Acellular tissue matrix compositions for tissue repair
View Patent ↗The invention provides tissue repair compositions and methods of making the tissue repair compositions. Also featured are methods of treatment using the tissue repair compositions and articles of manufacture that include the tissue repair compositions.
1. A method of making a biocompatible mesh composition, the method comprising:
a) selecting a tissue;
b) preparing an acellular tissue matrix (ATM) by treating the tissue to remove cellular material from the tissue, wherein the ATM retains biological functions which are provided by undenatured collagenous proteins and non-collagenous molecules;
c) processing the ATM to produce a plurality of particles, of intact ATM;
d) incubating the plurality of particles of intact ATM in an acidic solution to create a suspension of swollen ATM particles of intact ATM, wherein the acidic solution has a pH from about 1.0 to about 3.0; and
e) applying the suspension to a biocompatible mesh substrate composition and drying the composition to create a coated mesh substrate.
2. The method of claim 1 , wherein steps (d) and (e) are performed simultaneously.
3. The method of claim 1 , wherein the tissue is dermis.
4. The method of claim 1 , wherein the tissue is selected from the group consisting of fascia, pericardial tissue, dura, umbilical cord tissue, placental tissue, cardiac valve tissue, ligament tissue, tendon tissue, arterial tissue, venous tissue, neural connective tissue, urinary bladder tissue, ureter tissue, and intestinal tissue.
5. The method of claim 1 , wherein the tissue is human tissue.
6. The method of claim 1 , wherein the tissue is made from non-human mammalian tissue.
7. The method of claim 6 , wherein the non-human mammalian tissue is obtained from a pig.
8. The method of claim 6 , wherein the tissue is obtained from a non-human mammal that is genetically engineered to lack expression of α-1,3-galactosyl epitopes.
9. The method of claim 8 , wherein the non-human mammal lacks a functional α-1,3-galactosyltransferase gene.
10. The method of claim 1 , wherein the pH is from about 1.5 to about 2.5.
11. The method of claim 1 , wherein the pH is about 1.4.
12. The method of claim 1 , wherein the acidic solution is a solution comprising an acid selected from the group consisting of acetic acid, ascorbic acid, boric acid, carbonic acid, citric acid, hydrochloric acid, lactic acid, tannic acid, phosphoric acid, and sulfuric acid.
13. The method of claim 1 , wherein the acidic solution comprises 0.1 M acetic acid.
14. The method of claim 1 , wherein the acidic solution comprises 0.04 M hydrochloric acid.
15. The method of claim 1 , wherein the incubation step is for a period from about 0.5 hours to about 12 hours.
16. The method of claim 1 , wherein the incubation step is for a period from about 1.0 to about 10.0 hours.
17. The method of claim 1 , wherein the incubation step is for a period from about 2.0 to about 6.0 hours.
18. The method of claim 1 , wherein the incubation step is for a period from about 2.5 to about 5.0 hours.
19. The method of claim 1 , wherein the incubation step is for a period of about 3.0 hours.
20. The method of claim 1 , wherein the incubating step, the drying step, or the incubating and the drying steps are at a temperature of about 20° C. to about 42° C.
21. The method of claim 1 , wherein the incubating step, the drying step, or the incubating and the drying steps are at a temperature of about 20° C. to about 30° C.
22. The method of claim 1 , wherein the incubating step, the drying step, or the incubating and the drying steps are at a temperature of about 25° C. to about 35° C.
23. The method of claim 1 , wherein the incubating step, the drying step, or the incubating and the drying steps are at a temperature of about 30° C. to about 40° C.
24. The method of claim 1 , wherein the incubating step, the drying step, or the incubating and the drying steps are at a temperature of about 35° C. to about 38° C.
25. The method of claim 1 , wherein the incubating step, the drying step, or the incubating and the drying steps are at a temperature of about 37° C. to about 42° C.
26. The method of claim 1 , wherein the incubating step, the drying step, or the incubating and the drying steps are at a temperature of about 37° C.
27. The method of claim 1 , wherein the incubating step, the drying step, or the incubating and the drying steps are at a temperature of about 25° C.
28. The method of claim 1 , wherein the biocompatible mesh substrate is non-absorbable.
29. The method of claim 1 , wherein the biocompatible mesh substrate is absorbable.
30. The method of claim 29 , wherein the biocompatible mesh substrate is a polymer.
31. The method of claim 30 , wherein the polymer comprises poly-4-hydroxybutyrate.
32. The method of claim 29 , wherein the absorbable biocompatible mesh substrate is a polymer selected from the group consisting of polyhydroxyalkanoate, polyglycolic acid, poly-l-lactic acid, polylactic/polyglycolic acid (PLGA), polygalactin 910, and carboxymethyl cellulose.
33. The method of claim 1 , wherein the biocompatible mesh substrate is a synthetic substrate.
34. The method of claim 33 , wherein the synthetic substrate comprises polypropylene.
35. The method of claim 1 , wherein the drying step comprises drying in a nitrogen atmosphere.
36. The method of claim 1 , wherein the drying step comprises freeze-drying.
37. The method of claim 1 , wherein treating the tissue to remove cellular material from the tissue includes removal of all cellular material.
38. The method of claim 1 , wherein the pH is from about 2.0 to about 3.0.
39. A biocompatible mesh composition made by the method of claim 1 .