title: Acceleration of autologous in vivo recellularization of decellularized aortic conduits by fibronectin surface coating.
abstract: Decellularization is a promising option to diminish immune and inflammatory response against donor grafts. In order to accelerate the autologous in vivo recellularization of aortic conduits for an enhanced biocompatibility, we tested fibronectin surface coating in a standardized rat implantation model. Detergent-decellularized rat aortic conduits (n = 36) were surface-coated with covalently Alexa488-labeled fibronectin (50 μg/ml, 24 h) and implanted into the systemic circulation of Wistar rats for up to 8 weeks (group FN; n = 18). Uncoated implants served as controls (group C; n = 18). Fibronectin-bound fluorescence on both surfaces of the aortic conduits was persistent for at least 8 weeks. Cellular repopulation was examined by histology and immunofluorescence (n = 24). Luminal endothelialization was significantly accelerated in group FN (p = 0.006 after 8 weeks), however, local myofibroblast hyperplasia with significantly increased ratio of intima-to-media thickness occurred (p = 0.0002 after 8 weeks). Originating from the adventitial surface, alpha-smooth muscle actin and desmin positive cell invasion into the media of fibronectin-coated conduits was significantly increased as compared to group C (p < 0.0001). In these medial areas, in situ zymography revealed enhanced matrix metalloproteinase activity. In both groups, inflammatory cell markers (CD3 and CD68) and signs of thrombosis proved negative. With regard to several markers of cell adhesion, inflammation and calcification, quantitative real-time PCR (n = 12) revealed no significant inter-group differences. Fibronectin surface coating of decellularized cardiovascular implants proved feasible and persistent for at least 8 weeks in the systemic circulation. Biofunctional protein coating accelerated the autologous in vivo endothelialization and induced a significantly increased medial recellularization. Therefore, this strategy may contribute to the improvement of current clinically applied bioprostheses.
authors.affiliation: Department of Cardiovascular Surgery and Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Moorenstrasse 5, Duesseldorf D-40225, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Assmann
authors.forename: Christofer
authors.initials: C
authors.lastname: Delfs
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Munakata
authors.forename: Franziska
authors.initials: F
authors.lastname: Schiffer
authors.forename: Kim
authors.initials: K
authors.lastname: Horstkötter
authors.forename: Khon
authors.initials: K
authors.lastname: Huynh
authors.forename: Mareike
authors.initials: M
authors.lastname: Barth
authors.forename: Volker R
authors.initials: VR
authors.lastname: Stoldt
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiya
authors.forename: Udo
authors.initials: U
authors.lastname: Boeken
authors.forename: Artur
authors.initials: A
authors.lastname: Lichtenberg
authors.forename: Payam
authors.initials: P
authors.lastname: Akhyari
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000166:cytology* / Q000502:physiology; D001705:Bioprosthesis; D002448:Cell Adhesion / Q000502:physiology; D005353:Fibronectins / Q000737:chemistry*; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000379:methods
chemical_list: D005353:Fibronectins