Development of artificial cornea utilizing with Apatite-polymer composites technique and nano-micro-fabrication technique

本研究合成了纳米结构可控的高分子-蛋白质复合材料用于光学部件，高分子-胶原-羟基磷灰石复合材料用于人工角膜周边部件，为人工角膜材料的研究积累了基础数据。为了提高PVA水凝胶的生物相容性，我们采用胶原蛋白、RGDS、IKVAV等生物分子对PVA水凝胶进行表面改性。同时，我们还开发了新型的高分子量聚苹果酸衍生物作为表面改性剂，多糖和氨基酸固定技术作为人工配体，以增强生物学反应;为了实现人工角膜装置在宿主角膜上的牢固固定，我们开发了生物相容性PVA-羟基磷灰石复合材料。我们开发了两种不同的方法，交替浸泡法和颗粒捏合法，以制备聚乙烯醇-羟基磷灰石复合材料。我们 ...更多信息 我们利用微细加工技术成功地将多孔结构引入到PVA-羟基磷灰石复合材料中。我们利用穿孔技术和静电纺丝法制备的无纺织物来获得3D结构，并考察了物理锚定效应是否有助于表皮的稳定性，我们开始了利用兔角膜原代细胞进行材料评价和兔角膜的可行性研究。证实了作为光学部件材料的PVA-胶原复合物上的表皮的分层。此外，还证实了细胞的粘附和铺展与配体分子的密度相一致，粘附的细胞在粘附蛋白固定化的膜片上长期稳定。胶原固定化PVA水凝胶-羟基磷灰石复合材料对角膜细胞具有明显的亲和性，其表面形貌对人工角膜的上皮化和稳定性有明显的影响，为设计具有长期功能的人工角膜提供了重要指标。将PVA-HAp复合材料植入兔角膜的结果是，观察到血管和宿主组织侵入角膜结构，结果表明预期实现了装置的牢固固定。少

In this study, we synthesized the composites of the macromolecule - protein which controlled nano-structure to use for an optics part and composites such as macromolecule - collagen - hydoxyapatite complexes to use for a peripheral part of the corneal prosthesis, and accumulated the fundamental data as materials for artificial cornea. We developed surface modification technique of the PVA hydro-gel by the bio-molecules such as collagen, RGDS, IKVAV to improve the biocompatibility. And we also developed the new high molecular weight Poly(malic acid) derivatives as a surface modifier and polysaccharide and amino acids immobilization technique as a artificial ligand to enhance the biological responses.To achieve the strong fixation of the artificial corneal devices on the host cornea, we developed the biocompatible PVA-hydroxyapatite composites. We have developed two different methods, alternate soaking method and particles kneading method, to make the PVA-hydroxyapatite composites. We ha … More ve succeeded to introduce the porous structure into the PVA-hydroxyapatite composites by using micro-fabrication technique. We utilized the perforation technology and nanofiber nonwoven fabric prepared by the electrospinning methods to give the 3D structure and inspected whether an effect of physical anchoring contributed to stability of epidermis.We started the materials evaluation by using primary cells from rabbit cornea and the feasibility study on the rabbits cornea during the periods. Stratifications of epidermis were confirmed on the PVA-collagen composites as a material for optical part. In addition, the cell adhesion and spreading that agreed with density of a ligand molecule were confirmed.The adhered cells were stable for a long term on the adhesion protein immobilized nanofiber sheet. And clear affinity was given for the cornea cells on the collagen immobilization PVA hydro-gel-hydroxyapatite composites, The surface topology clearly influenced the epithelialization on an artificial cornea and the stabilization greatly, and a big indicator for a design of the artificial cornea which functioned for a long term was provided. As a result of implantation of PVA-HAp composites in the rabbit cornea, an invasion of a blood vessel and host tissues into the micropore structure were observed and the results suggested that the strong fixation of a device was realized was expected. Less