Biodegradable elastomers

• US 8,143,042 B2
• Filed: 01/12/2007
• Issued: 03/27/2012
• Est. Priority Date: 01/12/2006
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Nijst, Christiaan, Zumbuehl, Andreas, Burdick, Jason, Kim, Sonia J., Bettinger, Christopher J., Bruggeman, Joost P., Ferreira, Lino Da Silva, Karp, Jeffrey M., Langer, Robert S.
• Primary Examiner(s): NAFF, DAVID M
• Application Number:
  US11/623,041
• Publication Number:
  US 20090047256A1
• Time in Patent Office: 1,901 Days
• Field of Search: None
• US Class Current: 435/180
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/48 Reproductive organs
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3804 characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: C08G 63/6854 derived from polycarboxylic acids and polyhydroxy compounds
• CPC Class Codes: C08J 2367/00 Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08J2377/12; of polyester-imides C08J2379/08; Derivatives of such polymers
• CPC Class Codes: C08J 2367/07 having terminal carbon-to-carbon unsaturated bonds
• CPC Class Codes: C08J 3/24 Crosslinking, e.g. vulcanising, of macromolecules mechanical aspects B29C35/00; crosslinking agents C08K
• CPC Class Codes: C08J 3/246 Intercrosslinking of at least two polymers
• CPC Class Codes: C08K 5/0025 Crosslinking or vulcanising agents; including accelerators
• CPC Class Codes: C08L 67/00 Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain of polyester-amides C08L77/12; of polyester-imides C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 67/07 having terminal carbon-to-carbon unsaturated bonds
• CPC Class Codes: C12N 11/082 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: C12N 11/087 Acrylic polymers
• CPC Class Codes: C12N 11/096 : Polyesters; Polyamides

Abstract

The present inventions in various aspects provide elastic biodegradable polymers. In various embodiments, the polymers are formed by the reaction of a multifunctional alcohol or ether and a difunctional or higher order acid to form a pre-polymer, which is cross-linked to form the elastic biodegradable polymer. In preferred embodiments, the cross-linking is performed by functionalization of one or more OR groups on the pre-polymer backbone with vinyl, followed by photopolymerization to form the elastic biodegradable polymer composition or material. Preferably, acrylate is used to add one or more vinyls to the backbone of the pre-polymer to form an acrylated pre-polymer. In various embodiments, acrylated pre-polymers are co-polymerized with one or more acrylated co-polymers.

Claims

1. An elastomeric cross-linked polyester comprising:

a polymeric unit of the general formula (-A-B-)_n, cross-linked between a plurality of the A components of the polyester, wherein the crosslinks contain a single dioic acid ester functionality;

wherein,

A represents a substituted or unsubstituted ester, wherein A comprises a free hydroxyl group prior to crosslinking,

B represents a substituted or unsubstituted ester comprising at least two acid ester functionalities; and

n represents an integer greater than 1.

2. The elastomeric cross-linked polyester of claim 1, wherein the elastomeric cross-linked polyester has the general formula (I)

3. The elastomeric cross-linked polyester of claim 2, wherein p=8.

4. The elastomeric cross-linked polyester of claim 1, wherein the average ratio of the number of crosslinks to the number of (-A-B-)_n polymeric units is less than about 0.4.

5. The elastomeric cross-linked polyester of claim 1, wherein the average ratio of the number of crosslinks to the number of (-A-B-)_n polymeric units is greater than about 0.5.

6. The elastomeric cross-linked polyester of claim 1, wherein the cross-linked polyester comprises

a polymeric unit of the general formula (-A-B-)_n, cross-linked to a substituted or unsubstituted alkane through at least a portion of the A components of the polyester.

7. An elastic biodegradable composition comprising the elastomeric cross-linked polyester of claim 1, further comprising one or more of a growth factor, cell adhesion sequence, polynucleotide, polysaccharide, polypeptide, an extracellular matrix component, and combinations thereof.

8. An elastic biodegradable composition comprising the elastomeric cross-linked polyester of claim 1, wherein the elastic biodegradable composition is seeded with one or more connective tissue cells, organ cells, muscle cells, nerve cells, and combinations thereof.

9. An elastic biodegradable composition comprising the elastomeric cross-linked polyester of claim 1, wherein the elastic biodegradable composition is seeded with one or more tenocytes, fibroblasts, ligament cells, endothelial cells, lung cells, epithelial cells, smooth muscle cells, cardiac muscle cells, skeletal muscle cells, islet cells, nerve cells, hepatocytes, kidney cells, bladder cells, urothelial cells, chondrocytes, and bone-forming cells.

10. An elastic biodegradable composition comprising the elastomeric cross-linked polyester of claim 1, wherein a chromophore is covalently linked to the cross-linked polyester.

11. The elastic biodegradable composition of claim 10, wherein a receptor is covalently linked to the chromophore or interposed between the chromophore and the crosslinked polyester.

12. An elastic biodegradable composition comprising the elastomeric cross-linked polyester of claim 1, wherein the elastic biodegradable composition is porous.

13. An elastic biodegradable composition comprising the elastomeric cross-linked polyester of claim 1, wherein the composition comprises a porogen.

14. An elastic biodegradable composition comprising the elastomeric cross-linked polyester claim 1, wherein the composition comprises a bioactive agent.

15. An elastic biodegradable composition comprising the elastomeric cross-linked polyester of claim 1, wherein the elastic biodegradable composition is in the form of a particle, tube, sphere, strand, coiled strand, capillary network, film, fiber, mesh, or sheet.

16. A biodegradable composition comprising the elastomeric cross-linked polyester of claim 1.

17. The biodegradable composition of claim 16, wherein the cross-linked polyester has a tensile Young'"'"'s modulus less than about 1.5 MPa when measured according to ASTM standard D412-98 a.

18. The biodegradable composition of claim 16, wherein the cross-linked polyester has a tensile Young'"'"'s modulus greater than about 0.05 MPa and an elongation of greater than about 45%, both when measured according to ASTM standard D412-98 a.

19. The biodegradable composition of claim 16, wherein the cross-linked polyester has a Young'"'"'s modulus in the range between about 0.4 MPa and about 0.55 MPa when measured according to ASTM standard D412-98a.

20. The biodegradable composition of claim 16, wherein the cross-linked polyester has a maximum elongation greater than about 170%.

21. The biodegradable composition of claim 16, wherein the cross-linked polyester is one or more of non-toxic to humans, biocompatible and bioabsorbable.

22. An elastomeric cross-linked polyester comprising:

a polymeric unit of the general formula (-A-B-)_n cross-linked between at least a plurality of the A components of the polyester, the crosslinks forming a single dioic acid ester;

wherein,

A represents a substituted or unsubstituted ester, wherein A comprises a free hydroxyl group prior to crosslinking,

B represents a substituted or unsubstituted ester comprising at least two acid ester functionalities; and

n represents an integer greater than 1,

wherein the crosslinks are formed by reacting the free hydroxyl groups on a plurality of the A components of the polyester with an acrylate or an acrylic acid to form a mixture of acrylated pre-polymers; and

reacting the acrylated prepolymers to crosslink at least a portion of the acrylated pre-polymers.

23. The elastomeric cross-linked polyester of claim 22, wherein the elastomeric cross-linked polyester has the general formula (I)

24. The elastomeric cross-linked polyester of claim 23, wherein p=8.

25. The elastomeric cross-linked polyester of claim 22, wherein the average ratio of the number of crosslinks to the number of (-A-B-)_n, polymeric units is less than about 0.4.

26. The elastomeric cross-linked polyester of claim 22, wherein the average ratio of the number of crosslinks to the number of (-A-B-)_n polymeric units is greater than about 0.5.

27. The elastomeric cross-linked polyester of claim 22, wherein the acrylate or acrylic acid comprises one or more of

28. The elastomeric crosslinked polyester of claim 27, wherein the acrylate or acrylic acid comprises

29. The elastomeric cross-linked polyester of claim 22, wherein the reaction of the acrylated prepolymers is initiated by heat or irradiation.

30. The elastomeric cross-linked polyester of claim 29, wherein the pre-polymer mixture is not heated above about 45°

C. during irradiation.