Crosslinked hydrogels and related method of preparation
The present invention provides a method of manufacturing a hydrogel comprising the step of crosslinking a biopolymer using a carbodiimide crosslinker of Formula I wherein at least one of R 1 and R 2 is a functional group that is a bulky organic functional group. R 1 and R 2 can each independently be an optionally substituted saturated or unsaturated functional group selected from the group consisting of an alkyl, a cycloalkyl, a heterocyclic, and an aryl. The bulky organic functional group will slow down the crosslinking reaction of carbodiimide due to the steric effects and/or electronic effects, in comparison to a crosslinking reaction using EDC. Also provided are the hydrogels and ophthalmic devices prepared using the method of the invention and uses thereof.
1. A method of manufacturing a hydrogel having a white light transmission of at least 70%, the method comprising:
a) mixing at room temperature a collagen and a carbodiimide crosslinker, wherein the carbodiimide crosslinker is (N-Cyclohexyl-N′-(2-morpholinoethyl)carbodiimide) (CMC) or a metho-p-toluenesulfonate salt thereof,
and the molar equivalent ratio of carbodiimide crosslinker to collagen amine groups is from about 0.3 to about 0.7; and
b) casting the mixture into a mold prior to gelation, wherein the time to gelation at room temperature is increased relative to use of the crosslinker 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide (EDC).
2. The method of claim 1 , wherein the carbodiimide crosslinker is water soluble.
3. The method of claim 1 , wherein the collagen is recombinant human type III collagen.
4. The method of claim 1 , wherein the hydrogel is a composite additionally comprising a water-soluble acrylic, methacrylic, or acrylamide.
5. The method of claim 4 , wherein the water-soluble acrylic, methacrylic, or acrylamide is one or more of MPC (2-methacryloyloxyethyl phophorylcholine) and PEG-DA (polyethylene glycol-diacrylate).
6. The method of claim 1 , wherein prior to mixing, the collagen is treated to photo polymerization.
7. The method of claim 1 , wherein the molar equivalent ratio of carbodiimide crosslinker to collagen amine groups is about 0.5.
8. The method of claim 1 , wherein gelation time is 2.5- to 4-fold longer compared to crosslinking using EDC.