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Title: | 生醫材料於鼻顏面重建組織工程之應用 The applications of biomaterials in tissue engineering of nasofacial reconstruction |
Authors: | 邱昱勳 Yu-Hsun Chiu |
Advisor: | 楊台鴻 Tai-Horng Young |
Keyword: | 空鼻症,可注射性,半水硫酸鈣,磷酸鈣,人類鼻中隔軟骨細胞,幾丁聚醣,軟骨組織工程, Empty nose syndrome (ENS),Injectable,Calcium sulfate hemihydrate,Calcium phosphate,Nasal septal chondrocytes (NSCs),Chitosan,Cartilage tissue engineering, |
Publication Year : | 2023 |
Degree: | 博士 |
Abstract: | 自體軟骨不足是當前鼻顏面重建領域的一個重大挑戰,尤其在治療空鼻症和進行再次鼻整形手術時。
空鼻症是鼻甲手術後的一種少見但嚴重的併發症,其臨床症狀包括矛盾性鼻阻塞、鼻部乾燥感和呼吸困難。遺憾的是,目前尚無ㄧ致公認有效的空鼻症治療方法。目前的治療策略包括藥物治療,如鼻部潤滑劑、局部抗生素和皮質類固醇的使用,以及外科手術。然而,這些治療方法的缺點和局限性包括外科手術的困難度高、植入物感染的風險以及手術成效不明確。因此我們需要進一步研究,以開發有效和侵入性低的治療方式來改善空鼻症患者的症狀。為了克服現有治療的局限性,我們的第一個研究的目標是開發新型的可注射生物材料植入物,用於微創手術的方法來治療空鼻症。 我們製備了一種可注射的複合骨移植物,其中含有半水硫酸鈣、四鈣磷酸鹽和無水磷酸氫鈣(CSH/CaP糊劑),並調整了不同的CSH/CaP比例和添加劑的濃度。且對該注射複合骨糊劑的固化時間、可注射性、力學性能和生物相容性進行了評估。 經過研究,我們開發的可注射CSH/CaP糊劑(CSH/CaP比例為1:1,補充了6%檸檬酸和2%羥丙甲纖維素)具有良好的操控性能,很好的生物相容性和適當的機械強度。此外,該糊劑可以從裝有18G針頭的針筒中擠出,展現了可運用在微創手術中的巨大潛力。該開發的可注射植入物具有修復組織的潛力,將為治療空鼻症和鼻顏面重建提供理想的微創手術治療策略。 二次鼻整形手術被認為是整形外科領域中最具挑戰性的手術之一。我們第二個研究的目的是評估幾丁聚醣對鼻中隔軟骨細胞(NSCs)生長的影響。最終目標是建立一種新的方法來增強鼻中隔軟骨的再生。我們成功地從人體鼻中隔軟骨中分離出鼻中隔軟骨細胞,並使用阿爾西藍染色,在光學顯微鏡下觀察鼻中隔軟骨細胞的形態。我們以不同濃度的幾丁聚醣培養分離出來的鼻中隔軟骨細胞,並研究二型膠原蛋白基因(COL2A1)的表現。 我們的研究結果顯示,可從人體鼻中隔軟骨中成功地分離出鼻中隔軟骨細胞。與對照組細胞相比,與0.2%的幾丁聚醣共培養明顯增強了鼻中隔軟骨細胞的增殖。然而,0.5%的幾丁聚醣對鼻中隔軟骨細胞有害,導致細胞從培養皿上脫落。此外,添加0.2%的幾丁聚醣顯著提高了鼻中隔軟骨細胞中二型膠原蛋白基因的表現。 根據我們的了解,這是首次研究發表幾丁聚醣能有效地引導人類鼻中隔軟骨細胞的附著和生長。幾丁聚醣應是一種值得發展的人類鼻中隔軟骨細胞培養添加劑,為研究鼻中隔軟骨缺失和鼻顏面重建的組織再生奠定了基礎。 The insufficient cartilage is a significant obstacle within the present domain of nasofacial reconstruction, especially when treating empty nose syndrome and performing secondary rhinoplasty. Empty nose syndrome (ENS) is an infrequent occurrence following turbinate surgery, characterized by clinical symptoms such as paradoxical nasal obstruction, nasal dryness, and feeling of dyspnea. Unfortunately, there are no effective treatments for ENS up to date. Current management strategies include medical therapies such as nasal lubricants, local antibiotics and corticosteroids application, and surgical techniques. However, the surgical difficulties, risk of infection from implantation and ambiguous results of surgery are the disadvantages and limitations of these treatments. Therefore, to develop effective and low invasive treatments for improving ENS patient’s symptoms is necessary and requires further investigation. To overcome the existing treatment limitations, the aim of our first study is to develop novel injectable implants from biomaterials for minimally invasive surgery to treat ENS. An injectable composite bone graft containing calcium sulfate hemihydrate, tetracalcium phosphate and anhydrous calcium hydrogen phosphate (CSH/CaP paste) was prepared with different CSH/CaP ratios and different concentration of additives. Setting time, injectability, mechanical properties, and biocompatibility were evaluated. The developed injectable CSH/CaP paste (CSH/CaP 1:1 supplemented with 6% citric acid and 2% HPMC) presented good handling properties, great biocompatibility and adequate mechanical strength. Furthermore, the paste was demonstrated to be extruded from syringe equipped with 18G needles and exerted great potential for minimally invasive surgery. The developed injectable implants with tissue repairing potentials will provide an ideal therapeutic strategy for minimally invasive surgery to treat ENS and apply in nasofacial reconstruction. Within the realm of plastic surgery, performing secondary rhinoplasty is widely acknowledged as one of the most demanding procedures. Our secondary study aimed to assess the impact of chitosan on the growth of nasal septal chondrocytes (NSCs). The ultimate objective was to establish an innovative methodology to enhance nasal septal cartilage regeneration. Human NSCs were isolated and the morphology of NSCs was examined by Alcian blue staining and observed by light microscopy. The isolated NSCs were grown with various concentrations of chitosan and the expression of COL2A1 was investigated. NSCs were found to be successfully isolated from nasal septal cartilage. Treated with 0.2 % of chitosan greatly enhanced proliferation of NSCs compared to control cells. However, 0.5 % of chitosan was harmful to NSCs, resulting in cell detachment from the culture plate. Moreover, the inclusion of 0.2% chitosan notably enhanced the expression of COL2A1 in NSCs. To the best of our knowledge, this is the initial documentation showcasing the effectiveness of chitosan in facilitating the attachment and proliferation of human NSCs. Chitosan appears to be a promising additive for NSC culture, which lays the foundation for investigating tissue regeneration in the context of nasal septal cartilage deficiency and nasofacial reconstruction. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/88657 |
DOI: | 10.6342/NTU202302951 |
Fulltext Rights: | 同意授權(限校園內公開) |
Appears in Collections: | 醫學工程學研究所 |
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