Low friction hydrogels and hydrogel-containing composite materials

Patent metadata

Field	Value
Publication number	US-9901660-B2
Application number	US-201414902574-A
Country	US
Kind code	B2
Filing date	Jul 3, 2014
Priority date	Jul 4, 2013
Publication date	Feb 27, 2018
Grant date	Feb 27, 2018

Abstract

Hydrogels and composite material containing hydrogels and liposomes dispersed therein, which exhibit a reduced friction coefficient compared to neat hydrogels or composites containing hydrogels, processes for preparing the same, and methods for using the same are disclosed.

First claim

What is claimed is:

1. A composition comprising a hydrogel or a composite material containing a hydrogel, and a plurality of liposomes dispersed throughout the bulk of said hydrogel, the composition being characterized by a shear storage modulus (G′) of at least 1000 Pa at a temperature of 25° C. and a frequency of 1 Hz,
wherein:
an average diameter of said liposomes is larger than 80 nm; and/or
a degree of crosslinking of said hydrogel is higher than 0.2 molar percent, wherein said crosslinking comprises covalent crosslinking.

2. The composition or composite of claim 1 , wherein a concentration of said liposomes is higher than 4 mM.

3. The composition or composite of claim 1 , wherein an average diameter of said liposomes is larger than 80 nm.

4. The composition or composite of claim 3 , wherein a degree of covalent crosslinking of said hydrogel is higher than 0.2 molar percent.

5. The composition or composite of claim 3 , wherein a degree of covalent crosslinking of said hydrogel is 0.2 molar percent or lower.

6. The composition or composite of claim 1 , wherein a degree of covalent crosslinking of said hydrogel is higher than 0.2 molar percent and an average diameter of said liposomes is 80 nm or lower.

7. The composition or composite of claim 1 , wherein said liposomes further comprise an additional agent selected from the group consisting of a polymer, a hydrogel-forming polymer, cholesterol, a liposome-stabilizing agent, a labeling agent, a bioactive agent and a therapeutically active agent.

8. The composition or composite of claim 7 , wherein a concentration of said cholesterol ranges from 1 molar percent to 50 molar percent relative to a total lipid amount of said liposome.

9. The composition or composite of claim 1 , wherein said hydrogel comprises a hydrogel-forming agent being selected from the group consisting of hydroxyethyl methacrylate (HEMA), hydroxyethyl acrylate (HEA), acrylamide (AAm), methacrylamide (MAAm), acrylic acid (AAc), methacrylic acid (MAAc), hydroxyethyl acrylate (HEA), hexyl methacrylate, N-isopropylacrylamide (NiPAAm)), N-isopropylmethacrylamide, polylactic acid, polyamide, polyethylene-terephthalate (PET), polyvinyl alcohol, polyurethane, polycaprolactone, polyethylene-glycol (PEG), polyethyleneoxide dimethacrylate (PEOdMA), N,N-dimethacrylamide (nnDMAA), hyaluronic acid (HA), HA methacrylate, peptides, saccharides, gelatin, gelatin methacrylate, chitosan, chitosan methacrylate, glycol chitosan, glycol chitosan methacrylate, alginate, alginate methacrylate, cellulose, siloxanes, polysiloxanes, and any oligomer and/or polymer thereof, in any combination thereof.

10. The composition or composite of claim 9 , wherein said hydrogel-forming agent is gelatin methacrylate, and wherein a degree of methacrylation in said gelatin methacrylate ranges from 10 percents to 90 percents.

11. The composition or composite of claim 1 , being in a dry form.

12. The composition or composite of claim 1 , wherein said liposomes are selected from the group consisting of small unilamellar vesicles (SUV), large unilamellar vesicles (LUV) and multilamellar vesicles (MLV).

13. The composition or composite of claim 1 , wherein said liposomes comprise at least one phosphatidylcholine phospholipid.

14. The composition or composite of claim 1 , wherein said composite material comprises a material selected from the group consisting of a woven mesh of fibers, non-woven fibers, a plurality of rods and a net.

15. The composition or composite of claim 1 , being characterized by a dynamic friction coefficient in aqueous medium that ranges from 0.001 to 0.08 under a pressure of at least 1 atmosphere.

16. The composition or composite of claim 15 , wherein said friction coefficient is substantially maintained at room temperature and/or at 37° C. over a period of at least 60 minutes under essentially constant load and temperature.

17. The composition or composite of claim 15 , wherein said friction coefficient is substantially maintained at room temperature and/or at 37° C. after at least one dehydration-rehydration cycle.

18. A process for preparing the composition or composite of claim 1 , the process comprising:
mixing an aqueous suspension of said liposomes with a hydrogel-forming agent in the presence of a covalent crosslinking agent,
thereby obtaining the composition.

19. The process of claim 18 , wherein said suspension further comprises an initiator.

20. The process of claim 18 , wherein said suspension further comprises a catalyst.

21. The process of claim 18 , further comprising dehydrating the composition.

22. The process of claim 21 , further comprising, subsequent to said dehydrating, rehydrating the composition.

23. The process of claim 18 , wherein said hydrogel-forming agent is selected from the group consisting of hydroxyethyl methacrylate (HEMA), hydroxyethyl acrylate (HEA), acrylamide (AAm), methacrylamide (MAAm), acrylic acid (AAc), methacrylic acid (MAAc), hydroxyethyl acrylate (HEA), hexyl methacrylate, N-isopropylacrylamide (NiPAAm), N-isopropylmethacrylamide, polylactic acid, polyamide, polyethylene-terephthalate (PET), polyvinyl alcohol, polyurethane, polycaprolactone, polyethylene-glycol (PEG), polyethyleneoxide dimethacrylate (PEOdMA), N,N-dimethacrylamide (nnDMAA), hyaluronic acid (HA), HA methacrylate, gelatin, gelatin methacrylate, chitosan, chitosan methacrylate, glycol chitosan, glycol chitosan methacrylate, alginate, alginate methacrylate, cellulose, a siloxane, a polysiloxane, and any combination thereof.

24. The process of claim 18 , wherein said covalent crosslinking agent is selected from the group consisting of poly(ethylene glycol) n dimethacrylate (EGDMA), N,N′-methylenebis(acrylamide) (MBAm), N,N′-methylenebis(2-methylacrylamide), methylene diacrylate, methylene bis(2-methylacrylate), diethylene glycol diacrylate, hexamethylene diacrylate, oxybis(methylene) bis(2-methylacrylate) and oxybis(ethane-2,1-diyl) bis(2-methylacrylate).

25. A composition or composite prepared by the process of claim 18 .

26. An article-of-manufacturing comprising the composition or composite of claim 1 .

27. The article-of-manufacturing of claim 26 , selected from the group consisting of an implantable medical device, a drug-delivery system, a solid body, a disc, a fiber, a fabric, a tube, a film, a rod, a ring, a tubular mesh and any combination thereof.

28. A method of treating a living organism suffering from a medical condition associated with loss of or damaged cartilage, comprising replacing at least a portion of said cartilage with the composition or composite of claim 1 .

29. The method of claim 28 , wherein said medical condition is selected from the group consisting of a skeletal joint replacement or reconstruction, vertebrate replacement or reconstruction, tendon replacement, tissue regeneration and reduction of tissue irritation by an implantable device.

Assignees

• Yeda Res & Dev

Inventors

• Klein Jacob
• Goldberg Ronit
• Iuster Noa
• Sorkin Raya

Classifications

• A61L27/44

  having a macromolecular matrix · CPC title

• A61L2430/06

  for cartilage reconstruction, e.g. meniscus · CPC title

• C08F2/44

  Polymerisation in the presence of compounding ingredients, e.g. plasticisers, dyestuffs, fillers · CPC title

• A61L27/34

  Macromolecular materials · CPC title

• A61L2430/24

  for joint reconstruction · CPC title