Biodegradable network polymers for regenerative medicine and tissue engineering

Abstract

Biodegradable polyether network polymers crosslinked via ester linkages, to substrates, implants and scaffolds including the biodegradable polyether network polymers; methods for preparing such network polymers, implants and scaffolds; and methods of using substrates, implants and scaffolds including the network polymers, particularly for culturing cells and regenerating tissue.

1 . A biodegradable polyether network polymer crosslinked via ester linkages which is prepared by polymerising a monomer composition comprising a multifunctional polyether monomer and a multifunctional crosslinking monomer, wherein one of the polyether monomer and the crosslinking monomer comprises a hydroxy functional group and the other of the polyether monomer and the crosslinking monomer comprises a complementary functional group capable of reacting with the hydroxy functional group to form an ester linkage, and wherein at least one selected from the polyether monomer and the crosslinking monomer is branched. 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . A biodegradable polyether network polymer according to  claim 1 , wherein the polyether monomer comprises a plurality of hydroxy functional groups. 
     
     
         5 . (canceled) 
     
     
         6 . A biodegradable polyether network polymer according to  claim 1 , wherein the polyether monomer has a structure of formula (I):
   A(BX) n    (I)
   where:
 A is an n-valent core; 
 B is a polyether segment; 
 X is a hydroxy functional group; and 
 n represents the number of (BX) groups and is at least 3. 
   
     
     
         7 . A biodegradable polyether network polymer according to  claim 1 , wherein the polyether monomer comprises a polyether segment derived from a C2-C3 diol. 
     
     
         8 . A biodegradable polyether network polymer according to  claim 7 , wherein each polyether segment has a molecular weight in the range of from about 100 to about 10,000 Da. 
     
     
         9 . A biodegradable polyether network polymer according to  claim 1 , wherein the polyether monomer is selected from the group consisting of glycerol ethoxylate and pentaerythritol ethoxylate. 
     
     
         10 . (canceled) 
     
     
         11 . A biodegradable polyether network polymer according to  claim 1 , wherein the crosslinking monomer has a structure of formula (II):
   R(Y) m    (II)
   where:
 R is a hydrocarbyl group; 
 Y is a complementary functional group selected from the group consisting of carboxylic acid, carboxylic acid ester, carboxylic acid anhydride and carboxylic acid halide; and 
 m represents the number of Y groups and is at least 2. 
   
     
     
         12 . A biodegradable polyether network polymer according to  claim 11 , wherein the crosslinking monomer of formula (II) has a structure of formula (IIa) or (IIb): 
       
         
           
           
               
               
           
         
         wherein:
 R is a hydrocarbyl group; and 
 Y is a complementary functional group selected from the group consisting of carboxylic acid, carboxylic acid ester, carboxylic acid anhydride and carboxylic acid halide. 
 
       
     
     
         13 . A biodegradable polyether network polymer according to  claim 11 , wherein R comprises from 2 to 12 carbon atoms. 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . A biodegradable polyether network polymer according to  claim 1 , wherein the crosslinking monomer is selected from the group consisting of succinyl chloride, adipoyl chloride, sebacoyl chloride, glutaroyl chloride, pimeloyl chloride, suberoyl chloride and trimesoyl chloride, preferably succinyl chloride and sebacoyl chloride. 
     
     
         17 . A biodegradable polyether network polymer according to  claim 1 , wherein the molar ratio of polyether monomer to cros slinking monomer in the monomer composition is in the range of from about 5:1 to 1:5. 
     
     
         18 . A biodegradable polyether network polymer according to  claim 1 , wherein the monomer composition further comprises a mechanical property modifier. 
     
     
         19 . A biodegradable polyether network polymer according to  claim 18 , wherein the monomer composition comprises up to 20% (w/w) of mechanical property modifier. 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . A biodegradable polyether network polymer according to  claim 18 , wherein the hydrophobic macromolecule is dihydroxy poly(caprolactone). 
     
     
         23 .- 28 . (canceled) 
     
     
         29 . A process for preparing a biodegradable polyether network polymer crosslinked via ester linkages, the process comprising the step of reacting a monomer composition comprising a multifunctional polyether monomer and a multifunctional crosslinking monomer under conditions allowing formation of ester linkages between the polyether monomer and the crosslinking monomer, wherein one of the polyether monomer and the crosslinking monomer comprises a hydroxy functional group and the other of the polyether monomer and the cros slinking monomer comprises a complementary functional group capable of reacting with the hydroxy functional group to form an ester linkage, and wherein at least one selected from the polyether monomer and the crosslinking monomer is branched. 
     
     
         30 .- 36 . (canceled) 
     
     
         37 . A process according to  claim 29 , wherein the polyether monomer is selected from the group consisting of glycerol ethoxylate and pentaerythritol ethoxylate. 
     
     
         38 .- 43 . (canceled) 
     
     
         44 . A process according to  claim 29 , wherein the crosslinking monomer is selected from the group consisting of succinyl chloride, adipoyl chloride, sebacoyl chloride, glutaroyl chloride, pimeloyl chloride, suberoyl chloride and trimesoyl chloride. 
     
     
         45 . A process according to  claim 29 , wherein the molar ratio of polyether monomer to crosslinking monomer in the monomer composition is in the range of from about 5:1 to 1:5. 
     
     
         46 . (canceled) 
     
     
         47 . A process according to  claim 29 , wherein the monomer composition comprises up to 20% (w/w) of mechanical property modifier. 
     
     
         48 . (canceled) 
     
     
         49 . (canceled) 
     
     
         50 . A process according to  claim 47 , wherein the mechanical property modifier is dihydroxy poly(caprolactone). 
     
     
         51 .- 56 . (canceled)