以原位小角度X光散射與同調X光散射對殼聚醣自癒合水凝膠的凝膠化機制與結構動力學之研究

Gelation mechanism and structural dynamics of chitosan self-healing hydrogels by in-situ SAXS and coherent X-ray scattering

林鈺傑(Yu-Jie Lin)

指導教授 ： 徐善慧

國立臺灣大學/工學院/高分子科學與工程學研究所/碩士(2019年)

https://doi.org/10.6342/NTU201904235

摘要

具有自癒合能力、可注射性和生物相容性的水凝膠 (hydrogel)在生物醫學應用上有良好的潛力，而水凝膠的成膠時間和自癒合速率會影響水凝膠的應用性。目前對於自癒合水凝膠(self-healing hydrogel)的水凝膠性質和內部結構之間的關聯仍很少被探討，自癒合水凝膠的化學設計準則亦有待確立。在本研究中，我們合成了具有兩種不同取代度的N-羧乙基殼聚醣 （N-carboxyethyl chitosan, CEC） ，使用乙二醇殼聚醣 （glycol chitosan, GC）作為對照組，並使用遙爪雙官能化聚乙二醇（telechelic difunctional polyethylene glycol, DF-PEG）作為席夫交聯劑 (Schiff crosslinker)，製備三種不同殼聚醣自癒合的水凝膠。藉由使用不同的殼聚醣衍生物所製備的水凝膠，自癒合水凝膠的儲存模量G' (storage modulus) 可以被調控，儲存模量G'從約1.5 kPa調節到3 Pa。除此之外，水凝膠的注射性和自癒合能力也可以被調節。為研究水凝膠凝膠化過程中的結構變化和水凝膠自癒合能力的關聯，本文使用原位小角度X射線散射 （in-situ small angle X-ray scattering, in-situ SAXS） 結合流變學和同調X光射線散射 （coherent X-ray scattering, CXS）。In-situ SAXS結合時間掃描 (time-sweep) 的流變學實驗揭示了水凝膠在凝膠化過程的成核和生長機制 (nucleation and growth mechanism)，透過後續的實驗進一步證實了水凝膠的成核機制，並得到穿透式電子顯微鏡 (transmission electron microscope, TEM)圖像和CXS曲線的支持。從不同的自癒合水凝膠得到不同的臨界成核半徑（critical nucleation radius, CNR），CNR在7-20 nm的範圍內變化，而根據CNR的特性可能影響水凝膠在凝膠化過程中的時間和自癒合能力。另外，在連續曝光時間下的CXS曲線揭示了中尺度下水凝膠的不同動態自癒合行為，動態的希夫鹼、分子間的氫鍵與靜電作用力形成競爭關係，因此產生不同的自癒合性質，並從流變學的實驗得到驗證。藉由連接動態鍵結、奈米結構和自癒合能力等的相關資訊，期待未來可以透過化學設計開發出新型的自癒合水凝膠，用於在未來生物醫學應用上。

關鍵字

自癒合水凝膠 ； N-羧乙基殼聚醣 ； 原位小角度光散射 ； 同調 X光散射 ； 成核和生長

並列摘要

Hydrogels with intrinsic self-healing ability, injectability, and biocompatibility have good potential in biomedical applications. The gelation time and self-healing rate of hydrogels greatly affect the applicability of hydrogels. The relevance between the properties and inner structure of self-healing hydrogels, however, has rarely been examined and the design criteria remain to be established. In this study, we synthesized N-carboxyethyl chitosan (CEC) with two different substitution degrees, used glycol chitosan (GC) as the control, and employed the telechelic difunctional polyethylene glycol (DF-PEG) as the Schiff crosslinker for preparing three different chitosan-based self-healing hydrogels. With the different chitosan derivatives, the storage modulus G’ of self-healing hydrogels could be tuned from about 1.5 kPa to 3 Pa. The injectability and self-healing ability could also be modulated. Structural changes during gelation were elucidated using the in-situ small angle X-ray scattering (SAXS) and coherent X-ray scattering (CXS). In-situ SAXS with the time-sweep rheological experiment revealed the nucleation and growth mechanism for the gelation of each hydrogel, which was further supported by TEM images and CXS. The critical nucleation radius (CNR) varied in the range of 7 – 20 nm among the different self-healing hydrogels, while the CNR may influence the gelation rate and self-healing ability. The continuous time-resolved CXS profile unveiled the different dynamic self-healing behaviors in mesoscale. Dynamic Schiff base and intermolecular hydrogen bonds form a competitive relationship in self-healing hydrogels. Information linking the dynamic bonds, nanoscale structure and self-healing ability may be useful in developing novel self-healing hydrogels for future biomedical applications.

並列關鍵字

self-healing hydrogel ； N-carboxyethyl chitosan ； in-situ SAXS ； coherent X-ray scattering ； nucleation and growth.

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