分子動力學模擬探討纖維素奈米纖維交聯劑之醛基取代度對其自修復水凝膠分子結構與性質的影響

Abstract

透過席夫鹼化學反應製備的乙二醇幾丁聚醣（Glycol chitosan, GC）與多功能纖維素奈米纖維（Multifunctional Cellulose Nanofiber, MCNF）複合水凝膠，展現了優異的自修復剪切稀化以及可注射特性，在多種應用方面具有良好的前景。MCNF是纖維素奈米纖維（CNF）的衍生物，透過依序進行2,2,6,6-四甲基哌啶-1-氧基（2,2,6,6-Tetramethylpiperidine-1-oxyl，TEMPO）氧化和高碘酸鹽氧化引入二醛基。這些醛基能夠與 GC 的胺基形成動態席夫鹼鍵。纖維素和殼聚醣都是生物相容性的天然聚合物，而MCNF的過度醛改質會破壞水凝膠網絡的均勻性。為了釐清MCNF醛改質影響水凝膠網絡分子結構的潛在分子機制，我們對單一MCNF和具有不同醛基取代度程度的GC/MCNF複合水凝膠進行了分子動力學模擬。對於單一MCNF，增加醛基取代度最初會導致分子構象更加伸展，但在更高醛基取代度（超過15%）下，分子鏈捲曲程度加劇。相應地，MCNF的楊氏模量也隨著醛基取代度的增加而略有下降，這與實驗結果的趨勢一致，表明由於分子內氫鍵的喪失和分子鏈柔韌性的增加，導致MCNF的機械剛度降低。在GC/MCNF水凝膠中，醛基含量顯著影響交互作用和網狀結構。在低於15%的醛基取代度下，GC和MCNF之間的氫鍵增強且分佈均勻，從而形成均質且機械強度較高的水凝膠。在更高的醛基取代度下，過度的GC-MCNF相互作用會導致局部聚集、互連性降低以及拉伸模量下降。本研究從分子層面分析了MCNF的醛基修飾如何影響MCNF的構象以及GC/MCNF水凝膠的整體完整性。這些發現為改善醛改質CNF自修復水凝膠在生物醫學和工程應用方面提供了重要的幫助。

Glycol chitosan (GC) and multifunctional cellulose nanofiber (MCNF) composite hydrogel prepared via Schiff base chemistry has demonstrated excellent self-healing, shear-thinning, and injectable properties, holding promises for various applications. MCNF, a derivative of cellulose nanofibers (CNFs), is introduced with dialdehyde groups through sequential TEMPO-mediated oxidation and periodate oxidation. These aldehyde groups form dynamic Schiff base linkage with the amine groups of GC chains. While both cellulose and chitosan are biocompatible natural polymers, excessive aldehyde modification of MCNF can disrupt the uniformity of hydrogel network. To elucidate the underlying molecular mechanism of aldehyde modification of MCNF on affecting the molecular structure of the hydrogel network, here we performed molecular dynamics simulations on both single MCNF molecule and GC/MCNF composite hydrogel with varying degrees of aldehyde modification. For single MCNF, increased aldehyde modification initially resulted in a more extended molecular conformation, but at higher modification levels (above 15%), the chains became more curled. Correspondingly, the Young’s modulus of MCNF also decreased slightly with increased modification, consistent with the trends in experimental results suggesting reduced mechanical stiffness of the MCNF due to a loss in intramolecular hydrogen bonding and increased chain flexibility. Among GC/MCNF hydrogels, the aldehyde content significantly influenced the interaction and network structure. At modification levels below 15%, hydrogen bonding between GC and MCNF was enhanced and evenly distributed, supporting a homogeneous and mechanically robust hydrogel. At higher modification levels, excessive GC–MCNF interactions led to localized aggregation, reduced interconnectivity, and a decline in tensile modulus. This study provides molecular-level insights into how aldehyde modification of CNFs affects both the conformation of MCNF and the overall integrity of GC/MCNF hydrogels. These findings offer valuable guidance for optimizing aldehyde-modified CNF-based self-healing hydrogels for biomedical and engineering applications.