Decellularized biomaterial from non-mammalian tissue

• US 10,617,790 B2
• Filed: 01/09/2014
• Issued: 04/14/2020
• Est. Priority Date: 01/09/2013
• Status: Active Grant

• Current Assignee: NeXtGen Biologics
• Original Assignee: ISE Professional Testing & Consulting Services, Inc.
• Inventors: Early, Ryanne
• Primary Examiner(s): Davis, Ruth A
• Application Number:
  US14/759,895
• Publication Number:
  US 20150352257A1
• Time in Patent Office: 2,287 Days
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 35/65 Amphibians, e.g. toads, frogs, salamanders or newts
• CPC Class Codes: A61K 38/1703 from vertebrates
• CPC Class Codes: A61K 9/70 Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug hollow drug-filled fibres A61K9/0092
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• 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 27/362 Skin, e.g. dermal papillae
• CPC Class Codes: A61L 27/3625 Vascular tissue, e.g. heart valves
• CPC Class Codes: A61L 27/3633 Extracellular matrix [ECM]
• CPC Class Codes: A61L 27/3687 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
• CPC Class Codes: A61L 27/3691 characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• 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: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 27/60 : Materials for use in artificial skin
• CPC Class Codes: A61P 17/02 : for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2533/90 : Substrates of biological origin, e.g. extracellular matrix, decellularised tissue
• CPC Class Codes: C12N 2533/92 : Amnion; Decellularised dermis or mucosa
• CPC Class Codes: C12N 5/0625 : Epidermal cells, skin cells; Cells of the oral mucosa

Abstract

The growth factor profile, connective tissue matrix constituents, and immunoprivileged status of urodele extracellular matrix (ECM) and accompanying cutaneous tissue, plus the presence of antimicrobial peptides there, render urodele-derived tissue an ideal source for biological scaffolds for xenotransplantation. In particular, a biological scaffold biomaterial can be obtained by a process that entails (A) obtaining a tissue sample from a urodele, where the tissue comprises ECM, inclusive of the basement membrane, and (B) subjecting the tissue sample to a decellularization process that maintains the structural and functional integrity of the extracellular matrix, by virtue of retaining its fibrous and non-fibrous proteins, glycoaminoglycans (GAGs) and proteoglycans, while removing sufficient cellular components of the sample to reduce or eliminate antigenicity and immunogenicity for xenograft purposes. The resultant urodele-derived biomaterial can be used to enhance restoration of skin homeostasis, to reduce the severity, duration and associated damage caused by post-surgical inflammation, and to promote progression of natural healing and regeneration processes. In addition, the biomaterial promotes the formation of remodeled tissue that is comparable in quality, function, and compliance to undamaged human tissue.

Claims

1. A tissue graft comprising extracellular matrix components derived from a Urodele, said tissue graft derived by:

a. obtaining a tissue sample from a urodele, which tissue sample comprises extracellular matrix; and

b. decellularizing said tissue sample to produce decellularized extracellular matrix by removing sufficient cellular components of the sample to reduce or eliminate antigenicity of the biomaterial making it suitable for use as a xenograft.

2. The tissue graft of claim 1, wherein said decellularizing comprises subjecting said tissue sample to an alkaline treatment.

3. The tissue graft of claim 2, wherein said process further comprises subjecting said sample to sterilization.

4. The tissue graft of claim 1, wherein the Urodele is an Axolotl.

5. A tissue graft according to claim 1 comprising sterile, isolated, decellularized Urodele extra cellular matrix (ECM), wherein the ECM is a powder, a paste, a gel, a sheet, or a mesh, and wherein the ECM is parietal ECM, mesothelial ECM, thoracic cavity ECM, abdominal cavity ECM, pericardium ECM or dermal tissue ECM.

6. The tissue graft of claim 5, wherein the ECM is a powder.

7. The tissue graft of claim 6, wherein the powder has a particle size between 125 and 850 microns.

8. The tissue graft of claim 6, wherein the powder has a particle size of less than 250 microns.

9. The tissue graft of claim 5, wherein the ECM is a paste.

10. The tissue graft of claim 5, wherein the ECM is a gel.

11. The tissue graft of claim 10, wherein the gel comprises a synthetic polymer.

12. The tissue graft of claim 5, wherein the ECM is a mesh.

13. The tissue graft according to claim 5 wherein the Urodele ECM is Axolotl ECM and is in a form selected from the group consisting of:

a powder;

a paste;

a gel;

a mesh;

a sheet of parietal ECM, mesothelial ECM, thoracic cavity ECM, abdominal cavity ECM, pericardium ECM or dermal tissue ECM, and wherein the sheet of ECM is infused with, coated with, or attached to an agent xenogeneic to a Urodele that is a growth factor, a cytokine, a chemokine, a protein, a carbohydrate, a sugar, a steroid, an antimicrobial agent, a synthetic polymer, an adhesive, or a drug; and

at least two sheets of isolated Urodele decellularized ECM laminated to one another.

14. A tissue graft according to claim 1 comprising sterile, isolated, decellularized Urodele extra cellular matrix (ECM), wherein the ECM is a sheet, wherein the ECM is parietal ECM, mesothelial ECM, thoracic cavity ECM, abdominal cavity ECM, pericardium ECM or dermal tissue ECM, and the sheet of ECM is infused with, coated with, or attached to an agent xenogeneic to a Urodele that is a growth factor, a cytokine, a chemokine, a protein, a carbohydrate, a sugar, a steroid, an antimicrobial agent, a synthetic polymer, an adhesive, or a drug.

15. The tissue graft of claim 14, wherein the agent is an anti-microbial agent.

16. The tissue graft of claim 14, wherein the agent is a growth factor.

17. The tissue graft of claim 14, wherein the sheet is at least two sheets of isolated Urodele decellularized ECM laminated to one another.

18. A method for making the tissue graft of claim 1, comprising extracellular matrix components derived from a Urodele, said method comprising:

a. obtaining a tissue sample from a urodele, which tissue sample comprises extracellular matrix; and

b. decellularizing said tissue sample to produce decellularized extracellular matrix by removing sufficient cellular components of the sample to reduce or eliminate antigenicity of the biomaterial making it suitable for use as a xenograft.

19. The method according to claim 18, wherein said decellularizing comprises subjecting said tissue sample to an alkaline treatment, and wherein said process further optionally comprises subjecting said sample to sterilization, and wherein the Urodele is an Axolotl.

35. A device comprising a tissue graft according to claim 5 comprising at least two sheets of isolated Urodele decellularized ECM laminated to one another, wherein said extracellular matrix components are derived from a Urodele, said tissue graft derived by:

a. obtaining a tissue sample from a urodele, which tissue sample comprises extracellular matrix; and

b. decellularizing said tissue sample to produce decellularized extracellular matrix by removing sufficient cellular components of the sample to reduce or eliminate antigenicity of the biomaterial making it suitable for use as a xenograft.

36. The device of claim 35, wherein the Urodele ECM is Axolotl ECM.

20. A sterile medical implant comprising sterile, isolated, decellularized Urodele Extracellular Matrix (ECM) or a sterile Urodele fraction derived from the isolated, decellularized Urodele ECM produced by a process comprising:

a. obtaining a tissue sample from a urodele, which tissue sample comprises extracellular matrix;

b. decellularizing and sterilizing said tissue sample to produce decellularized extracellular matrix by removing sufficient cellular components of the sample to reduce or eliminate antigenicity of the biomaterial making it suitable for use as a xenograft; and

sterilizing said tissue.

21. The sterile medical implant of claim 20, wherein the implant is a biocompatible sheet, mesh, gel, graft, tissue or device.

22. The sterile medical implant of claim 20, wherein the Urodele ECM includes basement membrane.

23. The sterile medical implant of claim 20, wherein the Urodele ECM is derived from Axolotl tissue.

24. The sterile medical implant of claim 20, wherein the Urodele ECM is infused with, coated with, or attached to an agent xenogenic to a Urodele that is a growth factor, a cytokine, a chemokine, a protein, a carbohydrate, a sugar, a steroid, an antimicrobial agent, a synthetic polymer, an adhesive, or a drug.

25. The sterile medical implant of claim 20, further comprising a human cell and wherein the Urodele ECM is infused with, coated with, or attached to the human cell.

26. The sterile medical implant of claim 20, wherein the Urodele extracellular matrix (ECM) or a sterile Urodele fraction derived from the isolated, decellularized Urodele ECM is a sheet.

27. The sterile medical implant of claim 20, wherein the Urodele ECM is in the form of Urodele ECM particles.

28. The sterile medical implant of claim 20, wherein the Urodele ECM is a reconstituted gel.

29. A method for making the sterile medical implant of claim 20, comprising sterile, isolated, decellularized Urodele Extracellular Matrix (ECM) or a sterile Urodele fraction derived from the isolated, decellularized Urodele ECM, said method comprising:

a. obtaining a tissue sample from a urodele, which tissue sample comprises extracellular matrix;

b. decellularizing and sterilizing said tissue sample, to produce the sterile decellularized extracellular matrix comprised within said sterile medical implant, by removing sufficient cellular components of the sample to reduce or eliminate antigenicity of the biomaterial, making it suitable for use as a xenograft; and

sterilizing said tissue.

30. The method according to claim 29, wherein the implant is a biocompatible sheet, mesh, gel, graft, tissue, device, or is a material coated with, impregnated with, encapsulated with, or having attached thereto the isolated, decellularized Urodele ECM.

31. The method according to claim 29, wherein said decellularizing comprises subjecting said tissue sample to an alkaline treatment, wherein said process further comprises subjecting said sample to sterilization, wherein the Urodele is an Axolotl.

32. A material coated with, impregnated with, encapsulating, or having attached thereto isolated, decellularized Urodele ECM wherein said isolated, decellularized Urodele ECM is produced by a process comprising:

a. obtaining a tissue sample from a urodele, which tissue sample comprises extracellular matrix;

b. decellularizing said tissue sample to produce decellularized extracellular matrix by removing sufficient cellular components of the sample to reduce or eliminate antigenicity of the biomaterial making it suitable for use as a xenograft; and

sterilizing said tissue.

33. The material of claim 32, wherein the Urodele ECM is Axolotl ECM.

34. A method for making the material coated with, impregnated with, encapsulating, or having attached thereto isolated, decellularized Urodele ECM of claim 32, wherein said isolated, decellularized Urodele ECM is produced by a process comprising:

a. obtaining a tissue sample from a urodele, which tissue sample comprises extracellular matrix;

b. decellularizing said tissue sample to produce decellularized extracellular matrix by removing sufficient cellular components of the sample to reduce or eliminate antigenicity of the biomaterial making it suitable for use as a xenograft; and

sterilizing said tissue.