title: Design and Fabrication of Complex Scaffolds for Bone Defect Healing: Combined 3D Plotting of a Calcium Phosphate Cement and a Growth Factor-Loaded Hydrogel.
abstract: Additive manufacturing enables the fabrication of scaffolds with defined architecture. Versatile printing technologies such as extrusion-based 3D plotting allow in addition the incorporation of biological components increasing the capability to restore functional tissues. We have recently described the fabrication of calcium phosphate cement (CPC) scaffolds by 3D plotting of an oil-based CPC paste under mild conditions. In the present study, we have developed a strategy for growth factor loading based on multichannel plotting: a biphasic scaffold design was realised combining CPC with VEGF-laden, highly concentrated hydrogel strands. As hydrogel component, alginate and an alginate-gellan gum blend were evaluated; the blend exhibited a more favourable VEGF release profile and was chosen for biphasic scaffold fabrication. After plotting, two-step post-processing was performed for both, hydrogel crosslinking and CPC setting, which was shown to be compatible with both materials. Finally, a scaffold was designed and fabricated which can be applied for testing in a rat critical size femur defect. Optimization of CPC plotting enabled the fabrication of highly resolved structures with strand diameters of only 200 µm. Micro-computed tomography revealed a precise strand arrangement and an interconnected pore space within the biphasic scaffold even in swollen state of the hydrogel strands.
authors.affiliation: Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Ahlfeld
authors.affiliation: Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Ashwini Rahul
authors.initials: AR
authors.lastname: Akkineni
authors.affiliation: Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Förster
authors.affiliation: Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Tino
authors.initials: T
authors.lastname: Köhler
authors.affiliation: Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Knaack
authors.affiliation: Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gelinsky
authors.affiliation: Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany. anja.lode@tu-dresden.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Lode
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005269:Femur / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D066330:Printing, Three-Dimensional; D051381:Rats; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D001843:Bone Cements; D002130:Calcium Phosphates; D020100:Hydrogels; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C020243:calcium phosphate
keywords: 3D printing; Additive manufacturing; Alginate; Biphasic scaffolds; Calcium phosphate; Drug delivery; Gellan gum; Rapid prototyping