Cyclic implant perfusion, cleaning and passivation process and implant produced thereby

Abstract

This invention is a novel 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 (inactivation of pathogens, microorganisms, cells, viruses and the like and reduction in antigenicity thereof), and the novel implant produced by such treatment. The process presents 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 for implantation. Target decontamination goals for this process include between about a one (1) to twelve (12) log reduction in bacterial contamination, between about a one (1) to fifteen (15) log reduction in enveloped virus contamination, up to about a five (5) log reduction in non-enveloped virus contamination, between about a two (2) to ten (10) fold 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 - 35 . (canceled)  
     
     
         36 . An implant cleaning process which comprises subjecting an implant contained in a chamber to cyclic exposure of increased and decreased pressure above one atmosphere or below one atmosphere or both; the process comprising the steps of: 
 (a) filling a chamber with a cleaning solution or a mixture of cleaning solutions;    (b) evacuating said chamber;    (c) pressurizing said chamber; and    (d) cycling between steps (b) and (c) more than 2 cycles;    and wherein said implant comprises autograft, allograft or xenograft tissue, or combinations thereof.    
     
     
         37 . The process of  claim 36  wherein the steps are carried out sufficient times to produce an implant that is passivated.  
     
     
         38 . The process of  claim 36  wherein the implant produced is suitable for implantation or processing for implantation in humans.  
     
     
         39 . The process of  claim 36  wherein said implant is entirely enclosed in said chamber.  
     
     
         40 . The process of  claim 36  wherein the process is conducted under computer or programmable logic circuit control.  
     
     
         41 . The process of  claim 36  wherein said cleaning solution is selected from the group consisting of sterile water, Triton X-100, TNBP, 3% hydrogen peroxide, a water miscible alcohol, saline solution, providone iodine, ascorbic acid solution, aromatic hydrocarbons, aliphatic hydrocarbons, ethers, ketone, amines, urea, guanidine hydrochloride, esters, glycoproteins, proteins, saccharides, enzymes, gasseous acids, gasseous peroxides, and mixtures thereof.  
     
     
         42 . The process of  claim 36  wherein said implant comprises at least one of the following: cortical bone, cancellous bone, fascia, whole joints, tendons, ligaments, dura, pericardia, heart valves, veins, neural tissue, submucosal tissue, or cartilage, or combinations thereof.  
     
     
         43 . The process of  claim 36 , further comprising placing said implant into a sterile, sealable package.  
     
     
         44 . The process of  claim 43 , further comprising performing a surface decontamination step prior to or after sealing said package.  
     
     
         45 . The process of  claim 36  wherein the implant is perfused or coated with a bioactive substance.  
     
     
         46 . The process of  claim 36  wherein the steps are carried out sufficient times to produce an implant having one or more of the following properties: 
 (a) between about a one to twelve log reduction in bacterial contamination;    (b) between about a one to fifteen log reduction in enveloped virus contamination;    (c) up to about a five log reduction in non-enveloped virus contamination;    (d) between about a two to ten fold reduction in endotoxin;    (e) maintenance of implant biologic and biomechanical properties;    (f) absence of tissue toxicity due to cleaning solutions used;    (g) reduced implant antigenicity.    
     
     
         47 . The process of  claim 36  further comprising the step of machining said implant to final dimensions.  
     
     
         48 . The process of  claim 36  wherein one or more steps are conducted under elevated or reduced temperatures, with respect to ambient temperature.  
     
     
         49 . An implant cleaning process which comprises subjecting the entire implant to cyclic exposure of increased and decreased pressure above one atmosphere or below one atmosphere or both, wherein said implant comprises autograft, allograft or xenograft tissue, or combinations thereof; and wherein the decreased pressure is a pressure below one atmosphere.  
     
     
         50 . The process of  claim 49 , wherein the decreased pressure is a pressure between about 60 and 100 torr.  
     
     
         51 . The process of  claim 49  wherein the steps are carried out sufficient times to produce an implant that is passivated.  
     
     
         52 . The process of  claim 49  wherein the implant produced is suitable for implantation or processing for implantation in humans.  
     
     
         53 . The process of  claim 49  wherein said cyclic exposure is performed in a chamber in which said implant is entirely enclosed.  
     
     
         54 . The process of  claim 49  wherein the process is conducted under computer or programmable logic circuit control.  
     
     
         55 . The process of  claim 49  wherein said implant comprises at least one of the following: cortical bone, cancellous bone, fascia, whole joints, tendons, ligaments, dura, pericardia, heart valves, veins, neural tissue, submucosal tissue, or cartilage, or combinations thereof.  
     
     
         56 . The process of  claim 49 , further comprising placing said implant into a sterile, sealable package.  
     
     
         57 . The process of  claim 56 , further comprising performing a surface decontamination step prior to or after sealing said package.  
     
     
         58 . The process of  claim 49  wherein the implant is perfused or coated with a bioactive substance.  
     
     
         59 . The process of  claim 49  wherein the steps are carried out sufficient times to produce an implant having one or more of the following properties: 
 (a) between about a one to twelve log reduction in bacterial contamination;    (b) between about a one to fifteen log reduction in enveloped virus contamination;    (c) up to about a five log reduction in non-enveloped virus contamination;    (d) between about a two to ten fold reduction in endotoxin;    (e) maintenance of implant biologic and biomechanical properties;    (f) absence of tissue toxicity due to cleaning solutions used;    (g) reduced implant antigenicity.    
     
     
         60 . The process of  claim 49  further comprising the step of machining said implant to final dimensions.  
     
     
         61 . The process of  claim 49  wherein one or more steps are conducted under elevated or reduced temperatures, with respect to ambient temperature.  
     
     
         62 . An implant cleaning process which comprises subjecting the entire implant to cyclic exposure of increased and decreased pressure above one atmosphere or below one atmosphere or both, wherein said implant comprises autograft, allograft or xenograft tissue, or combinations thereof; and wherein the increased pressure is a pressure above one atmosphere.  
     
     
         63 . The process of  claim 62 , wherein the increased pressure is a pressure between about 6 and 10 atmospheres.  
     
     
         64 . The process of  claim 62  wherein the steps are carried out sufficient times to produce an implant that is passivated.  
     
     
         65 . The process of  claim 62  wherein the implant produced is suitable for implantation or processing for implantation in humans.  
     
     
         66 . The process of  claim 62  wherein said cyclic exposure is performed in a chamber in which said implant is entirely enclosed.  
     
     
         67 . The process of  claim 62  wherein the process is conducted under computer or programmable logic circuit control.  
     
     
         68 . The process of  claim 62  wherein said implant comprises at least one of the following: cortical bone, cancellous bone, fascia, whole joints, tendons, ligaments, dura, pericardia, heart valves, veins, neural tissue, submucosal tissue, or cartilage, or combinations thereof.  
     
     
         69 . The process of  claim 62 , further comprising placing said implant into a sterile, sealable package.  
     
     
         70 . The process of  claim 69 , further comprising performing a surface decontamination step prior to or after sealing said package.  
     
     
         71 . The process of  claim 62  wherein the implant is perfused or coated with a bioactive substance.  
     
     
         72 . The process of  claim 62  wherein the steps are carried out sufficient times to produce an implant having one or more of the following properties: 
 (a) between about a one to twelve log reduction in bacterial contamination;    (b) between about a one to fifteen log reduction in enveloped virus contamination;    (c) up to about a five log reduction in non-enveloped virus contamination;    (d) between about a two to ten fold reduction in endotoxin;    (e) maintenance of implant biologic and biomechanical properties;    (f) absence of tissue toxicity due to cleaning solutions used;    (g) reduced implant antigenicity.    
     
     
         73 . The process of  claim 62  further comprising the step of machining said implant to final dimensions.  
     
     
         74 . The process of  claim 62  wherein one or more steps are conducted under elevated or reduced temperatures, with respect to ambient temperature.  
     
     
         75 . An implant cleaning process which comprises exposing an implant to a cleaning solution for cycles of increased and decreased pressure above one atmosphere or below one atmosphere, or both, for sufficient cycles to render said implant passivated and to provide a 5 to 6 log reduction in any forms of viable organisms.  
     
     
         76 . The process of  claim 75  wherein the implant produced is suitable for implantation or processing for implantation in humans.  
     
     
         77 . The process of  claim 75  wherein said process occurs, at least in part, with concurrent exposure of said implant to sonication.  
     
     
         78 . The process of  claim 75  wherein said cycles are performed in a chamber in which said implant is entirely enclosed.  
     
     
         79 . The process of  claim 80  wherein the process is conducted under computer or programmable logic circuit control.  
     
     
         80 . The process of  claim 75  wherein said cleaning solution is selected from the group consisting of sterile water, Triton X-100, TNBP, 3% hydrogen peroxide, a water miscible alcohol, saline solution, providone iodine, ascorbic acid solution, aromatic hydrocarbons, aliphatic hydrocarbons, ethers, ketone, amines, urea, guanidine hydrochloride, esters, glycoproteins, proteins, saccharides, enzymes, gasseous acids, gasseous peroxides, and mixtures thereof.  
     
     
         81 . The process of  claim 75  wherein said implant comprises autograft, allograft or xenograft tissue, or combinations thereof.  
     
     
         82 . The process of  claim 75 , further comprising placing said implant into a sterile, sealable package.  
     
     
         83 . The process of  claim 82 , further comprising performing a surface decontamination step prior to or after sealing said package.  
     
     
         84 . The process of  claim 75  wherein the implant is perfused or coated with a bioactive substance.  
     
     
         85 . The process of  claim 75  further comprising the step of machining said implant to final dimensions.  
     
     
         86 . The process of  claim 75  wherein one or more steps are conducted under elevated or reduced temperatures, with respect to ambient temperature.  
     
     
         87 . An implant cleaning process which comprises exposing an implant to a cleaning solution for cycles of increased and decreased pressure above one atmosphere or below one atmosphere, or both; to render said implant passivated.  
     
     
         88 . The process of  claim 87  wherein the implant produced is suitable for implantation or processing for implantation in humans.  
     
     
         89 . The process of  claim 87  wherein said process occurs, at least in part, with concurrent exposure of said implant to sonication.  
     
     
         90 . The process of  claim 87  wherein said cycles are performed in a chamber in which said implant is entirely enclosed.  
     
     
         91 . The process of  claim 87  wherein the process is conducted under computer or programmable logic circuit control.  
     
     
         92 . The process of  claim 87  wherein said cleaning solution is selected from the group consisting of sterile water, Triton X-100, TNBP, 3% hydrogen peroxide, a water miscible alcohol, saline solution, providone iodine, ascorbic acid solution, aromatic hydrocarbons, aliphatic hydrocarbons, ethers, ketone, amines, urea, guanidine hydrochloride, esters, glycoproteins, proteins, saccharides, enzymes, gasseous acids, gasseous peroxides, and mixtures thereof.  
     
     
         93 . The process of  claim 87  wherein said implant comprises autograft, allograft or xenograft tissue, or combinations thereof.  
     
     
         94 . The process of  claim 87 , further comprising placing said implant into a sterile, sealable package.  
     
     
         95 . The process of  claim 94 , further comprising performing a surface decontamination step prior to or after sealing said package.  
     
     
         96 . The process of  claim 87  wherein the implant is perfused or coated with a bioactive substance.  
     
     
         97 . The process of  claim 87  wherein the steps are carried out sufficient times to produce an implant having one or more of the following properties: 
 (a) between about a one to twelve log reduction in bacterial contamination;    (b) between about a one to fifteen log reduction in enveloped virus contamination;    (c) up to about a five log reduction in non-enveloped virus contamination;    (d) between about a two to ten fold reduction in endotoxin;    (e) maintenance of implant biologic and biomechanical properties;    (f) absence of tissue toxicity due to cleaning solutions used;    (g) reduced implant antigenicity.    
     
     
         98 . The process of  claim 87  further comprising the step of machining said implant to final dimensions.  
     
     
         99 . The process of  claim 87  wherein one or more steps are conducted under elevated or reduced temperatures, with respect to ambient temperature.  
     
     
         100 . An implant cleaning process which comprises exposing an implant to rapid cycles of increased and decreased pressure above one atmosphere or below one atmosphere, or both; said implant being in contact with one or more cleaning solutions during at least a portion of said rapid cycles.  
     
     
         101 . The process of  claim 100  wherein the steps are carried out sufficient times to produce an implant that is passivated.  
     
     
         102 . The process of  claim 100  wherein the implant produced is suitable for implantation or processing for implantation in humans.  
     
     
         103 . The process of  claim 100  wherein said process occurs, at least in part, with concurrent exposure of said implant to sonication.  
     
     
         104 . The process of  claim 100  wherein said rapid cycles are performed in a chamber in which said implant is entirely enclosed.  
     
     
         105 . The process of  claim 100  wherein the process is conducted under computer or programmable logic circuit control.  
     
     
         106 . The process of  claim 100  wherein said cleaning solution is selected from the group consisting of sterile water, Triton X-100, TNBP, 3% hydrogen peroxide, a water miscible alcohol, saline solution, providone iodine, ascorbic acid solution, aromatic hydrocarbons, aliphatic hydrocarbons, ethers, ketone, amines, urea, guanidine hydrochloride, esters, glycoproteins, proteins, saccharides, enzymes, gasseous acids, gasseous peroxides, and mixtures thereof.  
     
     
         107 . The process of  claim 100  wherein said implant comprises autograft, allograft or xenograft tissue, or combinations thereof.  
     
     
         108 . The process of  claim 100 , further comprising placing said implant into a sterile, sealable package.  
     
     
         109 . The process of  claim 108 , further comprising performing a surface decontamination step prior to or after sealing said package.  
     
     
         110 . The process of  claim 100  wherein the implant is perfused or coated with a bioactive substance.  
     
     
         111 . The process of  claim 100  wherein the steps are carried out sufficient times to produce an implant having one or more of the following properties: 
 (a) between about a one to twelve log reduction in bacterial contamination;    (b) between about a one to fifteen log reduction in enveloped virus contamination;    (c) up to about a five log reduction in non-enveloped virus contamination;    (d) between about a two to ten fold reduction in endotoxin;    (e) maintenance of implant biologic and biomechanical properties;    (f) absence of tissue toxicity due to cleaning solutions used;    (g) reduced implant antigenicity.    
     
     
         112 . The process of  claim 100  further comprising the step of machining said implant to final dimensions.  
     
     
         113 . The process of  claim 100  wherein one or more steps are conducted under elevated or reduced temperatures, with respect to ambient temperature.