光交聯與降解雙控型明膠水凝膠之開發

Dual controlled photocrosslinkable and photodegradable gelatin hydrogel regeneration

劉羅元(Lo-Yuan Liu)

指導教授 ： 陳盈潔

國立清華大學/工學院/材料科學工程學系/碩士(2022年)

摘要

可植入填充物在臨床及生物醫學應用上已被廣泛應用，如骨骼肌修復、組織再生、藥物釋放、癌症治療等等，然而，植入後總會出現一些意想不到的問題，例如嚴重免疫反應或是需要對植入物進行調整，而需要再次手術去除植入物；在腫瘤治療方面，也需要水凝膠控制藥物釋放時間與模擬體內環境來幫助組織修復的功能，近年來，已經開發出許多可調控水凝膠以克服這些難題，但大多數都只擁有一個方向的調控機制來調整其機械性質，這導致水凝膠只能不可逆的增加或降低其剛度，若調控過度沒有補救方法，只能重新製作，而且也無法很好的模擬不斷變化的體內環境。在本篇研究中，我們將明膠與二苯基環辛炔(Dibenzocyclooctyne, DBCO)、可光降解分子鄰硝基芐基-疊氮化物(NBazide)和可光交聯分子甲基丙烯酰胺(methacrylamide, MA)結合，先利用DBCO與NBazide之間的點擊反應成膠，再以MA的光交聯特性與NBazide的光降解特性來達成可逆的水凝膠機械性質的雙向控制，透過包覆小鼠胚胎成纖維細胞(NIH3T3)以觀察機械性質的雙向調控對於細胞生長行為的影響，結果表明，此明膠基雙向調控水凝膠具有良好的生物相容性，暴露於紫外線後交聯和降解過程中的副產物對細胞無害，並且能通過對水凝膠的調控來影響細胞的增殖與伸展，此以明膠為基底製作的水凝膠未來在再生醫學和組織工程方面的應用具有巨大的潛力。

關鍵字

明膠 ； 光交聯 ； 光降解 ； 雙向調控 ； 細胞培養

並列摘要

Implantable fillers have been widely used in clinical and biomedical applications, such as skeletal muscle repair, tissue regeneration, drug release, cancer treatment …. etc. There always come out some unexpected problems following implantation, such as severe immune reactions or the need for implant adjustments, which need another surgery to remove implants. In tumor treatment, hydrogels are also required to control the drug release time and simulate the in vivo environment to help tissue repair. Recently, many types of hydrogel with controllable stiffness have been developed to overcome these problems, but most of them possess either irreversible increase or decrease their stiffness. It is no easy to post-tune hydrogel stiffness after gelation process, which limits its applications in mimicking microenvironments in animals.
Here, we conjugated Dibenzocyclooctyne (DBCO), photodegradable molecules (nitrobenzyl-azide, NBazide) and photocrosslinkable molecules (methacrylamide, MA) on gelatin molecules to synthesis gelatin-based hydrogels. First, the hydrogel was capable to crosslink by the click reaction between DBCO and NBazide and the light through MA gorups, and degraded by photodegradable NBazide to achieve two-direction control of the hydrogel mechanical property, which is reversible. Then, we encapsulated NIH3T3 cells into our hydrogel to evaluate the effect of dynamic stiffness of hydrogels on cell behavior. Result demonstrated that this gelatin-based hydrogel is biocompatible, and byproduct during crosslinking and degradation after exposing to UV light was shown harmless to cells. Cell proliferation and spreading could be controlled by controlling the mechanical property of the hydrogel, which represented that our gels have great potential used in regenerative medicine and tissue engineering.

並列關鍵字

gelatin ； photocrosslinkable ； photodegradable ； dual control ； cell culture

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