Method comprising contacting tissue with a cross-linkable polyester prepolymer

Patent metadata

Field	Value
Publication number	US-11458230-B2
Application number	US-202017097901-A
Country	US
Kind code	B2
Filing date	Nov 13, 2020
Priority date	Jan 12, 2006
Publication date	Oct 4, 2022
Grant date	Oct 4, 2022

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.

First claim

What is claimed is:

1. An elastomeric composition comprising a cross-linked polyester, the cross-linked polyester comprising:
a polymeric unit of the general formula (-A-B—) n cross-linked between at least a portion of the A components of the polyester, the cross-link forming a link comprising at least a portion of the general formula -(D) k -C—; wherein
A represents a substituted or unsubstituted ester,
B represents a substituted or unsubstituted acid ester comprising at least two acid ester functionalities;
C represents a substituted or unsubstituted dioic acid ester;
D represents one or more of a substituted or unsubstituted ester;
n represents an integer greater than 1; and
k represents an integer greater than 0.

2. The composition of claim 1 , wherein the cross-linked polyester comprises at least a portion that is represented by the general formula (II)

wherein m, n, p, q, and v each independently represent an integer greater than 1, and k represents an integer greater than 0.

3. The composition of claim 2 , wherein p=8, q=8 and v=4.

4. The composition of claim 1 , wherein the average ratio of the number of cross-links to the number of (-A-B—) n polymeric units is less than about 0.4.

5. The composition of claim 1 , wherein the average ratio of the number of cross-links to the number of (-A-B—) n polymeric units is greater than about 0.5.

6. The composition 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, at least a portion of the cross-links forming an acid ester; wherein,
A represents a substituted or unsubstituted ester,
B represents a substituted or unsubstituted acid ester comprising at least two acid ester functionalities; and
n represents an integer greater than 1.

7. A biodegradable material comprising the composition of claim 1 , the material having a tensile Young's modulus less than about 17 MPa when measured according to ASTM standard D412-98a.

8. A biodegradable material comprising the composition of claim 1 , the material having a tensile Young's modulus greater than about 0.6 MPa and an elongation of greater than about 20%, both when measured according to ASTM standard D412-98a.

9. A biodegradable material comprising the composition of claim 1 , the material having a tensile Young's modulus greater than about 0.25 MPa when measured according to ASTM standard D412-98a and a swelling in water of greater than about 1%.

10. A biodegradable material comprising the composition of claim 1 , the material having a tensile Young's modulus greater than about 0.25 MPa when measured according to ASTM standard D412-98a and a swelling in water of greater than about 40%.

11. A biodegradable material comprising the composition of claim 1 , the material having 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.

12. A biodegradable material comprising the composition of claim 1 , the material having a maximum elongation greater than about 60%.

13. A biodegradable material comprising the composition of claim 1 , wherein the biodegradable material is one or more of: non-toxic to humans, biocompatible and bioabsorbable.

14. An elastomeric biodegradable material comprising a cross-linked polyester, the elastomeric biodegradable material having a degradation rate that is substantially non-monotonic as a function of overall cross-link density.

15. The elastomeric biodegradable material of claim 14 , wherein the cross-linked elastomeric polyester comprises:
a polymeric unit of the general formula (-A-B—) n cross-linked between at least a portion of the A components of the polyester, the cross-link forming a link comprising at least a portion of the general formula -(D) k -C—; wherein
A represents a substituted or unsubstituted ester,
B represents a substituted or unsubstituted acid ester comprising at least two acid ester functionalities;
C represents a substituted or unsubstituted dioic acid ester;
D represents one or more of a substituted or unsubstituted ester;
n represents an integer greater than 1; and
k represents an integer greater than 0.

16. An elastic biodegradable material comprising the composition claim 1 , further comprising one or more of a growth factor, cell adhesion sequence, polynucleotide, polysaccharide, polypeptide, an extracellular matrix component, and combinations thereof.

17. An elastic biodegradable material comprising the composition of claim 1 , wherein the elastic biodegradable material is seeded with one or more connective tissue cells, organ cells, muscle cells, nerve cells, and combinations thereof.

18. An elastic biodegradable material comprising the composition of claim 1 , wherein the elastic biodegradable material 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.

19. An elastic biodegradable material comprising the composition of claim 1 , wherein the composition comprises a bioactive agent.

20. An elastic biodegradable material comprising the composition of claim 1 , wherein the elastic biodegradable material is in the form of a particle, tube, sphere, strand, coiled strand, capillary network, film, fiber, mesh, or sheet.

Assignees

• Massachusetts Inst Technology

Inventors

• Bettinger Christopher J
• Bruggeman Joost P
• Ferreira Lino Da Silva
• Karp Jeffrey M
• Langer Robert S
• Nijst Christiaan
• Zumbuehl Andreas
• Burdick Jason
• Kim Sonia J

Classifications

• C08J3/246

  Intercrosslinking of at least two polymers · CPC title

• A61L27/58

  Materials at least partially resorbable by the body · CPC title

• A61K35/12

  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 title

• C08J3/24

  Crosslinking, e.g. vulcanising, of macromolecules (mechanical aspects B29C35/00; crosslinking agents C08K) · CPC title

• C12N11/096

  Polyesters; Polyamides · CPC title