MULTI-MECHANISM SURGICAL COMPOSITIONS
The present disclosure provides hydrogel compositions having multiple gelation mechanisms. The composition includes at least one component which forms a hydrogel, in combination with a second component which includes a self-assembling peptide capable of forming a self-assembled macromer.
1 . A composition comprising:
at least one hydrogel precursor comprising functional groups selected from the group consisting of electrophilic groups, nucleophilic groups, and combinations thereof; and
at least one self-assembling peptide;
wherein the hydrogel precursor forms a hydrogel composition concurrently with the self-assembling peptide forming a self-assembled macromer.
2 . The composition of claim 1 , wherein the self-assembling peptide is an amphiphilic peptide.
3 . The composition of claim 1 , wherein the electrophilic functional groups are selected from the group consisting of carbodiimidazole groups, sulfonyl chloride groups, chlorocarbonate groups, n-hydroxysuccinimidyl ester groups, succinimidyl ester groups, sulfosuccinimidyl ester groups, N-hydroxyethoxylated succinimide ester groups, methane diisocyanate groups, methylene-bis(4-cyclohexylisocyanate) groups, isocyanate groups, cyanoacrylates, aldehydes, genipin, diisocyanate groups, hexamethylenediisocyanate groups, maleimide groups, and combinations thereof.
4 . The composition of claim 1 , wherein the nucleophilic functional group is selected from the group consisting —NH 2 , —SH, —OH, —PH 2 , and —CO—NH—NH 2 , and combinations thereof.
5 . The composition of claim 1 , wherein the at least one hydrogel precursor comprises a first hydrogel precursor comprising electrophilic groups in combination with a second hydrogel precursor comprising nucleophilic groups.
6 . The composition of claim 5 , wherein the electrophilic functional group of the first hydrogel precursor comprises an n-hydroxysuccinimdyl ester and wherein the second hydrogel precursor comprises trilysine.
7 . The composition of claim 1 , wherein the composition further comprises a bioactive agent.
8 . A hydrogel composition comprising:
at least one hydrogel precursor comprising electrophilic and nucleophilic functional groups; and
at least one self-assembling peptide;
wherein the hydrogel precursor forms a hydrogel composition prior to the self-assembling peptide forming a self-assembled macromer.
9 . An implant comprising:
at least one electrophilic polymer and at least one nucleophilic polymer; and,
at least one self-assembling peptide;
wherein the electrophilic polymer and the nucleophilic polymer form a composition prior to the self-assembling peptide forming a self-assembled macromer.
10 . The implant according to claim 9 , wherein the composition is selected from the group consisting of films, foams, tissue scaffolds, and drug delivery devices.
11 . The implant according to claim 9 , wherein the composition at least partially hydrated in a peptide solution.
12 . The implant according to claim 9 , wherein the self-assembling peptide is combined with an aqueous solution.
13 . A hydrogel composition comprising:
at least one hydrogel precursor comprising electrophilic and nucleophilic functional groups; and
at least one self-assembling peptide;
wherein the self-assembling peptide forms a self-assembled macromer prior to the hydrogel precursor forming a hydrogel.
14 . The hydrogel composition of claim 13 , wherein the hydrogel forms a hydrogel composition in from about 5 seconds to about 5 minutes.
15 . The hydrogel composition of claim 13 , wherein the nucleophilic functional group comprises a polymer selected from the group consisting of collagen, gelatin, or serum.
16 . The hydrogel composition of claim 15 , wherein the nucleophilic functional group further comprises the at least one self-assembling peptide.
17 . A method for forming a composition in situ comprising:
providing at least one hydrogel precursor comprising functional groups selected from the group consisting of electrophilic groups, nucleophilic groups, and combinations thereof;
providing a self-assembling peptide;
introducing the hydrogel precursor and the self-assembling peptide in situ; and
initiating gelation of the self-assembling peptide and the hydrogel in situ.
18 . The method of claim 17 , wherein the gelation of the self-assembling peptide and the hydrogel precursor occurs concurrently.
19 . The method of claim 17 , wherein the gelation of the self-assembling peptide occurs prior to gelation of the hydrogel precursor.
20 . The method of claim 17 , wherein the gelation of the self-assembling peptide occurs after gelation of the hydrogel precursor.
21 . The method of claim 17 , wherein the electrophilic functional groups are selected from the group consisting of carbodiimidazole groups, sulfonyl chloride groups, chlorocarbonate groups, n-hydroxysuccinimidyl ester groups, succinimidyl ester groups, sulfosuccinimidyl ester groups, N-hydroxyethoxylated succinimide ester groups, methane diisocyanate groups, methylene-bis(4-cyclohexylisocyanate) groups, isocyanate groups, cyanoacrylates, aldehydes, genipin, diisocyanate groups, hexamethylenediisocyanate groups, maleimide groups, and combinations thereof.
22 . The method of claim 17 , wherein the nucleophilic functional group is selected from the group consisting —NH 2 , —SH, —OH, —PH 2 , and —CO—NH—NH 2 , and combinations thereof.
23 . The method of claim 17 , wherein the at least one hydrogel precursor comprises a first hydrogel precursor comprising electrophilic groups in combination with a second hydrogel precursor comprising nucleophilic groups.
24 . The method of claim 17 , wherein the electrophilic functional group of the first hydrogel precursor comprises an n-hydroxysuccinimdyl ester and wherein the second hydrogel precursor comprises a polymer selected from the group consisting of trilysine, collagen, gelatin, and serum.