Dendritic macroporous hydrogels prepared by crystal templating

• US 9,896,561 B2
• Filed: 04/22/2016
• Issued: 02/20/2018
• Est. Priority Date: 02/26/2008
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Zawko, Scott, Schmidt, Christine
• Primary Examiner(s): Azpuru, Carlos
• Assistant Examiner(s): Alley, Genevieve S
• Application Number:
  US15/135,978
• Publication Number:
  US 20160237235A1
• Time in Patent Office: 669 Days
• CPC Class Codes: A61L 26/0023 Polysaccharides
• CPC Class Codes: A61L 26/0095 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B01J 13/0065 containing an organic phase
• CPC Class Codes: C08B 37/0015 Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes
• CPC Class Codes: C08B 37/003 Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
• CPC Class Codes: C08B 37/0045 alpha-D-Galacturonans, e.g. methyl ester of (alpha-1,4)-linked D-galacturonic acid units, i.e. pectin, or hydrolysis product of methyl ester of alpha-1,4-linked D-galacturonic acid units, i.e. pectinic acid; Derivatives thereof
• CPC Class Codes: C08B 37/0072 Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
• CPC Class Codes: C08B 37/0075 Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
• CPC Class Codes: C08B 37/0084 Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
• CPC Class Codes: C08H 1/06 derived from horn, hoofs, hair, skin or leather
• CPC Class Codes: C08J 2201/0424 containing halogen, nitrogen, sulphur or phosphorus atoms
• CPC Class Codes: C08J 2205/022 Hydrogel, i.e. a gel containing an aqueous composition
• CPC Class Codes: C08J 2205/04 characterised by the foam pores
• CPC Class Codes: C08J 2207/10 Medical applications, e.g. biocompatible scaffolds
• CPC Class Codes: C08J 2305/00 Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
• CPC Class Codes: C08J 2305/04 Alginic acid; Derivatives thereof
• CPC Class Codes: C08J 2305/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08J 3/075 Macromolecular gels
• CPC Class Codes: C08J 3/24 : Crosslinking, e.g. vulcanising, of macromolecules mechanical aspects B29C35/00; crosslinking agents C08K
• CPC Class Codes: C08J 3/242 : Applying crosslinking or accelerating agent onto compounding ingredients such as fillers, reinforcements
• CPC Class Codes: C08J 3/26 : of latex
• CPC Class Codes: C08J 3/28 : Treatment by wave energy or particle radiation
• CPC Class Codes: C08J 5/10 : characterised by the additives used in the polymer mixture
• CPC Class Codes: C08J 5/18 : Manufacture of films or sheets
• CPC Class Codes: C08J 9/26 : by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
• CPC Class Codes: C08K 5/0025 : Crosslinking or vulcanising agents; including accelerators
• CPC Class Codes: C08K 5/0083 : Nucleating agents promoting the crystallisation of the polymer matrix
• CPC Class Codes: C08K 5/21 : Urea; Derivatives thereof, e.g. biuret
• CPC Class Codes: C08L 5/00 : Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
• CPC Class Codes: C08L 5/04 : Alginic acid; Derivatives thereof
• CPC Class Codes: C08L 5/06 : Pectin; Derivatives thereof
• CPC Class Codes: C08L 5/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: C08L 5/10 : Heparin; Derivatives thereof
• CPC Class Codes: C08L 5/16 : Cyclodextrin; Derivatives thereof
• CPC Class Codes: C08L 89/06 : derived from leather or skin , e.g. gelatin

Abstract

The present invention includes a hydrogel and a method of making a porous hydrogel by preparing an aqueous mixture of an uncrosslinked polymer and a crystallizable molecule; casting the mixture into a vessel; allowing the cast mixture to dry to form an amorphous hydrogel film; seeding the cast mixture with a seed crystal of the crystallizable molecule; growing the crystallizable molecule into a crystal structure within the uncrosslinked polymer; crosslinking the polymer around the crystal structure under conditions in which the crystal structure within the crosslinked polymer is maintained; and dissolving the crystals within the crosslinked polymer to form the porous hydrogel.

Claims

1. A hydrogel film comprising:

first and second opposing ends;

chitosan;

urea; and

at least one crystal;

wherein the at least one crystal is (a) dendritically branched, (b) at least 1 micron in diameter, and (c) comprises the urea.

2. The hydrogel film of claim 1, wherein the hydrogel film has top and bottom surfaces connecting the first and second ends, and the at least one crystal is distributed from the top surface to the bottom surface and from the first end to the second end.

3. The hydrogel film of claim 1, wherein:

the at least one crystal forms a continuous crystal network, connecting the first and second ends, including first and second crystal portions; and

the hydrogel film further comprises a compressed fiber, including a ridge, compressed between the first and second crystal portions.

4. The hydrogel film of claim 3, wherein the compressed fiber is included in a plurality of compressed fibers formed among alternating valleys and ridges.

5. The hydrogel film of claim 1, wherein the at least one crystal forms a continuous crystal network.