Preservation of aortic root architecture and properties using a detergent-enzymatic perfusion protocol

Linda H. Friedrich, Philipp Jungebluth, Sebastian Sjoqvist, Vanessa Lundin, Johannes C. Haag, Greg Lemon, Ylva Gustafsson, Fatemeh Ajalloueian, Alexander Sotnichenko, Heike Kielstein, Miguel A. Burguillos, Bertrand Joseph, Ana I. Teixeira, Mei Ling Lim, Paolo Macchiarini

Research output: Contribution to journalJournal articleResearchpeer-review

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 decaularization 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. (C) 2013 Elsevier Ltd. All rights reserved.
Original languageEnglish
JournalBiomaterials
Volume35
Issue number6
Pages (from-to)1907-1913
ISSN0142-9612
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics
  • Aortic root
  • Decellularization
  • Durability
  • Mechanical properties
  • Tissue engineered
  • Extracellular matrix protein
  • Immunological properties
  • Immunological reactions
  • Mechanical valves
  • Tissue processing
  • Valve replacement
  • Biocompatibility
  • Biomechanics
  • Blood vessels
  • Cell adhesion
  • Heart valve prostheses
  • Network architecture
  • Optimization
  • Scaffolds (biology)
  • Soaps (detergents)
  • Valves (mechanical)
  • Tissue
  • aortic root scaffold
  • collagen type 1
  • collagen type 4
  • fibronectin
  • laminin
  • tissue scaffold
  • unclassified drug
  • von Willebrand factor
  • animal cell
  • animal experiment
  • aortic root architecture
  • article
  • atomic force microscopy
  • biocompatibility
  • cell activation
  • cell adhesion
  • cell viability
  • controlled study
  • decellularized tissue
  • detergent enzymatic perfusion protocol
  • extracellular matrix
  • immunohistochemistry
  • in vitro study
  • in vivo study
  • male
  • mesenchymal stem cell
  • nonhuman
  • priority journal
  • procedures concerning cells
  • rat
  • tissue degeneration
  • tissue engineering
  • tissue structure
  • Animals
  • Aortic Valve
  • Cell Adhesion
  • Cell Survival
  • Cells, Cultured
  • Detergents
  • Immunohistochemistry
  • Mesenchymal Stromal Cells
  • Tissue Engineering
  • mechanical-immunological properties
  • scaffold's biocompatibility
  • Rodentia Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals, Rodents, Vertebrates) - Muridae [86375] rat common mature male strain-Sprague Dawley
  • extracellular matrix proteins
  • matrix degenerating detergents
  • 10064, Biochemistry studies - Proteins, peptides and amino acids
  • 10511, Biophysics - Bioengineering
  • 10802, Enzymes - General and comparative studies: coenzymes
  • 14504, Cardiovascular system - Physiology and biochemistry
  • Allied Medical Sciences
  • Biochemistry and Molecular Biophysics
  • Transport and Circulation
  • aortic root circulatory system
  • aortic root engineering laboratory techniques
  • detergent-enzymatic perfusion method laboratory techniques
  • heterotopic implantation laboratory techniques
  • improved/innovative decellularization approach laboratory techniques
  • Biomedical Engineering
  • Cardiovascular System
  • Enzymology
  • Methods and Techniques
  • ENGINEERING,
  • MATERIALS
  • ENGINEERED HEART-VALVES
  • EXTRACELLULAR-MATRIX
  • ALLOGRAFTS
  • REPLACEMENT
  • DECELLULARIZATION
  • IMPLANTATION
  • PERFORMANCE
  • CONDUITS
  • MODEL
  • PERFUSION (Physiology)

Cite this

Friedrich, L. H., Jungebluth, P., Sjoqvist, S., Lundin, V., Haag, J. C., Lemon, G., Gustafsson, Y., Ajalloueian, F., Sotnichenko, A., Kielstein, H., Burguillos, M. A., Joseph, B., Teixeira, A. I., Lim, M. L., & Macchiarini, P. (2014). Preservation of aortic root architecture and properties using a detergent-enzymatic perfusion protocol. Biomaterials, 35(6), 1907-1913. https://doi.org/10.1016/j.biomaterials.2013.11.053