以導電高分子製備之三維孔洞支架及水凝膠在組織再生工程上的應用

Fabrication of Three-dimensional Porous Scaffold and Hydrogel from Conductive Polymer for Tissue Regeneration

陳方榕(Fang-Jung Chen)

指導教授 ： 游佳欣

國立臺灣大學/工學院/化學工程學研究所/碩士(2021年)

https://doi.org/10.6342/NTU202101295

摘要

導電高分子在生醫領域的應用隨著幹細胞療程及生物訊號探測的發展也越來越受到注目。首先，由導電高分子所製備而成的可導電生醫材料與電刺激的結合可以促進神經、硬骨以及肌肉的組織再生，使其在組織工程領域中發展成為相當有潛力的材料。許多研究已致力於導電高分子所製成的二維材料在分化上的應用，但三維孔洞結構的應用還未被多加關注。另外，導電水凝膠的發展在生物感測器的需求提升之下也越來越受到注目。然而在傳統上合成導電水凝膠時往往會混參含有細胞毒性的化合物或金屬。
因此，在這份研究中導電高分子聚(3,4-乙烯基二氧噻吩):聚(苯乙烯磺酸鹽) (PEDOT:PSS) 首先結合了奈米碳管 (MWCNT) 用於製備三維導電支架。電刺激結合PEDOT:PSS及MWCNT所作成的三維支架被應用於人類脂肪幹細胞的硬骨分化。研究結果顯示人類脂肪幹細胞可以成功地在支架內部生長，代表此導電三維支架的低細胞毒性。更重要的是，硬骨分化的分析結果顯示鈣沉積及硬骨分化特定基因在電刺激的作用下都可以顯著地提高。綜合這些結果表示PEDOT:PSS及MWCNT所製成的三維高孔洞支架可作為電刺激應用於幹細胞硬骨分化的平台。
另一方面，PEDOT:PSS更被混合入可光交聯的甲基丙烯酸酐化明膠 (GelMA) 來合成可導電的水凝膠。PEDOT:PSS及GelMA混合而成的水凝膠更進一步使用鈣離子進行物理性交聯，而結果顯示額外使用鈣離子交聯的導電水凝膠具有較低的彭潤效果及較慢的降解速率，使得PEDOT:PSS及GelMA所製備而成的水凝膠擁有可調控的物理及化學性質。而在細胞實驗中，結果也顯示此導電水凝膠具有低細胞毒性及良好的生物相容性，且可使小鼠成纖維母細胞L929在水凝膠內部增殖且生長。後續仍須進行更多實驗以及文獻來佐證導電水凝膠在電刺激組織工程或是生物訊號探測應用是否確有其效果。

關鍵字

導電高分子 ； 孔洞支架 ； 電刺激 ； 幹細胞 ； 硬骨組織再生 ； 導電水凝膠

並列摘要

Much research has been done on the conductive polymer as a two-dimensional structure for guiding the differentiation but less attention has been put on three-dimensional conductive porous scaffold. In addition, hydrogel with electroconductivity has also gained much interest due to increasing demand of biosensor or electrical actuators. However, approaches to design conductive hydrogel traditionally often have incorporation with cytotoxic conductive dopant materials. In this research, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) was used to prepare a 3D conductive scaffold with multi-walled (MWCNT) and a conductive hydrogel within photo-crosslinkable gelatin methacryloyl (GelMA).
Osteogenic differentiation of human adipose-derived stem cell (hASC) was performed on the PEDOT:PSS/MWCNT scaffold with electrical stimulation in this study. The results showed that the conductive scaffold has low cytotoxicity to hASC, which could grow and migrate in the 3D scaffold. Moreover, the analysis of osteogenic differentiation showed that calcium deposition concentration and osteogenic specific gene markers were significantly higher with electrical stimulation, making PEDOT:PSS/MWCNT scaffold a great platform for electrically activated osteogenesis. On the other hand, composite PEDOT:PSS/GelMA hydrogel further physically crosslinked by calcium ions possesses tunable properties by showing smaller swelling ratio and slower degradation rate. In cell culture experiment, PEDOT:PSS/GelMA hydrogel is shown to have good biocompatibility. Furthermore, encapsulated L929 could proliferate and attach in PEDOT:PSS/GelMA hydrogel.

並列關鍵字

conductive polymer ； PEDOT:PSS ； porous scaffold ； electrical stimulation ； stem cell ； bone tissue regeneration ； conductive hydrogel

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