COVALENTLY CROSS LINKED HYDROGELS AND METHODS OF MAKING AND USING SAME

• US 20140038826A1
• Filed: 01/27/2012
• Published: 02/06/2014
• Est. Priority Date: 01/28/2011
• Status: Abandoned Application

• Current Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Anseth, Kristi, Bowman, Christopher, Fairbanks, Ben
• Application Number:
  US13/981,885
• Publication Number:
  US 20140038826A1
• Time in Patent Office: Days
• US Class Current: 504/366
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 2430/06 for cartilage reconstruction, e.g. meniscus
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: C08F 38/00 Homopolymers and copolymers of compounds having one or more carbon-to-carbon triple bonds
• CPC Class Codes: C08G 75/045 from mercapto compounds and unsaturated compounds
• CPC Class Codes: C08G 75/12 Polythioether-ethers C08G75/0245 takes precedence
• CPC Class Codes: C08J 2300/16 Biodegradable polymers
• CPC Class Codes: C08J 2300/20 Polymers characterized by their physical structure
• CPC Class Codes: C08J 2371/02 Polyalkylene oxides
• CPC Class Codes: C08J 3/075 Macromolecular gels
• CPC Class Codes: C08L 101/02 characterised by the presence of specified groups , e.g. terminal or pendant functional groups
• CPC Class Codes: C08L 101/16 the macromolecular compounds being biodegradable
• CPC Class Codes: C08L 81/02 Polythioethers; Polythioether-ethers
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06

Abstract

A thiol-yne polymeric material and methods for producing said polymers are disclosed. The material is produced by the radically mediated polymerization of monomers having alkyne and thiol functional groups. The alkyne moiety, internal or terminal, may react with one or two thiols. Degradable monomers may be used to form degradable polymers.

Claims

1. A composition comprising a polymer comprising two or more types of monomers wherein at least a first monomer comprises at least two thiol moieties and at least a second monomer comprises at least one alkyne moiety and wherein the first and second monomers are crosslinked at bonds between the thiol and alkyne moieties.

2. The composition of claim 1, wherein the first monomer comprises at least 3, 4, 5, 6, 7, 8, 9 or 10 thiol moieties.

3. The composition of claim 1, wherein the second monomer comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 alkyne moieties.

4. The composition of claim 1, wherein the first and/or second monomer are derivatized to include a thiol or alkyne moiety.

5. The composition of claim 1, wherein the first and/or second monomer is selected from the group consisting of poly(lactic acid) (PLA), polyglycolide (PGA), copolymers of PLA and PGA (PLGA), poly(vinyl alcohol) (PVA), poly(ethylene glycol) (PEG), poly(ethylene oxide), poly(ethylene oxide)-co-poly(propylene oxide) block copolymers (poloxamers, meroxapols), poloxamines, polyanhydrides, polyorthoesters, poly(hydroxy acids), polydioxanones, polycarbonates, polyaminocarbonates, poly(vinyl pyrrolidone), poly(ethyl oxazoline), carboxymethyl cellulose, hydroxyalkylated celluloses such as hydroxyethyl cellulose and methylhydroxypropyl cellulose, and natural polymers such as nucleic acids, polypeptides, polysaccharides or carbohydrates such as polysucrose, hyaluranic acid, dextran and similar derivatives thereof, heparan sulfate, chondroitin sulfate, heparin, or alginate, and proteins including without limitation gelatin, collagen, albumin, or ovalbumin, or copolymers, or blends thereof. In particularly preferred embodiments, the monomers can be selected from poly(lactic acid) (PLA), poly(vinyl alcohol) (PVA), and poly(ethylene glycol) (PEG).

6. The composition of claim 1, wherein the composition comprises a hydrogel.

7. The composition of claim 5, wherein the hydrogel comprises more than 50% solvent by weight.

9. The composition of claim 1, wherein the first or second monomers are degradable.

10. The composition of claim 9, wherein the degradable monomer is hydrolytically, chemically or enzymatically degradable.

11. The composition of claim 1, wherein the first monomer comprises a peptide.

12. The composition of claim 11, wherein the peptide is enzymatically degradable.

13. The composition of claim 12, wherein the enzyme is a protease.

14. The composition of claim 11, wherein the peptide is selected from the group consisting of adhesion peptides (such as RGD adhesion sequence), growth factors, hormones, antihormones, signaling compounds, enzymes, serum proteins, albumins, macroglobulins, globulins, agglutinins, lectins, extracellular matrix proteins, antibodies, and antigens.

15. The composition of claim 1, further comprising an agent that has a biological function or activity.

16. The composition of claim 15, wherein the agent is a peptide selected from the group consisting of adhesion peptides (such as RGD adhesion sequence), growth factors, hormones, antihormones, signaling compounds, enzymes, serum proteins, albumins, macroglobulins, globulins, agglutinins, lectins, extracellular matrix proteins, antibodies, and antigens. Types of non-peptide agents that can be incorporated into the polymeric material include analgesics, antipyretics, nonsteriodal antiinflammatory drugs, antiallergics, antibacterial drugs, antianemia drugs, cytotoxic drugs, antihypertensive drugs, dermatological drugs, psychotherapeutic drugs, vitamins, minerals, anorexiants, dietetics, antiadiposity drugs, carbohydrate metabolism drugs, protein metabolism drugs, thyroid drugs, antithyroid drugs, and coenzymes.

17. The composition of claim 1, further comprising an agricultural chemical.

18. The composition of claim 17, wherein the agricultural chemical is selected from the group consisting of fungicides, herbicides, fertilizers, pesticides, carbohydrates, nucleic acids, organic molecules, and inorganic biologically active molecules.

19. A method for producing the composition of claim 1 comprising

(a) providing the first and second monomers;

(b) mixing the first and second monomers with a photoinitiator in solvent; and

(c) exposing the first and second monomers and photoinitiator to light, thereby producing the composition of claim 1.

20. The method of claim 19, wherein the photoinitiator is selected from the group consisting of Irgacure 2959, 184 and 651.

21. The method of claim 19, wherein the light is ultraviolet light.

22. The method of claim 21, wherein the ultraviolet light has a wavelength between 300 and 400 nm.

23. The method of claim 19, wherein the exposure to light lasts for less than two, five or 20 minutes.

24. The method of claim 19, wherein the solvent is present at greater than 50% of the mixture of the first and second monomer, photoinitiator and solvent.

25. A method of culturing cells comprising growing the cells on the composition of claim 1.

26. The method of claim 25, wherein the cells are mammalian cells.

27. The method of claim 26, wherein the cells are human cells.

28. The method of claim 25, wherein the cells are primary cells.

29. The method of claim 25, wherein the cells are stem cells.

30. A kit comprising the composition of claim 1.

31. The kit of claim 30, further comprising photoinitiator.

8. The composition of claim 8, wherein the hydrogel comprises between 50 and 95% water by weight.