Cyclic implant perfusion, cleaning and passivation process and implant produced thereby
View Patent ↗A method for perfusion of a porous implant which achieves efficient interpenetration of desired factors into and removal of undesirable factors from the pores of the implant, cleaning of the implant, efficient passivation of the implant, and the implant produced by such treatment. A system wherein the rate of pressure cycling, the fact of pressure cycling, and the amplitude of pressure cycling, results in highly cleaned tissues and other implants. Goals include between about a one to twelve log reduction in bacterial contamination, between about a one to fifteen log reduction in enveloped virus contamination, up to about a five log reduction in non-enveloped virus contamination, between about a two to tenfold reduction in endotoxin, maintenance of implant or graft biologic and biomechanical properties, absence of tissue toxicity due to cleaning solutions used, and reduced implant antigenicity.
1. A method for cleaning tissue comprising:
i. exposing said tissue to three or more different cleaning solutions in series;
ii. exposing said tissue to at least one rinsing step;
iii. cycling between step (i) and (ii) sufficient times to produce a cleaned tissue;
wherein said tissue is submerged in one of said three or more cleaning solutions in a sealed vessel during at least one of steps i, ii, or iii; and wherein said method occurs, at least in part, with concurrent exposure of said tissue to sonication; and further comprising a depressurization step that occurs before, during or after at least one of steps i, ii, or iii, wherein said depressurization step is a release of pressure.
2. The method of claim 1 , wherein step (iii) is carried out sufficient times to produce cleaned tissue that is passivated.
3. The method of claim 2 , wherein the tissue produced is suitable for implantation or processing for implantation in humans.
4. The method of claim 1 , wherein each said cleaning solution comprises at least one of sterile water, a nonionic surfactant, tri(n-butyl)phosphate (TNBP), hydrogen peroxide, a water miscible alcohol, saline solution, povidone iodine, ascorbic acid solution, an aromatic hydrocarbon, an aliphatic hydrocarbon, an ether, a ketone, an amine, urea, guanidine hydrochloride, an ester, a glycoprotein, a protein, a saccharide, an enzyme, a gaseous acid, a gaseous peroxide, or mixtures thereof.
5. The method of claim 1 , wherein each said cleaning solution comprises at least one of 6% by weight hydrogen peroxide, 1% by weight sodium hypochlorite, 6M urea, 4M guanidine hydrochloride, 1 N sodium hydroxide, isopropanol, sterile water, saline or mixtures thereof.
6. The method of claim 1 , wherein said tissue comprises at least one of the following: cortical bone, cancellous bone, fascia, whole joint, tendon, ligament, dura, pericardia, heart valve, vein, neural tissue, submucosal tissue, cartilage, or combinations thereof.
7. The method of claim 6 , wherein said tissue comprises at least one of the following: cortical bone or cancellous bone, or combinations thereof.
8. The method of claim 6 , wherein said tissue comprises at least one of the following: fascia, whole joint, tendon, ligament, dura, pericardia, heart valve, vein, neural tissue, submucosal tissue, or cartilage, or combinations thereof.
9. The method of claim 1 , wherein said tissue is derived from a single donor.
10. The method of claim 1 , wherein said tissue is derived from a pool of donor tissues.
11. The method of claim 1 , further comprising placing said cleaned tissue into a sterile, sealable package.
12. The method of claim 11 , further comprising performing a surface decontamination step prior to or after sealing said package.
13. The method of claim 1 , wherein the tissue is perfused or coated with a bioactive substance.
14. The method of claim 13 , wherein said bioactive substance is a drug or a growth factor.
15. The method of claim 14 , wherein said growth factor is a bone morphogenetic protein, tissue growth factor beta or a member of the tissue growth factor beta family of growth factors, cartilage-derived morphogenetic proteins I or II or both, a cartilage derived growth factor, an angiogenic factor, or platelet derived growth factor.
16. The method of claim 1 , further comprising the step of: iv. machining said tissue to final dimensions.
17. The method of claim 1 , wherein each of said three or more different cleaning solutions comprises, respectively:
a) a detergent;
b) a water-miscible alcohol; and
c) hydrogen peroxide.
18. The method of claim 1 , further comprising maintaining the temperature between about 35-40 degrees centigrade during at least one of steps i, ii, or iii.
19. The method of claim 17 , further comprising a depressurization step that occurs before, during or after treatment with each of said three or more different cleaning solutions.