title: Control of proliferation and osteogenic differentiation of human dental-pulp-derived stem cells by distinct surface structures.
abstract: The ability to control the behavior of stem cells provides crucial benefits, for example, in tissue engineering and toxicity/drug screening, which utilize the stem cell's capacity to engineer new tissues for regenerative purposes and the testing of new drugs in vitro. Recently, surface topography has been shown to influence stem cell differentiation; however, general trends are often difficult to establish due to differences in length scales, surface chemistries and detailed surface topographies. Here we apply a highly versatile screening approach to analyze the interplay of surface topographical parameters on cell attachment, morphology, proliferation and osteogenic differentiation of human mesenchymal dental-pulp-derived stem cells (DPSCs) cultured with and without osteogenic differentiation factors in the medium (ODM). Increasing the inter-pillar gap size from 1 to 6 μm for surfaces with small pillar sizes of 1 and 2 μm resulted in decreased proliferation and in more elongated cells with long pseudopodial protrusions. The same alterations of pillar topography, up to an inter-pillar gap size of 4 μm, also resulted in enhanced mineralization of DPSCs cultured without ODM, while no significant trend was observed for DPSCs cultured with ODM. Generally, cells cultured without ODM had a larger deposition of osteogenic markers on structured surfaces relative to the unstructured surfaces than what was found when culturing with ODM. We conclude that the topographical design of biomaterials can be optimized for the regulation of DPSC differentiation and speculate that the inclusion of ODM alters the ability of the cells to sense surface topographical cues. These results are essential in order to transfer the use of this highly proliferative, easily accessible stem cell into the clinic for use in cell therapy and regenerative medicine.
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Kolind
authors.affiliation: Department of Orthodontics, School of Dentistry, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: D
authors.initials: D
authors.lastname: Kraft
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Bøggild
authors.affiliation: Department of Molecular Biology, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Duch
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Lovmand
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark; Department of Molecular Biology, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: F S
authors.initials: FS
authors.lastname: Pedersen
authors.affiliation: Department of Orthodontics, School of Dentistry, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: D A
authors.initials: DA
authors.lastname: Bindslev
authors.affiliation: Department of Orthopaedic Surgery, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
authors.forename: C E
authors.initials: CE
authors.lastname: Bünger
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark. Electronic address: foss@inano.au.dk.
authors.forename: M
authors.initials: M
authors.lastname: Foss
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark; Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Besenbacher
mesh_terms: D002448:Cell Adhesion; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D006801:Humans; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D053495:Osteopontin / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013499:Surface Properties; D055815:Young Adult
chemical_list: D015675:Osteocalcin; D053495:Osteopontin
keywords: Dental-pulp-derived stem cells; Microtopography; Osteogenic differentiation; Screening approach