Methods and compositions for soft tissue repair

• US 8,691,946 B2
• Filed: 05/17/2011
• Issued: 04/08/2014
• Est. Priority Date: 11/18/2009
• Status: Active Grant

• Current Assignee: Affinergy, LLC
• Original Assignee: Affinergy, LLC
• Inventors: Sanford, Isaac Gilliam, Darby, Martyn Kerry, Hodges, Jonathan Allen, Nair, Shrikumar Ambujakshan, Chen, Yuchen, Hamilton, Paul Theodore, Sathya, Ganesan, Gron, Hanne, Jansen, Michelle Steffen
• Primary Examiner(s): Bradley, Christina
• Assistant Examiner(s): GARYU, LIANKO G
• Application Number:
  US13/109,802
• Publication Number:
  US 20110223142A1
• Time in Patent Office: 1,057 Days
• Field of Search: None
• US Class Current: 530/326
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/425 of phosphorus containing material, e.g. apatite
• CPC Class Codes: A61L 27/427 of other specific inorganic materials not covered by A61L27/422 or A61L27/425
• 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 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 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• 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

Compositions and methods for tissue repair are provided including cell binding peptides and growth factor binding peptides. The cell binding peptides bind to one or more of stem cells, fibroblasts, or endothelial cells. The growth factor binding peptides include platelet derived growth factor (PDGF) binding peptides and growth differentiation factor (GDF) binding peptides. The tissue for repair includes tendon, muscle, connective tissue, ligament, cardiac tissue, vascular tissue, or dermis. Implantable devices for tissue repair are provided to which the cell and growth factor binding peptides are attached, such as acellular extracellular matrix having attached binding peptide.

Claims

1. A cell binding peptide comprising a sequence selected from the group consisting of SEQ ID NO:

4, conservatively substituted variants of SEQ ID NO;

4, and variants having at least 70% sequence identity to SEQ ID NO;

4, wherein the variant cell binding peptide retains the ability to bind cells.

3. The cell binding peptide of claim 1, wherein the cell binding peptide comprises one or more modifications to the peptide N-terminus, peptide C-terminus, or within the peptide amino acid sequence, wherein the modification is selected from the group consisting of an aldehyde group, a hydroxyl group, a thiol group, an amino group, amino acids, a lysine, a cysteine, an acetyl group, polymers, synthetic polymers, polyethers, poly(ethylene glycol) (PEG), an 11 unit polyethylene glycol (PEG10), a 1 unit polyethylene glycol (mini-PEG or MP), and combinations thereof.

25. The cell binding peptide of claim 1, wherein the sequence is selected from the group consisting of SEQ ID NOs:

44-70 and 72-75.

2. A cell binding peptide comprising a sequence selected from the group consisting of SEQ ID NO:

4, conservatively substituted variants of SEQ ID NO;

4, and variants having at least 70% sequence identity to SEQ ID NO;

4, wherein the variant cell binding peptide retains the ability to bind cells, and wherein the peptide comprises up to 40 amino acids.

4. An implantable device for tissue repair comprising a polymer having a covalently attached cell binding peptide, wherein the cell binding peptide comprises a sequence selected from the group consisting of SEQ ID NO:

4, conservatively substituted variants of SEQ ID NO;

4, and variants having at least 70% sequence identity to SEQ ID NO;

4, wherein the variant cell binding peptide retains the ability to bind cells.

5. The implantable device of claim 4, wherein the cell binding peptide is attached to the polymer with or without a spacer.

6. The implantable device of claim 4, wherein the cell binding peptide binds to one or more of fibroblasts, endothelial cells, and stem cells.

7. The implantable device of claim 4, wherein the polymer is a biopolymer selected from the group consisting of a collagen, an injectable collagen, a keratin, a silk, a polysaccharide, an agarose, a dextran, a cellulose derivative, an oxidized cellulose, an oxidized regenerated cellulose, a carboxymethylcellulose, a hydroxypropylmethylcellulose, a chitosan, a chitin, a hyaluronic acid, derivatives thereof, and combinations thereof.

8. The implantable device of claim 4, wherein the implantable device comprising the polymer is selected from the group consisting of a gel, a hydrogel, an injectable material, an extracellular matrix, a decellularized tissue, a dermal matrix, an acellular human dermis, an acellular porcine dermis, an acellular bovine dermis, a porcine small intestinal submucosa (SIS), an acellular myocardium, a cardiac patch, a decellularized vascular conduit, a surgical mesh, a skin graft, a dural graft, a graft for foot ulcer repair, a hernia repair graft, a graft for abdominal repair, a tendon wrap, a tendon augmentation graft, a graft for rotator cuff repair, a graft or mesh for breast reconstruction, a composite surgical mesh comprising a synthetic polymer and a biopolymer, derivatives thereof, and combinations thereof.

9. A method for tissue repair comprising delivering to a subject an implantable device for tissue repair, wherein the implantable device comprises a polymer having a covalently attached cell binding peptide, wherein the cell binding peptide comprises a sequence selected from the group consisting of SEQ ID NO:

4, conservatively substituted variants of SEQ ID NO;

4, and variants having at least 70% sequence identity to SEQ ID NO;

4, wherein the variant cell binding peptide retains the ability to bind cells, and wherein the implantable device serves as a scaffold for tissue repair.

10. The method of claim 9, wherein the cell binding peptide binds to one or more of fibroblasts, endothelial cells, and stem cells.

11. The method of claim 9, wherein the polymer is a biopolymer selected from the group consisting of a collagen, an injectable collagen, a keratin, a silk, a polysaccharide, an agarose, a dextran, a cellulose derivative, an oxidized cellulose, an oxidized regenerated cellulose, a carboxymethylcellulose, a hydroxypropylmethylcellulose, a chitosan, a chitin, a hyaluronic acid, derivatives thereof, and combinations thereof.

12. The method of claim 9, wherein the implantable device comprising the polymer is selected from the group consisting of a gel, a hydrogel, an injectable material, an extracellular matrix, a decellularized tissue, a dermal matrix, an acellular human dermis, an acellular porcine dermis, an acellular bovine dermis, a porcine small intestinal submucosa (SIS), an acellular myocardium, a cardiac patch, a decellularized vascular conduit, a surgical mesh, a skin graft, a dural graft, a graft for foot ulcer repair, a hernia repair graft, a graft for abdominal repair, a tendon wrap, a tendon augmentation graft, a graft for rotator cuff repair, a graft or mesh for breast reconstruction, a composite surgical mesh comprising a synthetic polymer and a biopolymer, derivatives thereof, and combinations thereof.

13. The method of claim 9, wherein the tissue for repair comprises any one or more of tendon, muscle, connective tissue, ligament, cardiac tissue, vascular tissue, and dermis.

14. A method for capturing cells onto an implantable device for tissue repair, comprising:

contacting a sample comprising cells with the implantable device, wherein the implantable device comprises a polymer having a covalently attached cell binding peptide, wherein the cell binding peptide is selected from the group consisting of SEQ ID NO;

4, conservatively substituted variants of SEQ ID NO;

4, and variants having at least 70% sequence identity to SEQ ID NO;

4, wherein the variant cell binding peptide retains the ability to bind cells, and wherein the cells comprised in the sample are captured onto the implantable device through binding to the attached cell binding peptide.

15. The method of claim 14, wherein the cell binding peptide binds to one or more of fibroblasts, endothelial cells, and stem cells.

16. The method of claim 14, wherein the sample comprising cells comprises bone marrow, allogeneic stem cells, adipose tissue, stromal vascular fraction of adipose tissue, blood, blood products, platelets, platelet-rich plasma (PRP), umbilical cord blood, embryonic tissues, placenta, amniotic epithelial cells, tissue punch, omentum, a homogeneous population of cultured cells, a heterogeneous population of cultured cells, combinations thereof, or derivatives thereof.

17. The method of claim 14, wherein the polymer is a biopolymer selected from the group consisting of a collagen, an injectable collagen, a keratin, a silk, a polysaccharide, an agarose, a dextran, a cellulose derivative, an oxidized cellulose, an oxidized regenerated cellulose, a carboxymethylcellulose, a hydroxypropylmethylcellulose, a chitosan, a chitin, a hyaluronic acid, derivatives thereof, and combinations thereof.

18. The method of claim 14, wherein the implantable device comprising the polymer is selected from the group consisting of a gel, a hydrogel, an injectable material, an extracellular matrix, a decellularized tissue, a dermal matrix, an acellular human dermis, an acellular porcine dermis, an acellular bovine dermis, a porcine small intestinal submucosa (SIS), an acellular myocardium, a cardiac patch, a decellularized vascular conduit, a surgical mesh, a skin graft, a dural graft, a graft for foot ulcer repair, a hernia repair graft, a graft for abdominal repair, a tendon wrap, a tendon augmentation graft, a graft for rotator cuff repair, a graft or mesh for breast reconstruction, a composite surgical mesh comprising a synthetic polymer and a biopolymer, derivatives thereof, and combinations thereof.

19. A method for tissue repair, comprising:

a. contacting a sample comprising cells with an implantable device comprising a polymer having a covalently attached cell binding peptide, wherein the cell binding peptide comprises a sequence selected from the group consisting of SEQ ID NO;

4, conservatively substituted variants of SEQ ID NO;

4, and variants having at least 70% sequence identity to SEQ ID NO;

4, wherein the variant cell binding peptide retains the ability to bind cells, wherein the cells comprised in the sample are captured onto the implantable device through binding to the attached cell binding peptide; and

b. delivering to a subject the implantable device for tissue repair.

20. The method of claim 19, wherein the cells are one or more of fibroblasts, endothelial cells, and stem cells.

21. The method of claim 19, wherein the sample comprising cells comprises bone marrow, bone marrow, allogeneic stem cells, adipose tissue, stromal vascular fraction of adipose tissue, blood, blood products, platelets, platelet-rich plasma (PRP), umbilical cord blood, embryonic tissues, placenta, amniotic epithelial cells, tissue punch, omentum, a homogeneous population of cultured cells, a heterogeneous population of cultured cells, combinations thereof, or derivatives thereof.

22. The method of claim 19, wherein the polymer is a biopolymer selected from the group consisting of a collagen, an injectable collagen, a keratin, a silk, a polysaccharide, an agarose, a dextran, a cellulose derivative, an oxidized cellulose, an oxidized regenerated cellulose, a carboxymethylcellulose, a hydroxypropylmethylcellulose, a chitosan, a chitin, a hyaluronic acid, derivatives thereof, and combinations thereof.

23. The method of claim 19, wherein the implantable device comprising the polymer is selected from the group consisting of a gel, a hydrogel, an injectable material, an extracellular matrix, a decellularized tissue, a dermal matrix, an acellular human dermis, an acellular porcine dermis, an acellular bovine dermis, a porcine small intestinal submucosa (SIS), an acellular myocardium, a cardiac patch, a decellularized vascular conduit, a surgical mesh, a skin graft, a dural graft, a graft for foot ulcer repair, a hernia repair graft, a graft for abdominal repair, a tendon wrap, a tendon augmentation graft, a graft for rotator cuff repair, a graft or mesh for breast reconstruction, a composite surgical mesh comprising a synthetic polymer and a biopolymer, derivatives thereof, and combinations thereof.

24. The method of claim 19, wherein the tissue for repair comprises any one or more of connective tissue, muscle, tendon, ligament, vascular tissue, cardiac tissue, and dermis.