以多種交聯機制製備明膠為基材之黏合劑

Fabrication of Gelatin-Based Adhesives with Various Crosslinking Mechanisms

劉藝(Yi Liu)

指導教授 ： 游佳欣

國立臺灣大學/工學院/化學工程學研究所/碩士(2016年)

https://doi.org/10.6342/NTU201603140

摘要

組織黏合劑被開發用來克服傳統的傷口閉合方式（如縫線和吻合器）的局限性，包括造成進一步的傷害，以及無法阻止體液和氣體流出。雖然組織黏合劑具有諸多優點，如簡單的實施程序、更少的疼痛以及不需要移除，但是氰丙烯酸黏合劑和纖維蛋白黏合劑作為兩種具有代表性的黏合劑，卻分別受限於細胞毒性和較低的黏著力。
在該研究中，由於極好的生物相容性、生物降解性和低成本，明膠被選擇作為黏合劑的主幹。為了增加機械性質和組織黏著力，修飾明膠和雙交聯機制分別被應用在光交聯明膠和鐵離子交聯多巴胺修飾的明膠。首先，多巴胺修飾的明膠和根皮酸修飾的明膠被合成出來。然後，製備明膠為基材的黏合劑，包括光交聯明膠（PG）、光交聯根皮酸修飾的明膠（PPG）、光交聯多巴胺修飾的明膠（PDG）、光-鐵離子交聯多巴胺修飾的明膠（PFDG）、鐵離子交聯多巴胺修飾的明膠（FDG）、鐵離子-過氧化氫交聯多巴胺修飾的明膠（FHDG）。並對以明膠為基材的黏合劑的膨潤性、降解性、流變性、組織黏著性和細胞毒性進行了測試。
結果發現，明膠為基材的黏合劑也表現出較低的膨潤指數、不錯的生物降解性和不錯的生物相容性（除FHDG）。在單一光交聯的黏合劑的結果中，光交聯根皮酸修飾的明膠表現出最高的黏彈性和最高的黏著力，因為酚基的增加使得光交聯的密度上升。在改進鐵離子交聯黏合劑的結果中，透過鐵離子交聯及氧化交聯形成的鐵離子-過氧化氫交聯多巴胺修飾的明膠表現出最高的黏性，但也表現出細胞毒性。該研究指出明膠為基材的黏合劑有用作傷口治療的潛力。

關鍵字

組織黏合劑 ； 修飾的明膠 ； 多巴胺 ； 根皮酸 ； 鐵離子交聯 ； 光交聯

並列摘要

Tissue adhesives have been developed to overcome the limitations of conventional wound closure (e.g. sutures and staples) including further damage and no stop body fluid and gas. Tissue adhesives offer some advantages such as simple implementation procedure, less painful, and no need for removal. However, cyanoacrylates and fibrin glues, the representative types of adhesives, are limited by toxicity and low adhesion, respectively.
In this study, gelatin was chosen as backbone of adhesive, due to the biocompatibility, biodegradability, and low cost. For increasing the mechanical properties and tissue adhesion of the gelatin-based adhesives, modified gelatin and double-crosslinking mechanism were applied in photo-crosslinked gelatin and Fe(III)-crosslinked dopamine-modified gelatin, respectively. Firstly, the dopamine- modified gelatin and phloretic acid-modified gelatin were synthesized. Then, gelatin-based adhesives were formed including photo-crosslinked gelatin (PG), photo-crosslinked phloretic acid-modified gelatin (PPG), photo-crosslinked dopamine-modified gelatin (PDG), photo-Fe(III)-crosslinked dopamine-modified gelatin (PFDG), Fe(III)-crosslinked dopamine-modified gelatin (FDG), and Fe(III)-H2O2- crosslinked dopamine-modified gelatin (FHDG). The swelling properties, degradation properties, rheology, tissue adhesion, and cytotoxicity of gelatin-based adhesives were measured.
In the results, gelatin-based adhesives showed the low swelling index, great biodegradability, and great biocompatibility (except FHDG). In results of single photo-crosslinked adhesives, PPG showed the greatest viscoelasticity and highest tissue adhesive strength, because the photo-crosslinking density increased with addition of phenol group. In results of improving Fe(III)-crosslinked adhesives, FHDG showed the highest viscosity due to the application of both ion-crosslinking (Fe(III)-catechol) and oxidation-crosslinking (catechol-catechol), but the cytotoxicity limited it. The research presented potential of gelatin-based adhesives for wound closure and healing.

並列關鍵字

Tissue adhesive ； Modified gelatin ； Dopamine ； Phloretic acid ； Fe(III)-crosslinking ； Photo-crosslinking

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