Cell repopulated collagen matrix for soft tissue repair and regeneration

• US 10,568,990 B2
• Filed: 11/11/2015
• Issued: 02/25/2020
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: AlloSource
• Original Assignee: AlloSource
• Inventors: Stilwell, Reginald L., Atkinson, Brent, Shi, Yaling, Dittman, Brian
• Primary Examiner(s): Long, Scott
• Assistant Examiner(s): Pyla, Evelyn Y
• Application Number:
  US14/938,173
• Publication Number:
  US 20160263284A1
• Time in Patent Office: 1,567 Days
• Field of Search: None
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/426 Immunomodulating agents, i.e. cytokines, interleukins, interferons
• 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 27/24 Collagen
• 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 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• 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 27/3834 Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/60 Materials for use in artificial skin
• CPC Class Codes: C12N 2533/92 Amnion; Decellularised dermis or mucosa
• CPC Class Codes: C12N 5/0667 Adipose-derived stem cells [ADSC]; Adipose stromal stem cells

Abstract

The present invention provides compositions for treating soft tissue injuries comprising a collagen matrix and mesenchymal stem cells adhered to the collagen matrix. Methods of making and using compositions comprising a collagen matrix and mesenchymal stem cells adhered to the collagen matrix are also provided.

Claims

1. A composition for treating a soft tissue injury in a subject, the composition comprising:

a flowable acellular dermal collagen matrix, the flowable acellular dermal collagen matrix comprising cryofractured and thawed acellular dermal tissue having a disrupted extracellular matrix collagen or macrostructure and a partially disrupted collagen microfibrillar architecture; and

mesenchymal stem cells adhered to the flowable acellular dermal collagen matrix, wherein the mesenchymal stem cells are derived from a tissue processed to form a cell suspension comprising mesenchymal stem cells and non-mesenchymal stem cells that is seeded onto the collagen matrix, and wherein the mesenchymal stem cells are not cultured ex vivo after formation of the cell suspension and prior to seeding of the cell suspension on the collagen matrix.

2. The composition of claim 1, wherein the flowable acellular dermal collagen matrix is decellularized dermis.

3. The composition of claim 1, wherein the flowable acellular dermal collagen matrix is dermis from which the epidermis layer has been removed.

4. The composition of claim 1, wherein the collagen matrix is obtained from a human, a porcine, a bovine, or an equine donor.

5. The composition of claim 1, wherein the tissue that is processed to form the cell suspension is selected from adipose tissue, muscle tissue, birth tissue, skin tissue, bone tissue, or bone marrow tissue.

6. The composition of claim 1, wherein the collagen matrix and the tissue that is processed to form the cell suspension are from the same donor.

7. The composition of claim 1, wherein the collagen matrix and the tissue that is processed to form the cell suspension are from different donors.

8. The composition of claim 1, wherein the mesenchymal stem cells seeded on the collagen matrix express one or more positive mesenchymal stem cell markers.

9. The composition of claim 8, wherein the mesenchymal stem cells seeded on the collagen matrix do not express one or more negative mesenchymal stem cell markers.

10. The composition of claim 1, wherein the tissue that is digested to form the cell suspension is adipose tissue.

11. The composition of claim 1, wherein the flowable acellular dermal collagen matrix and the tissue that is digested to form the cell suspension are from a human donor.

12. The composition of claim 1, wherein the flowable acellular dermal collagen matrix and the tissue that is digested to form the cell suspension are from a single human donor.

13. The composition of claim 1, wherein the flowable acellular dermal collagen matrix comprises cryofractured and thawed acellular dermal tissue.

14. A method of treating a soft tissue injury in a subject, the method comprising contacting the soft tissue injury with the composition of claim 1.

15. The method of claim 14, wherein the soft tissue injury is an injury to a tendon tissue, a ligament tissue, a meniscus tissue, a muscle tissue, a skin tissue, a bladder tissue, or a dermal tissue.

16. The method of claim 14, wherein the soft tissue injury is a surgical wound, a trauma wound, a chronic wound, an acute wound, a deep channel wound, an exsanguinating site, or a burn.

17. The method of claim 14, wherein the composition is administered topically.

18. The method of claim 14, wherein the composition is administered by surgical implantation.

19. A method of making a composition for treating a soft tissue injury, the method comprising:

(a) digesting a tissue to form a cell suspension comprising mesenchymal stem cells and non-mesenchymal stem cells;

(b) seeding the cell suspension of step (a) onto a flowable acellular dermal collagen matrix, wherein the flowable acellular dermal collagen matrix comprises cryofractured and thawed acellular dermal tissue having a disrupted extracellular matrix collagen or macrostructure and a partially disrupted collagen microfibrillar architecture;

(c) incubating the flowable acellular dermal collagen matrix seeded with the cell suspension under conditions suitable for adhering the mesenchymal stem cells to the collagen matrix; and

(d) removing the non-adherent cells from the flowable acellular dermal collagen matrix.

20. The method of claim 19, wherein the flowable acellular dermal collagen matrix is obtained from a human, a porcine, a bovine, or an equine donor.

21. The method of claim 19, wherein the tissue that is digested to form the cell suspension is selected from adipose tissue, muscle tissue, birth tissue, skin tissue, bone tissue, or bone marrow tissue.

22. The method of claim 19, wherein the flowable acellular dermal collagen matrix and the tissue that is digested to form the cell suspension are from a single donor.

23. The method of claim 19, wherein the tissue that is digested to form the cell suspension is adipose tissue.

24. The method of claim 19, wherein the flowable acellular dermal collagen matrix and the tissue that is digested to form the cell suspension are from a human donor.

25. The method of claim 19, wherein the flowable acellular dermal collagen matrix and the tissue that is digested to form the cell suspension are from a single human donor.