【摘要】：角膜移植是目前治療角膜病致盲唯一有效的方法，角膜修復(fù)材料的匱乏極大地限制了角膜病治療的普及和開展本論文致力于具有較好理化性能和生物學(xué)性能的膠原基角膜修復(fù)材料的研究此外，，術(shù)后的細(xì)菌感染及炎癥反應(yīng)是導(dǎo)致角膜移植失敗最主要的原因之一，因此研究在角膜修復(fù)的同時還具有廣譜抗菌效果的功能化角膜修復(fù)材料也是本文的重點所在 與常見的角膜修復(fù)材料相比，本文構(gòu)建的結(jié)構(gòu)仿生膠原基材料具有以下優(yōu)點：優(yōu)良的力學(xué)性能和光學(xué)性能合適的保濕性能易于營養(yǎng)物質(zhì)透過的性能可控的孔洞和層狀結(jié)構(gòu)以及良好的體外和體內(nèi)生物相容性等負(fù)載抗菌藥物后的功能化角膜修復(fù)材料能夠在一周內(nèi)具有較好的抗革蘭氏陰性細(xì)菌和陽性細(xì)菌的效果，并且能夠較好地實現(xiàn)受損角膜組織的修復(fù)本文對膠原基角膜修復(fù)材料的結(jié)構(gòu)仿生構(gòu)建與抗菌功能化進(jìn)行了深入的研究和探討 1膠原基角膜修復(fù)材料的結(jié)構(gòu)仿生構(gòu)建研究 角膜修復(fù)材料需要具有較為合適的理化性能和生物學(xué)性能，而這些性能與材料的結(jié)構(gòu)密切相關(guān)類似于天然角膜組織的仿生結(jié)構(gòu)有利于材料較好較快地實現(xiàn)受損組織的修復(fù)本研究采用物理或化學(xué)手段經(jīng)不同的制備工藝研制出了一系列的膠原基膜材料（1）膠原-明膠-透明質(zhì)酸（CGH631）復(fù)合膜材料具有較好的抗張強(qiáng)度親疏水性和生物相容性，但是不能耐受手術(shù)線縫合（2）通過離子瀝濾技術(shù)在膠原膜材料內(nèi)部引入了納米級的孔洞，這些微孔的存在改變了膠原膜材料的內(nèi)部結(jié)構(gòu)，從而提高了材料的耐縫合性能；造孔劑含量在2.5%和5.0%之間的膠原膜材料具有較為合適的理化性能和生物學(xué)性能，可以作為膠原基角膜修復(fù)材料研究的基底材料（3）通過控制高分子溶液的成膜過程構(gòu)建出具有不同層狀仿生結(jié)構(gòu)的膠原基角膜修復(fù)材料，結(jié)果顯示這些材料具有類似于天然角膜的理化性能和生物相容性，具有不同層間結(jié)構(gòu)的材料能夠針對角膜組織的不同部位進(jìn)行替代和修復(fù)（4）通過冷凍干燥技術(shù)在結(jié)構(gòu)仿生膜的基礎(chǔ)上構(gòu)建了具有微粗糙表面結(jié)構(gòu)的膠原基角膜修復(fù)材料（FD-Col膜），F(xiàn)D-Col膜比光滑膜材料表面具有更多的蛋白吸附和細(xì)胞結(jié)合位點，角膜上皮細(xì)胞在FD-Col膜表面的上皮化過程要快于自然風(fēng)干膜的光滑表面；材料在兔眼表的上皮化過程在14天內(nèi)基本完成，明顯快于具有光滑表面結(jié)構(gòu)的材料 2膠原基角膜修復(fù)材料的抗菌功能化研究 本研究創(chuàng)造性地通過化學(xué)交聯(lián)的方法在膠原膜上負(fù)載了眼科手術(shù)中常用的光譜抗生素小分子Tobramycin，得到了能夠在一周內(nèi)具有藥物緩釋效果的抗菌功能化角膜修復(fù)材料膠原-妥布霉素膜（Col-Tob） Col-Tob膜保持了較好的光學(xué)性能，力學(xué)性能，保濕性能和生物相容性在PBS中浸泡了7天后的Col-Tob膜仍然對臨床上常見的革蘭氏陽性細(xì)菌金黃色葡萄球菌和陰性細(xì)菌大腸桿菌具有很好的抗菌效果人角膜上皮細(xì)胞能夠較好地在Col-Tob材料表面粘附鋪展生長和增殖，一周后有2~3層細(xì)胞緊密地粘合在Col-Tob膜的表面動物實驗結(jié)果表明Col-Tob膜能夠耐受手術(shù)線的縫合，在植入后能夠較好地與剩余正常角膜組織結(jié)合，眼表沒有發(fā)生細(xì)菌感染和炎癥反應(yīng)；術(shù)后一個月后，傷口完全愈合，眼表完成角膜上皮化過程；Col-Tob膜材料板層移植三個月后沒有出現(xiàn)明顯的新生血管和圓錐形角膜現(xiàn)象，起到了較好的修復(fù)效果
[Abstract]:Corneal transplantation is currently the only effective method for the treatment of corneal blindness. The lack of corneal repair materials has greatly limited the popularity of keratopathy treatment. This paper is devoted to the study of collagen-based corneal repair materials with good physical and chemical properties and biological properties. In addition, postoperative bacterial infection and inflammation are the main causes of corneal blindness. One of the main causes of graft failure is the study of functional corneal repair materials with broad-spectrum antibacterial effect.
Compared with common corneal repair materials, biomimetic collagen-based materials have the following advantages: excellent mechanical and optical properties, suitable moisture retention, easy nutrient permeability, controllable pore and layered structure, and good in vitro and in vivo biocompatibility after loading antibiotics. Corneal prosthetic materials can resist Gram-negative and positive bacteria well in one week, and can repair damaged corneal tissue. In this paper, the bionic construction of collagen-based corneal prosthetic materials and their antibacterial function were studied and discussed.
Biomimetic construction of 1 collagen based corneal repair materials
Corneal repair materials need to have more appropriate physical and chemical properties and biological properties, and these properties are closely related to the structure of materials similar to the natural corneal tissue bionic structure is conducive to better and faster repair of damaged tissues. This study developed a series of physical or chemical means through different preparation processes. Collagen-gelatin-hyaluronic acid (CGH631) composite membrane materials have good tensile strength, hydrophobicity and biocompatibility, but can not tolerate suture of surgical line (2) nano-pore was introduced into the collagen membrane materials by Ion Leaching technology, and the existence of these micropores changed the collagen membrane materials. The collagen membrane material with pore-forming agent content between 2.5% and 5.0% has better physical and chemical properties and biological properties, and can be used as the substrate material for collagen-based corneal repair materials (3) Different layered bionic junctions were constructed by controlling the film-forming process of polymer solution. The results show that these materials have similar physical and chemical properties and biocompatibility to natural corneas. The materials with different interlayer structures can be used to replace and repair different parts of corneal tissue. (4) The micro-rough surface was constructed on the basis of the Bionic Membrane by freeze-drying technology. The epithelialization process of corneal epithelial cells on the surface of FD-Col membrane was faster than that on the smooth surface of natural air-dried membrane. The epithelialization process of the materials on the surface of rabbit eyes was basically completed within 14 days, significantly faster than that on the smooth surface of natural air-dried membrane. Materials with smooth surface structure
Antibacterial function of 2 collagen based corneal repair materials
In this study, a novel antibacterial functional corneal repair material Col-Tob Col-Tob membrane was prepared by loading Tobramycin, a small spectral antibiotic commonly used in ophthalmic surgery, onto the collagen membrane by chemical cross-linking method. Col-Tob membrane still has good antibacterial effect against Gram-positive bacteria Staphylococcus aureus and negative bacterial Escherichia coli. Human corneal epithelial cells can adhere and proliferate well on the surface of Col-Tob material, and 2-3 weeks later. The results of animal experiment showed that Col-Tob membrane could tolerate the suture of surgical line, and could combine with the remaining normal corneal tissue well after implantation, and there was no bacterial infection and inflammation on the ocular surface. There was no obvious neovascularization and keratoconus after three months of lamellar transplantation of ob membranes, which had a good repair effect.
【學(xué)位授予單位】：華南理工大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R318.08

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