Poly(vinyl alcohol)-bacterial cellulose nanocomposite

Abstract

Hydrogel-bacterial cellulose nano-composite materials are created using a hydrogel and never dried bacterial cellulose fibers. Such materials are suitable for a broad range of soft tissue replacement applications. In addition controlled release of bioactive agents properties can be designed into medical devices fabricated from such composite materials.

1 . A hydrogel/cellulose composite material, comprising: 
 a hydrogel present in an amount from about 5% by weight to about 20% by weight, cellulose present in a range from about 0.05% by weight to about 5% by weight and a remainder being a solvent, the cellulose including fibers having nanometer scale cross sectional dimensions.    
     
     
         2 . The composite material according to  claim 1  wherein the solvent is water.  
     
     
         3 . The composite material according to  claim 2  wherein said cellulose having nanometer scale cross sectional dimensions is produced using a microbial fermentation process using one of a bacterium and a fungus.  
     
     
         4 . The composite material according to  claim 3  wherein the bacterium is from a genus of one of  Acetobacter, Pseudomonas, Achromobacter, Alcaligene, Aerobacter  and  Azotobacter.    
     
     
         5 . The composite material according to  claim 2  wherein said cellulose having nanometer scale cross sectional dimensions is produced from a microbial fermentation process using a bacterium.  
     
     
         6 . The process according to  claim 5  wherein the bacterium is  Acetobacter xylinum  (ATCC#700178).  
     
     
         7 . The composite material according to  claim 3  wherein the fungus is from a genus of one of  Chaetomium, Saccharomyces, Candida, Pichia  and  Fusarium.    
     
     
         8 . The composite material according to  claim 3  wherein said hydrogel is selected from the group consisting of polyvinyl alcohol (PVA), poly(vinyl pyrrolidone) (PVP), poly(ethylene glycol) (PEG), poly(hydroxyethyl methacrylate) (PHEMA) and polyacrylamide.  
     
     
         9 . The composite material according to  claim 3  wherein said hydrogel is polyvinyl alcohol (PVA).  
     
     
         10 . The composite material according to  claim 6  wherein the hydrogel is polyvinyl alcohol (PVA).  
     
     
         11 . The composite material according to  claim 10  wherein the polyvinyl alcohol (PVA) has a molecular weight in a range from about 100,000 to about 200,000.  
     
     
         12 . The composite material according to  claim 10  formed into a pre-selected shape for a medical application.  
     
     
         13 . The composite material according to  claim 12  wherein the pre-selected shape is selected from the group consisting of substantially planar sheets for wound dressings, dental implants, vascular grafts, catheter covering dressing, dialysis membranes, coatings for cardiovascular stents, coatings for cranial stents, and membranes for tissue guided regeneration.  
     
     
         14 . The composite material according to  claim 12  further including an effective bioactive agent contained therein which is released in a controlled manner from the composite material.  
     
     
         15 . A hydrogel/cellulose composite material, comprising: 
 a hydrogel including polyvinyl alcohol (PVA) present in an amount from about 5% by weight to about 20% by weight, cellulose present in a range from about 0.05% by weight to about 5% by weight and a remainder being water, the cellulose including fibers having nanometer scale cross sectional dimensions produced using a microbial fermentation process using a bacterium  Acetobacter xylinum.      
     
     
         16 . The composite material according to  claim 15  wherein said polyvinyl alcohol (PVA) has a molecular weight in a range from about 100,000 to about 200,000.  
     
     
         17 . The composite material according to  claim 15  formed into a pre-selected shape for a medical application.  
     
     
         18 . The composite material according to  claim 17  wherein the pre-selected shape is selected from the group consisting of substantially planar sheets for wound dressings, dental implants, vascular grafts, catheter covering dressing, dialysis membranes, coatings for cardiovascular stents, coatings for cranial stents, and membranes for tissue guided regeneration.  
     
     
         19 . The composite material according to  claim 17  further including a selected bioactive agent contained therein which is released in a controlled manner from the composite material.  
     
     
         20 . A process of producing a composite material comprising a hydrogel and cellulose, comprising the steps of: 
 synthesizing cellulose using an effective bacteria in a microbial fermentation synthesis process to give a suspension of cellulose fibers having nanometer scale cross sectional dimensions, isolating the cellulose fibers produced by the microbial fermentation process and forming an aqueous cellulose suspension of the cellulose fibers while preventing the cellulose fibers from being dried out between the time they are produced and suspended in an aqueous liquid; and    forming a mixture by mixing a hydrogel material with the aqueous cellulose suspension, and heating the resulting mixture at a sufficiently high temperature for a sufficiently long period of time for the hydrogel material to dissolve into solution, thereafter solidifying the mixture to form the composite material.    
     
     
         21 . The process according to  claim 20  wherein in the composite material the hydrogel material is present in an amount from about 5% by weight to about 20% by weight, the cellulose is present in a range from about 0.05% by weight to about 5% by weight, and wherein a remainder of the composite material is water.  
     
     
         22 . The process according to  claim 21  wherein the hydrogel material is polyvinyl alcohol (PVA).  
     
     
         23 . The process according to  claim 21  wherein the hydrogel material is mixed with the aqueous cellulose suspension in powdered form.  
     
     
         24 . The process according to  claim 21  wherein the hydrogel material mixed with the aqueous cellulose suspension is a mixture formed by mixing powder hydrogel material with a hydroxylic solvent.  
     
     
         25 . The process according to  claim 24  wherein the hydroxylic solvent is selected from the group consisting of water, an alcohol, ketones, aldehydes and carboxylic acid and aprotic solvents.  
     
     
         26 . The process according to  claim 25  wherein the dipolar aprotic solvents include dimtheyl sulfoxide (DMSO), dimethyl formamide (DMF), dimethyl acetamide (DMAc) and N-methyl pyrrolidone (NMP).  
     
     
         27 . The process according to  claim 25  wherein when the hydroxylic solvent is not water, including a step of removing the hydroxylic solvent by solvent exchange with water to remove the hydroxylic solvent.  
     
     
         28 . The process according to  claim 27  wherein the hydrogel material is polyvinyl alcohol (PVA).  
     
     
         29 . The composite material according to  claim 20  wherein the effective bacterium is selected from a genus of  Acetobacter, Pseudomonas, Achromobacter, Alcaligene, Aerobacter  or  Azotobacter.    
     
     
         30 . The process according to  claim 28  wherein the effective bacteria is  Acetobacter xylinum ) (ATCC#700178).  
     
     
         31 . The process according to  claim 29  wherein the step of synthesizing cellulose using an effective bacteria in a microbial fermentation synthesis process includes preparing an incoulum using the bacteria  Acetobacter xylinum  and adding the incoulum to a culture medium including fructose 4% w/v, corn steep liquor 4% v/v, ammonium sulphate 0.33% w/v, potassium dihydrogen phosphate 0.1% w/v, magnesium sulphate heptahydrate 0.025% w/v, tri-sodium citrate 0.42% w/v and citric acid 0.88% w/v, and allowing the mixture to react at a suitable temperature and suitable pH for a suitable length of time for cellulose fibers to be produced, and thereafter isolating the cellulose fibers from the media and forming the aqueous suspension.  
     
     
         32 . The process according to  claim 31  wherein the step of isolating the cellulose includes treating the bacterially produced cellulose with sodium hydroxide at about 90° C. for about 30 minutes to remove bacteria from the cellulose fibers, centrifuging the medium to recover therefrom the bacterially produced cellulose, and washing the isolated bacterially produced cellulose in water to remove excess sodium hydroxide, and storing the isolated and purified bacterial cellulose in purified water.  
     
     
         33 . The process according to  claim 31  wherein the step of mixing a hydrogel material into a hydroxylic solvent and mixing it with the cellulose suspension includes removing gas bubbles from a reaction chamber containing the hydrogel material and the cellulose suspension.  
     
     
         34 . The process according to  claim 31  including thermally cycling the composite material between selected temperatures an effective number of times at selected cooling and heating rates to give the composite material desired tensile properties.  
     
     
         35 . The process according to  claim 34  wherein the selected temperatures are from about −20° C. to about +20° C., and the cooling and heating rate is about 0.1° C./minute.  
     
     
         36 . The process according to  claim 31  wherein the suitable temperature is about 28° C., the suitable pH is about 5, and wherein air is flowed through the medium at an air flow rate of about 1 L/min and the medium is mixed for about 72 hours.  
     
     
         37 . The process according to  claim 31  wherein the hydrogel material is polyvinyl alcohol (PVA).  
     
     
         38 . The process according to  claim 37  wherein the polyvinyl alcohol (PVA) has a molecular weight in a range from about 100,000 to about 200,000.  
     
     
         39 . The process according to  claim 22  wherein the polyvinyl alcohol (PVA) has a molecular weight in a range from about 100,000 to about 200,000.  
     
     
         40 . The process according to  claim 31  including molding the composite material into a desired shape of a medical device.  
     
     
         41 . The process according to  claim 40  further including mixing an effective bioactive agent contained therein which is released in a controlled manner from the composite material.  
     
     
         42 . A process of producing a composite material comprising a hydrogel and cellulose, comprising the steps of: 
 synthesizing cellulose using an effective bacteria in a microbial fermentation synthesis process to give a suspension of cellulose fibers having nanometer scale cross sectional dimensions, isolating the cellulose fibers produced by the microbial fermentation process and forming an aqueous cellulose suspension of the cellulose fibers while preventing the cellulose fibers from being dried out between the time they are produced and suspended in an aqueous liquid;    forming a mixture by mixing a hydrogel material with the aqueous cellulose suspension, and heating the resulting mixture at a sufficiently high temperature and for a sufficiently long period of time for the hydrogel material to dissolve into solution, thereafter solidifying the mixture to form the composite material; and    thermally cycling the composite material between selected temperatures an effective number of times at selected cooling and heating rates to give the composite material pre-selected tensile properties.    
     
     
         43 . The process according to  claim 42  wherein in the composite material the hydrogel material is present in an amount from about 5% by weight to about 20% by weight, the cellulose is present in a range from about 0.05% by weight to about 5% by weight, and wherein a remainder of the composite material is water.  
     
     
         44 . The process according to  claim 43  wherein the hydrogel material is polyvinyl alcohol (PVA), and wherein the effective bacteria is  Acetobacter xylinum.    
     
     
         45 . The process according to  claim 44  wherein the polyvinyl alcohol is mixed with the aqueous cellulose suspension in powdered form.  
     
     
         46 . The process according to  claim 44  wherein the hydrogel material mixed with the aqueous cellulose suspension is a mixture formed by mixing powder hydrogel material with a hydroxylic solvent.  
     
     
         47 . The process according to  claim 46  wherein the hydroxylic solvent is selected from the group consisting of water, an alcohol, ketones, aldehydes and carboxylic acid and aprotic solvents.  
     
     
         48 . The process according to  claim 47  wherein the dipolar aprotic solvents include dimtheyl sulfoxide (DMSO), dimethyl formamide (DMF), dimethyl acetamide (DMAc) and N-methyl pyrrolidone (NMP).  
     
     
         49 . The process according to  claim 47  wherein when the hydroxylic solvent is not water, including a step of removing the hydroxylic solvent by solvent exchange with water to remove all the hydroxylic solvent.  
     
     
         50 . The process according to  claim 43  wherein the selected temperatures are about −20° C. and about +20° C., and the selected cooling and heating rates are about 0.1° C./minute.  
     
     
         51 . The process according to  claim 43  including molding the composite material into a desired shape of a medical device.  
     
     
         52 . The process according to  claim 51  further including mixing an effective bioactive agent contained therein which is released in a controlled manner from said composite material.  
     
     
         53 . A composite material comprising a hydrogel and a cellulose, the composite material produced according to a method comprising the steps of: 
 synthesizing cellulose using an effective bacteria in a microbial fermentation synthesis process to give a suspension of cellulose fibers having nanometer scale cross sectional dimensions, isolating the cellulose fibers produced by the microbial fermentation process and forming an aqueous cellulose suspension of the cellulose fibers while preventing the cellulose fibers from being dried out between the time they are produced and suspended in an aqueous liquid; and    forming a mixture by mixing a hydrogel material with the aqueous cellulose suspension, and heating the resulting mixture at a sufficiently high temperature for a sufficiently long period of time for the hydrogel material to dissolve into solution, thereafter solidifying the mixture to form the composite material, the hydrogel being present in an amount from about 5% by weight to about 20% by weight and the cellulose present in a range from about 0.05% by weight to about 5% by weight, and a remainder being water.    
     
     
         54 . The composite material according to  claim 53  including thermally cycling the composite material between selected temperatures an effective number of times at selected cooling and heating rates to give the composite material desired tensile properties.  
     
     
         55 . The composite material according to  claim 54  wherein in the composite material the hydrogel material is present in an amount from about 5% by weight to about 20% by weight, the cellulose is present in a range from about 0.05% by weight to about 5% by weight, and wherein a remainder of the composite material is water.  
     
     
         56 . The composite material according to  claim 55  wherein the hydrogel material is polyvinyl alcohol (PVA), and wherein the effective bacteria is  Acetobacter xylinum.    
     
     
         57 . The composite material according to  claim 56  wherein the polyvinyl alcohol is mixed with the aqueous cellulose suspension in powdered form.  
     
     
         58 . The composite material according to  claim 56  wherein the polyvinyl alcohol mixed with the aqueous cellulose suspension is a mixture formed by mixing powder polyvinyl alcohol with a hydroxylic solvent.  
     
     
         59 . The composite material according to  claim 58  wherein the hydroxylic solvent is selected from the group consisting of water, an alcohol, ketones, aldehydes and carboxylic acid and aprotic solvents.  
     
     
         60 . The composite material according to  claim 59  wherein the aprotic solvents include dimtheyl sulfoxide (DMSO), dimethyl formamide (DMF), dimethyl acetamide (DMAc) and N-methyl pyrrolidone (NMP).  
     
     
         61 . The composite material according to  claim 59  wherein when the hydroxylic solvent is not water, including a step of removing the hydroxylic solvent by solvent exchange with water to remove all the hydroxylic solvent.  
     
     
         62 . The composite material according to  claim 54  wherein the selected temperatures are about −20° C. and about +20° C., and the selected cooling and heating rates are about 0.1° C./minute.  
     
     
         63 . The composite material according to  claim 55  including molding the composite material into a desired shape of a medical device.  
     
     
         64 . The composite material according to  claim 63  further including mixing an effective bioactive agent contained therein which is released in a controlled manner from said composite material.  
     
     
         65 . A process of producing a composite material comprising a hydrogel and cellulose, comprising the steps of: 
 synthesizing cellulose using an effective fungus in a microbial fermentation synthesis process to give a suspension of cellulose fibers having nanometer scale cross sectional dimensions, isolating the cellulose fibers produced by the microbial fermentation process and forming an aqueous cellulose suspension of the cellulose fibers while preventing the cellulose fibers from being dried out between the time they are produced and suspended in an aqueous liquid; and    forming a mixture by mixing a hydrogel material with the aqueous cellulose suspension, and heating the resulting mixture at a sufficiently high temperature for a sufficiently long period of time for the hydrogel material to dissolve into solution, thereafter solidifying the mixture to form the composite material.    
     
     
         66 . The composite material according to  claim 65  wherein the selected Fungus is from a genus of  Chaetomium, Saccharomyces, Candida, Pichia  or  Fusarium.    
     
     
         67 . The composite material according to  claim 66  including thermally cycling the composite material between selected temperatures an effective number of times at selected cooling and heating rates to give the composite material desired tensile properties.  
     
     
         68 . The composite material according to  claim 67  wherein in the composite material the hydrogel material is present in an amount from about 5% by weight to about 20% by weight, the cellulose is present in a range from about 0.05% by weight to about 5% by weight, and wherein a remainder of the composite material is water.  
     
     
         69 . The composite material according to  claim 68  wherein the hydrogel material is polyvinyl alcohol (PVA).  
     
     
         70 . The composite material according to  claim 68  wherein the selected temperatures are about −20° C. and about +20° C., and the selected cooling and heating rates are about 0.1° C./minute.