Compliant surgical adhesive
Surgical adhesives that include a blend of two different thermoreversible gelling polymers and a crosslinking agent are described. The first thermoreversible gelling polymer is partially or fully acrylated and the second thermoreversible gelling polymer includes dual functionality including acrylate functionality and amine-reactive functionality. The adhesives can provide gelling and covalent crosslinking within the polymers of the adhesive as well as crosslinking with surrounding tissue.
1. A gel-forming composition comprising:
a first thermoreversible gelling block copolymer that includes a hydrophilic block and a hydrophobic block, the first thermoreversible gelling copolymer including acrylate functionality in at least a portion of the termini of the copolymer;
a second thermoreversible gelling block copolymer that differs from the first thermoreversible gelling block copolymer and includes a hydrophilic block and a hydrophobic block, the second thermoreversible gelling copolymer including acrylate functionality on a portion of the termini of the copolymer and further including amine-reactive functionality on a portion of the termini, the hydrophilic block of the second thermoreversible gelling block copolymer being the same or different as the hydrophilic block of the first thermoreversible gelling block copolymer and the hydrophobic block of the second thermo reversible gelling block copolymer being the same or different as the hydrophobic block of the first thermoreversible gelling block copolymer; and
a polyfunctional thiol crosslinker;
the composition comprising the first thermoreversible gelling block copolymer and the second thermoreversible gelling block copolymer in a blend at a ratio of from about 10:90 to about 90:10 by weight, respectively.
2. The composition of claim 1 , wherein the first and/or the second thermoreversible gelling block copolymer includes a polyethylene oxide as the hydrophilic block.
3. The composition of claim 1 , wherein the first and/or the second thermoreversible gelling block copolymer includes a polypropylene oxide as the hydrophobic block.
4. The composition of claim 1 , wherein the first and second thermoreversible gelling copolymers each independently include between about 10% and about 50% of the hydrophobic block.
5. The composition of claim 1 , wherein at least one of the first and second thermoreversible gelling copolymers is a linear polymer.
6. The composition of claim 1 , wherein at least one of the first and second thermoreversible gelling copolymers is a multi-armed polymer.
7. The composition of claim 1 , wherein at least one of the thermoreversible gelling copolymers is a 4 arm-polypropylene oxide-polyethylene oxide block copolymer.
8. The composition of claim 1 , wherein at both of the thermoreversible gelling copolymers include a 4 arm-polypropylene oxide-polyethylene oxide block copolymer.
9. The composition of claim 8 , wherein the 4 arm-polypropylene oxide-polyethylene oxide block copolymer is a tetra functional poloxamine.
10. The composition of claim 1 , wherein the first thermoreversible gelling block copolymer is fully acrylated.
11. The composition of claim 1 , wherein the first thermoreversible gelling block copolymer is partially acrylated.
12. The composition of claim 11 , wherein the first thermoreversible gelling block copolymer is from about 50% to about 95% acrylated.
13. The composition of claim 11 , wherein the partially acrylated copolymer comprising remaining termini, the remaining termini carrying one or more biologically active agents.
14. The composition of claim 1 , the amine-reactive functionality of the second thermoreversible gelling block copolymer comprising functionality selected from the group consisting of aldehyde, carbodiimide, sulfonyl chloride, isothiocyanate, isocyanate, acyl azide, anhydride, fluorobenzene, carbonate, N-hydroxysuccinimide ester, imidoester, epoxide, fluorophenyl ester, phenol derivatives, aniline derivatives, and combinations thereof.
15. The composition of claim 1 , the amine-reactive functionality of the second thermoreversible gelling block copolymer comprising a dihydroxyphenyl derivative.
16. The composition of claim 15 , the dihydroxyphenyl derivative comprising L-3-4-dihydroxyphenylalanine, dopamine, 3,4-dihydroxyphenyl ethanol, 3,4-dihydroxyhydrocinnamic acid, norepinephrine, epinephrine, derivatives thereof, and/or combinations thereof.
17. The composition of claim 1 , the second thermoreversible gelling block copolymer comprising the acrylate functionality and the amine-reactive functionality in a ratio of from about 1:3 to about 3:1.
18. The composition of claim 1 , comprising the first thermoreversible gelling block copolymer and the second thermoreversible gelling block copolymer in the blend at a ratio of from about 50:50 to about 80:20 by weight.
19. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
20. The composition of claim 1 , wherein the polyfunctional thiol crosslinker is monomeric.
21. The composition of claim 1 , wherein the polyfunctional thiol crosslinker is polymeric.
22. An application device containing the composition of claim 1 in the form of a surgical adhesive, comprising the blend of the first and second thermoreversible gelling block copolymers and the polyfunctional thiol crosslinker held separately from the blend of the first and second thermoreversible gelling block copolymers.