Anna Christina Biermann1,2,3, Julia Marzi3, Eva Brauchle3, Julian Lukas Wichmann4, Christophe Theo Arendt4, Valentina Puntmann4, Eike Nagel4, Sherif Abdelaziz1, Andreas Gerhard Winter1, Kelvin Gordon Mashader Brockbank5,6, Shannon Layland3, Katja Schenke-Layland3,7,8, Ulrich Alfred Stock1,2,9,10. 1. Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. 2. Department of Cardiothoracic Surgery, Royal Brompton and Harefield Foundation Trust, Harefield, UK. 3. Department of Women's Health, Research Institute for Women's Health, Eberhard-Karls-University Tuebingen, Tuebingen, Germany. 4. Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. 5. Tissue Testing Technologies LLC, North Charleston, SC, USA. 6. Department of Bioengineering, Clemson University, North Charleston, SC, USA. 7. Department of Medicine/Cardiology, Cardiovascular Research Laboratories, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 8. Natural and Medical Sciences Institute at the University of Tuebingen (NMI), Reutlingen, Germany. 9. Faculty of Medicine, Imperial College London, London, UK. 10. Magdi Yacoube Institute, Heart Science Center, Harefield, UK.
Abstract
OBJECTIVES: Frozen cryopreservation (FC) with the vapour phase of liquid nitrogen storage (-135°C) is a standard biobank technique to preserve allogeneic heart valves to enable a preferable allograft valve replacement in clinical settings. However, their long-term function is limited by immune responses, inflammation and structural degeneration. Ice-free cryopreserved (IFC) valves with warmer storage possibilities at -80°C showed better matrix preservation and decreased immunological response in preliminary short-term in vivo studies. Our study aimed to assess the prolonged performance of IFC allografts in an orthotopic pulmonary sheep model. METHODS: FC (n = 6) and IFC (n = 6) allografts were transplanted into juvenile Merino sheep. After 12 months of implantation, functionality testing via 2-dimensional echocardiography and histological analyses was performed. In addition, multiphoton autofluorescence imaging and Raman microspectroscopy analysis were applied to qualitatively and quantitatively assess the matrix integrity of the leaflets. RESULTS: Six animals from the FC group and 5 animals from the IFC group were included in the analysis. Histological explant analysis showed early inflammation in the FC valves, whereas sustainable, fully functional, devitalized acellular IFC grafts were obtained. IFC valves showed excellent haemodynamic data with fewer gradients, no pulmonary regurgitation, no calcification and acellularity. Structural remodelling of the leaflet matrix structure was only detected in FC-treated tissue, whereas IFC valves maintained matrix integrity comparable to that of native controls. The collagen crimp period and amplitude and elastin structure were significantly different in the FC valve cusps compared to IFC and native cusps. Collagen fibres in the FC valves were less aligned and straightened. CONCLUSIONS: IFC heart valves with good haemodynamic function, reduced immunogenicity and preserved matrix structures have the potential to overcome the known limitations of the clinically applied FC valve.
OBJECTIVES: Frozen cryopreservation (FC) with the vapour phase of liquid nitrogen storage (-135°C) is a standard biobank technique to preserve allogeneic heart valves to enable a preferable allograft valve replacement in clinical settings. However, their long-term function is limited by immune responses, inflammation and structural degeneration. Ice-free cryopreserved (IFC) valves with warmer storage possibilities at -80°C showed better matrix preservation and decreased immunological response in preliminary short-term in vivo studies. Our study aimed to assess the prolonged performance of IFC allografts in an orthotopic pulmonary sheep model. METHODS:FC (n = 6) and IFC (n = 6) allografts were transplanted into juvenile Merino sheep. After 12 months of implantation, functionality testing via 2-dimensional echocardiography and histological analyses was performed. In addition, multiphoton autofluorescence imaging and Raman microspectroscopy analysis were applied to qualitatively and quantitatively assess the matrix integrity of the leaflets. RESULTS: Six animals from the FC group and 5 animals from the IFC group were included in the analysis. Histological explant analysis showed early inflammation in the FC valves, whereas sustainable, fully functional, devitalized acellular IFC grafts were obtained. IFC valves showed excellent haemodynamic data with fewer gradients, no pulmonary regurgitation, no calcification and acellularity. Structural remodelling of the leaflet matrix structure was only detected in FC-treated tissue, whereas IFC valves maintained matrix integrity comparable to that of native controls. The collagen crimp period and amplitude and elastin structure were significantly different in the FC valve cusps compared to IFC and native cusps. Collagen fibres in the FC valves were less aligned and straightened. CONCLUSIONS:IFC heart valves with good haemodynamic function, reduced immunogenicity and preserved matrix structures have the potential to overcome the known limitations of the clinically applied FC valve.
Authors: Emanuela S Fioretta; Sarah E Motta; Valentina Lintas; Sandra Loerakker; Kevin K Parker; Frank P T Baaijens; Volkmar Falk; Simon P Hoerstrup; Maximilian Y Emmert Journal: Nat Rev Cardiol Date: 2020-09-09 Impact factor: 32.419
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Authors: Julia Marzi; Emma C Munnig Schmidt; Eva M Brauchle; Tamar B Wissing; Hannah Bauer; Aurelie Serrero; Serge H M Söntjens; Anton W Bosman; Martijn A J Cox; Anthal I P M Smits; Katja Schenke-Layland Journal: Front Cardiovasc Med Date: 2022-05-17
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