New Techniques in Allograft Tissue Processing

      With the increasing reliance on tissue allografts in orthopedic reconstructive and sports surgery, there is a realistic concern on behalf of both the surgeon and the patient as to the safety of these implanted tissues and the possibility of disease transmission. New Food and Drug Administration guidelines in association with independent agency scrutiny have served to decrease this risk in light of recent publicized reports of infection transmission associated with allograft use. In addition, tissue banks are constantly developing new proprietary techniques for allograft processing and sterilization. However, clinical studies are needed to validate disinfection efficacy and to evaluate the effect of these processes on tissue structural properties. This article serves as a review of historical disease transmission, current governmental and nongovernmental tissue regulations, and specific processing techniques used by tissue banks.

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      References

      1. Centers for Disease Control and Prevention.
        About tissue transplants. 2006; (Available at:) (Accessed May 22, 2008)
        • Vangsness Jr., C.T.
        Soft-tissue allograft processing controversies.
        J Knee Surg. 2006; 19: 215-219
        • Nemzek J.A.
        • Swenson C.L.
        • Arnoczky S.P.
        Retroviral transmission by the transplantation of connective tissue allografts. An experimental study.
        J Bone Joint Surg Am. 1994; 76: 1036-1041
        • Vangsness Jr., C.T.
        • Garcia I.A.
        • Mills C.R.
        • et al.
        Allograft transplantation in the knee: tissue regulation, procurement, processing, and sterilization.
        Am J Sports Med. 2003; 31: 474-481
      2. 2006 AOSSM Orthopaedic Surgical Procedure Survey on Allografts.
        Leever Research Services, Naperville (IL)2006
        • McAllister D.R.
        • Joyce M.J.
        • Mann B.J.
        • et al.
        Allograft update: the current status of tissue regulation, procurement, processing, and sterilization.
        Am J Sports Med. 2007; 35: 2148-2158
      3. Joyce MJ, Greenwald AS, Rigney R, et al. Report on musculoskeletal allograft tissue safety. Presented at the American Academy of Orthopaedic Surgeons 71st Annual Meeting, San Francisco, March 10–14, 2004.

        • Centers for Disease Control and Prevention (CDC)
        Hepatitis C virus transmission from an antibody-negative organ and tissue donor–United States, 2000–2002.
        MMWR Morb Mortal Wkly Rep. 2003; 52 (276): 273-274
        • Eastlund T.
        • Strong D.M.
        Infectious disease transmission through tissue transplantation.
        in: Phillips G.O. Advances in tissue banking. vol. 7. World Scientific, Singapore2004: 51-131
        • Zou S.
        • Dodd R.Y.
        • Stramer S.L.
        • et al.
        Probability of viremia with HBV, HCV, HIV, and HTLV among tissue donors in the United States.
        N Engl J Med. 2004; 351: 751-759
        • Centers for Disease Control and Prevention (CDC)
        Epidemiologic notes and reports transmission of hiv through bone transplantation: case report and public health recommendations.
        MMWR Morb Mortal Wkly Rep. 1988; 37: 597-599
        • Asselmeier M.A.
        • Caspari R.B.
        • Bottenfield S.
        A review of allograft processing and sterilization techniques and their role in transmission of the human immunodeficiency virus.
        Am J Sports Med. 1993; 21: 170-175
        • Simonds R.J.
        • Holmberg S.D.
        • Hurwitz R.L.
        • et al.
        Transmission of human immunodeficiency virus type 1 from a seronegative organ and tissue donor.
        N Engl J Med. 1992; 326: 726-732
        • Simonds R.J.
        HIV transmission by organ and tissue transplantation.
        AIDS. 1993; 7: S35-S38
        • Li C.M.
        • Ho Y.R.
        • Liu Y.C.
        Transmission of human immunodeficiency virus through bone transplantation: a case report.
        J Formos Med Assoc. 2001; 100: 350-351
        • Vangsness Jr., C.T.
        • Wagner P.P.
        • Moore T.M.
        • et al.
        Overview of safety issues concerning the preparation and processing of soft-tissue allografts.
        Arthroscopy. 2006; 22: 1351-1358
        • Sanzen L.
        • Carlsson A.
        Transmission of human T-cell lymphotrophic virus type 1 by a deep-frozen bone allograft.
        Acta Orthop Scand. 1997; 68: 72-74
        • Centers for Disease Control and Prevention (CDC)
        Update: Allograft-associated bacterial infections—United States, 2002.
        MMWR Morb Mortal Wkly Rep. 2002; : 207-210
        • Blakeslee S.
        Knee ligament in a transplant leads to illness.
        NY Times. December 5, 2003; (Health section)
        • Kainer M.A.
        • Linden J.V.
        • Whaley D.N.
        • et al.
        Clostridium infections associated with musculoskeletal-tissue allografts.
        N Engl J Med. 2004; 350: 2564-2571
        • Centers for Disease Control and Prevention (CDC)
        Invasive Streptococcus pyogenes after allograft implantation—Colorado, 2003.
        MMWR Morb Mortal Wkly Rep. 2003; : 1173-1176
        • US Food and Drug Administration
        Eligibility determination for donors of human cells tissues, and cellular and tissue based products: final rule 21 CFR parts 210, 211, 820, 1271.
        Fed Regist. 2004; 69 (Available at:) (Accessed July 15, 2008): 29786-29834
      4. US Food and Drug Administration. Current good tissue practice for human cell, tissue, and cellular and tissue-based product establishments: inspection and enforcement; final rule 21 CFR parts 16, 1270, and 1271 (D,E,F). Fed Reg 2004;document #16–611-68688. Available at: http://a257.g.akamaitech.net/7/257/2422/06jun20041800/edocket.access.gpo.gov/2004/pdf/04-25798.pdf. Accessed July 15, 2008.

        • Patel R.
        • Trampuz A.
        Infections transmitted through musculoskeletal-tissue allografts.
        N Engl J Med. 2004; 350: 2544-2546
      5. The Joint Commission: tissue storage and issuance standards. 2007. Available at: http://www.jointcommission.org/AccreditationPrograms/Hospitals/Standards/FAQs/Provision+of+Care/Tissue+Storage+Issuance/app_tsis.htm. Accessed July 15, 2008.

      6. The American Association of Tissue Banks.
        (Available at:) (Accessed July 15, 2008)
        • Dodd R.Y.
        • Notari 4th, E.P.
        • Stramer S.L.
        Current prevalence and incidence of infectious disease markers and estimated window-period risk in the American red cross blood donor population.
        Transfusion. 2002; 42: 975-979
        • Buck B.E.
        • Malinin T.I.
        Human bone and tissue allografts. Preparation and safety.
        Clin Orthop Relat Res. 1994; : 8-17
        • Gocke D.J.
        Tissue donor selection and safety.
        Clin Orthop. 2005; 435: 17-21
        • Fang C.T.
        • Chambers L.A.
        • Kennedy J.
        • et al.
        American Red Cross Regional Blood Centers. Detection of bacterial contamination in apheresis platelet products: American Red Cross experience 2004.
        Transfusion. 2005; : 1845-1852
        • Strong D.M.
        • Katz L.
        Blood-bank testing for infectious diseases: how safe is blood transfusion?.
        Trends Mol Med. 2002; 8: 355-358
        • Centers for Disease Control and Prevention
        Semiannual Report of the National Nosocomial Infection Surveillance (NNIS) System.
        Centers for Disease Control and Prevention, US Dept of Health and Human Services, Atlanta (GA)2000 (11–13 [tables 5 and 6])
        • Srinivasan A.
        Epidemiology of organ- and tissue-transmitted infections. Presented at: workshop on preventing organ- and tissue allograft-transmitted infection: priorities for public health intervention 2005; Atlanta (GA). Proceedings.
        (Available at:) (Accessed July 15, 2008)
        • Hirn M.Y.
        • Salmela P.M.
        • Vuento R.E.
        High-pressure saline washing of allografts reduces bacterial contamination.
        Acta Orthop Scand. 2001; 72: 83-85
        • Chiu C.K.
        • Lau P.Y.
        • Chan S.W.
        • Fong C.M.
        • Sun L.K.
        Microbial contamination of femoral head allografts.
        Hong Kong Med J. 2004; 10: 401-405
        • Veen M.R.
        • Bloem R.M.
        • Petit P.L.
        Sensitivity and negative predictive value of swab cultures in musculoskeletal allograft procurement.
        Clin Orthop Relat Res. 1994; 299: 259-263
        • United States Pharmacopeial Convention
        Sterilization and sterility assurance of compendial articles. Chapter 1211.
        in: United States Pharmacopeia and National Formulary (USP 25-NF 20). United States Pharmacopeial Convention, Rockville (MD)2002
        • Block S.S.
        Peroxygen compounds.
        in: Block S.S. Disinfection, sterilization, and preservation. 5th edition. Lippincott, Williams & Wilkins, Philadelphia2001: 1162
      7. ANSI/AAMI/ISO 11137-1994: Sterilization of health care products—requirements for validation and routine control—radiation sterilization.
        American National Standards Institute, New York1994
        • Forsell J.H.
        Irradiation of musculoskeletal tissue.
        in: Tomford W.W. Musculoskeletal tissue banking. Raven Press, New York1993: 149-180
      8. How safe are soft-tissue allografts? American Academy of Orthopaedic Surgeons.
        (Available at:) (Accessed July 15, 2008)
        • Nguyen H.
        • Morgan D.A.F.
        • Forwood M.R.
        Sterilization of allograft bone: is 25 kGy the gold standard for gamma irradiation?.
        Cell Tissue Bank. 2007; 8: 81-91
        • Pelker R.R.
        • Friedlaender G.E.
        • Markham T.C.
        • et al.
        Effects of freezing and freeze-drying on the biomechanical properties of rat bone.
        J Orthop Res. 1984; 1: 405-411
        • Kang J.S.
        • Kim N.H.
        The biomechanical properties of deep freezing and freeze drying bones and their biomechanical changes after in-vivo allograft.
        Yonsei Med J. 1995; 36: 332-335
        • Pelker R.R.
        • McKay J.
        • Troiano N.
        • et al.
        Allograft incorporation: a biomechanical evaluation in a rat model.
        J Orthop Res. 1989; 7: 585-589
        • Stevenson S.
        • Emery S.E.
        • Goldberg V.M.
        Factors affecting bone graft incorporation.
        Clin Orthop. 1996; 324: 6-74
        • Conrad E.U.
        • Ericksen D.P.
        • Tencer A.F.
        • et al.
        The effects of freeze-drying and rehydration on cancellous bone.
        Clin Orthop. 1993; 290: 279-284
        • Pelker R.R.
        • Friedlaender G.E.
        • Markham T.C.
        Biomechanical properties of bone allografts.
        Clin Orthop. 1983; 174: 54-57
        • Cornu O.
        • Banse X.
        • Docquier P.L.
        • et al.
        Effect of freeze-drying and gamma irradiation on the mechanical properties of human cancellous bone.
        J Orthop Res. 2000; 18: 426-431
        • Gazdag A.R.
        • Lane J.M.
        • Glaser D.
        • et al.
        Alternatives to autogenous bone graft: efficacy and indications.
        J Am Acad Orthop Surg. 1995; 3: 1-8
        • Akkus O.
        • Rimnac C.M.
        Fracture resistance of gamma sterilized cortical bone allografts.
        J Orthop Res. 2001; 19: 927-934
        • Currey J.D.
        • Foreman J.
        • Laketic I.
        • et al.
        Effects of ionizing radiation on the mechanical properties of human bone.
        J Orthop Res. 1997; 15: 111-117
        • Akkus O.
        • Belaney R.M.
        • Das P.
        Free radical scavenging alleviates the biomechanical impairment of gamma radiation sterilized bone tissue.
        J Orthop Res. 2005; 23: 838-845
        • Seto A.
        • Gatt Jr., C.J.
        • Dunn M.G.
        Radioprotection of tendon tissue via crosslinking and free radical scavenging.
        Clin Orthop Relat Res. 2008; (May 30)
        • Grieb T.A.
        • Forng R.Y.
        • Stafford R.E.
        • et al.
        Effective use of optimized, high-dose (50 kGy) gamma irradiation for pathogen inactivation of human bone allografts.
        Biomaterials. 2005; 26: 2033-2042
        • Grieb T.A.
        • Forng R.Y.
        • Bogdansky S.
        • et al.
        High-dose gamma irradiation for soft tissue allografts: high margin of safety with biomechanical integrity.
        J Orthop Res. 2006; 24: 1011-1018
        • Rappe M.
        • Horodyski M.
        • Meister K.
        • et al.
        Nonirradiated versus irradiated Achilles allograft: in vivo failure comparison.
        Am J Sports Med. 2007; 35: 1653-1658
        • Schwartz H.E.
        • Matava M.J.
        • Proch F.S.
        • et al.
        The effect of gamma irradiation on anterior cruciate ligament allograft biomechanical and biochemical properties in the caprine model at time zero and at 6 months after surgery.
        Am J Sports Med. 2006; 34: 1747-1755
      9. AATB. Standards for tissue banking.
        American association of tissue banks, McLean (VA)2002
        • Brockbank K.G.
        • Carpenter J.F.
        • Dawson P.E.
        Effects of storage temperature on viable bioprosthetic heart valves.
        Cryobiology. 1992; 29: 537-542
        • Crawford M.J.
        • Swenson C.L.
        • Arnoczky S.P.
        • et al.
        Lyophilization does not inactivate infectious retrovirus in systemically infected bone and tendon allografts.
        Am J Sports Med. 2004; 32: 580-586
        • Schimizzi A.
        • Wedemeyer M.
        • Odell T.
        • et al.
        Effects of a novel sterilization process on soft tissue mechanical properties for anterior cruciate ligament allografts.
        Am J Sports Med. 2007; 35: 612-616
        • Jones D.B.
        • Huddleston P.M.
        • Zobitz M.E.
        • et al.
        Mechanical properties of patellar tendon allografts subjected to chemical sterilization.
        Arthroscopy. 2007; 23: 400-404
        • Jordy A.
        • Hoff-Jorgensen R.
        • Flagstad A.
        • et al.
        Virus inactivation by ethylene oxide containing gases.
        Acta Vet Scand. 1975; 16: 379-387
        • Prolo D.J.
        • Pedrotti P.W.
        • White D.H.
        Ethylene oxide sterilization of bone, dura mater, and fascia lata for human transplantation.
        Neurosurgery. 1980; 6: 529-539
        • Kakiuchi M.
        • Ono K.
        Preparation of bank bone using defatting, freeze-drying and sterilisation with ethylene oxide gas. Part 2. Clinical evaluation of its efficacy and safety.
        Int Orthop. 1996; 20: 147-152
        • Kakiuchi M.
        • Ono K.
        • Nishimura A.
        • et al.
        Preparation of bank bone using defatting, freeze-drying and sterilisation with ethylene oxide gas. Part 1. Experimental evaluation of its efficacy and safety.
        Int Orthop. 1996; 20: 142-146
        • Jackson D.W.
        • Windier G.E.
        • Simon T.M.
        Intraarticular reaction associated with the use of freeze-dried, ethylene oxide-sterilized bone-patella tendon-bone allografts in the reconstruction of the anterior cruciate ligament.
        Am J Sports Med. 1990; 18: 1-11
        • Roberts T.S.
        • Drez Jr., D.
        • McCarthy W.
        • et al.
        Anterior cruciate ligament reconstruction using freeze-dried, ethylene oxidesterilized, bone-patellar tendon-bone allografts. Two year results in thirty-six patients.
        Am J Sports Med. 1991; 19: 35-41
        • Moore T.M.
        • Gendler E.
        • Gendler E.
        Viruses adsorbed on musculoskeletal allografts are inactivated by terminal ethylene oxide disinfection.
        J Orthop Res. 2004; 22: 1358-1361
        • Campbell D.G.
        • Li P.
        Sterilization of HIV with irradiation: Relevance to infected bone allografts.
        Aust N Z J Surg. 1999; 69: 517-521
        • Conway B.
        • Tomford W.
        • Hirsch M.
        • et al.
        Effects of gamma irradiation on HIV-1 in a bone allograft model.
        Trans Orthop Res Soc. 1990; 15: 225