Regenerative materials
View Patent ↗Methods of making tissue fillers are provided. In certain embodiments, the tissue is flake-like and has regenerative properties.
1. A method for preparing a tissue matrix composition comprising:
selecting a collagen-based tissue matrix;
contacting the tissue matrix with a cryoprotectant solution;
freezing the tissue matrix and cryoprotective solution;
cutting the frozen tissue matrix and cryoprotective solution into a plurality of cut tissue pieces having irregular size and shape, wherein the temperature of the tissue matrix ranges from −10 ° C. to −40° C. for the cutting step and wherein the cut tissue has a size distribution ranging from 0.2-5 mm in length, 0.2-3 mm in width, and 0.02-0 3 mm in thickness;
placing the plurality of cut tissue pieces into a liquid to form a suspension of interconnected irregularly shaped particles, and
removing liquid from the suspension to form a device having inter-connected channels that permit body fluid to flow freely therethrough.
2. The method of claim 1 , wherein the tissue matrix comprises an acellular tissue matrix.
3. The method of claim 2 , wherein the acellular tissue matrix comprises an acellular dermal matrix.
4. The method of claim 2 , wherein the acellular tissue matrix comprises an acellular porcine dermal matrix.
5. The method of claim 1 , wherein the cryoprotectant solution comprises at least one of a maltodextrin, sucrose, polyethylene glycol (PEG), or polyvinylpyrrolidone (PVP) solution, or a combination thereof.
6. The method of claim 1 , wherein the cryoprotectant solution comprises a maltodextrin solution.
7. The method of claim 6 , wherein the maltodextrin solution comprises 5-50% (w/v) maltodextrin.
8. The method of claim 6 , wherein the maltodextrin solution comprises 15-25% (w/v) maltodextrin.
9. The method of claim 1 , wherein cutting comprises grating.
10. The method of claim 1 , wherein the tissue matrix is cut with a grater.
11. The method of claim 1 , wherein the tissue matrix is cut with a grating wheel.
12. The method of claim 1 , further comprising exposing the tissue matrix to a disinfectant.
13. The method of claim 12 , wherein the disinfectant is isopropyl alcohol.
14. The method of claim 1 , further comprising sterilizing the plurality of cut tissue pieces by application of at least one of ethylene oxide, propylene oxide, gamma irradiation or e-beam irradiation.
15. The method of claim 1 , further comprising adding a bioactive substance to the cut matrix.
16. The method of claim 15 , wherein the bioactive substance comprises an antimicrobial agent.
17. The method of claim 15 , wherein the bioactive substance comprises a cytokine.
18. The method of claim 15 , wherein the bioactive substance comprises a growth factor.
19. The method of claim 15 , wherein the bioactive substance comprises non-collagenous tissue.
20. The method of claim 19 , wherein the non-collagenous tissue comprises adipose tissue.
21. The method of claim 15 , wherein the bioactive substance comprises cells.
22. The method of claim 21 , wherein the cells comprise stem cells.
23. The method of claim 1 , wherein removing liquid comprises freeze-drying the suspension.