研究生: |
黃律捷 Huang, Lu-Chieh |
---|---|
論文名稱: |
生物啟發自聚合奈米胜肽水膠搭載糖胺聚醣輔助生長因子釋放與血管新生之研究 Bioinspired Self-assembling Peptide Hydrogel with Proteoglycan-assisted Growth Factor Delivery for Therapeutic Angiogenesis |
指導教授: |
王子威
Wang, Tzu-Wei |
口試委員: |
張建文
Chang, Chien-Wen 林睿哲 Lin, Jui-Che 孫瑞昇 Sun, Jui-Sheng |
學位類別: |
碩士 Master |
系所名稱: |
工學院 - 材料科學工程學系 Materials Science and Engineering |
論文出版年: | 2018 |
畢業學年度: | 107 |
語文別: | 英文 |
論文頁數: | 76 |
中文關鍵詞: | 自我聚合 、奈米胜肽 、糖胺聚醣 、生長因子 、內源性交聯 、血管新生 |
外文關鍵詞: | self-assembling peptide, proteoglycan, growth factors, intrinsic crosslinking |
相關次數: | 點閱:1 下載:0 |
分享至: |
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當臨床上進行手術或處理意外創傷時,如何快速有效的達到止血以及傷口癒合的目的,到目前為止對於醫生來說仍然是個十分棘手的問題。另一方面,對於慢性潰瘍或長久無法癒合的傷口,如何提供創傷部位足夠的新生血管亦是促進此類型傷口修復重要且必需的步驟。為了解決上述所提到的醫療問題,在此研究中,我們開發出功能化的自聚合胜肽水膠,分別由兩段具不同功能的奈米胜肽序列 RADA16-GGQQLK (QLK) 和 RADA16-GGLRKKLGKA (LRK) 所組成。具有功能性序列QLK修飾的胜肽水膠,其經由轉谷氨酰胺酶交聯後,能顯著提升水膠的機械性質;值得注意的是,轉谷氨酰胺酶同時也屬於一種內源性的酵素,可在止血階段促使纖維蛋白之交聯強化。我們預期可利用此一特性來交聯自聚合水膠,而不需額外添加交聯劑,是另一個潛在的優勢。另一方面,藉由功能性序列LRK和蛋白聚醣硫酸乙酰肝素之間良好的結合親和力,此自聚合胜肽水膠能緩效釋放出搭載包覆於其中的血管内皮生長因子和肝細胞生長因子。實驗結果顯示,此胜肽分子溶液能在接觸到生理環境時立即自組裝形成水膠,並且此自聚合水膠具有良好剪切恢復之特性,證明其屬於一種可注射式材料。經由酸鹼值之調整,自聚合水膠能產生連續緻密的奈米纖維纏繞,並建構出模仿細胞外間質微結構的三維立體網狀支架。透過將纖維母細胞包覆於水膠之中,我們證實水膠支架內的微結構能提供適合細胞生長存活的環境,並且藉由從水膠支架中釋放出的兩種生長因子,可經由協同作用進一步促進人類臍帶靜脈內皮細胞形成類血管狀的結構。在雞胚胎絨毛尿囊膜的實驗當中,我們發現搭載生長因子的水膠相較於單純水膠的組別,可以有效促進其周圍的血管以輻射狀向水膠處增生。總結整個研究,我們期望此功能化的自組裝胜肽水膠能成為一具有新穎及前瞻性的生醫材料應用於微創手術,並且對於缺血性疾病和慢性傷口的再生及修復能達到良好的治療效果。
How to efficiently stop bleeding and effectively facilitate wound healing is a critical challenge for surgical operation and emergency treatment in clinical settings. For ischemic diseases treatment, proper angiogenesis is potent and necessary via providing suitable vasculature supply to the injury sites. In view of these clinical unmet needs, we propose an applicable approach by designing functionalized self-assembling peptide (SAP) hydrogel with two sequences of RADA16-GGQQLK (QLK) and RADA16-GGLRKKLGKA (LRK) in this study. The SAP hydrogel conjugated with QLK functional motif can be cross-linked by endogenous transglutaminase, one of the intrinsic factors secreted during hemostasis process; thus, enhancing the mechanical property of the hydrogel without the need of external supply. On the other hand, the LRK sequence owns good binding affinity with heparan sulfate proteoglycan and can act as a cofactor by sustaining the release of embedded growth factors. The results show that this SAP solution undergoes self-assembling process in physiological environment, forms hydrogel in situ, and possesses good shear thinning property with injectability. After pH adjustment, the SAP develops densely-compacted fiber entanglements that closely mimics the three-dimensional fibrous framework of natural extracellular matrix. Such scaffold can not only support the survival of encapsulating cells but also promote the capillary-like tubular structure formation by dual angiogenic factors. The in vivo chicken chorioallantoic membrane assay demonstrates that the growth factor-loaded hydrogel promotes the growth of surrounding vessels in a spoke-wheel pattern compared to growth factor-free counterparts. In conclusion, we suggest that the designer bioinspired SAP hydrogel may be an attractive and promising therapeutic modality for non-invasive surgery and with niche for administration to ischemic tissue disorders and chronic wound healing.
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