Mineralization and cellular patterning on biomaterial surfaces

Abstract

Disclosed are advantageous methods for patterning and/or mineralizing biomaterial surfaces. The techniques described are particularly useful for generating three-dimensional or contoured bioimplant materials with patterned surfaces or patterned, mineralized surfaces. Also provided are various methods of using the mineralized and/or patterned biomaterials in tissue engineering, such as bone tissue engineering, providing more control over ongoing biological processes, such as mineralization, growth factor release, cellular attachment and tissue growth.

1 . canceled  
     
     
         2 . The method of  claim 53 , wherein said surface mineralization comprises a patterned mineral layer comprising a plurality of discrete mineral islands.  
     
     
         3 . The method of  claim 53 , wherein said surface mineralization comprises a substantially homogeneous mineral coating.  
     
     
         4 - 8 . canceled.  
     
     
         9 . The method of  claim 53 , wherein said biomaterial comprises at least a first portion that is a 3-dimensional biomaterial scaffold.  
     
     
         10 . The method of  claim 53 , wherein said biomaterial comprises at least a first portion that is a porous, degradable polymer biomaterial.  
     
     
         11 . The method of  claim 10 , wherein said biomaterial comprises at least a first portion that is a polylactic acid (PLA) polymer, polyglycolic acid (PGA) polymer or polylactic-co-glycolic acid (PLG) copolymer biomaterial.  
     
     
         12 . The method of  claim 10  wherein said biomaterial comprises at least a first portion that is a porous, degradable polymer biomaterial that has an interconnected pore structure and that is degradable over a controllable time scale.  
     
     
         13 . canceled.  
     
     
         14 . The method of  claim 93 , wherein said processing technique comprises a gas foaming and particulate leaching technique.  
     
     
         15 - 17 . canceled.  
     
     
         18 . The method of  claim 9 , wherein said biomaterial comprises at least a first portion that is a 3-dimensional biomaterial scaffold comprising an inner pore surface and wherein said surface mineralization is generated on said inner pore surface.  
     
     
         19 . The method of  claim 53 , wherein said surface mineralization comprises calcium.  
     
     
         20 . The method of  claim 53 , wherein said surface mineralization comprises a mixture of at least a first and second mineral.  
     
     
         21 - 25 . canceled.  
     
     
         26 . The method of  claim 53 , wherein said biomaterial is operatively associated with a biologically effective amount of at least a first bioactive substance or biological cell.  
     
     
         27 - 35 . canceled.  
     
     
         36 . The method of  claim 26 , wherein said at least a first bioactive substance or biological cell is incorporated into said biomaterial prior to executing said at least a first surface mineralization process.  
     
     
         37 . The method of  claim 26  wherein said at least a first bioactive substance or biological cell is incorporated into said biomaterial during said at least a first surface mineralization process.  
     
     
         38 . The method of  claim 26 , wherein said at least a first bioactive substance or biological cell is incorporated into said biomaterial subsequent to said at least a first surface mineralization process.  
     
     
         39 . The method of  claim 26 , wherein the generation of said surface mineralization controls the release of said bioactive substance or biological cell from said biomaterial.  
     
     
         40 - 43 . canceled.  
     
     
         44 . The method of  claim 26 , wherein said biomaterial is operatively associated with a biologically effective amount of at least a first mineral-adherent cell and wherein the generation of said surface mineralization controls the association of said mineral-adherent cell with said biomaterial.  
     
     
         45 - 52 . canceled.  
     
     
         53 . A method for controlling the surface mineralization of a biomaterial polymer, comprising altering the polymer composition or surface properties of said biomaterial polymer prior to executing at least a first surface mineralization process.  
     
     
         54 . The method of  claim 89 , wherein controlled surface defects are provided to said biomaterial polymer to provide a controlled nucleation of discrete mineral islands at the surface of said biomaterial polymer during said surface mineralization process.  
     
     
         55 . The method of  claim 92 , wherein said biomaterial polymer is a polylactic-co-glycolic acid copolymer biomaterial and wherein the ratio of lactide and glycolide components within said copolymer composition is altered.  
     
     
         56 - 88 . canceled  
     
     
         89 . The method of  claim 53 , comprising altering the surface properties of said biomaterial polymer prior to executing at least a first surface mineralization process.  
     
     
         90 . The method of  claim 53 , comprising altering the polymer composition of said biomaterial polymer prior to executing at least a first surface mineralization process.  
     
     
         91 . The method of  claim 90 , wherein the molecular weight of said biomaterial polymer is altered.  
     
     
         92 . The method of  claim 90 , wherein the ratio of components within said biomaterial polymer is altered.  
     
     
         93 . The method of  claim 90 , wherein the processing technique used to prepare said biomaterial polymer is altered.  
     
     
         94 . The method of  claim 93 , wherein said processing technique comprises a solvent casting processing technique.  
     
     
         95 . The method of  claim 93 , wherein said processing technique comprises a heat pressing processing technique.  
     
     
         96 . The method of  claim 93 , wherein said processing technique comprises a gas foaming processing technique.  
     
     
         97 . The method of  claim 53 , comprising altering the incubation time of said at least a first surface mineralization process.  
     
     
         98 . The method of  claim 53 , comprising altering the pH, ionic concentrations or temperatures used in said at least a first surface mineralization process.  
     
     
         99 . A method for controlling the surface mineralization of a gas foaming/particulate leaching biomaterial, comprising altering the polymer composition or surface properties of said gas foaming/particulate leaching biomaterial and executing at least a first surface mineralization process; wherein said gas foaming/particulate leaching biomaterial comprises at least a first portion that is prepared by a process comprising gas foaming and particulate leaching.