Cryogels of PVA-boronic acid containing co-polymers for cell culture
View Patent ↗The present invention relates to a cryogel which contains a polyol selected from polyvinyl alcohol or galactomannan and a co-polymer of Formula I: The cryogel is formed by mixing the monomers of the co-polymer of Formula I at a temperature of less about 5 degrees C. with the polyol and a free radical initiator in an aqueous solution and polymerizing the solution to form the cryogel. The cryogel is used for culturing cells and can be decomposed by contact with a monosaccharide.
1. A cryogel comprising a polyol and a co-polymer of Formula I:
wherein,
m is from 150000 to 220000;
n is from 4000 to 6000;
p is 0 or from 3500 to 5500;
x is from 1 to 5;
L is a bond or —CONH— wherein the nitrogen is attached to the boron-substituted phenyl group;
R 1 , R 2 , R 3 , and R 4 are independently H or C 1 -C 6 alkyl;
each R 5 independently is H or C 1 -C 3 alkyl; and
either X 1 is H and X 2 is —B(OH) 2 , or X is —B(OH) 2 and X 2 is H;
wherein the polyol is polyvinyl alcohol or galactomannan.
2. The cryogel of claim 1 , wherein R 1 , R 2 , R 3 , and R 4 are H.
3. The cryogel of claim 1 , wherein at least two of R 1 , R 2 , R 3 , and R 4 are C 1 -C 6 alkyl.
4. The cryogel of claim 1 , wherein R 1 , R 2 , R 3 , and R 4 are C 1 -C 6 alkyl.
5. The cryogel of claim 1 , wherein L is a bond and X 1 is —B(OH) 2 or X 2 is —B(OH) 2 .
6. The cryogel of claim 1 , wherein L is —CO—NH— and X 1 is H or X 2 is H.
7. The cryogel of claim 1 , wherein R 5 is H.
8. The cryogel of claim 1 , wherein x is 1 or 2.
9. The cryogel of claim 1 , wherein the co-polymer is:
poly-((AAm) m -co-(VPBA) n );
poly-((NIPAAm) m -co-VPBA) n );
poly-((AAm) m -co-(AAPBA) n -co-(DMAEMA) p );
poly-((NIPAAm) m -co-(AAPBA) n -co-(DMAEMA) p );
poly-((NIPAAM) m -co-(VPBA) n -co-(DMAEMA) p );
poly-((AAm) m -co-(VPBA) n -co-(DMAEMA) p ); or
poly-((DMAAm) m -co-(VPBA) n -co-(DMAEMA) p ).
10. A cell culture medium comprising the cryogel of claim 1 .
11. The cryogel of claim 1 that is a xerogel.
12. A method of preparing an aqueous mixture comprising:
mixing at a temperature of less than about 5° C., a polyol, a radical initiator, a compound of Formula II, a compound of Formula III, and optionally a compound of Formula IV to form the aqueous mixture:
wherein
L is a bond or —CONH— wherein the nitrogen is attached to the boron-substituted phenyl group;
R 1 , R 2 , R 3 , and R 4 are independently H or C 1 -C 6 alkyl;
x is from 1 to 5;
each R 5 independently is H or C 1 -C 3 alkyl; and
either X 1 is H and X 2 is —B(OH) 2 , or X 1 is —B(OH) 2 and X 2 is H;
wherein the polyol is polyvinyl alcohol or galactomannan.
13. The method of claim 12 , further comprising polymerizing the compounds of the aqueous mixture to form a cryogel.
14. The method of claim 12 , wherein the cryogel comprises the polyol and a co-polymer which is:
poly-((AAm) m -co-((VPBA) n );
poly-((NIPAAm) m -co-(VPBA) n );
poly-((AAm) m -co-(AAPBA) n -co-(DMAEMA) p ),
poly-((NIPAAm) m -co-(AAPBA) n -co-(DMAEMA) p );
poly-((NIPAAM) m -co-(VPBA) n -co-(DMAEMA) p );
poly-((AAm) m -co-(VPBA) n -co-(DMAEMA) p ); or
poly-((DMAAm) m -co-(VPBA) n -co-(DMAEMA) p );
wherein
m is from 150000 to 220000;
n is from 4000 to 6000; and
p is 0 or is from 3500 to 5500.
15. A method of cell culture comprising contacting a cell with a culture medium comprising the cryogel of claim 1 , thereby culturing the cell.
16. A method of disintegrating the cryogel of claim 1 , comprising contacting the cryogel with a monosaccharide, thereby disintegrating the cryogel.