PVA-PAA Hydrogels

Abstract

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

What is claimed is: 
     
         1 . A method of making a PVA-hydrogel comprising:
 a) contacting an aqueous solution of poly(vinyl alcohol) (PVA) with an aqueous solution of poly(acrylic acid) (PAA) at a temperature above room temperature, thereby forming a homogenous PVA-PAA solution;   b) cooling the PVA-PAA solution down to room temperature, thereby allowing formation of the PVA-hydrogel;   c) cooling the PVA-hydrogel by freezing at a temperature below 0° C.; and   d) thawing the PVA-hydrogel to a temperature above 0° C.   
     
     
         2 . The method of  claim 1 , further comprising dehydrating the PVA-hydrogel to remove part or all of the water content. 
     
     
         3 . The method of  claim 2 , wherein the dehydration is carried out at about 40° C., about 80° C., about 90° C., about 100° C., about 150° C., about 160° C., about 180° C., about 200° C., or above 200° C. for about an hour. 
     
     
         4 . The method of  claim 2 , wherein the dehydration is carried out by heating the hydrogel in air or in inert atmosphere to an elevated temperature, wherein a heating rate ranges from about 0.01° C./minute to about 10° C./minute. 
     
     
         5 . The method of  claim 2 , wherein the dehydrated hydrogel is re-hydrated by placing the dehydrated hydrogel:
 i) in water, saline solution, Ringer's solution, salinated water, buffer solution, and the like,   ii) in a humid chamber, or   iii) at room temperature or at an elevated temperature.   
     
     
         6 . A PVA-hydrogel made by a process comprising:
 a) contacting an aqueous solution of poly(vinyl alcohol) (PVA) with an aqueous solution of poly(acrylic acid) (PAA) at a temperature above room temperature, thereby forming a homogenous PVA-PAA solution;   b) cooling the PVA-PAA solution down to room temperature, thereby allowing formation of the PVA-hydrogel;   c) cooling the PVA-hydrogel by freezing at a temperature below 0° C.; and   d) thawing the PVA-hydrogel to a temperature above 0° C.,   wherein the PVA-hydrogel comprises one or more hydrophilic polymers selected from the group consisting of: PVA-PAA copolymer, poly(ethylene oxide)(PEO)—PAA copolymer, poly(methacrylic acid) (PMAA), polyvinylpyrrolidone (PYP), hyaluronic acid (HA), and poly(allylamine hydrochloride) (PAH).   
     
     
         7 . The PVA-hydrogel of  claim 6 , wherein the hydrogel comprises water and/or one or more other ingredients. 
     
     
         8 . The PVA-hydrogel of  claim 7 , wherein the ingredient is PVA, PAA, PEG, and/or salt, proteoglycan, water soluble polymer, amino acid, alcohol, DMSO, or water soluble vitamin, and wherein the ingredient is partially or completely soluble in water. 
     
     
         9 . The PVA-hydrogel of  claim 7 , wherein the ingredient is PEG, wherein the PEG is in a solution of water, ethanol, ethylene glycol, DMSO, or a suitable solvent. 
     
     
         10 . The PVA-hydrogel of  claim 7 , wherein the ingredient is non-volatile. 
     
     
         11 . The PVA-hydrogel of  claim 7 , wherein the ingredient is at least partially miscible in water. 
     
     
         12 . The PVA-hydrogel of  claim 7 , wherein the ingredient is selected from the group consisting of PEG, salt, NaCl, KCl, CaCl 2 , vitamins, carboxylic acids, hydrocarbons, esters, and amino acids. 
     
     
         13 . The PVA-hydrogel of  claim 7 , wherein the ingredient is PEG of different molecular weights or a blend of PEGs of different molecular weights. 
     
     
         14 . The PVA-hydrogel of  claim 7 , wherein the ingredient is a water miscible polymer. 
     
     
         15 . The PVA-hydrogel of  claim 14 , wherein the water miscible polymer is PEO, Pluronic, amino acids, proteoglycans, polyvinylpyrrolidone, polysaccharides, dermatin sulfate, keratin sulfate, chondroitin sulfate, or dextran sulfate. 
     
     
         16 . A medical implant comprising a PVA-hydrogel according to  claim 6 . 
     
     
         17 . The medical implant of  claim 16  wherein the medical implant is an interpositional device. 
     
     
         18 . The medical implant of  claim 17 , wherein the interpositional device a unispacer, wherein the unispacer is a free floating articular implant in a human joint. 
     
     
         19 . The medical implant of  claim 18 , wherein the human joint is a knee, a hip, a shoulder, an elbow, or an upper or an extremity joint.