title: Improvement of the in vivo cellular repopulation of decellularized cardiovascular tissues by a detergent-free, non-proteolytic, actin-disassembling regimen.
abstract: Low immunogenicity and high repopulation capacity are crucial determinants for the functional and structural performance of acellular cardiovascular implants. The present study evaluates a detergent-free, non-proteolytic, actin-disassembling regimen (BIO) for decellularization of heart valve and vessel grafts, particularly focusing on their bio-functionality. Rat aortic conduits (rAoC; n = 89) and porcine aortic valve samples (n = 106) are decellularized using detergents (group DET) or the BIO regimen. BIO decellularization results in effective elimination of cellular proteins and significantly improves removal of DNA as compared with group DET, while the extracellular matrix (ECM) structure as well as mechanical properties are preserved. The architecture of rAoC in group BIO allows for improved bio-functionalization with fibronectin (FN) in a standardized rat implantation model: BIO treatment significantly increases speed and amount of autologous medial cellular repopulation in vivo (p < 0.001) and decreases the formation of hyperplastic intima (p < 0.001) as compared with FN-coated DET-decellularized grafts. Moreover, there are no signs of infiltration with inflammatory cells. The present biological, detergent-free, non-proteolytic regimen balances effective decellularization and ECM preservation in cardiovascular grafts, and provides optimized bio-functionality. Additionally, this study implies that the actin-disassembling regimen may be a promising approach for bioengineering of acellular scaffolds from other muscular tissues, as for example myocardium or intestine. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Assmann
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Struß
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Schiffer
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Heidelberg
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Munakata
authors.affiliation: Department of Laser and Biotechnical Systems, Samara State Aerospace University, Samara, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Timchenko
authors.affiliation: Department of Laser and Biotechnical Systems, Samara State Aerospace University, Samara, Russia.
authors.forename: Pavel E
authors.initials: PE
authors.lastname: Timchenko
authors.affiliation: Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Kaufmann
authors.affiliation: Institute of Haemostaseology, Haemotherapy and Transfusion Medicine, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Khon
authors.initials: K
authors.lastname: Huynh
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Yukiharu
authors.initials: Y
authors.lastname: Sugimura
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Leidl
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Institute of Haemostaseology, Haemotherapy and Transfusion Medicine, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Volker R
authors.initials: VR
authors.lastname: Stoldt
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Artur
authors.initials: A
authors.lastname: Lichtenberg
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Payam
authors.initials: P
authors.lastname: Akhyari
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001021:Aortic Valve / Q000502:physiology; D001696:Biomechanical Phenomena; D002319:Cardiovascular System / Q000166:cytology*; D016923:Cell Death / Q000187:drug effects; D003902:Detergents / Q000494:pharmacology*; D005353:Fibronectins / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008297:Male; D059748:Proteolysis; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D034421:Sus scrofa
chemical_list: D000199:Actins; D003902:Detergents; D005353:Fibronectins
keywords: bio-functionalization; decellularization; glycosaminoglycan; graft repopulation; heart valve; tissue engineering; vascular graft