Plasticized bone and soft tissue grafts and methods of making and using same
View Patent ↗The present invention provides a plasticized dehydrated or freeze-dried bone and/or soft tissue product that does not require special conditions of storage, for example refrigeration or freezing, exhibits materials properties that approximate those properties present in normal hydrated tissue, is not brittle, does not necessitate rehydration prior to clinical implantation and is not a potential source for disease transmission. The invention replaces water in the molecular structure of the bone or soft tissue matrix with one or more plasticizers allowing for dehydration of the tissue, yet not resulting in an increase in brittleness of the plasticized product, and resulting in compressive and/or tensile properties similar to those of normal hydrated bone. Replacement of the chemical plasticizers by water prior to implantation is not required and thus, the dehydrated bone or soft tissue plasticized product can be placed directly into an implant site without significant preparation in the operating room.
1. A plasticized soft tissue graft suitable for transplantation into a human, comprising:
a cleaned soft tissue graft having an internal matrix; and
one or more plasticizers contained in said internal matrix, said one or more plasticizers not being removed from said internal matrix prior to packaging,
wherein said plasticized soft tissue graft does not require refrigeration or freezing for storage,
wherein the plasticized soft tissue graft has mechanical properties approximating mechanical properties of natural soft tissue.
2. A plasticized soft tissue graft of claim 1 , wherein said plasticized soft tissue graft is suitable for storage at room temperature.
3. The plasticized soft tissue graft of claim 1 , wherein cellular elements have been removed from the soft tissue graft.
4. The plasticized soft tissue graft of claim 3 , wherein said soft tissue graft comprises cadaveric skin and said one or more plasticizers comprise glycerol.
5. The plasticized soft tissue graft of claim 1 , wherein said soft tissue graft comprises cadaveric skin, pericardium, dura mater, fascia lata, ligaments, or tendons.
6. The plasticized soft tissue graft of claim 1 , wherein said soft tissue graft comprises cadaveric skin and said one or more plasticizers comprise glycerol.
7. The plasticized soft tissue graft of claim 6 , wherein said one or more plasticizers comprise a solution having a concentration of plasticizer of 10% to 100% by weight/volume.
8. The plasticized soft tissue graft of claim 6 , wherein said one or more plasticizers has a concentration of 3 to 30% by weight of the soft tissue graft.
9. The plasticized soft tissue graft of claim 1 , wherein said one or more plasticizers is selected from the group consisting of glycerol, adonitol, sorbitol, ribitol, galactitol, D-galactose, 1,3-dihydroxypropanol, ethylene glycol, triethylene glycol, propylene glycol, glucose, sucrose, mannitol, xylitol, meso-erythritol, adipic acid, proline, hydroxyproline, polyol compounds, monoglycerides, short- and medium-chain free fatty acids, and monoacylglycerol esters.
10. A plasticized soft tissue graft suitable for transplantation into a human, comprising:
a cleaned soft tissue graft comprising cadaveric skin having an internal matrix, wherein cellular elements have been removed from the soft tissue graft; and
one or more plasticizers comprising glycerol contained in said internal matrix, said one or more plasticizers not being removed from said internal matrix prior to packaging,
wherein said plasticized soft tissue graft is suitable for storage at room temperature and has strength and tensile properties of natural tissue.
11. A soft tissue graft, comprising:
soft tissue obtained from a human or animal donor; and
a plasticizer, wherein
cellular elements are substantially removed from said soft tissue,
said plasticizer is contained in said soft tissue, and
the plasticized soft tissue has mechanical properties approximating mechanical properties of natural soft tissue.
12. A method for producing a soft tissue graft, comprising:
substantially removing cellular elements from soft tissue obtained from a human or animal donor;
impregnating the soft tissue with a biocompatible, water-soluble plasticizer, said plasticizer not requiring substantial removal prior to packaging of the soft tissue graft,
wherein the plasticized soft tissue has mechanical properties approximating mechanical properties of natural soft tissue.
13. A method for producing a plasticized soft tissue graft suitable for transplantation into a human, comprising:
impregnating a cleaned soft tissue graft having an internal matrix with a biocompatible, water-soluble plasticizer to produce the plasticized soft tissue graft, wherein the plasticized soft tissue graft has mechanical properties approximating mechanical properties of natural soft tissue; and
packaging the plasticized soft tissue graft without refrigeration or freezing or removal of the plasticizer from the internal matrix of the soft tissue graft.
14. The method of claim 13 , wherein said storing is at room temperature.
15. The method of claim 13 , comprising removing cellular elements from said soft tissue graft.
16. The method of claim 15 , wherein said soft tissue graft comprises cadaveric skin and said one or more plasticizers comprise glycerol.
17. The method of claim 13 , further comprising cleaning said soft tissue graft with a detergent composition.
18. The method of claim 17 , wherein said soft tissue graft comprises cadaveric skin and said one or more plasticizers comprise glycerol.
19. The method of claim 13 , wherein said soft tissue graft comprises cadaveric skin, pericardium, dura mater, fascia lata, ligaments, or tendons.
20. The method of claim 13 , wherein said soft tissue graft comprises cadaveric skin and said one or more plasticizers comprise glycerol.
21. The method of claim 20 , wherein said impregnating is with a solution having a concentration of plasticizer of 10% to 100% by weight/volume.
22. The method of claim 20 , wherein said plasticizer has a concentration of 3 to 30% by weight of the soft tissue graft.
23. The method of claim 13 , comprising impregnating the cleaned soft tissue graft with a plasticizer composition comprising one or more water-soluble plasticizers and one or more biocompatible solvents selected from the group consisting of water and alcohols.
24. The method of claim 13 , wherein said water-soluble plasticizer is selected from the group consisting of glycerol, adonitol, sorbitol, ribitol, galactitol, D-galactose, 1,3-dihydroxypropanol, ethylene glycol, triethylene glycol, propylene glycol, glucose, sucrose, mannitol, xylitol, meso-erythritol, adipic acid, proline, hydroxyproline, polyol compounds, monoglycerides, short- and medium-chain free fatty acids, and monoacylglycerol esters.
25. The method of claim 13 , further comprising washing the plasticized soft tissue graft to remove plasticizer from a surface of the plasticized soft tissue graft.
26. The method of claim 25 , further comprising surgically implanting the plasticized soft tissue graft into a patient without rehydration.
27. A method for producing a plasticized soft tissue graft suitable for transplantation into a human, comprising:
cleaning a soft tissue graft comprising cadaveric skin having an internal matrix with a detergent composition;
rinsing the soft tissue graft;
impregnating said cleaned soft tissue graft with glycerol to produce the plasticized soft tissue graft, wherein the plasticizer is contained in the soft tissue graft in spaces previously occupied by water, and wherein the plasticized sot tissue graft has mechanical properties approximating mechanical properties of natural soft tissue; and
storing the plasticized soft tissue graft without refrigeration or freezing or removal of the plasticizer from the internal matrix of the soft tissue graft.