以分子動力學探討不同取代度之甲基丙烯酸酯改質乙二醇殼聚醣分子結構及交互作用

Abstract

在生物醫學領域中，有許多研究開發自然界中存在的物體做為生物材料，使用在三維列印技術上，應用在組織工程。為了達到更良好的機械性質以及符合特定目標，過去常見的一種方法是進行甲基丙烯酸酯基團(Methacrylate，簡稱 MA) 的化學改質，形成化學交聯的材料，讓原始溶液可以轉化為透明且有彈性的水凝膠。這種水凝膠可以用作生物墨水，以構建複雜且功能性的組織結構，幫助修復受損之器官及部位。乙二醇殼聚醣 (Glycol Chitosan，簡稱 GC)來自甲殼素的生物，本身具有良好的生物相容性及無毒性，也是一種適合細胞生長的基礎材料。乙二醇殼聚醣進一步與甲基丙烯酸酯基團(Glycol Chitosan Methacrylate，簡稱 GCMA)進行化學修飾、化學交聯，可以調節其機械性質和生物相關特性。在此研究中，我們選用分子動力學(Molecular Dynamics，簡稱 MD)模擬，觀察微觀尺度下的 GC 和 GCMA 的分子鏈結構及分子間交互作用。另外，我們也探討系統濃度的變化以及甲基丙烯酸酯取代度高低所帶來的影響。透過比較模型中氫鍵的數量和結構的量測，我們的結果顯示，GCMA 比 GC 更容易聚集並具有更強的分子間相互作用，這個現象隨著甲基丙烯酸酯修飾數量的增加而更加明顯。接下來發現甲基丙烯酸酯基團的接枝，改變原始材料的分子構型，進而導致了疏水的特性。最後是隨著濃度升高，分子鏈之間的相互作用增加，更容易形成交聯網絡。我們的研究使用全原子的模擬，提供微觀尺度下的觀察結果，讓我們更瞭解乙二醇殼聚醣以及甲基丙烯 酸酯乙二醇殼聚醣的基礎性質，給予未來的水凝膠策略性設計的參考依據，達到特定需求。

In the field of biomedical research, numerous studies have been conducted on three-dimensional bioprinting technology for manufacturing biological tissues and organs. With chemical modification and chemical crosslinking, the solution transforms into a transparent and flexible hydrogel. The hydrogel can be used as bio-ink to construct complicate and functional tissue structures. Glycol chitosan (GC) exhibits excellent biocompatibility, non-toxic properties, and serves as a fundamental material adaptable for cell loading. Glycol chitosan can be further chemically modified with methacrylate (GCMA) ,and these methacrylate chemical connections can tune its mechanical properties and biological-related characteristics. In our study, we employ molecular dynamic (MD) simulation methods to analyze the material structure of GC and GCMA and their molecular interaction at the microscopic scale. Additionally, we investigate the effect of the varying degrees of methacrylate substitution on GCMA and the influence of the concentrations. We compared the number of hydrogen bonds and structural changes within these models. Our results indicate that GCMA tends to aggregate and has the stronger intermolecular interaction than GC, a phenomenon that becomes more evident as the methacrylate-modification enhances. Also, the presence of methacrylate groups changes the molecular configuration and results in hydrophobic materials. As the concentration increases, the chains gathering and make an increase of interaction between molecular chains. Our study provides an in-depth atomic-level analysis to investigate the fundamental properties of glycol chitosan (GC) and methacrylate-modified glycol chitosan (GCMA) to boost the strategic design of material.