title: Effective use of optimized, high-dose (50 kGy) gamma irradiation for pathogen inactivation of human bone allografts.
abstract: The safety of tissue allografts has come under increased scrutiny due to recent reports of allograft-associated bacterial and viral infections in tissue recipients. We report that 50 kGy of gamma irradiation, nearly three times the dose currently used, is an effective pathogen inactivation method when used under optimized conditions that minimize damage to the tissue. Cancellous bone dowels treated with a radioprotectant solution and 50 kGy of optimized irradiation had an ultimate compressive strength and modulus of elasticity equal to conventionally irradiated (18 kGy) and non-irradiated control bone grafts. We subjected bone dowels treated with this pathogen inactivation method to an in vitro cytotoxicity test using three different mammalian cell lines and concluded that the treated grafts were not cytotoxic. The log reduction of nine pathogens spiked into radioprotectant-treated bone irradiated to 50 kGy was also tested. We achieved 4.9 logs of inactivation of a model virus for HIV and hepatitis C and 5 logs inactivation of a model virus for human parvovirus B-19. Complete inactivation (6.0-9.2 logs) of seven clinically relevant microorganisms was demonstrated. The results show that a combination of radioprotectants and optimized, high-dose gamma irradiation is a viable method for producing safer cancellous bone grafts that have the mechanical strength of existing grafts.
authors.affiliation: Clearant, Inc., 401 Professional Drive, Gaithersburg, MD 20879, USA.
authors.forename: Teri A
authors.initials: TA
authors.lastname: Grieb
authors.forename: Ren-Yo
authors.initials: RY
authors.lastname: Forng
authors.forename: Richard E
authors.initials: RE
authors.lastname: Stafford
authors.forename: Jack
authors.initials: J
authors.lastname: Lin
authors.forename: Jamie
authors.initials: J
authors.lastname: Almeida
authors.forename: Simon
authors.initials: S
authors.lastname: Bogdansky
authors.forename: Chad
authors.initials: C
authors.lastname: Ronholdt
authors.forename: William N
authors.initials: WN
authors.lastname: Drohan
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Burgess
mesh_terms: D001419:Bacteria / Q000528:radiation effects*; D016025:Bone Transplantation / Q000379:methods; D001842:Bone and Bones / Q000382:microbiology* / Q000503:physiopathology / Q000528:radiation effects*; D019245:Compressive Strength / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005658:Fungi / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D013242:Sterilization / Q000379:methods*; D014780:Viruses / Q000528:radiation effects*
chemical_list: D011837:Radiation-Protective Agents