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標題: | 聚胺酯與石墨烯奈米複合材料之製備及對神經血管再生之效益評估 Preparation of polyurethane-graphene nanocomposite and evaluation of neurovascular regeneration |
作者: | Tsung-Han Lee 李宗翰 |
指導教授: | 徐善慧(Shan-hui Hsu) |
關鍵字: | 石墨烯,奈米複合材料,共培養,神經再生,組織工程, graphene,nanocomposite,co-culture,neural regeneration,tissue engineering, |
出版年 : | 2019 |
學位: | 碩士 |
摘要: | 石墨烯,一種以具有優異導電性而聞名的無機碳材料,除了在導電材料的開發及應用外,在生物醫學領域也被證實可以促進神經幹細胞(Neural stem cells, NSCs)的生長和分化,然而,由於石墨烯過於硬脆的性質,限制了石墨烯在神經組織工程中的直接應用。在這項研究中,筆者將以實驗室過去開發、以聚己內酯(Poly(ε-caprolactone), PCL)作為軟鏈段的可生物降解水性聚胺酯(biodegradable waterborne polyurethane, PU),用作聚胺酯石墨烯奈米複合材料的基質,以使石墨烯不受硬脆性質的限制,應用於製備成具生物相容性的支架。從實驗結果之SEM影像中,可以於包含5wt %石墨烯的聚胺酯石墨烯複合材料(PU-G5)表面上觀察到石墨烯片的存在。聚胺酯石墨烯複合材料保留了石墨烯對細胞行為的優點和正面影響,而另一方面,PU成為聚胺酯石墨烯奈米複合材料具有足夠的柔韌性的關鍵基材,同時可以降低了石墨烯對於細胞的毒性及傷害。在沒有加入分化誘導培養基的情況下,聚胺酯石墨烯複合材料上共培養的內皮細胞(Endothelial cells, ECs)和NSCs變得具有類似血管化和神經膠化的傾象。並且,隨著在複合材料中石墨烯含量的增加(0-5 wt%),特定的血管相關和神經相關之基因表現KDR、VE-cadherin和GFAP上調兩倍以上,於動物體內實驗中測試外來物反應時,在皮下植入PU-G5薄膜的組別,其外來物反應造成的纖維囊厚度約為38 μm,該厚度僅為未加入石墨烯的PU組別之一半。在動物實驗也發現,由聚胺酯石墨烯奈米複合材料製成的神經導管可以促進大鼠坐骨神經在10 mm間隙橫切模型中週邊神經的再生。而PU-G5製成的神經導管在和PU製成的神經導管中相比,再生組織的軸突和血管數量分別增加了72%和50%。PU-G5神經導管中神經的再生區域也比純PU神經導管中的再生區域較為大25%。在和與美國食品和藥物管理局(U.S. Food and Drug Administration, FDA)批准的導管Neurotube相比,PU-G5中的再生神經是Neurotube中的再生神經的1.7倍。更重要的是,PU-G5導管中的再生組織相比於PU導管中的再生組織顯示出與正常神經組織更相似的形態學特徵。除了快速的恢復率之外,再生具有正常形態的組織的能力是此研究的重要發現並可能應用在未來的臨床治療上。因此,聚胺酯石墨烯奈米複合材料在神經組織工程中具有應用的潛力。 Graphene, with excellent conductivity can promote the growth and differentiation of neural stem cells (NSCs), but the rigidity has limited its direct applications in neural tissue engineering. In this study, waterborne biodegradable polyurethane (PU) was used as the matrix for the graphene nanocomposite materials to make graphene applicable to biocompatible scaffolds. The graphene sheets were observed on the surface of the composites which contained 5 wt% graphene (PU–G5). The nanocomposite retained the positive effect of graphene on cell behavior, while PU was flexible enough for further fabrication. Endothelial cells (ECs) and NSCs co-cultured on the nanocomposite became more vascular-like and glial-like without induction culture medium. The specific vascular-related and neural-related gene markers, KDR, VE-Cadherin, and GFAP were upregulated more than twice as the contents of graphene increased (5 wt%). The fibrous capsule of PU–G5 film group was about 38 m in thickness in subcutaneous implantation, which was only a half of that of graphene-free group. Nerve conduits made of the PU-graphene nanocomposite were found to promote the regeneration of peripheral nerve in a rat sciatic nerve 10 mm gap transection model. The nerve conduit made of PU–G5 had 72% and 50% enhancement on the numbers of axons and blood vessels of regenerated tissue, respectively. The regenerated area of nerve in PU–G5 was 25% larger than that of in pristine PU. Compared with the U.S. food and drug administration (FDA) approved conduit, Neurotube, the regenerated nerve in PU–G5 was 1.7 times more than that in Neurotube. In particular, the regenerated tissue in PU–G5 conduits showed morphological features more similar to the normal nerve tissue morphology than that in PU conduits. In addition to the fast recovery rate, the ability to regenerate tissue with normal morphology is a significant finding of this study that may lead to clinical applications in the future. PU-graphene nanocomposites thus have potential applications in neural tissue engineering. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/73737 |
DOI: | 10.6342/NTU201903715 |
全文授權: | 有償授權 |
顯示於系所單位: | 高分子科學與工程學研究所 |
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