Pva hydrogels having improved creep resistance, lubricity, and toughness

Abstract

The invention provides creep resistant, lubricious and tough PV A-PAAm-hydrogels, creep resistant, lubricious, tough PVA-PAAm-hydrogel-containing compositions, and methods of making the same. The invention also provides methods of implanting or administering the creep resistant, lubricious and tough PV A-PAAm-hydrogels, or the PVAPAAm-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-PAAm-hydrogels, and cross-linked PVA-PAAm-hydrogel-containing compositions also are disclosed herein.

1 . A method of making a creep resistant, lubricious and tough PVA-PAAm-hydrogel comprising:
 a) contacting an aqueous solution of poly(vinyl alcohol) (PVA) with an aqueous solution of acrylamide monomer (AAm) solution in presence of an initiator, thereby forming a PVA-AAm solution;   b) heating or irradiating the PVA-AAm solution, thereby forming an inter-penetrating network (IPN) structure of polymerized PAAm in the PVA solution; and   c) subjecting the PVA-PAAm IPN to at least one or more freeze-thaw cycles, thereby forming a tough PVA-PAAm hydrogel.   
     
     
         2 . The method of  claim 1  further comprising:
 a) dehydrating the tough PVA-PAAm hydrogel in a vacuum, thereby increasing the melting point of the PVA-PAAm hydrogel;   b) annealing the dehydrated PVA-PAAm hydrogel at a temperature below the melting point of the dehydrated PVA-PAAm hydrogel; and   c) re-hydrating the PVA-PAAm hydrogel, thereby forming a creep resistant, lubricious and tough PVA-PAAm-hydrogel.   
     
     
         3 . A method of making a creep resistant, lubricious and tough PVA-PAAm-hydrogel comprising:
 a) contacting an aqueous solution of poly(vinyl alcohol) (PVA) with an aqueous solution of poly(acrylamide) (PAAm), thereby forming a homogenous PVA-PAAm solution; and   b) subjecting the PVA-PAAm solution to at least one or more freeze-thaw cycles, thereby forming a tough PVA-PAAm hydrogel.   
     
     
         4 . The method of  claim 3  further comprising:
 a) dehydrating the tough PVA-PAAm hydrogel at room temperature in a vacuum, thereby increasing the melting point of the PVA-PAAm hydrogel;   b) annealing the dehydrated PVA-PAAm hydrogel at a temperature below the melting point of the dehydrated PVA-PAAm hydrogel; and   c) re-hydrating the PVA-PAAm hydrogel, thereby forming a creep resistant, lubricious and tough PVA-PAAm-hydrogel.   
     
     
         5 . A method of making a creep resistant, lubricious and tough PVA-PAAm-hydrogel comprising:
 a) contacting an aqueous solution of poly(vinyl alcohol) (PVA) with an aqueous solution of poly(acrylamide) (PAAm), thereby forming a homogenous PVA-PAAm solution;   b) pouring the PVA-PAAm solution onto a mold;   c) cooling the PVA-PAAm-hydrogel by freezing at a temperature below 0° C.; and   d) thawing the PVA-PAAm-hydrogel to a temperature above 0° C.   
     
     
         6 .- 7 . (canceled) 
     
     
         8 . The method of  claim 5  further comprising:
 a) dehydrating the PVA-PAAm-hydrogel at room temperature in a vacuum;   b) annealing the dehydrated PVA-PAAm hydrogel at a temperature below the melting point of the dehydrated PVA-PAAm hydrogel; and   c) re-hydrating the PVA-PAAm hydrogel, thereby forming a creep resistant, lubricious and tough PVA-PAAm-hydrogel.   
     
     
         9 . The method according to  claim 1 , wherein the PVA-AAm solution is heated at a temperature below the boiling point of the PVA-AAm solution, thereby forming an inter-penetrating network (IPN) structure of polymerized PAAm in the PVA solution. 
     
     
         10 .- 12 . (canceled) 
     
     
         13 . The method according to  claim 2 , wherein the PVA-PAAm hydrogel is dehydrated by immersing in a PEG solution to allow diffusion of the PEG into the PVA-PAAm-hydrogel. 
     
     
         14 . The method according to  claim 2 , wherein the dehydrated PVA-PAAm hydrogel is annealed at a temperature about 80° C. to about 200° C., for about an hour or less to a few weeks. 
     
     
         15 .- 16 . (canceled) 
     
     
         17 . The method according to  claim 2 , wherein the PVA-PAAm hydrogel is re-hydrated by soaking in a saline solution or in water. 
     
     
         18 . The method according to  claim 1 , wherein the PVA:PAAm ratio is about 1:1, 1:2 or 1:3. 
     
     
         19 . The method according to  claim 1 , wherein the total polymer content in PVA-PAAm solution is about 10 wt % to about 50 wt %. 
     
     
         20 . (canceled) 
     
     
         21 . The method according to  claim 1 , wherein the PVA-PAAm solution is heated to a temperature above room temperature to about 90° C. 
     
     
         22 . (canceled) 
     
     
         23 . The method according to  claim 1 , wherein the freeze-thaw step is repeated for at least 1 to 100 cycles. 
     
     
         24 . (canceled) 
     
     
         25 . The method according to  claim 2 , wherein the PVA-PAAm hydrogel is dehydrated to remove part or all of the water content. 
     
     
         26 . The method according to  claim 2 , wherein the PVA-PAAm hydrogel is dehydrated by a method comprising the steps of:
 a) contacting the PVA-PAAm hydrogel with an organic solvent, wherein the PVA-PAAm hydrogel comprises a polymer which is not soluble in the solvent, and wherein the solvent is at least partially miscible in water;   b) heating the PVA-PAAm hydrogel to a temperature below or above the melting point of the PVA-PAAm hydrogel; and   c) cooling the heated PVA-PAAm hydrogel to room temperature.   
     
     
         27 .- 28 . (canceled) 
     
     
         29 . The method according to  claim 25 , wherein the dehydration is carried out by placing the PVA-PAAm hydrogel in:
 a) a non-solvent, wherein
 i) the non-solvent is PEG, alcohols, acetones, saturated salinated water, vitamin, or carboxylic acid, aqueous solution of a salt of an alkali metal, and 
 ii) the non-solvent contains more than one ingredient including water, PEG, vitamin, polymer, ester, proteoglycan, and carboxylic acid, or 
   b) in a supercritical fluid.   
     
     
         30 . (canceled) 
     
     
         31 . The method according to  claim 25 , wherein the dehydrated PVA-PAAm hydrogel is re-hydrated by placing the dehydrated PVA-PAAm 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.   
     
     
         32 . The method according to  claim 2 , wherein the method further comprising a step of heating the PVA-PAAm to a temperature about 40° C. to about 200° C. or more. 
     
     
         33 .- 34 . (canceled) 
     
     
         35 . The method according to  claim 2 , wherein the PVA-PAAm hydrogel is re-hydrated in water or a salt solution. 
     
     
         36 . A PVA-PAAm-hydrogel made by a process according to  claim 1 . 
     
     
         37 .- 49 . (canceled) 
     
     
         50 . A PVA-PAAm-hydrogel comprising dehydrated hydrogel made by a process according to  claim 2 . 
     
     
         51 . A medical implant comprising a PVA-PAAm-hydrogel according to  claim 2 . 
     
     
         52 .- 58 . (canceled)