聚乙烯醇人工角膜中心材料的修饰改性研究

发布时间：2018-04-28 17:21

本文选题：人工角膜光学中心材料 + 聚乙烯醇　；参考：《深圳大学》2016年硕士论文

【摘要】：人工角膜是用生物医用材料制成的类似供体角膜的人造屈光装置,用来替代病变的角膜以达到治疗角膜病的目的。供体角膜来源匮乏以及同种异体角膜移植成功率低,导致供体角膜远远不能满足角膜病治疗的需求,所以人工角膜具有重大研究意义。人工角膜移植就目前而言存在的主要问题有:术后位置异常或脱出;光学中心区前、后增殖膜的形成。人工角膜光学中心材料是整个人工角膜的核心部分,其性能是否优异是影响人工角膜应用前景的重要因素。聚乙烯醇(PVA)水凝胶具有良好的亲水性能、力学性能、光学性能和生物相容性。在课题前期研究中发现,将PVA水凝胶作为中心区材料的人工角膜移植到动物眼内时,材料能够满足基本要求,但在手术后期出现了少量的角膜上皮细胞在光学中心区粘附生长的现象。在本研究中以PVA水凝胶作为光学中心材料,并对其进行修饰改性,以期获得既具有良好基础性能,又具有抗细胞粘附性能的改性PVA人工角膜光学中心材料。本文通过表面涂覆改性、复合改性以及表面接枝改性等方法对人工角膜光学中心材料(PVA水凝胶)进行修饰改性,并对修饰改性后的PVA水凝胶的各种性能进行研究。主要研究内容和结果如下:1.用N,N-二甲基丙烯酰胺(DMA)和甲基丙烯酸(MAA)作为共聚单体来制备共聚物N,N-二甲基丙烯酰胺-甲基丙烯酸(DMA-MAA),采用FTIR对共聚物进行表征,将共聚物涂覆于PVA水凝胶表面。探讨了DMA-MAA修饰涂覆液的浓度对PVA水凝胶的透光率、含水率、溶胀性能、亲水性等性能的影响,并对修饰改性后的材料的抗细胞粘附性能进行研究。结果表明,经DMA-MAA修饰改性后的PVA水凝胶材料的可见光透过率在90%以上,含水率为71%~73%,亲水性获得极大提升,材料表面与水的接触角值由41°降到了14°,溶胀比为3.5~3.7,抗细胞粘附能力获得显著提升。2.采用循环冷冻-解冻法,制成肝素钠/聚乙烯醇(HS/PVA)复合水凝胶。探讨了不同质量分数肝素钠对复合水凝胶的透光率、含水率、溶胀性能、亲水性、力学性能以及肝素钠释放量的影响。结果表明,复合水凝胶可见光透过率有少量下降,为92%以上,含水率为72%~78%,亲水性获得提升,材料与水接触角值由41°降到了22°,平衡溶胀比为4.0~4.5,溶胀平衡时间由60min逐渐降到了45min,复合材料的拉伸强度为0.55~0.76MPa,且断裂伸长率也在200%以上,适量肝素钠的释放可以达到减少细胞粘附的效果。3.采用共价接枝的方法将肝素分子接枝到PVA水凝胶表面,用ATR-FTIR对水凝胶材料表面的修饰物进行表征。分别探讨了3-氨基丙基三乙氧基硅烷(APTS)的浓度和肝素(Hep)的浓度对水凝胶材料的透光率、含水率、溶胀性能、亲水性以及肝素固定量等性能的影响。结果表明,修饰改性后的水凝胶材料的可见光透过率在94%以上,含水率为68~72%,溶胀平衡时间为60min,溶胀比在3.0~3.5,亲水性得到显著提升,随着修饰液浓度的增加,材料表面接触角由空白样的41°逐渐降低到了28°左右,材料表面能共价结合一定量的肝素分子,肝素分子的高亲水性和高负电荷性能提高了PVA水凝胶材料的抗细胞粘附能力。4.对上述三种修饰改性后的PVA水凝胶材料进行急性全身毒性、体外细胞毒性、皮内反应这三种生物相容性试验。试验结果显示,被测样品浸提液未导致动物死亡或引起急性全身毒性反应的迹象,体外细胞毒性均为1级,皮内反应类型为极轻微级。试验结果说明修饰改性后的PVA水凝胶光学中心材料生物相容性可以达到国标要求,属于合格的医用材料。
[Abstract]:Artificial cornea is an artificial refractive device similar to the donor cornea made of biomedical materials, which is used to replace the cornea of the lesion to achieve the purpose of treating keratopathy. The donor cornea is scarce and the success rate of allograft cornea is low. The donor cornea can not meet the needs of the cornea treatment. So the artificial cornea is of great importance. Major research significance. The main problems of artificial corneal transplantation are: abnormal position or release after operation, the formation of the posterior proliferating membrane in the optical center area. The central part of the artificial cornea is the central part of the whole artificial cornea. Its excellent performance is an important factor affecting the application prospect of human cornea. Polyvinyl alcohol (PVA The hydrogels have good hydrophilic properties, mechanical properties, optical properties and biocompatibility. In the previous study, it was found that the material could meet the basic requirements when the PVA hydrogel was transplanted into the eye of the animal's eye as the central material, but a small amount of corneal epithelial cells adhered to the optical center in the later period of the operation. In this study, the PVA hydrogel was used as an optical center material and modified to modify the optical center material of modified PVA artificial cornea, which had good basic properties and anti cell adhesion properties. This paper was made by surface coating modification, compound modification and surface grafting modification. The modified corneal optical center material (PVA hydrogel) was modified and the properties of modified PVA hydrogels were studied. The main contents and results were as follows: 1. the copolymers were prepared by N, N- two methylacrylamide (DMA) and methacrylic acid (MAA) as copolymers to prepare copolymer N, N- two methyl acrylamide methacrylic acid (DMA-MAA). The copolymer was characterized by FTIR, and the copolymer was coated on the surface of PVA hydrogel. The effects of the concentration of DMA-MAA modified coating on the transmittance, water content, swelling and hydrophilic properties of the PVA hydrogel were investigated, and the anti cell adhesion properties of the modified modified materials were studied. The results showed that the modified DMA-MAA modification was modified by DMA-MAA modification. The visible light transmittance of the PVA hydrogel is above 90%, the moisture content is 71%~73%, the hydrophilic property is greatly improved, the contact angle of the surface and water is reduced from 41 degrees to 14, the swelling ratio is 3.5~3.7, the anti cell adhesion ability is improved significantly by the cycle freezing thawing method, and the heparin sodium / polyvinyl alcohol (HS/PVA) composite water is prepared. The effects of different mass fraction of heparin sodium on the transmittance, water content, swelling property, hydrophilic properties, hydrophilic properties, mechanical properties and the release of heparin sodium were investigated. The results showed that the visible light transmittance of the composite hydrogel decreased slightly, the moisture content was more than 92%, the water content was 72%~ 78%, the hydrophilic property was improved, and the value of the material and water contact angle was 41 degrees. To 22 degree, the equilibrium swelling ratio is 4.0~4.5, the equilibrium time of swelling is reduced from 60min to 45min, the tensile strength of the composite is 0.55~0.76MPa, and the elongation at break is also above 200%. The release of heparin sodium can reduce the effect of cell adhesion,.3. grafting the heparin molecule onto the PVA hydrogel form by covalent grafting. The surface modification of the hydrogels was characterized by ATR-FTIR. The effects of the concentration of 3- amino propyl triethoxane (APTS) and the concentration of heparin (Hep) on the transmittance, water content, swelling, hydrophilicity, and heparin fixed amount of the hydrogel were investigated. The results showed that the modified hydrogel material was modified. The transmittance of visible light is above 94%, the water content is 68~72%, the swelling equilibrium time is 60min, the swelling ratio is higher than that of 3.0~3.5, the hydrophilic property of the material is greatly improved. With the increase of the concentration of the modified liquid, the contact angle of the material decreases gradually from the blank sample to about 28 degrees. The surface of the material can covalently combine a certain amount of heparin molecule and the high heparin molecule. The hydrophile and high negative charge performance improved the anti cell adhesion ability of PVA hydrogel.4. on the acute systemic toxicity of the three modified PVA hydrogels, in vitro cytotoxicity and intradermal reaction. The results showed that the samples were not killed or acute. The cytotoxicity in vitro is 1 and the type of intradermal reaction is extremely light. The results show that the biocompatibility of the modified PVA hydrogel optical center material can reach the national standard, and it belongs to the qualified medical materials.

【学位授予单位】：深圳大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：TQ427.26;R318.08

【参考文献】