開發一紫外光敏感二氧化鈦水凝膠系統應用於順型定位手術腫瘤床

Taipei Medical University Institutional Repository > 醫學工程學院 > 生醫材料暨組織工程研究所 > 博碩士論文 > Item 987654321/58420

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題名:	開發一紫外光敏感二氧化鈦水凝膠系統應用於順型定位手術腫瘤床 Development of Novel UV-Photosensitive TiO2 Hydrogel System For Conformal Labeling of Surgical Tumor Bed
作者:	賴宜暄 Lai, Yi-Hsuan
貢獻者:	生醫材料暨組織工程研究所呂隆昇蔡協致
關鍵詞:	部分乳房放射治療;二氧化鈦光敏感性水凝膠;二氧化鈦;組織填充;紫外光 partial breast irradiation;TiO2 photosensitive hydrogel;TiO2;tissue filling;UV light
日期:	2019-06-26
上傳時間:	2020-01-14 11:59:21 (UTC+8)
摘要:	早期乳癌患者接受部分乳房放射治療與傳統全乳放射治療具有相當的治療效果，並可降低正常組織受到的輻射劑量，減少副作用的發生，將成為乳癌治療主要的放射線治療技術之一。然而，清楚定義腫瘤切除空腔以明確地標示出放射線治療標靶區域是目前的限制之一。以顯影材料搭配光敏感性水凝膠具有生物相容性、組織順型性、組織支撐及X光顯影的功能，可以滿足需求。本實驗利用高生物相容性的雙離子單體與交聯劑混合後，添加紫外光起始劑使水凝膠可經由紫外光的照射形成網狀的交聯結構，並添加奈米二氧化鈦使其能夠在電腦斷層下顯影。隨後，二氧化鈦光敏感性水凝膠進行材料性質檢測，並測試其生物相容性，最後以動物實驗觀察其在生物體內的效能。結果顯示，10wt%二氧化鈦光敏感性水凝膠在電腦斷層影像中具有辨別性與組織順型性。拉曼光譜及流變儀檢測確認了二氧化鈦光敏感性水凝膠膠體性質與機械性質。然而，二氧化鈦的光催化特性與光吸收性質限制了紫外光的穿透深度。細胞毒性、生化檢測與組織切片結果顯示二氧化鈦光敏感性水凝膠的無毒性。並且透過動物實驗觀察到二氧化鈦光敏感性水凝膠可以在體內維持足夠的顯影能力至少24天。未來將持續優化紫外光成膠系統與二氧化鈦光敏感性水凝膠成膠性質以符合臨床應用。期待二氧化鈦光敏感性水凝膠成為新一代貼近臨床需求的顯影填充醫材。 Background Radiotherapy is a powerful adjuvant to reduce cancer recurrence after surgical excision. Accurate labeling of the tissue defect after surgery / wound healing (surgical tumor bed) is critical for maximal precision of post-operative radiotherapy, as in the case of accelerated partial breast irradiation (APBI) after breast-conserving surgery. Photosensitive hydrogel is suitable for conformal delineation of the surgical tumor bed. In order to visualize the defect-filling hydrogel under X-ray imaging, titanium dioxide (TiO2) is an excellent radiopaque marker due to its biocompatibility as well as its photocatalyst properties. In this research, we develop a manufacturing process for titanium-loaded photosensitive hydrogel and characterize its physical and radiological properties. Aims A TiO2-containing photosensitive hydrogel system with both biocompatibility and X-ray contrast ability was developed to fill the tumor bed that it can be identified in X-ray images. Material and Method A zwitterionic monomer sulfobetaine methacrylate was mixed with N,N’-Methylene-bis-acrylamide to prepare the hydrogel matrix. Nano-sized titanium dioxide (TiO2) was added to hydrogel matrix under UV irradiation to form photosensitive hydrogels. The gelation homogeneity, X-ray contrast and conformal defect filling efficiency were measured with computed tomography. UV absorption properties and UV shielding test were performed to check the effects of characteristic absorption of TiO2 on photosensitive gelation. The hydrogel properties and mechanical properties were examined by rheology and Raman spectroscopy. The cytotoxicity of hydrogel before and after gelation and the effect of UV light on the cells were examined by cell culture. The X-ray contrast and morphology of TiO2-containing photosensitive hydrogel in vivo over time was determined under computed tomography (CT) by animal models. Finally, biosafety was determined by biochemistry and histology in animal models. Results TiO2 nanoparticles concentration-dependently increase Hounsfield number of photosensitive hydrogel under CT imaging. The 10wt% of TiO2 content was found to provide a reasonable tissue contrast under X-ray. In the material properties tests, the different structure bonding after hydrogel gelation indicated cross-linking formation, and the viscoelastic properties of hydrogel increased as the concentration of TiO2 increased. However, the UV-absorption properties of TiO2 in sol state caused UV light shielding and jeopardized polymerization homogeneity and gelation efficiency. The hydrogel containing 10wt% TiO2 can efficiently form gel when the thickness is 5mm. The biosafety of TiO2-containing photosensitive hydrogel before and after gelation was confirmed by cell culture. It was found that no significant cytotoxicity after UV irradiated for 30 minutes and continued culture for 24 hours. Finally, the TiO2-containing photosensitive hydrogel could retain in target area and had enough X-ray contrast for at least 24 days. The results of biochemistry and histology were showed that the TiO2-containing photosensitive hydrogel was no-toxic. Conclusions The TiO2-containing photosensitive hydrogel system with biocompatibility, X-ray contrast ability was developed. However, the property of TiO2 affects the hydrogel thickness. The optimal parameters for hydrogel in the UV light source are still being tested and a standard procedure for UV gelation will be established. The TiO2-containing photosensitive hydrogel system will continue to be optimized in the future and is expected to be clinically useful to aid patients.
描述:	碩士指導教授：呂隆昇共同指導教授：蔡協致委員：陳祥和委員：洪進昇委員：陳盈汝
資料類型:	thesis
顯示於類別:	[生醫材料暨組織工程研究所] 博碩士論文

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