Polymerizable emulsions for tissue engineering

• US 7,537,754 B2
• Filed: 05/01/2007
• Issued: 05/26/2009
• Est. Priority Date: 10/29/2003
• Status: Expired due to Fees

• Current Assignee: Gentis, Inc.
• Original Assignee: Gentis, Inc.
• Inventors: Cohen, Charles, Ducheyne, Paul, Devore, David
• Primary Examiner(s): Foley; Shanon A
• Application Number:
  US11/799,145
• Publication Number:
  US 20070248643A1
• Time in Patent Office: 756 Days
• Field of Search: None
• US Class Current: 424/78.08
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 27/26 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• 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 290/048 Polymers of monomers having two or more carbon-to-carbon double bonds as defined in group C08F36/00

Abstract

Provided are biocompatible viscoelastic solid materials derived from polymerization of fluid water-in-oil emulsions, along with methods of their preparation and methods for their use for tissue engineering applications, including for reforming diseased, damaged or degenerated intervertebral discs by acceptably non-invasive means.

Claims

1. A method of using a biocompatible, nontoxic, viscoelastic material comprising a polymerized emulsion having two discrete aqueous and organic phases for repair, regeneration or tissue engineering, the method comprising forming the viscoelastic material into a tissue implant, scaffold for cell growth, or bioadhesive for joining or repairing living tissue, wherein the viscoelastic material comprises:

a) a continuous hydrophobic organic phase comprised of polymerized ethylenically unsaturated acrylate monomers; and

b) a discontinuous aqueous (“

water”

) phase comprising water;

wherein the viscoelastic material is formed by in situ polymerization of a non toxic, inverse (“

water-in-oil”

) fluid emulsion comprising two discrete phases and;

wherein the aqueous phase is present in the emulsion an amount of about 0.5% to about 90% weight/weight of the organic phase.

2. The method of claim 1, further comprising delivering the emulsion to a site in need of repair, regeneration or tissue engineering in a mammal, and polymerizing the emulsion into the viscoelastic material in situ.

3. The method of claim 2, wherein the emulsion is delivered to the site in need of repair, regeneration or tissue engineering in the mammal by an acceptably noninvasive method.

4. The method of claim 2, wherein the emulsion is delivered to the site in need of repair, regeneration or tissue engineering in the mammal by injection.

5. The method of claim 2, further comprising replacing or repairing at least one intervertebral disc in the spinal column of the mammal.

6. The method of claim 5, further comprising delivering the emulsion into an evacuated region of a nucleus pulposus of the intervertebral disc of the mammal;

and then polymerizing the emulsion in situ to form the viscoelastic material, thereby forming an implant in the mammal.

7. The method of claim 6, further comprising fully or partially evacuating a degenerated nucleus pulposus from the intervertebral disc of the mammal by a minimally invasive surgical method prior to the step of delivering the emulsion to the nucleus pulposus.

8. The method of claim 7, wherein the emulsion further comprises particles, solutions or dispersions of at least one inert, bioactive or biological material.

9. The method of claim 8, wherein the inert, bioactive or biological material is selected from the group consisting of biological cells or cell fragments, tissue fragments derived from in vitro or in vivo cell culture, biological cell or tissue growth factors, agents to facilitate cell delivery or cell growth and their delivery, antibodies, antibody fragments, hormones, cell targeting moieties, inert ceramics, inert glasses, bioactive ceramics and bioactive glasses.

10. The method of claim 9, further comprising delivering the inert bioactive or biological material to the mammal from the viscoelastic material.

11. The method of claim 1, further comprising prepolymerizing the emulsion, or portion thereof, into the viscoelastic material, before forming the emulsion into a tissue implant, scaffold for cell growth, or bioadhesive for joining or repairing living tissue.

12. The method of claim 11, further comprising delivering the prepolymerized emulsion to a site in need of repair, regeneration or tissue engineering in a mammal.

13. The method of claim 12, wherein the emulsion is delivered to the site in need of repair, regeneration or tissue engineering in the mammal by an acceptably noninvasive method.

14. The method of claim 12, wherein the emulsion is delivered to the site in need of repair, regeneration or tissue engineering in the mammal by injection.

15. The method of claim 13, further comprising replacing or repairing at least one intervertebral disc in the spinal column of the mammal.

16. The method of claim 15, further comprising delivering the emulsion into an evacuated region of a nucleus pulposus of the intervertebral disc of the mammal;

and then polymerizing the emulsion in situ to form the viscoelastic material, thereby forming an implant in the mammal.

17. The method of claim 16, further comprising frilly or partially evacuating a degenerated nucleus pulposus from the intervertebral disc of the mammal by a minimally invasive surgical method prior to the step of delivering the emulsion to the nucleus pulposus.

18. The method of claim 17, wherein the emulsion further comprises particles, solutions or dispersions of at least one inert, bioactive or biological material.

19. The method of claim 18, wherein the inert, bioactive or biological material is selected from the group consisting of biological cells or cell fragments, tissue fragments derived from in vitro or in vivo cell culture, biological cell or tissue growth factors, agents to facilitate cell delivery or cell growth and their delivery, antibodies, antibody fragments, hormones, cell targeting moieties, inert ceramics, inert glasses, bioactive ceramics and bioactive glasses.

20. The method of claim 19, further comprising delivering the inert bioactive or biological material to the mammal from the viscoelastic material.

21. A method of using a kit for repair, regeneration or tissue engineering comprising a dual component cartridge having first and second individual compartments, comprising:

a) combining the contents of the first and second compartments;

b) delivering the combination to a site in need of repair, regeneration or tissue engineering in a mammal, and

c) polymerizing the combination in situ into a biocompatible, nontoxic, viscoelastic material to form a viscoelastic material into a tissue implant, scaffold for cell growth, or bioadhesive for joining or repairing living tissue comprising a polymerized emulsion having two discrete aqueous and organic phases comprising;

i)a continuous hydrophobic organic phase comprised of polymerized ethylenically unsaturated acrylate monomers; and

ii) a discontinuous aqueous (“

water”

) phase comprising water;

wherein the first compartment contains i) benzoyl peroxide and ii) a biocompatible, non toxic, inverse (“

water-in-oil”

) fluid emulsion for tissue engineering, comprising two discrete phases;

a continuous hydrophobic organic phase comprising lauryl acrylate, bisphenol A diglycidylether, and an inert glass filler, and a discontinuous aqueous phase comprising water, wherein the aqueous phase is a solution that contains about 1% hydroxypropyl methyl cellulose and is present in an amount of about 5% weight/weight of the organic phase, and

the second compartment contains i) a tertiary amine and ii) a biocompatible, non toxic, inverse (“

water-in-oil”

) fluid emulsion for tissue engineering, comprising two discrete phases;

a continuous hydrophobic organic phase comprising lauryl acrylate, bisphenol A diglycidylether, and an inert glass filler, and a discontinuous aqueous phase comprising water, wherein the aqueous phase is a solution that contains about 1% hydroxypropyl methyl cellulose and is present in an amount of about 5% weight/weight of the organic phase.