title: Customized Interface Biofunctionalization of Decellularized Extracellular Matrix: Toward Enhanced Endothelialization.
abstract: Interface biofunctionalization strategies try to enhance and control the interaction between implants and host organism. Decellularized extracellular matrix (dECM) is widely used as a platform for bioengineering of medical implants, having shown its suitability in a variety of preclinical as well as clinical models. In this study, specifically designed, custom-made synthetic peptides were used to functionalize dECM with different cell adhesive sequences (RGD, REDV, and YIGSR). Effects on in vitro endothelial cell adhesion and in vivo endothelialization were evaluated in standardized models using decellularized ovine pulmonary heart valve cusps (dPVCs) and decellularized aortic grafts (dAoGs), respectively. Contact angle measurements and fluorescent labeling of custom-made peptides showed successful functionalization of dPVCs and dAoGs. The functionalization of dPVCs with a combination of bioactive sequences significantly increased in vitro human umbilical vein endothelial cell adhesion compared to nonfunctionalized controls. In a functional rodent aortic transplantation model, fluorescent-labeled peptides on dAoGs were persistent up to 10 days in vivo under exposure to systemic circulation. Although there was a trend toward enhanced in vivo endothelialization of functionalized grafts compared to nonfunctionalized controls, there was no statistical significance and a large biological variability in both groups. Despite failing to show a clear biological effect in the used in vivo model system, our initial findings do suggest that endothelialization onto dECM may be modulated by customized interface biofunctionalization using the presented method. Since bioactive sequences within the dECM-synthetic peptide platform are easily interchangeable and combinable, further control of host cell proliferation, function, and differentiation seems to be feasible, possibly paving the way to a new generation of multifunctional dECM scaffolds for regenerative medicine.
authors.affiliation: 1 Department of Cardiovascular Surgery, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .|2 Research Group for Experimental Surgery, Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .
authors.forename: Hug
authors.initials: H
authors.lastname: Aubin
authors.affiliation: 3 Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC) , Barcelona, Spain .|4 Center for Research in NanoEngineering (CRNE), Technical University of Catalonia (UPC) , Barcelona, Spain .
authors.forename: Carlos
authors.initials: C
authors.lastname: Mas-Moruno
authors.affiliation: 2 Research Group for Experimental Surgery, Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .
authors.forename: Makoto
authors.initials: M
authors.lastname: Iijima
authors.affiliation: 2 Research Group for Experimental Surgery, Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schütterle
authors.affiliation: 2 Research Group for Experimental Surgery, Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .
authors.forename: Meike
authors.initials: M
authors.lastname: Steinbrink
authors.affiliation: 1 Department of Cardiovascular Surgery, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .|2 Research Group for Experimental Surgery, Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .
authors.forename: Alexander
authors.initials: A
authors.lastname: Assmann
authors.affiliation: 3 Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC) , Barcelona, Spain .|4 Center for Research in NanoEngineering (CRNE), Technical University of Catalonia (UPC) , Barcelona, Spain .
authors.forename: Francesc Javier
authors.initials: FJ
authors.lastname: Gil
authors.affiliation: 1 Department of Cardiovascular Surgery, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .|2 Research Group for Experimental Surgery, Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .
authors.forename: Artur
authors.initials: A
authors.lastname: Lichtenberg
authors.affiliation: 3 Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Technical University of Catalonia (UPC) , Barcelona, Spain .|4 Center for Research in NanoEngineering (CRNE), Technical University of Catalonia (UPC) , Barcelona, Spain .
authors.forename: Marta
authors.initials: M
authors.lastname: Pegueroles
authors.affiliation: 1 Department of Cardiovascular Surgery, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .|2 Research Group for Experimental Surgery, Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .
authors.forename: Payam
authors.initials: P
authors.lastname: Akhyari
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry*; D006351:Heart Valves / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology*; D006801:Humans; D008297:Male; D011664:Pulmonary Valve / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry