title: Preservation of aortic root architecture and properties using a detergent-enzymatic perfusion protocol.
abstract: Aortic valve degeneration and dysfunction is one of the leading causes for morbidity and mortality. The conventional heart-valve prostheses have significant limitations with either life-long anticoagulation therapeutic associated bleeding complications (mechanical valves) or limited durability (biological valves). Tissue engineered valve replacement recently showed encouraging results, but the unpredictable outcome of tissue degeneration is likely associated to the extensive tissue processing methods. We believe that optimized decellularization procedures may provide aortic valve/root grafts improved durability. We present an improved/innovative decellularization approach using a detergent-enzymatic perfusion method, which is both quicker and has less exposure of matrix degenerating detergents, compared to previous protocols. The obtained graft was characterized for its architecture, extracellular matrix proteins, mechanical and immunological properties. We further analyzed the engineered aortic root for biocompatibility by cell adhesion and viability in vitro and heterotopic implantation in vivo. The developed decellularization protocol was substantially reduced in processing time whilst maintaining tissue integrity. Furthermore, the decellularized aortic root remained bioactive without eliciting any adverse immunological reaction. Cell adhesion and viability demonstrated the scaffold's biocompatibility. Our optimized decellularization protocol may be useful to develop the next generation of clinical valve prosthesis with a focus on improved mechanical properties and durability.
authors: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
authors: Linda H
authors: LH
authors: Friedrich
authors: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
authors: Philipp
authors: P
authors: Jungebluth
authors: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
authors: Sebastian
authors: S
authors: Sjöqvist
authors: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors: Vanessa
authors: V
authors: Lundin
authors: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
authors: Johannes C
authors: JC
authors: Haag
authors: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
authors: Greg
authors: G
authors: Lemon
authors: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
authors: Ylva
authors: Y
authors: Gustafsson
authors: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
authors: Fatemeh
authors: F
authors: Ajalloueian
authors: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
authors: Alexander
authors: A
authors: Sotnichenko
authors: Department of Anatomy and Cell Biology, Martin Luther University, Faculty of Medicine, Halle (Saale), Germany.
authors: Heike
authors: H
authors: Kielstein
authors: Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.
authors: Miguel A
authors: MA
authors: Burguillos
authors: Cancer Centrum Karolinska, Karolinska Institutet, Stockholm, Sweden.
authors: Bertrand
authors: B
authors: Joseph
authors: Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
authors: Ana I
authors: AI
authors: Teixeira
authors: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
authors: Mei Ling
authors: ML
authors: Lim
authors: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden. Electronic address: paolo.macchiarini@ki.se.
authors: Paolo
authors: P
authors: Macchiarini
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000166:cytology*; D002448:Cell Adhesion / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003902:Detergents; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D003902:Detergents
keywords: Aortic root; Decellularization; Durability; Mechanical properties; Tissue engineered