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 . A method for cleaning allograft tissue comprising in any order: 
 i. exposing allograft tissue to a cleaning solution at a pressure greater than atmospheric pressure to cause said cleaning solution to enter the pores of said allograft tissue;    ii. exposing said allograft tissue to a pressure less than atmospheric pressure to remove adventitious materials and solution from said pores; and    iii. cycling between step (i) and (ii) sufficient times to loosen and remove said adventitious materials in said pores, leaving a cleaned allograft tissue.    
     
     
         37 . The method of  claim 36  wherein step (iii) is carried out sufficient times to produce cleaned allograft tissue that is passivated.  
     
     
         38 . The method of  claim 37  wherein the allograft tissue produced is suitable for implantation or processing for implantation in humans.  
     
     
         39 . The method of  claim 36  wherein said method occurs, at least in part, with concurrent exposure of said allograft tissue to sonication.  
     
     
         40 . The method of  claim 36  wherein said cycling is performed in a chamber containing said allograft tissue.  
     
     
         41 . The method of  claim 36  wherein said cycling occurs according to a defined program.  
     
     
         42 . The method 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.  
     
     
         43 . The method of  claim 36  wherein said cleaning solution is selected from the group consisting of 6% hydrogen peroxide, 1% sodium hypochlorite, 6M urea, 4M guanidine hydrochloride, 1 N sodium hydroxide, isopropanol, water, saline and mixtures thereof.  
     
     
         44 . The method of  claim 36  wherein said allograft tissue 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.  
     
     
         45 . The method of  claim 44  wherein said allograft tissue comprises at least one of the following: cortical bone or cancellous bone, or combinations thereof.  
     
     
         46 . The method of  claim 44  wherein said allograft tissue comprises at least one of the following: fascia, whole joints, tendons, ligaments, dura, pericardia, heart valves, veins, neural tissue, submucosal tissue, or cartilage, or combinations thereof.  
     
     
         47 . The method of  claim 36  wherein said allograft tissue is derived from a single donor.  
     
     
         48 . The method of  claim 36  wherein said allograft tissue is derived from a pool of donor tissues.  
     
     
         49 . The method of  claim 36 , further comprising placing said cleaned allograft tissue into a sterile, sealable package.  
     
     
         50 . The method of  claim 49 , further comprising performing a surface decontamination step prior to or after sealing said package.  
     
     
         51 . The method of  claim 36  wherein the allograft tissue is perfused or coated with a bioactive substance.  
     
     
         52 . The method of  claim 51  wherein said bioactive substance is a drug or a growth factor.  
     
     
         53 . The method of  claim 52  wherein said growth factor is selected from the group consisting of a bone morphogenetic protein, tissue growth factor beta or member of the tissue growth factor beta family of growth factors, cartilage derived morphogenetic proteins I or  11  or both, and any related cartilage derived growth factors, angiogenic factors, and platelet derived growth factor.  
     
     
         54 . The method of  claim 36  wherein step (iii) is carried out sufficient times to produce cleaned allograft tissue having any one or all 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 or graft biologic and biomechanical properties;    (f) absence of tissue toxicity due to cleaning solutions used;    (g) reduced implant antigenicity.    
     
     
         55 . The method of  claim 36  wherein pressures less than atmospheric pressure down to 60 torr are employed.  
     
     
         56 . The method of  claim 55  wherein the pressures less than atmospheric pressure are between about 60 to 100 torr.  
     
     
         57 . The method of  claim 36  wherein pressures greater than atmospheric pressure up to 10 atmospheres are employed.  
     
     
         58 . The method of  claim 57  wherein the pressures greater than atmospheric pressure are between about 6 to 10 atmospheres.  
     
     
         59 . The method of  claim 36  wherein said cleaned allograft tissue is pooled with similarly treated tissue, and is further cleaned by conducting steps (i)-(iii) using the same or different cleaning solutions.  
     
     
         60 . The method of  claim 36 , further comprising the step of: 
 iv. machining said allograft tissue to final dimensions.    
     
     
         61 . The method of  claim 60 , further comprising the step of: 
 v. conducting steps (i)-(iii) using the same or different cleaning solutions.    
     
     
         62 . The method of  claim 60 , further comprising placing said cleaned allograft tissue into a sterile, sealable package.  
     
     
         63 . The method of  claim 62 , further comprising performing a surface decontamination step prior to or after sealing said package.  
     
     
         64 . The method of  claim 36  wherein any or all steps are conducted under elevated or reduced temperatures, with respect to ambient temperature.  
     
     
         65 . The method of  claim 64  wherein any or all steps are conducted at a temperature between about 37 degrees centigrade and about 80 degrees centigrade.  
     
     
         66 . The method of  claim 65  wherein any or all steps are conducted at about 50-60 degrees centigrade.  
     
     
         67 . A method for making an implant which comprises combining allograft tissue to form a composite implant wherein said allograft tissue is treated according to the method of  claim 36 .  
     
     
         68 . A method for making an implant which comprises combining allograft tissue and other material to form a composite implant wherein at least said allograft tissue is treated according to the method of  claim 36 .  
     
     
         69 . The method of  claim 65  wherein the other material is selected from the group consisting of metallic, synthetic, ceramic, autograft and xenograft materials.