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Vafaee, T; Thomas, D; Desai, A; Jennings, LM; Berry, H; Rooney, P; Kearney, J; Fisher, J; Ingham, E
Publisher: Wiley
Languages: English
Types: Article
The clinical use of decellularised cardiac valve allografts is increasing. Long term data will be required to determine whether they outperform conventional cryopreserved allografts. Valves decellularised using different processes may show varied long-term outcomes. It is therefore important to understand the effects of specific decellularisation technologies on the characteristics of donor heart valves. Human cryopreserved aortic and pulmonary valved conduits were decellularised using hypotonic buffer, 0.1% (w/v) SDS and nuclease digestion. The decellularised tissues were compared to cellular cryopreserved valve tissues using histology, immunohistochemistry, quantitation of total DNA, collagen and glycosaminoglycan content, in vitro cytotoxicity assays, uniaxial tensile testing and subcutaneous implantation in mice. The decellularised tissues showed no histological evidence of cells or cell remnants and over 97% DNA removal in all regions (arterial wall, muscle, leaflet and junction). The decellularised tissues retained collagen IV and von Willebrand factor staining with some loss of fibronectin, laminin and chondroitin sulphate staining. There was an absence of MHC Class I staining in decellularised pulmonary valve tissues, with only residual staining in isolated areas of decellularised aortic valve tissues. The collagen content of the tissues was not decreased following decellularisation however the glycosaminoglycan content was reduced. Only moderate changes in the maximum load to failure of the tissues were recorded post-decellularisation. The decellularised tissues were non-cytotoxic in vitro, and were biocompatible in vivo in a mouse subcutaneous implant model. The decellularisation process will now be translated into a GMP compatible process for donor cryopreserved valves with a view to future clinical use.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • Baskett RJ, Nanton MA, Warren AE et al. 2003; Human leucocyte antigen-DR and ABO mismatch are associated with accelerated homograft failure in children: implications for therapeutic interventions. J Thorac Cardiovasc Surg 126(1): 232-239.
    • Bechtel JF, Gellissen J, Erasmi AW et al. 2005; Mid-term findings on echocardiography and computed tomography after RVOT-reconstruction: comparison of decellularized (SynerGraft) and conventional allografts. Eur J Cardiothorac Surg 27(3): 410-415.
    • Bechtel JF, Stierle U, Sievers HH. 2008; Fifty-two months' mean follow-up of decellularised SynerGraft-treated pulmonary valve allografts. J Heart Valve Dis 17(1): 98-104.
    • Booth C, Korossis S, Wilcox HE et al. 2002; Tissue engineering a cardiac valve prosthesis I: development and histological characterisation of an acellular porcine scaffold. J Heart Valve Dis 11(4): 457-462.
    • Brown JW, Elkins RC, Clarke RC et al. 2010; Performance of the CryoValveSG human decellularised pulmonary valve in 342 patients relative to conventional CryoValve at a mean follow-up of four years. J Thorac Cardiovasc Surg 139(2): 339-348.
    • Brown BN, Ratner BD, Goodman SB et al. 2012; Macrophage polarisation: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials 33(15): 3792-3802.
    • Burch PT, Kaza AK, Lambert LM et al. 2010; Clinical performance of decellularised cryopreserved valved allografts compared with standard allografts in the right ventricular outflow tract. Ann Thorac Surg 90(4): 1301-1306.
    • Carr-White GS, Kilner PJ, Hon JKF et al. 2001; Incidence, location, pathology and significance of pulmonary homograft stenosis after the Ross operation. Circulation 104(12 Suppl 1): I16-I20.
    • Cebotari S, Tudorache I, Ciubotaru A et al. 2011; Use of fresh decellularised allografts for pulmonary valve replacement may reduce the reoperation rate in children and young adults: early report. Circulation 124(11 Suppl): S115-S123.
    • da Costa FDA, Santos LR, Collatusso C et al. 2009; Thirteen years experience with the Ross operation. J Heart Valve Dis 18(1): 84-94.
    • da Costa FDA, Costa ACBA, Prestes R et al. 2010; The early and midterm function of decellularised aortic valve allografts. Ann Thorac Surg 90(6):1854-1861.
    • da Costa FDA, Takkenberg JJM, Fornazari D et al. 2014; Long term results of the Ross operation: an 18-year single institution experience. Eur J Cardiothorac Surg 46(3): 415-422.
    • Crapo PM, Gilbert TW, Badylak SF. 2011; An overview of tissue and whole organ decellularisation processes. Biomaterials 32(12):3233-3243.
    • Dignan R, O'Brien M, Hogan P et al. 2003; Aortic valve allograft structural deterioration is associated with a subset of antibodies to human leukocyte antigens. J Heart Valve Dis 12(3): 382-390.
    • Eckert CE, Fan R, Mikuli B et al. 2013; On the biomechanical role of glycosaminoglycans in the aortic heart valve leaflet. Acta Biomater 9(1): 4653-4660.
    • Elkins RC, Lane MM, Cappa SB et al. 2001a; Humoral immune responds to allograft valve tissue pretreated with an antigen reduction process. Sem Thorac Cardiovasc Surg 13(4 Suppl 1): 82-86.
    • Elkins RC, Dawson PE, Goldstein S et al. 2001b; Decellularized human valve allografts. Ann Thorac Surg 71(5 Suppl): S428-S432.
    • Etnel JRG, Elmont LC, Ertekin E et al. 2016; Outcome after aortic valve replacement in children: a systematic review and meta-analysis. J Thorac Cardiovasc Surg 151(1): 143-152.
    • Gao G, Wu Y, Grunkemeier GL et al. 2004; Durability of pericardial versus porcine aortic valves. J Am Coll Cardiol 44(2): 384-388.
    • Gerson CJ, Elkins RC, Goldstein S et al. 2012; Structural integrity of collagen and elastin in Synergraft┬« decellularised-cryopreserved human heart valves. Cryobiology 64(1): 33-42.
    • Hawkins JA, Hillman ND, Lambert LM et al. 2003; Immunogenicity of decellularized cryopreserved allografts in pediatric cardiac surgery: comparison with standard cryopreserved allografts. J Thorac Cardiovasc Surg 126(1): 247-252
    • Helder MR, Hennessy RS, Spoon DB et al. 2016; Low-dose gamma irradiation of decellularised heart valves results in tissue injury in vitro and in vivo. Ann Thorac Surg 101(2): 667-674.
    • Herbst TJ, McCarthy JB, Tsilibary EC et al. 1988; Differential effects of laminin, intact type IV collagen, and specific domains of type IV collagen on endothelial cell adhesion and migration. J Cell Biol 106(4):1365-1373.
    • Hogan PG, O'Brien MF. 2003; Improving the allograft valve: does the immune response matter? J Thorac Cardiovasc Surg 126(5): 1251-1253.
    • Konuma T, Devaney EJ, Bove EL et al. 2009; Performance of CryoValve SG decellularised pulmomary allografts compared with standard cryopreserved allografts. Ann Thorac Surg 88(3): 849-855.
    • Korossis SA, Wilcox HE, Watterson KG et al. 2005; In vitro assessment of the functional performance of the decellularised intact porcine aortic root. J Heart Valve Dis 14(3): 408-422.
    • Luo J, Korossis SA, Wilshaw SP et al. 2014; Development and characterisation of acellular porcine pulmonary valve scaffolds for tissue engineering. Tissue Eng A 20 (21-22): 2963-2974.
    • Mirsadraee S, Wilcox HE, Watterson KG et al. 2007; Biocompatibility of acellular human pericardium. J Surg Res 143(2): 407-414.
    • Neuman RE, Logan MA. 1950; The determination of hydroxyproline. J Biol Chem 184(1): 299-306.
    • Neumann A, Sarikouch S, Breymann T et al. 2014; Early systemic cellular immune response in children and young adults receiving decellularised fresh allografts for pulmonary valve replacement. Tissue Eng A 20(5-6): 1003-1011.
    • O'Brien MF, Goldstein S, Walsh S et al. 1999; The SynerGraft valve: a new acellular (non-gluteraldehydefixed) tissue heart valve for autologous recellularisation; first experimental studies before clinical implantation. Sem Thorac Cardiovasc Surg 11(4 Suppl 1): S194-S200.
    • O'Brien MF, Harrocks S, Stafford EG et al. 2001; The homograft aortic valve: a 29-year, 99.3% follow up of 1,022 valve replacements. J Heart Valve Dis 10(3): 334-345.
    • Paniagua Gutierrez JR, Wilcox-Berry H, Korossis SA et al. 2015; Regenerative potential of low concentration SDS decellularised porcine aortic valved conduits in vivo. Tissue Eng A 21(1-2): 332-342.
    • Rothenburger M, Volker W, Vischer P et al. 2002; Ultrastructure of proteoglycans in tissue engineered cardiovascular structures. Tissue Eng 8(6): 1049-1056 Ruzmetov M, Shah JJ, Geiss DM et al. 2012; Decellularized versus standard valve allografts for right ventricular outflow tract reconstruction: a single institution comparison. J Thorac Cardiovasc Surg 143(3): 543-549.
    • Ryan WH, Herbert MA, Dewey TM et al. 2006; The occurence of postoperative pulmonary homograft stenosis in adult patients undergoing the Ross procedure. J Heart Valve Dis 15(1): 108-114.
    • Sarathchandra P, Smolenski RT, Yuen AH et al. 2012; Impact of ╬│-irradiation on extracellular matrix of porcine pulmonary valves. J Surg Res 176(2): 376-85.
    • Schoen FJ, Levy RJ. 2005; Calcification of tissue heart valve substitutes: progress toward understanding and prevention. Ann Thorac Surg 79(3): 1072-80.
    • Senthilnathan V, Treasure T, Grunkemeier G et al. 1999; Heart valves: which is the best choice? Cardiovasc Surg 7(4): 393-397.
    • Shaddy RE, Hawkins JA. 2002; Immunology and failure of valved allografts in children. Ann Thorac Surg 74(4): 1271-5 .
    • Tavakkol Z, Gelehrter S, Goldberg CS et al. 2005; Superior durability of SynerGraft pulmonary allografts compared with standard cryopreserved allografts. Ann Thorac Surg 80(5): 1610-1614.
    • Wilcox HE, Korossis SA, Booth C et al. 2005; Biocompatibility and recellularization potential of an acellular porcine heart valve matrix. J Heart Valve Dis 14(3): 228-237.
    • Zehr KJ, Yagubyan M, Connolly HM et al. 2005; Aortic root replacement with a novel decellularized cryopreserved aortic homograft: postoperative immunoreactivity and early results. J Thorac Cardiovasc Surg 130(4): 1010-1015.
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    The results below are discovered through our pilot algorithms. Let us know how we are doing!

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