Novel biomaterials and a method for making and using same

Abstract

Novel biomaterials are disclosed having unique properties that make it a useful material in adhesives, local drug delivery applications and as filler or bulking material. The biomaterials are strong, safe and easily used as a surgical adhesive. Treated chitosan, modified chitosan or modified and treated chitosan compositions are disclosed displaying strengths suitable for general surgical applications. The materials can be used as a drug delivery vehicle which allows for the localization of the delivered drug as well as a programmable tether which allows for the release of the drug on a timed basis or in response to a physiological state such as the release of proteolytic enzymes. The materials of this invention can also be modified and treated to optimize the retention of water, thereby serving as a useful filler or bulking material.

1 .- 19 . (canceled) 
     
     
         20 . An adhesive composition comprising a treated chitosan, a modified chitosan, a modified or treated chitosan or a mixture thereof, where each chitosan exhibit changes in one or more chemical, physical and/or performance properties or characteristics relative to a corresponding untreated chitosan. 
     
     
         21 . The composition of  claim 20 , further comprising:
 an additive package adapted to render the composition suitable for a desired adhesive purpose.   
     
     
         22 . The composition of  claim 21 , wherein the additive package comprises a biocompatible filler, an adhesive augmenting agent, a biological agent, a preservative, an excipient, a buffers, a vehicle, or mixtures thereof. 
     
     
         23 . A filler composition comprising a modified chitosan, a modified and treated chitosan or a mixture thereof, where each modified chitosan includes one functional group or a plurality of functional groups that absorbs and retains water to a greater extent than a corresponding untreated chitosan. 
     
     
         24 . The composition of  claim 23 , further comprising:
 an additive package adapted to enhance the filler properties of the filler composition.   
     
     
         25 . The composition of  claim 24 , wherein the additive package comprises a biocompatible filler, a water retention additive, a biological agent, a preservative, an excipient, a buffer, a vehicle, or mixtures thereof. 
     
     
         26 . A method of bonding tissue comprising the step of:
 applying to the surface of a tissue site an effective amount of an aqueous treating solution comprising chitosan composition to form a coated surface,   where the chitosan composition comprises a treated chitosan, a modified chitosan, a modified and treated chitosan or a mixture thereof, where each chitosan exhibits changes in one or more chemical, physical and/or performance properties or characteristics relative to a corresponding untreated chitosan,   where the chitosan composition adheres to the surface with sufficient bond strength and sufficient retention to the surface to persist on the surface for a desired period of time.   
     
     
         27 . The method of  claim 26 , further comprising the step of:
 contacting the coated surface with a surface of a substrate,   where the contacting is for a time, at a temperature, at a pressure and at a humidity sufficient to allow the chitosan composition to bond the tissue site surface to the substrate surface with a force greater than a chitosan composition comprising corresponding untreated chitosans.   
     
     
         28 . The method of  claim 27 , wherein the substrate is a second tissue site. 
     
     
         29 . The method of  claim 28 , wherein the substrate is a synthetic material, a biological material or a mixture thereof. 
     
     
         30 . The method of  claim 26 , wherein each modified chitosan includes a functionalizing effective amount of one functional group or a plurality of functional groups covalently bonded to amine or alcohol moieties of the chitosan, where the effective amount is sufficient to change one or more properties of the chitosan and where the functional group or groups are the same or different in each modified chitosan. 
     
     
         31 . The method of  claim 30 , wherein the functionalizing effective amount is between about 0.01% and about 100% of the amine or alcohol moieties of the chitosan. 
     
     
         32 . The method of  claim 30 , wherein the functionalizing effective amount is between about 0.1% and about 10% of the amine or alcohol moieties of the chitosan. 
     
     
         33 . The method of  claim 30 , wherein the functionalizing effective amount is between about 0.5% and about 2% of the amine or alcohol moieties of the chitosan. 
     
     
         34 . The method of  claim 30 , wherein the functional groups are selected from the group consisting of hydrophobic functional groups, hydrophilic functional groups, ionic functional groups, quantum dots, atomic clusters, NMR active groups, fluorescent groups, dyes, and mixtures thereof. 
     
     
         35 . The method of  claim 34 , wherein the hydrophobic functional groups are selected from the group consisting of alkyl groups, alkenyl groups, araalkyl groups, alkaryl groups, and mixtures thereof having between 1 and 100 carbon atoms, where one or more of carbon atoms of the groups are replace by a hetero atom and/or hetero atom moieties selected from the group consisting of oxygen atoms, sulfur atoms, silicon atoms, germanium, ester moiety, amide moiety, urea moiety, urethane moiethy, and mixtures or combinations thereof and where one or more of the hydrogen atoms are replaced by a hetero atom and/or hetero atom moieties selected from the group consisting the halogen atoms, an alkoxide groups, an amide group, and mixtures or combinations thereof. 
     
     
         36 . The method of  claim 34 , wherein the hydrophobic functional groups are selected from the group consisting of carboxyl acids, organo sulfonic acids, polyethers, polyether amines, sterols, porphyrins and mixtures or combinations thereof. 
     
     
         37 . The method of  claim 34 , wherein the hydrophilic functional groups are selected from the group consisting of diamines, polyamines, diols, polyols, diacids, poly acids, crown ethers, glymes, polyalkenylethers, polyalkenylamines, polyalkenyletheramines, polyacrylic acids, polyvinylacohols, or mixtures or combinations thereof. 
     
     
         38 . The method of  claim 34 , wherein the ionic functional groups are selected from the group consisting of a metal salt, an ammonium salt, a phosphonium salt, a sulfate salt, a carboxylic acid salt, a phosphate salt, dicarboxylic acids or poly carboxylic acids, where one carboxylic acid is used to form a covalent linkage with chitosan and the other acid groups can take a charge, diamines or poly amines, where one amine is used to form a covalent linkage with chitosan and the other amino groups can take a charge, metal ions, ionic atomic clusters, ionic molecular structures, simple anions, polyatomic anions, deprotonated oxoacids, substituted deprotonated oxoacids or deprotonated organic acids where these groups interact with the chitosan via an electrostatic interaction, and mixtures or combinations thereof. 
     
     
         39 . The method of  claim 26 , wherein each chitosan in the chitosan composition is in the form of a hydrogel and the chitosan composition is present in a concentration between about 0.1 mg/mL and about 100 mg/mL and water is present in an amount between about 90 and 99.99 v/v percent. 
     
     
         40 . The method of  claim 39 , wherein the chitosan composition is present in a concentration between about 1 mg/mL and about 50 mg/mL and the solvent is present in an amount between about 95 and about 99.99 v/v percent. 
     
     
         41 . The method of  claim 39 , wherein the chitosan composition is present in a concentration is between about 3 mg/mL and about 30 mg/mL, and the solvent is present in an amount between about 97 and 99.7 v/v percent. 
     
     
         42 . The method of  claim 26 , wherein the chitosan composition further comprises an effective amount of a biological agent. 
     
     
         43 . The method of  claim 42 , wherein each chitosan in the chitosan composition is in the form of a hydrogel and the chitosan composition is present in a concentration between about 0.1 mg/mL and about 100 mg/mL and the solvent is present in an amount between about 90 and about 99.99 v/v percent. 
     
     
         44 . The method of  claim 43 , wherein the chitosan composition is present in a concentration between about 1 mg/mL and about 50 mg/mL and the solvent is present in an amount between about 95 and about 99.99 v/v percent. 
     
     
         45 . The method of  claim 43 , wherein the chitosan composition is present in a concentration is between about 3 mg/mL and about 30 mg/mL, and the solvent is present in an amount between about 97 and 99.7 v/v percent. 
     
     
         46 .- 60 . (canceled)