Virus Inactivation Technology And Its Properties Characterization Of Animal’s Pericardium Tissue

Animal-derived biomaterials from wild or raised animals are widely used in medical device industry.However,animals often carry a large number of pathogens which can be transmitted to the patients through medical devices utilizing animal-derived biomaterials and may bring unforeseen risks to the patients.In recent years,there are many kinds of bioprosthetic valves in China market.The main component of bioprosthetic valve is animal’s pericardial tissue which shall be subject to virus inactivation in the early stage.Generally,the pericardial tissue will be soaked with formaldehyde or glutaraldehyde in high chemical soaking concentration for the virus inactivation process.However,even if such tissue will be cleaned before use,its chemical residues are still uncertain and storage&use are inconvenient.In this paper,the formaldehyde procyanidins in low concentration are used to make virus inactivation.After that,the chemical residues will be thoroughly cleaned and cobalt 60 irradiation will be used to make further inactivation,being characterized by low chemical residues and easy storage.(1)Animal-derived biomaterials were treated with different concentrations of formaldehyde procyanidins,and it was found that the viral drops in pericardium decreased significantly.Based on the requirements of Guiding Principles for Technical reviewed of Registration of Animal-derived Medical Devices,swinish pericardium and bovine pericardium were selected as biological materials of animal origin for virus inactivation research.Representative encephalomyocarditis virus EMCV(non-lipid envelope RNA),porcine parvovirus PPV(non-lipid envelope DNA),pseudorabies virus PRV(lipid envelope DNA)and vesicular stomatitis virus VSV(lipid envelope RNA)were chosen as indicator viruses.Samples were treated with different concentrations of formaldehyde procyanidins(0.1%,0.2%and 0.4%)for 12,24 and 36 hours respectively.It suggested that after pericardial tissue was treated with 0.1%procyanidin for 36 hours,the drops of PRV,VSV,EMCV and PPV decreased by more than 4.01ogs;After being treated with 0.2%formaldehyde procyanidins for 24 hours,the drops also shrank by more than 4.01ogs.(2)The viral drops were further lowered by irradiation with various doses of cobalt 60.After the function of formaldehyde procyanidin,different doses of cobalt 60(12-18 KGy,18～25 KGy,25～30 KGy)were used.When the irradiation was 25～30 KGy,PRV,VSV,EMCV and PPV in pericardium fell by more than 4.9logs.(3)Through the formaldehyde residue and biology test of pericardial tissue via procyanidins and cobalt 60,it was spotted that the formaldehyde residue,cytotoxicity,hemolysis rate,skin irritation test and skin sensitization were all within the acceptable range.The swinish and bovine tissues were treated with 0.1%formaldehyde procyanidins for 36 hours,then irradiated with cobalt 60 of 25～30KGy,or treated with 0.2%formaldehyde procyanidins for 24 hours,then cobalt 60 of 25～30KGy.It turned out that the free formaldehyde residues were 36.6±4.6,36.1±1.5,35.5±0.9and 52.5±0.8 respectively;the cytotoxicity 77.8%,76.5%,74.6%and 77.2%respectively;the hemolysis rates 3.1%,2.2%,4.6%,4.8%respectively.There was no skin irritation or sensitization.Conclusion:The swinish and bovine tissues were treated with 0.1%formaldehyde procyanidins for 36 hours,then irradiated with cobalt 60 of 25～30KGy,or treated with 0.2%formaldehyde procyanidins for 24 hours,then cobalt 60 of 25～30KGy.Both methods are effective to inactivate PRV,EMCV,VSV and PPV in animal tissue.Meanwhile,the treated pericardial tissue is still eligible for biomedical materials.