Polymer hydrogel adhesives formed with multiple crosslinking mechanisms at physiologic pH
The present invention encompasses biocompatible reactants, biocompatible product hydrogels, methods of use thereof, and methods of synthesis thereof using a novel crosslinking mechanism between a first reactant compound including an N-Hydroxysuccinimide (NHS) ester group and a second reactant compound including a N-terminal cysteine amine group. In certain embodiments, one or more of the reactant compounds may be a macromonomer.
1. A hydrogel obtained by covalently cross-linking a first macromonomer comprising an N-Hydroxysuccinimide (NHS) ester group with a second macromonomer comprising a N-terminal cysteine group, wherein covalently cross-linking the first and second macromonomers comprises:
(a) forming an amide bond between the carboxyl carbon of the N-Hydroxysuccinimide (NHS) ester group of the first macromonomer and the primary amine of the N-terminal cysteine group of the second macromonomer to form a third macromonomer, and
(b) forming a disulfide bond between primary thiol groups on two of the third macromonomers produced in step (a).
2. The hydrogel of claim 1 wherein the hydrogel is biocompatible.
3. The hydrogel of claim 1 wherein the first macromonomer, the second macromonomer, or both, comprise polyethylene glycol.
4. The hydrogel of claim 3 , wherein the second macromonomer further comprises a catechol group.
5. The hydrogel of claim 1 , wherein the first macromonomer is selected from the group consisting of:
and wherein the second macromonomer comprises the chemical structure:
6. The hydrogel of claim 5 , wherein each n has a value in the range of from 1 to 201, and wherein each R comprises a hexaglycerin core or a tripentaerythritol core.
7. A method of synthesizing a hydrogel comprising covalently cross-linking an effective amount of a first macromonomer comprising an N-Hydroxysuccinimide (NHS) ester group with an effective amount of a second macromonomer comprising a N-terminal cysteine group, wherein a hydrogel is formed, wherein the step of covalently cross-linking the first and second macromonomers comprises:
(a) forming an amide bond between the carboxyl carbon of the N-Hydroxysuccinimide (NHS) ester group of the first macromonomer and the primary amine of the N-terminal cysteine group of the second macromonomer to form a third macromonomer, and
(b) forming a disulfide bond between primary thiol groups on two of the third macromonomers produced in step (a).
8. The method of claim 7 , wherein the hydrogel formed is biocompatible.
9. The method of claim 7 , wherein the step of covalently cross-linking the first and second macromonomers occurs at physiological pH.
10. The method of claim 7 , wherein the first macromonomer, the second macromonomer, or both, comprise polyethylene glycol.
11. The method of claim 7 , wherein the second macromonomer further comprises a catechol group.