title: Bioprinting Organotypic Hydrogels with Improved Mesenchymal Stem Cell Remodeling and Mineralization Properties for Bone Tissue Engineering.
abstract: 3D-manufactured hydrogels with precise contours and biological adhesion motifs are interesting candidates in the regenerative medicine field for the culture and differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). 3D-bioprinting is a powerful technique to approach one step closer the native organization of cells. This study investigates the effect of the incorporation of collagen type I in 3D-bioprinted polysaccharide-based hydrogels to the modulation of cell morphology, osteogenic remodeling potential, and mineralization. By combining thermo-responsive agarose hydrogels with collagen type I, the mechanical stiffness and printing contours of printed constructs can be improved compared to pure collagen hydrogels which are typically used as standard materials for MSC osteogenic differentiation. The results presented here show that MSC not only survive the 3D-bioprinting process but also maintain the mesenchymal phenotype, as proved by live/dead staining and immunocytochemistry (vimentin positive, CD34 negative). Increased solids concentrations of collagen in the hydrogel blend induce changes in cell morphology, namely, by enhancing cell spreading, that ultimately contribute to enhanced and directed MSC osteogenic differentiation. 3D-bioprinted agarose-collagen hydrogels with high-collagen ratio are therefore feasible for MSC osteogenic differentiation, contrarily to low-collagen blends, as proved by two-photon microscopy, Alizarin Red staining, and real-time polymerase chain reaction.
authors.affiliation: Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Daniela Filipa
authors.initials: DF
authors.lastname: Duarte Campos
authors.affiliation: Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Blaeser
authors.affiliation: Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany.|Harvard School of Engineering and Applied Sciences, 02138, Cambridge, MA, USA.
authors.forename: Kate
authors.initials: K
authors.lastname: Buellesbach
authors.affiliation: Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Kshama Shree
authors.initials: KS
authors.lastname: Sen
authors.affiliation: Institute of Physical Chemistry II, RWTH Aachen University, 52074, Aachen, Germany.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Xun
authors.affiliation: DWI Leibniz Institute for Interactive Materials, RWTH Aachen University, 52056, Aachen, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Tillmann
authors.affiliation: Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Fischer
mesh_terms: D062028:Bioprinting / Q000379:methods; D001853:Bone Marrow / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D066330:Printing, Three-Dimensional; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D024042:Collagen Type I; D020100:Hydrogels
keywords: 3D-bioprinting; human bone marrow-derived mesenchymal stem cells; hydrogels; mineralization; osteogenesis