Polymerizable emulsions for tissue engineering

• US 20070248643A1
• Filed: 05/01/2007
• Published: 10/25/2007
• Est. Priority Date: 10/29/2003
• Status: Active Grant

• Current Assignee: Gentis, Inc.
• Original Assignee: Gentis, Inc., Regents of The University of Minnesota (University of Minnesota), Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: Cohen, Charles, Ducheyne, Paul, Devore, David
• Granted Patent: US 7,537,754 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• 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, polymerized, viscoelastic material two discrete phases (an organic phase and an aqueous phase) formed by in situ polymerization of a non toxic, inverse (water-in-oil) fluid emulsion, wherein the emulsion comprises:

a continuous hydrophobic organic (oil) phase, comprising one or more reactive, ethylenically unsaturated, polymerizable monomers, at least one polymerization initiator; and

a discontinuous aqueous (water) phase, wherein the aqueous phase concentration ranges from about 0.5% to about 90% weight/weight of the oil phase; and

the method comprises forming the emulsion into a tissue implant, scaffold for cell growth, or bioadhesive for joining or repairing living tissue.

2. The method of claim 1, 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, further comprising delivering the emulsion by acceptably noninvasive means to the site in need of repair, regeneration or tissue engineering in the mammal.

4. The method of claim 3, wherein the delivery is effected by injection of the emulsion means to the site in need of repair, regeneration or tissue engineering in the mammal.

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 nucleous pulposus of the intervertebral disc of the mammal;

and then

polymerizing the emulsion in situ to form the viscoeleastic 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 minimally invasive surgical means prior to the step of delivering the emulsion to the nucleus pulposus.

8. The method of claim 7, further comprising selecting and adding to the emulsion, in either the organic or aqueous phase, particles, solutions or dispersions of one or more inert, bioactive or biological materials.

9. The method of claim 8, further comprising selecting and adding to the emulsion, one or more inert, bioactive or biological materials 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 one or more inert bioactive or biological materials 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, 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.

13. The method of claim 12, further comprising delivering the emulsion by acceptably noninvasive means to the site in need of repair, regeneration or tissue engineering in the mammal.

14. The method of claim 13, wherein the delivery is effected by injection of the emulsion means to the site in need of repair, regeneration or tissue engineering in the mammal.

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 nucleous pulposus of the intervertebral disc of the mammal;

and then

polymerizing the emulsion in situ to form the viscoeleastic material, thereby forming an implant in the mammal.

17. The method of claim 16, further comprising

fully or partially evacuating a degenerated nucleus pulposus from the intervertebral disc of the mammal by minimally invasive surgical means prior to the step of delivering the emulsion to the nucleus pulposus.

18. The method of claim 17, further comprising selecting and adding to the emulsion, in either the organic or aqueous phase, particles, solutions or dispersions of one or more inert, bioactive or biological materials.

19. The method of claim 18, further comprising selecting and adding to the emulsion, one or more inert, bioactive or biological materials 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 one or more inert bioactive or biological materials to the mammal from the viscoelastic material.