。支架的制备采用不同浓度(0、1、3 和 10wt%)的(3-缩水甘油丙基)三甲氧基硅烷(GOPS)作为交联剂和添加剂,以调整支架的性能。为了全面了解 PEDOT:PSS 支架的材料特性和相聚集现象,研究人员对 PSS、PSS-GOPS 和 PEDOT 聚合物的溶解度参数和表面能进行了理论计算和材料分析。此外,该研究还探讨了通过对 PEDOT:PSS CP 支架施加外部 ES 或 MS 来促进人脂肪干细胞软骨分化的潜力。与未受刺激的组相比,受刺激的组中软骨生成特征基因(如 SOX9 和 COL2A1)的表达水平显著上调。此外,免疫荧光染色图像显示 SOX9 和 COL II 蛋白的荧光强度更强,这与基因表达结果的趋势一致。在 MS 实验中,模拟并转化支架上的应变激励为应力。模拟的应力响应表明,峰值随时间逐渐降低并趋近于一个恒定值,应力的负值表示拉伸应力的产生。这种对应力响应的量化有助于研究人员确定组织工程中各种材料的特定 MS 条件,并且可以进一步优化施加的应力条件。总的来说,这些发现为未来的软骨修复和组织工程中的生物物理 ES/MS 研究做出了重要贡献。

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