Development Of High Refractive Index Polythiourethane Hydrogels And Its Potential Application In Artificial Cornea Implants

Corneal implant materials are the key factor affecting the performance of artificial cornea.Ideal artificial corneal implants require stable physical and chemical properties,good biocompatibility,high light transmittance and good permeability,with biomechanical properties equal or somewhat stiffer than the cornea and a refractive index to allow the optical correction.Hydrogel biomaterials have been widely used in the area of ophthalmic materials,due to good biocompatibility and high permeability to water soluble metabolites such as glucose,small molecule nutrients,oxygen and so on.However,high water content hydrogel usually has poor mechanical performance and low refractive index,which limits its application in artificial cornea.In this dissertation,the following works have been investigated:1.A series of double-bond terminated polythiourethane precursors(PTUP)based on ethylene glycol bis(mercaptoacetate)(EGBMA)and glycerol tri(mercaptoacetate)(GTMA)were successfully synthesized,by using UV induced radical polymerization,a series of colorless transparent polythiourethane hydrogels were also prepared.Introduction of sulfur improved the refractive index of hydrogels in hydrated state,the equilibrium water content of the polythiourethane/AA hydrogels with 1/1 weight ratio of PTUP/AA hydrogel were62.9-76.5% and the RIs were measured to be as high as 1.396-1.441 and 1.514-1.548 in the dry and hydrated states,respectively.When branched trithiol GTMA was introduced into polythiourethane units,due to the smaller molecular dimension and similar spherical compact structure of branched polymer,which enhanced the hydrogen bonding between water molecules and polymers,so GTMA-based polythiourethane/AA hydrogels have relatively higher RIs together with high water content.For example,the RI of G-IP-1 hydrogel inhydrated state was 1.409,which is much higher than human corneal stromas at 1.373-1.380,in the meanwhile its equilibrium water content was 76.5%,very closed to human corneas at78%.Moreover,it also showed good mechanical properties,the elongation at break,tensile strength,and Young's modulus of hydrogel G-P-1 was 56.4%,1490 kPa,780 kPa,respectively.In vitro cytotoxicity assays suggested all the hydrogels exhibited minimal cytotoxicity towards human corneal epithelial cells(HCECs).2.A novel pentaerythrotol tetra(mercaptoacetate)(PETMA)was synthesized,characterized and applied to polythiourethane preparation.The water contents of the prepared hydrogels were 60.2-81.3%,and the RIs of the hydrogels in dry and hydrated state were1.504-1.589 and 1.381-1.445,respectively.Compared to linear and branched hydrogels,four arm hydrogels exhibited higher water content and higher refractive index.The prepared hydrogels show good biocompatibility.3.Three novel polyethylene glycol bis(mercaptoacetate)s with different molecular weight(PEG200BMA,PEG400 BMA and PEG1000BMA)were synthesized and reacted with different diisocyanates to obtain polythiourethane precursors(PTUP).A series of colorless transparent PEG-based polythiourethane hydrogels were also successfully prepared by copolymerization with acrylic acid(AA)using UV induced radical polymerization.The water contents of the prepared hydrogels were 42.8-69.1%,and their RIs were 1.509-1.559,1.425-1.468(1/1)and 1.502-1.543,1.378-1.419(1/2)in dry and hydrated state,respectively.Moreover,the prepared hydrogels exhibited good mechanical properties,the elongation at break,tensile strength,and Young's modulus of hydrogel 2-M-1 was 275%,3240 kPa,1310 kPa,respectively.These PEG-based polythiourethane hydrogels exerted minimal cytotoxicity towards human corneal epithelial cells.4.A series of highly refractive index organic-inorganic nanocomposite hydrogels were prepared by doping inorganic nanoparticles(ME-ZnS)with high refractive index into polythiourethane precursors,followed by UV induced radical copolymerization with AA.The prepared hydrogels are colorless and transparent,the equilibrium water contents of the hydrogels were 50.0-73.4%,the RIs were 1.522-1.596 and 1.389-1.454 in dry and hydrated states,respectively.With increasing the content of ZnS NPs,the water content of hydrogels decreased,and the RI increased linearly,which can be tuned by varying the ZnS content.Invitro cytotoxicity assays suggested that the introduction of ZnS NPs added little cytotoxicity to the polythiourethane hydrogels and all the hydrogel nanocomposites exhibited minimal cytotoxicity towards HCECs.