Biomimic Construction And Functionalization Of Collagen Based Substrate For Corneal Repair

Corneal disease is one of the most important reasons which cause human visual defect andblindness. Corneal transplantation is the only effective way to treat some blindness caused bycorneal disease. Lacking of the cornea repair materials immensely limited the developing andpopularity of corneal disease treatment. This thesis dedicated to researching collagen basedcornea repair materials which have better physicochemical and biological properties.Bacterium infection and inflammation is one of the most important reasons which cause thefailure of corneal transplantation. Thus, a cornea repair material with broad-spectrumantibacterial activity is also the key point of this research.Compared with usual cornea repair materials, the structural bionics collagen based materialprepared in this thesis has the following advantages: excellent mechanical and opticalproperty; easy to penetrate for the nutrient substance; pore structure and layered structure arecontrolled; good biocompatibility in vitro and in vivo, etc. Functional cornea repair materialwith loading antibacterial agents has good properties of anti-gram negative bacterial and anti-gram positive bacterial, can repair damaged cornea tissue nicely. As one of the maincomponents of natural corneal tissue, this research carries through thorough research anddiscussion on the fabrication and functionalizes of the collagen based cornea repair material.1. Fabrication of collagen based cornea repair material which has bionic structuresCornea repair material should have appropriate physicochemical and biological propertieswhich are closely related with the structure of the material. Materials have similar structure asnature cornea tissue is helpful for restoration of damaged tissue. By using physical orchemical methods, the author fabricates a series of collagen based cornea repair materials byvarious preparation technologies.(1) Collagen-gelatin-hyaluronic acid (CGH631) compositemembrane has good tensile strength, hydrophility and biocompatibility, but it is unable to bearthe suture in clinical.(2) Introduce the holes with nano scale in collagen membrane by ionleaching technology, the nano-holes change the inter structure and enhance the property ofsuture of the collagen membrane; collagen membranes with2.5%-5.0%pore-forming materialhave appropriate physicochemical and biological properties, is able to be the substratematerial of collagen based cornea repair material.(3) Collagen based cornea repair materialswhich have various layered structure was fabricated by controlling the process of the polymer film formation. The films have similar properties as nature cornea, and can replace and repairdifferent part of the damaged cornea tissue.(4) Collagen based cornea repair material (FD-Col) with micro-rough surface was prepared by freeze drying technical. FD-Col film has moreprotein adsorption site and cell-binding site than the AD-Col film. The epithelization processof FD-Col film in vivo (rabbit) was completed in2weeks, obvious faster than the materialwhich has smooth surface.2. Research on the anti-bacterial property of the collagen based cornea repair materialThis research successfully crosslinks a broad-spectrum antibiotic named tobramycin withcollagen and obtain a collagen-tobramycin membrane (Col-Tob) which have drug sustainedrelease effect in one week and anti-bacterial function. Col-Tob film has good optical,mechanical, moisturizing property and biocompatibility. After steeping in PBS7days, theCol-Tob film still havs good properties of anti-gram negative bacteria and anti-gram positivebacteria. Corneal epithelium can grow and proliferation well on the Col-Tob film, there were2~3layers of corneal epithelial cells adhered on the membrane after one week. Col-Tob isable to bear the suture in clinical was demonstrate by animal experiment. No bacterialinfection and inflammatory reaction was found after corneal transplantation. After one month,the wound healing well, epithelization process completed successfully, no vessel andkeratoconus appeared. Col-Tob displayed a good repair effect in vivo.