幽門螺桿菌主要存在於胃黏膜的上皮細胞中，它也是唯一可以在人體胃中存活的細菌。感染幽門螺桿菌後，容易引起胃炎、胃十二指腸潰瘍、胃癌和胃黏膜相關淋巴瘤的危險因素。胃癌是世界上第五大最常見的癌症，致死率排名為第三名，所以胃癌的防治不容忽視。目前幽門螺桿菌的常用治療方法的缺點是治療時間過長，藥物停留在體內的時間不足，且體外測試大多在2D系統中進行，缺乏人體胃部的擬真性，所以開發更有效的藥物遞送方法以及藥物測試平台成為時下最迫切的問題。
爲解決藥物傳輸與藥物測試平台的問題，本研究分為三部分。第一部分為製備攜帶tetracycline的核殼材漂浮顆粒，透過調整和殼材比例調控藥物釋放效果。第二部分則是開發具有高度仿生性的3D胃部模擬模型，作為藥物測試平台。有了緩釋藥物及測試平台，第三部分則是建立胃部模擬系統，並結合前兩部分實驗進行細胞與胃部菌群培養的模擬實驗。
在本研究的第一部分，製備了攜帶tetracycline的核殼材漂浮顆粒。改變殼層中chitosan和xanthan gum的比例以改變聚合物的緻密性。陰離子xanthan gum和陽離子chitosan之間的相互作用使殼層緻密，抵抗殼層中的質傳阻力。由於對水滲透的高傳質阻力，顆粒緻密表面會造成的較長的漂浮和輸送時間。研究結果證明，通過調整可促進胃滯留藥物功能的殼層配方，可以很好地控制殼材漂浮顆粒的漂浮和釋放進程。
第二部分，利用光固化3D列印技術製作了具有胃皺的人體胃的模型。透過 cis-1,4 polyisoprene (IR) 的光固化樹脂進行列印的胃模型，具高度仿生的機械性和柔韌性，促進了幽門螺桿菌在胃模型上的貼附率，且促進了持續貼附的時間。 H. pylori 在光固化 3D 模型上的生長優於 ABS，表明本研究開發的模型非常適合作為胃部模擬模型。
第三部分實驗中，我們建立了一個動態胃模擬系統，以觀察體內液體流動胃液中H. pylori的生長情況。透過胃的柔韌性、皺褶形態、流體動力學和胃液排空行為的結合，創建了一個高度仿生的胃模擬系統。在模型表面培養幽門螺桿菌和胃癌細胞 MKN-45，並投入抗生素和抗癌藥物進行模型的確效性。系統評估了幽門螺桿菌和 MKN-45 在 2D/3D 模型上的存活率，表明使用本研究開發的胃模型修正了以往2D的高治療活性。
體外消化系統已被廣泛運用在許多領域中。利用此系統可有效的取代動物實驗，降低實驗過程中動物個體差異所造成的誤差，提高實驗重複性和準確性，有效降低實驗成本，以及方便研究人員直接進行實驗觀察等。

Helicobacter pylori (H. pylori) mainly exists in the epithelial cells of the gastric mucosa. It is the only bacteria that can survive in the human stomach and also the important factor to induce gastric cancer, the fifth most common cancer worldwide. Therefore, the prevention and treatment of gastric cancer cannot be ignored. However, the disadvantages of the most current treatment for H. pylori are the short residence time and insufficient antibiotic effects. The inadequate period is due to gastric emptying and high acidity, and the low efficiency is due to the protection caused by specific topographical and mechanical properties of stomach. Thus, the development of an efficient gastric drug delivery system and bionic model for in vitro tests are the purposes of this study.
In the first part of this research, floating core-shell beads carrying tetracycline were prepared. The ratio of chitosan and xanthan gum in the shell layer was changed to modify polymer compactness. The interaction between anionic xanthan gum and cationic chitosan made the shell layer dense, resulting in low mass transfer and swelling in the shell layer. Notably, the beads with tetracycline showed a significant prolonged anti-bacterial effect. Our experimental results proved that core-shell beads' floating and releasing progress was well controlled by adjusting the shell layer formulation that could promote the function of gastroretentive drugs.
In the second part, the photo-curing 3D printing technology was used to create a model with gastric rugae as the human stomach. The mechanical properties of the model stomach were also close to human stomach tissues, which was achieved by photo-resin based on cis-1,4 polyisoprene (IR). After plasma treatment, the growth of H. pylori on the photocured 3D model was better than that on ABS, indicating the printed model developed in this research would be more suitable as a stomach model due to its good biocompatibility and biomimetic properties.
In the third part, we established a dynamic gastric simulation system with cultured bacteria or cells under the fluid flow as gastric juice in vivo. Due to the combination of stomach flexibility, rugae morphology, fluid dynamic, and gastric juice emptying behavior, a highly biomimetic gastric model was created. The model was examined with antibiotic and anticancer drugs, where H. pylori and gastric cancer cells, MKN-45, were cultured on model surfaces. The survival rates of H. pylori and MKN-45 on 2D/3D models were systematically evaluated, indicating that the 3D-printed gastric rugae were a shelter for bacteria and cancer cells. This protection would be more dominant under shear stress caused by gastric juice. Compared with the conventional 2D model, the efficacy of drugs was lower in the biomimetic model, modifying the overestimated therapeutic activity in previous in vitro experiments.

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