Biodegradable nanocomposites with enhance mechanical properties for soft tissue

Abstract

The present invention is directed to a novel poly(diol citrates)-based nanocomposite materials created using completely biodegradable and biocompatible polymers that may be used in tissue engineering. More specifically, the specification describes methods and compositions for making and using nanocomposites comprised of citric acid copolymers and polymers including but not limited to poly(L-lactic acid) (PLLA) and poly(lactic-co-glycolic acid) (PLGA).

1 . A composition comprising a composite of: 
 a) a citric acid polyester having the generic formula (A-B-C)n, wherein 
 A is a linear aliphatic dihydroxy monomer;  
 B is citric acid,  
 C is a linear aliphatic dihydroxy monomer, and  
 n is an integer greater than 1; and  
   b) a biodegradable polymer used for implantable tissue devices.    
   
   
       2 . The composition of  claim 1 , wherein A is a linear diol comprising between about 2 and about 20 carbons.  
   
   
       3 . The composition of  claim 1 , wherein C is a linear diol comprising between about 2 and about 20 carbons.  
   
   
       4 . The composition of  claim 1 , wherein both A and C are the same linear diol.  
   
   
       5 . The composition of  claim 4 , wherein said linear diol is 1,8, octanediol.  
   
   
       6 . The composition of  claim 1 , wherein A and C are different linear diols.  
   
   
       7 . The composition of  claim 5 , wherein said linear aliphatic dihydroxy poly 1,8-octanediol co-citric acid.  
   
   
       8 . The composition of  claim 5 , wherein said linear aliphatic dihydroxy poly 1,10-decanediol co-citric acid.  
   
   
       9 . The composition of  claim 1 , wherein said polymer is selected from the group consisting of poly(hydroxyvalerate), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolide), poly(L-lactic acid), poly(L-lactide), poly(D,L-lactic acid), poly(D,L-lactide), poly(caprolactone), poly(trimethylene carbonate), and polyester amide.  
   
   
       10 . The composition of  claim 1 , wherein said polymer is poly(L-lactic acid.  
   
   
       11 . The composition of  claim 1 , wherein said polymer is poly(lactic-co-glycolic acid) (PLGA).  
   
   
       12 . The composition of  claim 1 , wherein said composition further comprises a drug.  
   
   
       13 . A substrate for use in tissue engineering comprising a citric acid polymer of any of claims  1 - 11  formulated into a cell culture substrate.  
   
   
       14 . The substrate of  claim 13 , wherein said substrate further comprises a surface modification.  
   
   
       15 . The substrate of  claim 13 , wherein said polymer is biodegradeable.  
   
   
       16 . A method of producing engineered tissue, comprising: 
 a. preparing a scaffold of a composition of any of claims  1 - 11 ; and    b. culturing cells of said tissue on the scaffold of part (a).    
   
   
       17 . The method of  claim 16 , wherein said cells are selected from the group consisting of endothelial cells, ligament tissue, muscle cells, bone cells, cartilage cells.  
   
   
       18 . The method of  claim 16 , wherein said engineered tissue is produced in a bioreactor.  
   
   
       19 . A drug delivery device comprising a drug interspersed in the polymer composition of any of claims a composition of any of claims  1 - 11 .  
   
   
       20 . The composition of  claim 1  wherein said biodegradable polymer is fabricated into one or more nanostructures.  
   
   
       21 . The composition of  claim 1 , wherein said biodegradable polymer is fabricated into nanofibers.  
   
   
       22 . The composition of  claim 1 , wherein said biodegradable polymer is formulated into nanoparticles.  
   
   
       23 . A biocompatible, biodegradable composition comprising: 
 a. an elastomeric component comprised of a biodegradeable biocompatible polymer and    b. a strengthening component comprised of a second biodegradable biocompatible polymer, wherein said second biodegradable, biocompatible polymer is fabricated into one or more nanostructures.