高折射水凝胶纳米复合材料的制备及其在人工角膜植入上的应用

Myopia, hyperopia and other forms of cornea-related refractive errors represent the commonest cause of visual disability today. An estimated 10 million people around the world suffer from vision loss due to corneal disease or damage, and China has 400 billion people myopia, ranking first in the world. Up-to-date, the most common medical treatment for vision correction is laser-assisted in situ keratomileusis (LASIK) surgery through irreversible reshaping of the cornea by laser energy. The use of polymer-based artificial cornea implants is relatively obvious as the preferred method for creating a successful long-term refractive change of the cornea either for myopia or hyperopia. The ability to specify an accurate refractive change would increase and the most importantly the procedure is additive and reversible, not removing tissue. Hydrogels are crosslinked hydrophilic polymers that incorporate large quantities of water and take on physical characteristics similar to soft tissue. They represent an important class of biomaterials for a variety of medical applications (including tissue engineering) because of their excellent biocompatibility and high permeability to oxygen, nutrients, and other water-soluble metabolites. This proposed program will utilize the latest advances in hydrogel and inorganic nanomaterials science and technologies to develop hydrogel-based new corneal implants for the treatment of myopia and other refractive errors. We try to use hydrogel based methacrylate-terminated polythiourethane (PTU) filled with ex situ precipitated nano-sized inorganic particles like TiO2 and ZnS. The water soluble polythiourethane shall be photocrosslinked in the presence of the inorganic particles to make a series of hydrogel nanocomposites with an adjustable and high refractive index by incorporating different amount of nanosized high refractive inorganic fillers. PTU used has a relative higher refractive index than other conventional polyurethane (PU) materials due to the existence of sulfur. It has been reported to exhibit high tensile strength, excellent abrasion resistance and other good mechanical properties and used in many industrial and biomedical fields including lenses. These inorganic/polymer nanohybrid materials will be evaluated for corneal biocompatibility, safety and efficacy for in vitro studies. Several fundamental questions will be systematically addressed, including the structure-dependent properties of polymer materials and the intrinsic relationship between the physicochemical properties, biological characterization and the content of nanoparticle, optimal design and controllable synthesis of the hydrogel nanocomposites. The proposed project will create a new methodology of design, preparation and application of artificial cornea implants, and have important scientific significance and medical application value.

近视、远视或其他与角膜相关的屈光不正是眼科的常见病，中国的近视人数有4亿，居世界首位。目前为止，准分子激光手术（LASIK）是最常见的屈光矫正手术，但LASIK手术会不可逆地对角膜瓣进行屈光性切削，因此，从长远的视力变化来看，采用高分子人工角膜植入材料，来代替LASIK手术，无疑是一种更好的选择。本项目拟结合高分子科学和纳米科学，开发一种新型的水凝胶纳米复合材料，主要以高折射的聚硫氨酯为基体，掺杂不同含量的无机纳米颗粒，制备一系列具有高折射率且折射率可调的水凝胶纳米复合材料。研究聚合物结构对材料性能的影响，探讨纳米颗粒含量与复合材料物理化学性能及生物表征之间关系的基本规律，尝试从理论角度对复合材料的设计合成进行诠释，以期实现复合材料的可控合成。本项目的成功实施将为人工角膜植入材料的设计、制备及其在眼科材料上的真正应用提供一定的理论支持和实际指导，无疑具有重要的科学意义和医学应用价值。

本项目利用巯基乙酸及几种不同结构的多元醇和不同分子量的聚乙二醇为原料，制备了6钟不同结构的端巯基乙酸酯。再将其与不同结构的过量二异氰酸酯反应后用甲基丙烯酸羟乙酯（HEMA）封端，得到一系列具有不同多元硫醇结构及二异氰酸酯结构的、可聚合的聚硫胺酯前聚体。最后与高折射的ZnS纳米粒子混合，经紫外引发自由基聚合，即可得到一系列高折射的水凝胶纳米复合材料。考察、分析了聚硫胺酯结构、性能以及纳米粒子含量对复合材料性能的影响，研究了其在人工角膜上的应用前景。为高折射率水凝胶型人工角膜材料的研制提供了理论依据。主要研究如下：.1. 将巯基乙酸分别与乙二醇、丙三醇及季戊四醇反应，得到巯基封端的端巯基乙酸乙二醇酯、端巯基乙酸丙三醇酯和端巯基乙酸季戊四醇酯，再将其与过量的不同二异氰酸酯（MDI、TDI、IPDI和HDI）反应，以DMPA为亲水性扩链剂，再利用HEMA将端异氰酸根封端，制备出一系列不同结构的双键封端的聚硫氨酯。最后通过紫外引发自由基共聚合，即可制备出一系列不同结构的聚硫氨酯/丙烯酸水凝胶，并对水凝胶的物理化学性能以及体外细胞毒性进行表征分析。.2. 将巯基乙酸分别与不同分子量的聚乙二醇反应，得到巯基封端的端巯基乙酸聚乙二醇酯，再将其与不同的二异氰酸酯（MDI、TDI、IPDI和HDI）反应，然后利用HEMA将过量的异氰酸端基封端，制备出一系列不同结、可聚合的PEG型聚硫氨酯前体。最后通过紫外引发自由基共聚合，即可制备出一系列PEG型聚硫氨酯/丙烯酸水凝胶，并对水凝胶的物理化学性能以及体外细胞毒性进行表征分析。.3. 将高折射率的ME-ZnS纳米粒子以不同的比例掺杂到前面所制备的聚硫氨酯基体中。采用紫外光引发自由基聚合的方式，制备出一系列基于不同多元醇结构及PEG型的高折射有机-无机纳米复合水凝胶，并对水凝胶的物理化学性能以及体外细胞毒性进行表征分析。