title: Directing collagen fibers using counter-rotating cone extrusion.
abstract: The bio-inspired engineering of tissue equivalents should take into account anisotropic morphology and the mechanical properties of the extracellular matrix. This especially applies to collagen fibrils, which have various, but highly defined, orientations throughout tissues and organs. There are several methods available to control the alignment of soluble collagen monomers, but the options to direct native insoluble collagen fibers are limited. Here we apply a controlled counter-rotating cone extrusion technology to engineer tubular collagen constructs with defined anisotropy. Driven by diverging inner and outer cone rotation speeds, collagen fibrils from bovine skin were extruded and precipitated onto mandrels as tubes with oriented fibers and bundles, as examined by second harmonic generation microscopy and quantitative image analysis. A clear correlation was found whereby the direction and extent of collagen fiber alignment during extrusion were a function of the shear forces caused by a combination of the cone rotation and flow direction. A gradual change in the fiber direction, spanning +50 to -40°, was observed throughout the sections of the sample, with an average decrease ranging from 2.3 to 2.6° every 10μm. By varying the cone speeds, the collagen constructs showed differences in elasticity and toughness, spanning 900-2000kPa and 19-35mJ, respectively. Rotational extrusion presents an enabling technology to create and control the (an)isotropic architecture of collagen constructs for application in tissue engineering and regenerative medicine.
authors.affiliation: Department of Biochemistry 280, RIMLS, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, Netherlands. Electronic address: Henk.Hoogenkamp@Radboudumc.nl.
authors.forename: Henk R
authors.initials: HR
authors.lastname: Hoogenkamp
authors.affiliation: Department of Cell Biology 283, RIMLS, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Bakker
authors.affiliation: Department of Cell Biology 283, RIMLS, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Wolf
authors.affiliation: Marel Townsend Further Processing, Handelstraat 3, 5831 AV Boxmeer, Netherlands.
authors.forename: Patricia
authors.initials: P
authors.lastname: Suurs
authors.affiliation: Marel Townsend Further Processing, Handelstraat 3, 5831 AV Boxmeer, Netherlands.
authors.forename: Bertus
authors.initials: B
authors.lastname: Dunnewind
authors.affiliation: Department of Food Science, University of Guelph, 88 McGilvray Street, Guelph, ON N1G 2W1, Canada.
authors.forename: Shai
authors.initials: S
authors.lastname: Barbut
authors.affiliation: Department of Cell Biology 283, RIMLS, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, Netherlands; David H. Koch Center for Applied Research of Genitourinary Cancers, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Cancer Genomics Center Netherlands,(1) HP Stratenum 3.217, Universiteitsweg 100, 3584 CG Utrecht, Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Friedl
authors.affiliation: Department of Biochemistry 280, RIMLS, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.affiliation: Department of Biochemistry 280, RIMLS, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, Netherlands.
authors.forename: Willeke F
authors.initials: WF
authors.lastname: Daamen
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D013552:Swine; D023822:Tissue Engineering
chemical_list: D003094:Collagen
keywords: Collagen structure; ECM; Extrusion; Image analysis; Scaffold