Decellularized Homografts

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In decellularized homograft is heart valve from human donors. The decellularization process removes all cells from the donor . There are different methods of decellularization. In the most common method, the heart valves are first treated with various surfactants (soaps) and then rinsed several times so that all cells and chemical additives are removed and the basic structure of the valve made of connective tissue is retained.

Top view of a decellularized, non-repopulated homograft of the aortic valve with three delicate pockets

background

Young patients in particular who have a heart valve defect and need aortic valve replacement can choose between a mechanical heart valve , which requires lifelong blood-thinning treatment to reduce the risk of blood clots and the associated risk of stroke , and a biological valve of animal origin that shows a limited lifespan due to mechanical wear. The blood thinning associated with the mechanical valves leads to an increased risk of bleeding, which in everyday life leads to restrictions both in the professional and private sphere, so that young people in particular try to avoid blood thinners.

Another option is the so-called Ross operation , in which the diseased aortic valve is replaced by the patient's own pulmonary artery valve ( autologous transplantation ). The pulmonary valve must also be replaced during this procedure (usually with a donated human pulmonary valve), so this procedure results in "2-valve" disease in the affected patient. However, both the valve homografts and the biological valves (xenografts) described above wear out quickly in some patients, so that these two procedures result in repeated operations. Re-operations are associated with increased mortality due to adhesions from previous interventions.

Tissue engineered flaps

Tissue engineering means changing or manufacturing tissues using technical and chemical-biological measures. The basis for tissue-engineered valves are both synthetic scaffolds (mostly polymers) and biological scaffolds (so-called scaffolds) that originate from human tissue donations (allogeneic) or from animals (xenogeneic). A fully synthetic manufacture would address many clinical challenges such as the availability of the valves in various sizes and lengths. The concept of completely synthetic heart valves showed good results in research with regard to technical feasibility and was successfully used for in vitro and in vivo cultivation of various (stem) cell lines. However, long-term animal models of exclusively synthetically produced valves did not show satisfactory results due to their limited mechanical stability. Tissue-engineered animal valves have not given good results, especially in children, so that this has led to reluctance and skepticism about the use of xenogenic heart valves.

Human heart valves (homografts)

The first aortic valve replacement with a homograft was first performed on July 24, 1962 by Donald Ross at Guy's Hospital in London, evaluated in prospective randomized studies and compared with other surgical procedures such as the Ross operation. Aortic valve replacement using normal homografts is only used in 3% of patients today, mostly in the case of acute bacterial inflammation of the aortic valve. The leading reason for the cautious use is the frequent heavy calcifications on the conventional homografts.

Decellularized aortic homografts (DAH)

Decellularized aortic homografts (DAH) for aortic valve replacement and decellularized pulmonary homografts (DPH) for pulmonary valve replacement have been developed by various groups and companies. DPH have been used clinically in children and young adults since 2002 and show excellent results in short to medium-term clinical observation. They have replaced conventional (cryopreserved) homografts as the gold standard for pulmonary valve replacement in patients with congenital heart defects.

At the Medical University of Hanover, decellularized aortic homografts (DAH) have been developed, which have complete mechanical stability in the system cycle with the greatest possible antigen elimination, and evaluations from long-term animal models are available. The first implantations in humans gave promising results and thus DAH represent another option for aortic valve replacement. So far, no calcifications have been observed on the DAH, in contrast to the untreated human heart valves.

Decellularized human heart valves are approved both for the replacement of the pulmonary artery valve and for the body artery replacement.

Web links

Individual evidence

  1. ↑ LG Svensson, DH Adams, RO Bonow, NT Kouchoukos, DC Miller, PT O'Gara, DM Shahian, HV Schaff, CW Akins, JE Bavaria, EH Blackstone, TE David, ND Desai, TM Dewey, RS D'Agostino, TG Gleason, KB Harrington, S. Kodali, S. Kapadia, MB Leon, B. Lima, BW Lytle, MJ Mack, M. Reardon, TB Reece, GR Reiss, EE Roselli, CR Smith, VH Thourani, EM Tuzcu, J Webb, MR Williams: Aortic valve and ascending aorta guidelines for management and quality measures. In: The Annals of Thoracic Surgery . 95 (6 Suppl), 2013, pp. S1-S66.
  2. ^ HH Sievers, U. Stierle, EI Charitos, JJ Takkenberg, J. Hörer, R. Lange, U. Franke, M. Albert, A. Gorski, RG Leyh, A. Riso, J. Sachweh, A. Moritz, R Hetzer, W. Hemmer: A multicenter evaluation of the autograft procedure for young patients undergoing aortic valve replacement: update on the German Ross Registry. In: Eur J Cardiothorac Surg. 49 (1), Jan 2016, pp. 212-218.
  3. ↑ F. Onorati et al .: Mid-term results of aortic valve surgery in redo scenarios in the current practice: results from the multicentre European RECORD (REdo Cardiac Operation Research Database) initiative. In: Eur J Cardiothorac Surg. 47 (2), Feb 2015, pp. 269-280.
  4. ^ MY Emmert, B. Weber, L. Behr, S. Sammut, T. Frauenfelder, P. Wolint, J. Scherman, D. Bettex, J. Grünenfelder, V. Falk, SP Hoerstrup: Transcatheter aortic valve implantation using anatomically oriented , marrow stromal cell-based, stented, tissue-engineered heart valves: technical considerations and implications for translational cell-based heart valve concepts. In: Eur J Cardiothorac Surg. 45 (1), 2014, pp. 61-68.
  5. ↑ MT Kasimir, E. Rieder, G. Seebacher, A. Nigisch, B. Dekan, E. Wolner, G. Weigel, P. Simon: Decellularization does not eliminate thrombogenicity and inflammatory stimulation in tissue-engineered porcine heart valves. In: J Heart Valve Dis. 15 (2), 2006, pp. 278-286.
  6. ↑ I. El-Hamamsy, Z. Eryigit, LM Stevens, Z. Sarang, R. George, L. Clark, G. Melina, JJ Takkenberg, MH Yacoub: Long-term outcomes after autograft versus homograft aortic root replacement in adults with aortic valve disease: a randomized controlled trial. In: The Lancet . 376, 2010, pp. 524-531.
  7. ↑ S. Cebotari, I. Tudorache, A. Ciubotaru, D. Boethig, S. Sarikouch, A. Goerler, A. Lichtenberg, E. Cheptanaru, S. Barnaciuc, A. Cazacu, O. Maliga, O. Repin, L Maniuc, T. Breymann, A. Haverich: Use of fresh decellularized allografts for pulmonary valve replacement may reduce the reoperation rate in children and young adults: early report. In: Circulation . 124 (11 Suppl), 2011, pp. S115-S123.
  8. ↑ A. Neumann, S. Sarikouch, T. Breymann, S. Cebotari, D. Boethig, A. Horke, P. Beerbaum, M. Westhoff-Bleck, B. Harald, M. Ono, I. Tudorache, A. Haverich , G. Bags: Early systemic cellular immune response in children and young adults receiving decellularized fresh allografts for pulmonary valve replacement. In: Tissue Eng Part A. 20, 2014, pp. 1003-1011.
  9. ↑ S. Sarikouch, A. Horke, I. Tudorache, P. Beerbaum, M. Westhoff-Bleck, D. Boethig, O. Repin, L. Maniuc, A. Ciubotaru, A. Haverich, S. Cebotari: Decellularized fresh homografts for pulmonary valve replacement: A decade of clinical experience. In: Eur J Cardiothorac Surg. 50 (2), Aug 2016, pp. 281-290.
  10. ^ I. Tudorache, S. Horke, S. Cebotari, S. Sarikouch, D. Boethig, T. Breymann, P. Beerbaum, H. Bertram, M. Westhoff-Bleck, K. Theodoridis, D. Bobylev, E. Cheptanaru , A. Ciubotaru, A. Haverich: Decellularized aortic homografts for aortic valve and aorta ascendens replacement. In: Eur J Cardiothorac Surg. 50 (1), Jul 2016, pp. 89-97.
  11. ↑ pei.de
  12. ↑ www.arise-clinicaltrial.eu ; www.espoir-clinicaltrial.eu