Biocompatibility Evaluation And Anti-infection Functional Modification Of Collagen-based Corneal Implants

Infectious keratitis is one of the main cause of blindness,especially in our country and other developing countries.To restore vision for these patients,the only widely accepted and effective treatment is to transplant a healthy cornea.However,the lack of donors makes the preparation of corneal implants using natural biomaterials as a research hotspot.Postoperative infection of infectious keratitis is an important reason for failure of corneal transplantation,and local application of drugs(such as eyedrops)is usually used to prevent infection.Unfortunately,it is difficult for disease treatment due to low bioavailability of ophthalmic drugs.Therefore,it is of great significance to seek a corneal implant with sustained drug release.The main contents of this paper are as follows:1.Biocompatibility evaluation in vivo of collagen-based corneal implant developed by our team was implemented.The experimental animal models and methods of operation and nursing were preliminarily established to provide reference for the animal type testing of these implants.Animal experimental results showed that collagen-based corneal implant possesed good biocompatibility,and effectively promoted corneal epithelium.However,there was no obvious effect for suture eyelid on inhibiting degradation or shedding of the implant,so it is suggested that this step should not be taken in future animal experiments.In addition,it was observed that the resistance to suture of the implant was not strong enough to meet the needs of corneal transplantation.Furthermore,it is susceptible to infection after surgey and should be given antiinfection function.2.?-cyclodextrin dialdehyde(?-CD-DA),which can be used in not only crosslinking agent of collagen,but also the loading of ophthalmological anti-infective drugs by cyclodextrin hydrophobic cavity,was synthesized by 2-iodine acyl benzoic acid(IBX)oxidation.Then,Ofloxacin,Voriconazole and Ganciclovir against bacteria,fungi and viruses,respectively were encapsulated with ?-CD-DA.The results of FTIR,PXRD and ROESY showed that inclusion complexs were successfully prepared,and the inclusion rates were 81.2%,57.5% and 76.8% respectively.Ultimately,inclusion complexs of ?-CD-DA and anti-infective drugs were used as crosslinking agents for collagen to prepare incorporate collagen-based corneal implants with appropriate mechanical strength and sustained drug release.The physicochemical performance results showed that three kinds of anti-infection collagen membranes possessed layer structure and saturated water content similar to natural cornea.Compared with EDC/NHS cross-linking collagen membrane,the tensile strength of anti-infection collagen membranes was about twice,and the transmittance and enzymatic hydrolysis performance were also improved.In addition,cell experiments proved that antiinfection collagen membranes were more conducive to cell adhesion and proliferation,indicating a good biocompatibility in vitro.Drug release results showed that all three antiinfection collagen membranes possessed at least one week drug release effect.The inhibition zone test results demonstrated that bacteriostasis of antibacterial collagen membrane(?-CDDA/OFLX-Col)was obvius against S.aureus and E.coli,and fungistasis of antifungal collagen membrane(?-CD-DA/Vor-Col)was obvius against A.fumigatus.Therefore,anti-infection corneal implants have potential application value in the treatment of infectious keratitis.