自癒性可注射型中性殼聚醣水膠之合成、鑑定、性質探討及其在傷口癒合之應用研究

本研究主要探討以自癒性可注射型之中性殼聚醣水膠，作為全深度 (Full-thickness) 傷口的治療材料，並探討材料對於斑馬魚胚胎之毒性及其對傷口癒合之修復效果。首先，將市售的中性羥乙基脫乙醯殼聚醣(Glycol Chitosan, GC) 與不同分子量及不同濃度的二苯甲醛封端之聚乙二醇(Dibenzaldehyde terminated poly(ethylene glycol), DF-PEG) 進行混和製備出一系列具動態亞胺鍵(-C=N-)的自癒性水膠，分別為2GC/1DP2、2GC/1DP4、2GC/1DP6、2GC/5DP2、2GC/5DP4、2GC/5DP6，並以FTIR、NMR確認DF-PEG之結構以及亞胺鍵之成功生成，同時藉NMR更正聚乙二醇 (PEG) 之正確化學結構。接著以流變儀探討自癒性水膠之流變行為，得其儲存模數數值介於99 Pa ~ 625 Pa之間，表明此水膠具可調控性質；於自癒能力測試之結果中顯示所製備的水膠具有良好自癒能力 (> 90%)。結合SEM之觀察結果可知，當DF-PEG濃度越高或分子量越低時，水膠的交聯密度越緊密，則其機械強度越高，自癒能力越低。在生物相容性部分，以斑馬魚胚胎測試後顯示其具有良好的存活率，LC50數值皆> 998，表明水膠為低毒性。最後於斑馬魚傷口修復實驗結果中得自癒性水膠之促進傷口癒合效果介於 87.5% ± 0.94 ~ 93.4% ± 0.88間，故得知本論文之中性乙二醇殼聚醣自癒性水膠可大幅促進傷口之自癒。

關鍵字

乙二醇殼聚醣；自癒性水膠；中性；流變；斑馬魚；傷口癒合

並列摘要

This study focused on the preparation of different crosslinking degrees of self-healing hydrogels and the application to full-thickness burn treatment. Hydrogels were prepared by mixing neutral glycol chitosan (GC) with different molecular weights and different concentrations of di-benzaldehyde-terminated poly(ethylene glycol) (DF-PEG). The series of hydrogels with dynamic imine bond and self-healing property prepared were 2GC/1DP2、2GC/1DP4、2GC/1DP6、2GC/5DP2、2GC/5DP4、2GC/5DP6. In order to identify chemical structure and explore rheological behavior of self-healing hydrogels, Fourier-Transformation Fourier-transform Infrared Spectrometer (FT-IR), Nuclear Magnetic Resonance (NMR) and Rheometer were used. Research results showed that the decreasing of DF-PEG’s molecular weight or the increasing of DF-PEG’s concentration increased the crosslinking degree and the tensile strength of hydrogels. In study of rheological behavior showed the hydrogels’ storage modulus are between 99 Pa and 625 Pa. In zebrafish’s toxicity test, depending on LC50 values, three groups of IV the hydrogels’ LC50 values are larger than 998, showed that the materials have good biocompatibility, and the last is about the wound repairing of zebrafish, the degree of promotion are between 87.5% ± 0.94 and 93.4% ± 0.88, showed groups of hydrogels have excellent effect on enhancing the wound healed.