本文選題：改性殼聚糖 + 膠原�。� 參考：《華南理工大學(xué)》2012年碩士論文

【摘要】：角膜病已經(jīng)成為全球第二大致盲眼病，目前角膜移植是角膜盲患者重見(jiàn)光明的唯一有效手段。然而角膜移植存在供體來(lái)源匱乏的問(wèn)題。為解決這一問(wèn)題，需要尋找可靠的供體來(lái)源，角膜修復(fù)材料成為研究的熱點(diǎn)。角膜修復(fù)與重建為角膜盲患者重見(jiàn)光明提供了新的途徑，這一領(lǐng)域的一個(gè)重要方面就是角膜修復(fù)材料的制備。角膜修復(fù)材料要求具有優(yōu)異的眼組織相容性、可控降解性，良好的光學(xué)性能，適宜的力學(xué)強(qiáng)度與良好的營(yíng)養(yǎng)物質(zhì)透過(guò)性，以保證能與眼組織相容，并促進(jìn)角膜組織的再生與修復(fù)。本研究以膠原、明膠為基體，通過(guò)與改性殼聚糖、生物表面活性劑A15等交聯(lián)復(fù)合的方法制備出光學(xué)性能良好、眼組織相容性?xún)?yōu)異，具有良好營(yíng)養(yǎng)物質(zhì)透過(guò)性和適宜力學(xué)強(qiáng)度的角膜修復(fù)材料，并對(duì)其眼組織相容性和促進(jìn)組織再生性能進(jìn)行初步探討。 采用碳二亞胺交聯(lián)法制備了膠原交聯(lián)膜和不同A15含量的A15-膠原復(fù)合膜，考察A15組分的比例對(duì)復(fù)合膜性能的影響。結(jié)果表明，隨著A15含量增加，復(fù)合膜的透光率逐漸升高，最大值達(dá)90%；折光率隨著A15含量的增加而減小，與透光率變化趨勢(shì)相反；隨著A15含量增加，復(fù)合膜含水量增加，濕態(tài)拉伸強(qiáng)度下降，當(dāng)A15含量大于10%時(shí)，復(fù)合膜含水量達(dá)到98%以上；各復(fù)合膜對(duì)葡萄糖、色氨酸和氯化鈉均具有良好的滲透性，其中A15含量為2%的復(fù)合膜對(duì)三種物質(zhì)的滲透性能最優(yōu)。人角膜上皮細(xì)胞（HCEC）在A15-膠原復(fù)合膜上的黏附、生長(zhǎng)與增殖優(yōu)于膠原交聯(lián)膜，且后期的細(xì)胞增殖優(yōu)勢(shì)較明顯。A15-膠原復(fù)合膜植入兔眼角膜后在眼內(nèi)維持透明，，無(wú)明顯炎性與排斥反應(yīng)，術(shù)后5個(gè)月可觀察到少量基質(zhì)細(xì)胞長(zhǎng)入植片表面，顯示出良好的眼組織相容性。 為提高膠原膜的眼組織相容性，本研究將具有良好抗菌抗炎性的改性殼聚糖與膠原復(fù)合，采用碳二亞胺交聯(lián)法制備了改性殼聚糖-膠原交聯(lián)膜，并與膠原交聯(lián)膜的理化性能和生物相容性進(jìn)行比較。結(jié)果表明，改性殼聚糖的加入改善了膠原膜的透光率，折光率則略低于膠原交聯(lián)膜；改性膜的含水量為72.9%，低于膠原膜的含水量，與人角膜接近；改性殼聚糖的加入顯著提高了復(fù)合膜的拉伸強(qiáng)度，達(dá)到2MPa以上；膠原膜和改性膜對(duì)葡萄糖、色氨酸和氯化鈉的滲透率均接近或優(yōu)于人角膜。HCEC在改性膜上的黏附、生長(zhǎng)良好，改性殼聚糖的加入有利于細(xì)胞增殖。改性膜植入兔眼角膜后無(wú)明顯炎性和排斥反應(yīng)，術(shù)后7個(gè)月植片表面可觀察到少量基質(zhì)細(xì)胞長(zhǎng)入，顯示出良好的眼組織相容性。但改性膜植入后發(fā)白，眼內(nèi)透明性較低。 為改善殼聚糖復(fù)合膜的眼組織相容性，本研究采用碳二亞胺交聯(lián)法，將改性殼聚糖與明膠復(fù)合制備改性殼聚糖-明膠交聯(lián)膜，并與殼聚糖-明膠交聯(lián)膜的理化性能和生物相容性進(jìn)行比較。結(jié)果表明，改性殼聚糖復(fù)合膜較殼聚糖復(fù)合膜具有更高的含水量，達(dá)73.47%，濕態(tài)拉伸強(qiáng)度則低于殼聚糖復(fù)合膜，為0.94MPa；兩復(fù)合膜均具有較高的透光率，最大值達(dá)95%；改性殼聚糖復(fù)合膜的折光率略高于殼聚糖復(fù)合膜，對(duì)葡萄糖、色氨酸和氯化鈉的滲透性能亦優(yōu)于殼聚糖復(fù)合膜。HCEC在兩種膜上生長(zhǎng)、增殖良好；改性殼聚糖復(fù)合膜植入兔眼角膜后，無(wú)明顯炎性反應(yīng)，角膜與植片維持透明；術(shù)后16周植片完全降解，降解產(chǎn)物對(duì)眼組織無(wú)毒、無(wú)刺激，表現(xiàn)出良好的眼組織相容性。殼聚糖復(fù)合膜在兔角膜內(nèi)則引起較嚴(yán)重的炎性反應(yīng)，角膜化膿、水腫，眼組織相容性較差。
[Abstract]:Corneal diseases have become the only effective method for corneal transplantation , which is the only effective method to treat corneal diseases .

A15 - collagen composite membrane with collagen cross - linked membrane and different A15 content was prepared by carbodiimide crosslinking method . The influence of the ratio of A15 components on the properties of composite membrane was investigated . The results showed that the light transmittance of composite membrane increased with the increase of A15 content , and the maximum value reached 90 % .
The refractive index decreases with the increase of A15 content , which is opposite to the change trend of light transmittance ;
With the increase of the content of A15 , the water content of the composite membrane is increased and the wet tensile strength decreases , and when the content of A15 is more than 10 % , the water content of the composite membrane reaches above 98 % ;
Human corneal epithelial cells ( HCEC ) had an excellent permeability to glucose , tryptophan and sodium chloride . The adhesion , growth and proliferation of human corneal epithelial cells ( HCEC ) on A15 - collagen composite membranes were superior to that of collagen cross - linked membranes .

In order to improve the ocular tissue compatibility of collagen membrane , the modified chitosan - collagen cross - linked membrane was prepared by carbodiimide crosslinking method , and the physicochemical properties and biocompatibility of collagen cross - linked membrane were compared . The results showed that the addition of modified chitosan improved the light transmittance of collagen membrane , while the refractive index was slightly lower than that of collagen cross - linked membrane .
The water content of the modified membrane was 72.9 % , which was lower than the water content of the collagen membrane and was close to the human cornea .
the addition of the modified chitosan remarkably improves the tensile strength of the composite membrane and reaches above 2MPa ;
The permeability of the collagen membrane and the modified membrane to glucose , tryptophan and sodium chloride was close to or better than that of the human cornea . The adhesion and growth of HCEC on the modified membrane were good . The addition of modified chitosan was beneficial to cell proliferation . After the modified membrane was implanted in the rabbit cornea , there was no obvious inflammatory and rejection reaction .

In order to improve the ocular tissue compatibility of chitosan composite membrane , the modified chitosan - gelatin crosslinked membrane was prepared by compounding modified chitosan and gelatin by carbodiimide crosslinking method . The results showed that the modified chitosan composite membrane had higher water content , 73.47 % than that of chitosan composite membrane , and the wet tensile strength was lower than that of chitosan composite membrane , which was 0.94 MPa ;
the two composite films have high light transmittance , and the maximum value is up to 95 percent ;
The refractive index of the modified chitosan composite membrane was slightly higher than that of chitosan composite membrane . The permeation properties of glucose , tryptophan and sodium chloride were better than that of chitosan composite membrane .
After the modified chitosan composite membrane was implanted into rabbit cornea , there was no obvious inflammatory reaction , and the cornea and the implant remained transparent ;
After 16 weeks of operation , the grafts were completely degraded , and the degradation products were non - toxic and non - irritating to the ocular tissues . The chitosan composite membrane caused severe inflammatory reaction , corneal pus , edema and poor ocular tissue compatibility in the rabbit cornea .
【學(xué)位授予單位】：華南理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R318.08

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