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Production of a sterilised decellularised tendon allograft for clinical use

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Abstract

Application of a high-level decontamination or sterilisation procedure and cell removal technique to tendon allograft can reduce the concerns of disease transmission, immune reaction, and may improve remodelling of the graft after implantation. The decellularised matrix can also be used as a matrix for tendon tissue engineering. One such sterilisation factor, Peracetic acid (PAA) has the advantage of not producing harmful reaction residues. The aim of this study was to evaluate the effects of PAA treatment and a cell removal procedure on the production of tendon matrix. Human patellar tendons, thawed from frozen were treated respectively as: Group 1, control with no treatment; Group 2, sterilised with PAA (0.1 % (w/v) PAA for 3 h) Group 3, decellularised (incubation successively in hypotonic buffer, 0.1 % (w/v) sodium dodecyl sulphate, and a nuclease solution); Group 4, decellularised and PAA sterilised. Histological analysis showed that no cells were visible after the decellularisation treatment. The integrity of tendon structure was maintained after decellularisation and PAA sterilisation, however, the collagen waveform was slightly loosened. No contact cytotoxicity was found in any of the groups. Determination of de-natured collagen showed no significant increase when compared with the control. This suggested that the decellularisation and sterilisation processing procedures did not compromise the major properties of the tendon. The sterilised, decellularised tendon could be suitable for clinical use.

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References

  • Arnoczky SP, Warren RF, Ashlock MA (1986) Replacement of the anterior cruciate ligament using a patellar tendon allograft. An experimental study. J Bone Joint Surg 68:376–385

    PubMed  CAS  Google Scholar 

  • Bank RA, Krikken M, Beekman B, Stoop R, Maroudas A, Lefeber F, te Koppele JM (1997) A simplified measurement of degraded collagen in tissue: application in healthy, fibrillated and osteoarthritic cartilage. Matrix Biol 16:233–243

    Article  PubMed  CAS  Google Scholar 

  • Berg JM, Tymoszko JL, Stryer L (2002) Biochemistry, 5th edn. WH Freeman & Co., New York, pp 227–239

    Google Scholar 

  • Block SS (1991) Disinfection, sterilisation and preservation, 4th edn. Lea & Febiger, Philadelphia, pp 167–181

    Google Scholar 

  • Booth C, Korossis SA, Wilcox HE, Watterson KG, Kearney JN, Fisher J, Ingham E (2002) Tissue engineering of cardiac valve prosthesis I: development and histological characterization of an acellular porcine scaffold. J Heart Valve Dis 11:457–462

    PubMed  Google Scholar 

  • Cartmell JS, Dunn MG (2000) Effects of chemical treatments on tendon cellularity and mechanical properties. J Biomed Mater Res 49:134–140

    Article  PubMed  CAS  Google Scholar 

  • Centre for Disease Control (2008) Guidelines for disinfection and sterilisation in healthcare facilities

  • Centre for Disease Control Update (2002) Allograft-associated bacterial infections, MMWR 51:207–210

    Google Scholar 

  • Chang SK, Egami DK, Shaieb MD, Kan DM, Richardson AB (2003) Anterior cruciate ligament reconstruction: allograft versus autograft. Arthroscopy 19:453–462

    Article  PubMed  Google Scholar 

  • De Deyne P, Haut RC (1991) Some effects of gamma irradiation on patella tendon allografts. Connect Tissue Res 27:51–62

    Article  PubMed  Google Scholar 

  • Dheerendra SK, Khan WS, Singhal R, Shivarathre DG, Pydisetty R, Johnstone D (2012) Anterior cruciate ligament graft choices: a review of current concepts. Open Orthop J 6:281–286

    Article  PubMed  Google Scholar 

  • Durselen L, Claes L, Ingnatius A, Rubenacker S (1996) Comparative animal study of three ligament prostheses for the replacement of the anterior cruciate and medial collateral ligaments. Biomaterials 17:977–982

    Article  PubMed  CAS  Google Scholar 

  • Farrington M, Wreghitt T, Matthews I, Scarr D, Sutehall G, Hunt CJ, Santigo T, Gruys E, Voorhout W, Ramos T, Pegg DE (2002) Processing of cardiac valve allografts 2. Effects of antimicrobial treatment on sterility, structure and mechanical properties. Cell Tissue Bank 3:91–103

    Article  PubMed  CAS  Google Scholar 

  • Fideler BM, Vangsness CT, Lu B, Orlanso C, Moore T (1995) Gamma irradiation: effects on biomechanical properties of human bone-patellar tendon-bone allografts. Am J Sports Med 23:643–646

    Article  PubMed  CAS  Google Scholar 

  • Ghosh MM, Boyce S, Layton C, Freedlander E, MacNeil S (1997) A comparison of methodologies for the preparation of human epidermal-dermal composites. Ann Plast Surg 39:390–404

    Article  PubMed  CAS  Google Scholar 

  • Gibbons MJ, Butler DJ, Grood ES, Bylski-Austrow DI, Levy MS (1991) Noyes Fr. Effects of gamma irradiation on the initial mechanical properties of goat bone-patellar tendon-bone allografts. J Orthop Res 9:209–218

    Article  PubMed  CAS  Google Scholar 

  • Harner CD, Olsen E, Irrgang JJ, Silverstein S, Fu FH, Silbey M (1996) Allograft versus autograft anterior cruciate ligament reconstruction: 3 to 5 year outcome. Clin Orthop 324:134–144

    Article  PubMed  Google Scholar 

  • Hoburg A, Keshlaf S, Schmidt T, Smith W, Gohs U, Perka C, Pruss A, Scheffler S (2011) Fractionation of high-dose electron beam irradiation for BPTB grafts provided significantly improved viscoelastic and structural properties compared to standard gamma irradiation. Knee Surg Sports Traumatol Arthrosc 11:1955–1961

    Article  Google Scholar 

  • Hodde J, Hiles M (2002) Viruses safety of a porcine-derived medical device: evaluation of a viral inactivation method. Biotechnol Bioeng 79:211–216

    Article  PubMed  CAS  Google Scholar 

  • Hogg P, Rooney P, Ingham E, Kearney J (2012) Development of a decellularised dermis. Cell Tissue Bank (Aug 9, e-pub ahead of print)

  • Huang Q, Dawson RA, Peg DE, Kearney JN, MacNeil S (2004) Use of Peracetic acid to sterilise donor skin for production of acellular dermal matrices for clinical use. Wound Repair Regen 12:276–286

    Article  PubMed  Google Scholar 

  • IAEA (2008) Radiation sterilisation of tissue allografts: requirements for validation and routine control. A Code of Practice. International Atomic Energy Agency, Vienna, pp 1–65

  • Ingram JH, Korossis S, Howling G, Fisher J, Ingham E (2007) The use of ultrasonication to aid recellularisation of acellular natural tissue scaffolds for use in anterior cruciate ligament reconstruction. Tissue Eng 13:1561–1572

    Article  PubMed  CAS  Google Scholar 

  • Jackson DW, Grood ES, Wilcox P, Butler DL, Simon TM, Holden JP (1988) The effects of processing techniques on the mechanical properties of bone-anterior cruciate ligament-bone allografts. An experimental study in goats. Am J Sports Med 16:101–105

    Article  PubMed  CAS  Google Scholar 

  • Jackson DW, Corsetti J, Simon TM (1996) Biological incorporation of allograft anterior cruciate ligament replacements. Clin Orthop 324:126–133

    Article  PubMed  Google Scholar 

  • Kainer MA, Linden JV, Whaley DN, Holmes HT, Jarvis WR, Jernigan DB, Archibold LK (2004) Clostridium infections associated with musculoskeletal tissue allograft. N Engl J Med 350:2564–2572

    Article  PubMed  CAS  Google Scholar 

  • Laxdal G, Kartus J, Ejerhed L, Sernert N, Magnusson L, Faxon E, Karlsson J (2005) Outcome and risk factors after anterior cruciate ligament reconstruction: a follow up study of 948 patients. Arthroscopy 21:958–964

    Google Scholar 

  • Lomas RJ, Cruse-Sawyer JE, Simpson C, Ingham E, Bojar R, Kearney JN (2003) Assessment of the biological properties of human split skin allografts disinfected with Peracetic acid and preserved in glycerol. Burns 29:515–525

    Article  PubMed  CAS  Google Scholar 

  • Lomas RJ, Jennings LM, Fisher J, Kearney JN (2004) Effects of a Peracetic acid disinfection protocol on the biocompatibility and biomechanical properties of human patellar tendon allografts. Cell Tissue Bank 5:149–160

    Article  PubMed  CAS  Google Scholar 

  • Mirsadraee S, Wilcox HE, Watterson KG, Kearney JN, Hunt J, Fisher J, Ingham E (2007) Biocompatibility of acellular human pericardium. J Surg Res 143:407–414

    Article  PubMed  CAS  Google Scholar 

  • Noh JH, Yi SR, Song SJ, Kim SW, Kim W (2011) Comparison between hamstring autograft and free tendon Achilles allograft: minimum 2-year follow-up after anterior cruciate ligament reconstruction using EndoButton and Intrafix. Knee Surg Sports Traumatol Arthrosc 19:816–822

    Article  PubMed  Google Scholar 

  • Omae H, Sun YL, An KN, Amadio PC, Zhao C (2012) Engineered tendon with decellularized xenotendon slices and bone marrow stromal cells : an in vivo animal study. J Tissue Eng Regen Med 6:238–244

    Article  PubMed  CAS  Google Scholar 

  • Pearle AD, Bates JE, Tolo ET, Windsor RE (2003) Clostridium infection in a knee extensor mechanism allograft: case report and review. Knee 10:149–153

    Article  PubMed  Google Scholar 

  • Pinkowski JL, Rodrigo JJ, Sharkey NA, Vaseur PB (1996) Immune response to nonspecific and altered tissue antigens in soft tissue allografts. Clin Orthop 326:80–85

    Article  PubMed  Google Scholar 

  • Pridgen BC, Woon CY, Kim A, Thorfinn J, Lindsey D, Pham H, Cheng J (2011) Flexor tendon tissue engineering: acellularization of human flexor tendons with preservation of biomechanical properties and biocompatibility. Tissue Eng Part C 17:819–828

    Article  CAS  Google Scholar 

  • Pruss A, Kao M, Kiesewetter H, von Versen R, Pauli G (1999) Virus safety of avital bone tissue transplants: evaluation of sterilisation steps of spongiosa cuboids using a Peracetic acid-methanol mixture. Biologicals 27:195–201

    Article  PubMed  CAS  Google Scholar 

  • Pruss A, Kao M, Gohs U, Koscielny J, van Versen R, Pauli G (2002) Effects of gamma irradiation on human cortical bone transplants contaminated with enveloped and non-enveloped viruses. Biologicals 30:125–133

    Article  PubMed  Google Scholar 

  • Raghavan SS, Woon CY, Kraus A, Megerle K, Choi MS, Pridgen BC, Pham H, Chang J (2012) Human flexor tendon tissue engineering: decellularisation of human flexor tendons reduces immunogenicity in vivo. Tissue Eng Part A 18:796–805

    Article  PubMed  CAS  Google Scholar 

  • Rasmussen TJ, Feder SM, Butler DL, Noyes FR (1994) The effect of 4 Mrad of gamma irradiation on the initial mechanical properties of bone-patellar tendon-bone grafts. Arthroscopy 10:188–197

    Article  PubMed  CAS  Google Scholar 

  • Reddy GK, Enwememka CS (1996) A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem 29:225–229

    Article  PubMed  CAS  Google Scholar 

  • Riley GP, Curry V, De Groot J, van El B, Verzijl N, Hazleman BL, Bank RA (2002) Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology. Matrix Biol 21:185–195

    Article  PubMed  CAS  Google Scholar 

  • Rodrigo JJ, Jackson DW, Simon TM, Muto KN (1993) The immune response to freeze dried bone-tendon-bone allografts in humans. Am J Knee Surg 6:347–352

    Google Scholar 

  • Rutala WA, Gergen MF, Weber DJ (1998) Comparative evaluation of the sporicidal activity of new low-temperature sterilisation technologies: ethylene oxide, 2 plasma sterilisation systems and liquid Peracetic acid. Am J Infect Control 26:393–398

    Article  PubMed  CAS  Google Scholar 

  • Scheffler SU, Scherler J, Pruss A, von Versen R, Weiler A (2005) Biomechanical comparison of human bone-patellar tendon-bone grafts after sterilisation with Peracetic acid ethanol. Cell Tissue Bank 6:109–115

    Article  PubMed  CAS  Google Scholar 

  • Scheffler SU, Gonermann J, Kamp J, Przybilla D, Pruss A (2008) Remodelling of ACL allografts is inhibited by Peracetic acid sterilisation. Clin Orthop Relat Res 466:1810–1818

    Article  PubMed  Google Scholar 

  • Schmidt T, Hoburg A, Broziat C, Smith MD, Gohs U, Pruss A, Scheffler S (2012a) Sterilisation with electron beam irradiation influences the biomechanical properties and the early remodelling of tendon allografts for reconstruction of the anterior cruciate ligament (ACL). Cell Tissue Bank 13:387–400

    Article  PubMed  CAS  Google Scholar 

  • Schmidt T, Hoburg AT, Gohs U, Schumann W, Sim-Brandenburg JW, Nitsche A, Scheffler S, Pruss A (2012b) Effect of standard and fractionated electron beam irradiation on enveloped and non-enveloped viruses in a tendon transplant model. Transfus Med Hemother 39:29–35

    Article  PubMed  Google Scholar 

  • Smith CW, Young IS, Kearney JN (1996) Mechanical properties of tendons: changes with sterilisation and preservation. J Biomech Eng 118:56–61

    Article  PubMed  CAS  Google Scholar 

  • Smith RA, Ingels J, Lochemes JJ, Dutkowsky JP, Pifer LL (2001) Gamma irradiation of HIV-1. J Orthop Res 19:815–819

    Article  PubMed  CAS  Google Scholar 

  • Stapleton TW, Ingram J, Katta J, Knight R, Korossis S, Fisher J, Ingham E (2008) Development and characterisation of an acellular porcine medial meniscus for use in tissue engineering. Tissue Eng (Part A) 14:505–518

    Article  CAS  Google Scholar 

  • Turner IG, Thomas NP (1990) Comparative analysis of four types of synthetic anterior cruciate ligament replacement in the goat: in vivo histological and mechanical findings. Biomaterials 11:321–329

    Article  PubMed  CAS  Google Scholar 

  • Turner WD, Vasseur P, Gorek JE, Rodrigo JJ, Wedell JR (1988) An in vitro study of the structural properties of deep frozen versus freeze dried, ethylene oxide-sterilised canine anterior cruciate bone-ligament preparations. Clin Orthop 230:251–256

    PubMed  Google Scholar 

  • Wang X, Shen X, Li X, Agrawal CM (2002) Age-related changes in the collagen network and toughness of bone. Bone 31:1–7

    Article  PubMed  Google Scholar 

  • Weitzel PP, Richmond JC, Altman GH, Calabro T, Kaplan DL (2002) Future direction of the treatment of ACL ruptures. Orthop Clin North Am 33:653–661

    Article  PubMed  Google Scholar 

  • Wilshaw SP, Rooney P, Berry H, Kearney JN, Homer-Vanniasinkam S, Fisher J, Ingham E (2012) Development and characterisation of acellular arterial matrices. Tissue Eng (Part A) 18:471–483

    Article  CAS  Google Scholar 

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Acknowledgments

We would like to thank NHS Blood and Transplant for support and the funding of the project.

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Correspondence to P. Rooney.

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Huang, Q., Ingham, E., Rooney, P. et al. Production of a sterilised decellularised tendon allograft for clinical use. Cell Tissue Bank 14, 645–654 (2013). https://doi.org/10.1007/s10561-013-9366-0

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  • DOI: https://doi.org/10.1007/s10561-013-9366-0

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