Acellular bioabsorbable tissue regeneration matrices

• US 9,314,420 B2
• Filed: 09/14/2012
• Issued: 04/19/2016
• Est. Priority Date: 10/26/2005
• Status: Active Grant

• Current Assignee: Genesis Technologies Limited
• Original Assignee: Jan-Eric Ahlfors
• Inventors: Ahlfors, Jan-Eric
• Primary Examiner(s): Fox, Allison
• Application Number:
  US13/617,150
• Publication Number:
  US 20130136796A1
• Time in Patent Office: 1,313 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 35/30 Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
• CPC Class Codes: A61K 35/545 Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/385 Serum albumin
• CPC Class Codes: A61K 38/40 Transferrins, e.g. lactoferrins, ovotransferrins
• CPC Class Codes: A61K 38/51 Lyases (4)
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/00 Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2430/32 for nerve reconstruction
• CPC Class Codes: A61L 2430/38 for reconstruction of the spine, vertebrae or intervertebral discs
• CPC Class Codes: A61L 2430/40 Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
• CPC Class Codes: A61L 27/3604 characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
• CPC Class Codes: A61L 27/3616 Blood, e.g. platelet-rich plasma
• CPC Class Codes: A61L 27/3683 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61P 1/16 : for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

The present invention provides methods and compositions useful in the regeneration of damaged, lost and/or degenerated tissue in humans and animals. In certain embodiments, the present invention provides an acellular bioabsorbable tissue regeneration matrix, methods of making such a matrix, and methods of using such a matrix for the regeneration of damaged, lost and/or degenerated tissue. In certain embodiments, methods and compositions of the present invention are useful in the treatment of damaged, lost and/or degenerated nerve tissue.

Claims

1. An isolated acellular bioabsorbable tissue regeneration matrix derived from blood or bone marrow comprising a heterogeneous mixture of proteins and salts, wherein the overall protein content of the matrix is at least 1%, wherein the matrix is characterized by

aggregates of spherical structures with a diameter of approximately at least 100 nm, wherein the acellular bioabsorbable tissue regeneration matrix lacks substantial metabolic activity as compared to that initially present in blood or bone marrow;

and further wherein the acellular bioabsorbable tissue regeneration matrix is capable of initiating tissue regeneration in a subject with tissue damage, increasing tissue regeneration in a subject with tissue damage compared with untreated tissue, or both.

2. The isolated acellular bioabsorbable tissue regeneration matrix of claim 1, further comprising one or more proteins selected from the group consisting of:

transferrin, serum albumin, serum albumin precursor, complement component 3, chains A-D hemoglobin, IgM, IgG1, medullasin inhibitor 2, carbonic anhydrase, CA1 protein, and combinations thereof.

3. The isolated acellular bioabsorbable tissue regeneration matrix of claim 1, wherein the spherical structures are recognized by CD56 antibodies.

4. The acellular bioabsorbable tissue regeneration matrix of claim 1, wherein the spherical structures have a diameter of about 1-2 μ

m.

5. The acellular bioabsorbable tissue regeneration matrix of claim 1, wherein the spherical structures have a diameter of about 2-4 μ

m.

6. The acellular bioabsorbable tissue regeneration matrix of claim 1, further comprising a therapeutic agent.

7. The acellular bioabsorbable tissue regeneration matrix of claim 6, wherein the therapeutic agent is distributed heterogeneously within the acellular bioabsorbable tissue regeneration matrix.

8. The acellular bioabsorbable tissue regeneration matrix of claim 6, wherein the therapeutic agent is distributed homogeneously within the acellular bioabsorbable tissue regeneration matrix.

9. The acellular bioabsorbable tissue regeneration matrix of claim 6, wherein the acellular bioabsorbable tissue regeneration matrix comprises two or more therapeutic agents.

10. The acellular bioabsorbable tissue regeneration matrix of claim 6, wherein the therapeutic agent is selected from the group consisting of:

proteins, peptides, drugs, cytokines, extracellular matrix molecules, growth factors, and combinations thereof.

11. The acellular bioabsorbable tissue regeneration matrix of claim 10, wherein the acellular bioabsorbable tissue regeneration matrix increases the magnitude of one or more beneficial effects of the therapeutic agent.

12. The acellular bioabsorbable tissue regeneration matrix of claim 10, wherein the acellular bioabsorbable tissue regeneration matrix prolongs one or more beneficial effects of the therapeutic agent by slowly releasing the therapeutic agent over time in the subject.

13. The acellular bioabsorbable tissue regeneration matrix of claim 10, wherein the acellular bioabsorbable tissue regeneration matrix protects one or more beneficial effects of the therapeutic agent from substantially decreasing over time.

14. The acellular bioabsorbable tissue regeneration matrix of claim 1, further comprising exogenous cells that have been added to the matrix.

15. The acellular bioabsorbable tissue regeneration matrix of claim 14, wherein the cells are selected from the group consisting of:

stem cells, progenitor cells, somatic cells, and combinations thereof.

16. The acellular bioabsorbable tissue regeneration matrix of claim 14, wherein the cells are cells selected from the group consisting of:

embryonic stem cells, neural stem cells, neuroprogenitor cells, neurons, glial cells, and combinations thereof.

17. The acellular bioabsorbable regeneration matrix of claim 1, comprising fibers interspersed throughout the aggregates.

18. The acellular bioabsorbable regeneration matrix of claim 1, wherein the matrix is self-assembled.

19. The acellular bioabsorbable regeneration matrix of claim 1, wherein said regeneration matrix is in solid or semi-solid form, in the form of a three-dimensional matrix or in the form of a suspension.

20. The acellular bioabsorbable regeneration matrix of claim 1, wherein the aggregates of spherical structures are 100 nm-4 microns in diameter.

21. The acellular bioabsorbable regeneration matrix of claim 1, wherein the matrix further comprises lipids, carbohydrates and/or nucleic acids.