Process development of a virally-safe dental xenograft material from porcine bones = 바이러스 안전성이 보증된 돼지유래 골 이식재 제조 공정 개발

다국어 초록 (Multilingual Abstract)

A process for manufacturing virally-safe porcine bone hydroxyapatite (HA) has been developed to serve as advanced xenograft material for dental applications. Porcine bone pieces were defatted with successive treatments of 30% hydrogen peroxide and 80% ethyl alcohol. The defatted porcine bone pieces were heat-treated in an oxygen atmosphere box furnace at $1,300^{\circ}C$ to remove collagen and organic compounds. The bone pieces were ground with a grinder and then the bone powder was sterilized by gamma irradiation. Morphological characteristics such as SEM (Scanning Electron Microscopy) and TEM (Transmission Electron Microscopy) images of the resulting porcine bone HA (THE Graft$^{(R)}$) were similar to those of a commercial bovine bone HA (Bio-Oss$^{(R)}$). In order to evaluate the efficacy of $1,300^{\circ}C$ heat treatment and gamma irradiation at a dose of 25 kGy for the inactivation of porcine viruses during the manufacture of porcine bone HA, a variety of experimental porcine viruses including transmissible gastroenteritis virus (TGEV), pseudorabies virus (PRV), porcine rotavirus (PRoV), and porcine parvovirus (PPV) were chosen. TGEV, PRV, PRoV, and PPV were completely inactivated to undetectable levels during the $1,300^{\circ}C$ heat treatment. The mean log reduction factors achieved were $${\geq_-}4.65$$ for TGEV, $${\geq_-}5.81$$ for PRV, $${\geq_-}6.28$$ for PRoV, and $${\geq_-}5.21$$ for PPV. Gamma irradiation was also very effective at inactivating the viruses. TGEV, PRV, PRoV, and PPV were completely inactivated to undetectable levels during the gamma irradiation. The mean log reduction factors achieved were $${\geq_-}4.65$$ for TGEV, $${\geq_-}5.87$$ for PRV, $${\geq_-}6.05$$ for PRoV, and $${\geq_-}4.89$$ for PPV. The cumulative log reduction factors achieved using the two different virus inactivation processes were $${\geq_-}9.30$$ for TGEV, $${\geq_-}11.68$$ for PRV, $${\geq_-}12.33$$ for PRoV, and $${\geq_-}10.10$$ for PPV. These results indicate that the manufacturing process for porcine bone HA from porcine-bone material has sufficient virus-reducing capacity to achieve a high margin of virus safety.

참고문헌 (Reference)

• 1 배정은, "바이러스 안전성이 보증된 무세포 소 양막 생물창상피복재 제조 공정 개발" 한국미생물·생명공학회 38 (38): 420-427, 2010
• 2 Hodde, J., "Virus safety of a porcine-derived medical device: evaluation of a viral inactivation method" 79 : 211-216, 2002
• 3 배정은, "Virus Inactivation during the Manufacture of a Collagen Type I from Bovine Hides" 한국미생물학회 48 (48): 314-318, 2012
• 4 Forest, P., "Validation of a viral and bacterial inactivation step during the extraction and purification process of porcine collagen" 17 : 199-208, 2007
• 5 Kim, Y., "The risk of prion infection through bovine grafting materials" 2016
• 6 Khan, S. N., "The biology of bone grafting" 13 : 77-86, 2005
• 7 International Organization for Standardization, "Sterilization of health care products – radiation -- Part 2:Establishing the sterilization dose"
• 8 Accorsi-Mendonça, T., "Physicochemical characterization of two deproteinized bovine xenografts" 22 : 5-10, 2008
• 9 Välimäki, V.V., "Molecular basis for action of bioactive glasses as bone graft substitute" 95 : 95-102, 2006
• 10 Kim, D.M., "Method of funtionalize surface of bone graft with bone nano particle and bone graft having funtionalized surface by bone nano particle"
• 11 International Organization for Standardization, "Medical devices utilizing animal tissues and their derivatives-Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agent"
• 12 Park, J. W., "Increased new bone formation with a surface magnesiumincorporated deproteinized porcine bone substitute in rabbit calvarial defects" 100 : 834-840, 2012
• 13 International Conference on Harmonisation, "Guidance on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin" 63 : 51074-51084, 1998
• 14 유경훈, "Effect of Porcine Cancellous Bones on Regeneration in Rats with Calvarial Defect" 한국생명과학회 20 (20): 1207-1213, 2010
• 15 Venkataraman, N., "Dynamics of bone graft healing around implants" 7 : 40-47, 2015
• 16 Haas, R., "Bovine hydroxyapatite for maxillary sinus augmentation: analysis of interfacial bond strength of dental implants using pull-out tests" 9 : 117-122, 1998
• 17 Hallman, M., "Bone substitutes and growth factors as an alternative/complement to autogenous bone for grafting in implant dentistry" 47 : 172-192, 2008
• 18 Concannon, M. J., "Bone induction using demineralized bone in the rabbit femur: A longterm study" 99 : 1983-1988, 1997
• 19 Bauer, T.W., "Bone graft materials: an overview of the basic science" 371 : 10-27, 2000
• 20 Damien, C.J., "Bone graft and bone graft substitutes: a review of current technology and applications" 2 : 187-208, 1991
• 21 Ducheyne, P.E., "Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function" 20 : 2287-2303, 1999
• 22 Kärber, J, "Beitrag zur kollectiven Behandlung pharmakologische Reihenversuche" 162 : 480-483, 1931
• 23 Pinholt, E. M., "Alveolar ridge augmentation in rats by Bio-Oss" 99 : 154-161, 1991
• 24 Kim, D.M., "A method for preparing a porcine bone graft with an excellent performance in cell adhesion and bone formation using nano hydroxyapatite surface modification technology, and a porcine bone graft prepared thereby"
• 25 Jensen, S. S., "20 Years of Guided Bone Regeneration in Implant Dentistry" Quintessence Publishing 1-96, 2009