Connective-tissue-based or dermal-tissue-based grafts/implants
The present invention is directed to a composition comprising a matrix suitable for implantation in humans, comprising defatted, shredded, allogeneic human muscle tissue that has been combined with an aqueous carrier and dried in a predetermined shape. Also disclosed is a tissue graft or implant comprising a matrix suitable for implantation in humans, comprising defatted, shredded, allogeneic human muscle tissue that has been combined with an aqueous carrier and dried in a predetermined shape. The composition and/or tissue graft or implant of the invention is usable in combination with seeded cells, a tissue growth factor, and/or a chemotactic gent to attract a desired cell.
1. An intermediate composition for producing an implant suitable for implantation in humans comprising:
a) a matrix of shredded allogeneic or xenogeneic tissue that has been combined with
b) an aqueous carrier to form a tissue slurry having a viscosity within the range of 1 centistoke to 20,000 centistokes at 25° C., and
c) particles of demineralized bone matrix (DBM), mineralized bone matrix; cortical cancellous chips (CCC), crushed cancellous chips; tricalcium phosphate, hydroxyapatite, or biphasic calcium phosphate dispersed in the matrix.
2. The intermediate composition of claim 1 , wherein said tissue slurry has a viscosity within the range of 1 centistoke to 10,000 centistokes at 25° C.
3. The intermediate composition of claim 2 , wherein said tissue slurry has a viscosity within the range of 1 centistoke to 5,000 centistokes at 25° C.
4. The intermediate composition of claim 1 , wherein said shredded allogeneic tissue is also defatted.
5. The intermediate composition of claim 1 , wherein the ratio of aqueous carrier in milliliters to tissue in grams is within the range from 80:1 to 20:1.
6. The intermediate composition of claim 5 , wherein the ratio of aqueous carrier in milliliters to tissue in grams is within the range from 70:1 to 30:1.
7. The intermediate composition of claim 1 , wherein said shredded allogenic tissue is muscle, tendon, fascia, ligament or dermis.
8. The intermediate composition of claim 1 , wherein the composition comprises demineralized bone matrix (DBM).
9. The intermediate composition of claim 1 , further comprising a bone morphogenic protein (BMP), a LIM mineralization protein, a RUNX-2 protein, a transforming growth factor-α, a transforming growth factor-β, a fibroblast growth factor, a platelet derived growth factor, an epidermal growth factor, an insulin-like growth factor, or a combination thereof.
10. The intermediate composition of claim 9 , wherein said BMP is selected from the group consisting of BMP-2, BMP-4 and BMP-7.
11. The intermediate composition of claim 1 , wherein the composition further comprises seeded cells, a growth factor, a chemotactic agent, or a combination thereof.
12. The intermediate composition of claim 1 , further comprising a growth factor suitable for inducing the growth of fibroblasts, melanocytes, osteogenic cells, stem cells, skin cells or a combination thereof.
13. The intermediate composition of claim 11 , further comprising seeded cells that are dermatocytes, fibroblasts, melanocytes, osteogenic cells, stem cells, skin cells or a combination thereof.
14. The intermediate composition of claim 1 , which has been treated to remove or neutralize antigenic proteins, bacteria and viruses.
15. The intermediate composition of claim 1 , wherein said aqueous carrier comprises a biocompatible acid selected from the group consisting of acetic acid, citric acid, formic acid, hydrochloric acid, phosphoric acid, phosphorus acid and sulfuric acid.
16. An implant suitable for treating an injury or a medical condition in a human comprising the intermediate composition of claim 1 .
17. The implant of claim 16 , wherein said implant is implantable in liquid form.
18. The implant of claim 16 , wherein said implant forms a scaffold material for tissue regeneration in humans.
19. A method for making the intermediate tissue slurry composition of claim 1 , comprising the steps of:
i. removing the fat and soluble proteins from allogeneic or xenogenic tissue;
ii. lyophilizing the tissue from step (i);
iii. shredding the lyophilized tissue;
iv. mixing the shredded tissue with an aqueous carrier to form a tissue slurry having a viscosity within the range of 1 centistoke to 20; 000 centistoke:
v. adding particles of demineralized bone matrix (DBM), mineralized bone matrix, cortical cancellous chips (CCC), crushed cancellous chips, tricalcium phosphate, hydroxyapatite, or biphasic calcium phosphate to the tissue slurry made in step (iv); and dispersing the demineralized bone matrix (DBM), mineralized bone matrix, cortical cancellous chips (CCC), crushed cancellous chips, tricalcium phosphate, hydroxyapalite, or biphasic calcium phosphate in the slurry.