Tough Hydrogels

• US 20080208347A1
• Filed: 09/27/2005
• Published: 08/28/2008
• Est. Priority Date: 06/06/2005
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Muratoglu, Orhun K., Bodugoz-Senturk, Hatice, Spiegelberg, Stephen H., Braithwaite, Gavin J.C., Choi, Jeeyoung
• Granted Patent: US 9,394,384 B2
• Time in Patent Office: Days
• US Class Current: 623/18.11
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/32 for the hip
• CPC Class Codes: A61F 2/38 for elbows or knees
• CPC Class Codes: A61F 2/3804 for elbows
• CPC Class Codes: A61F 2002/30754 Implants for interposition between two natural articular surfaces
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: C08F 6/10 Removal of volatile materials, e.g. solvents C08F6/001, C08F6/003, C08F6/005, C08F6/006, C08F6/008, C08F6/02, C08F6/04 take precedence
• CPC Class Codes: C08J 2329/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08J 3/075 Macromolecular gels
• CPC Class Codes: C08L 2666/14 Macromolecular compounds according to C08L59/00 - C08L87/00; Derivatives thereof
• CPC Class Codes: C08L 29/04 Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

The invention provides fabricated tough hydrogels, hydrogel-containing compositions, and methods of making the same. The invention also provides methods of implanting or administering the tough hydrogels, or the hydrogel-containing compositions to treat a subject in need. Methods of cross-linking pre-solidified or pre-gelled hydrogel particles and making cross-linked tough hydrogels, and crosslinked tough hydrogel-containing compositions also are disclosed herein.

Claims

1-51. -51. (canceled)

52. A method of making a tough hydrogel comprising:

a) annealing a hydrogel by heating to a temperature that is below the melting point of the hydrogel that is being annealed; and

b) cooling the heated hydrogel to room temperature, thereby forming a tough hydrogel.

53. The method according to claim 52, wherein the hydrogel is annealed in air, an inert gas, or under vacuum.

54. The method of claim 52 further comprising dehydrating the hydrogel prior to annealing by:

(i) contacting the hydrogel with a solvent,

(ii) air-drying the hydrogel at room temperature,

(iii) heating the hydrogel to a temperature below the melting point of the hydrogel that is being dehydrated,

(iv) placing the hydrogel under vacuum, or

(v) a combination of thereof.

55. The method according to claim 54, wherein the hydrogel is dehydrated by contacting with a solvent selected from the group consisting of alcohols or their solutions in an organic solvent or water, PEG or its solutions, ethanol, functional groups carrying organic solvents selected from acetones, salt solutions including aqueous NaCl, and DMSO.

56. The method of claim 54 further comprising re-hydrating the dehydrated hydrogel by placing the dehydrated hydrogel in one or more of:

(i) in water, saline solution, Ringer'"'"'s solution, salinated water, buffer solution, and the like, or a mixture thereof, and

(ii) in a humid chamber, wherein the placing is performed at room temperature or at an elevated temperature that is below the melting point of the hydrogel.

57. The method according to claim 52, wherein the hydrogel contains a non-volatile ingredient.

58. The method according to claim 57, wherein the non-volatile ingredient is added to the hydrogel prior to annealing or dehydrating.

59. The method according to claim 58, wherein the non-volatile ingredient is added to the hydrogel by immersing the hydrogel in the ingredient or in a solution of the ingredient in water or an organic solvent.

60. The method according to claim 57, wherein the ingredient is an alcohol or its solution in an organic solvent or water, including PEG and its solution.

61. The method according to claim 58, wherein the added non-volatile ingredient is subsequently removed from the hydrogel prior to annealing or dehydrating.

62. The method according to claim 61, wherein the ingredient is removed from the hydrogel by:

(i) immersing the hydrogel in water, organic solvents, or salt solutions, or

(ii) placing the hydrogel in a supercritical fluid.

63. The method according to claim 52, wherein the hydrogel is PVA, a copolymer of PVA, a blend of PVA with another polymer, or a hydrophilic polymer.

64. The method according to claim 52, wherein the hydrogel is deformed at a temperature that is below the melting point of the hydrogel before and/or after annealing or dehydrating.

65. The method according to claim 52, wherein the hydrogel is subjected to at least one freeze-thaw cycle before or after annealing or dehydrating.

66. A tough hydrogel made by a method according to claim 52.

67. A medical implant comprising the tough hydrogel according to claim 66.

68. The medical implant of claim 67 is an interpositional device or a mosaicplasty plug.

69. The medical implant of claim 68, wherein the interpositional device is a unispacer, wherein the unispacer is a free floating articular implant in a human joint.

70. The medical implant of claim 69, wherein the human joint is a knee, a hip, a shoulder, an elbow, or an upper or a lower extremity joint.

71. The medical implant according to claims 67 is further sterilized by radiation sterilization, gas plasma sterilization, or ethylene oxide sterilization.