title: Osteogenic differentiation of human mesenchymal stem cells in the absence of osteogenic supplements: A surface-roughness gradient study.
abstract: The use of biomaterials to direct osteogenic differentiation of human mesenchymal stem cells (hMSCs) in the absence of osteogenic supplements is thought to be part of the next generation of orthopedic implants. We previously engineered surface-roughness gradients of average roughness (Ra) varying from the sub-micron to the micrometer range (∼0.5-4.7 μm), and mean distance between peaks (RSm) gradually varying from ∼214 μm to 33 μm. Here we have screened the ability of such surface-gradients of polycaprolactone to influence the expression of alkaline phosphatase (ALP), collagen type 1 (COL1) and mineralization by hMSCs cultured in dexamethasone (Dex)-deprived osteogenic induction medium (OIM) and in basal growth medium (BGM). Ra∼1.53 μm/RSm∼79 μm in Dex-deprived OI medium, and Ra∼0.93 μm/RSm∼135 μm in BGM consistently showed higher effectiveness at supporting the expression of the osteogenic markers ALP, COL1 and mineralization, compared to the tissue culture polystyrene (TCP) control in complete OIM. The superior effectiveness of specific surface-roughness revealed that this strategy may be used as a compelling alternative to soluble osteogenic inducers in orthopedic applications featuring the clinically relevant biodegradable polymer polycaprolactone.
  
  
  CONCLUSIONS
  Biodegradable polymers, such as polycaprolactone (PCL), are promising materials in the field of tissue engineering and regenerative medicine, which aims at creating viable options to replace permanent orthopedic implants. The material, cells, and growth-stimulating factors are often referred to as the key components of engineered tissues. In this article, we studied the hypothesis of specific surface modification of PCL being capable of inducing mesenchymal stem cell differentiation in bone cells in the absence of cell-differentiating factors. The systematic investigation of the linearly varying surface-roughness gradient showed that an average PCL roughness of 0.93 μm alone can serve as a compelling alternative to soluble osteogenic inducers in orthopedic applications featuring the clinically relevant biodegradable polymer polycaprolactone.
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco GMR, Portugal; ICVS/3B's - PT Government Associate Laboratory, Guimarães, Portugal; Laboratory for Surface Science and Technology, Department of Materials, ETH Zurich, CH-8093 Zürich, Switzerland.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Faia-Torres
authors.affiliation: Laboratory for Surface Science and Technology, Department of Materials, ETH Zurich, CH-8093 Zürich, Switzerland; Centre for Micro-Photonics, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Victoria 3122, Australia; Industrial Research Institute Swinburne, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Victoria 3122, Australia.
authors.forename: Mirren
authors.initials: M
authors.lastname: Charnley
authors.affiliation: Laboratory for Surface Science and Technology, Department of Materials, ETH Zurich, CH-8093 Zürich, Switzerland.
authors.forename: Tolga
authors.initials: T
authors.lastname: Goren
authors.affiliation: Laboratory for Materials-Biology Interactions, Empa Swiss Federal Laboratories for Materials Science and Technology, CH-9014 St. Gallen, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Guimond-Lischer
authors.affiliation: Laboratory for Materials-Biology Interactions, Empa Swiss Federal Laboratories for Materials Science and Technology, CH-9014 St. Gallen, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Rottmar
authors.affiliation: Laboratory for Materials-Biology Interactions, Empa Swiss Federal Laboratories for Materials Science and Technology, CH-9014 St. Gallen, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Maniura-Weber
authors.affiliation: Laboratory for Surface Science and Technology, Department of Materials, ETH Zurich, CH-8093 Zürich, Switzerland.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Spencer
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco GMR, Portugal; ICVS/3B's - PT Government Associate Laboratory, Guimarães, Portugal.
authors.forename: Rui L
authors.initials: RL
authors.lastname: Reis
authors.affiliation: Laboratory for Surface Science and Technology, Department of Materials, ETH Zurich, CH-8093 Zürich, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Textor
authors.affiliation: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco GMR, Portugal; ICVS/3B's - PT Government Associate Laboratory, Guimarães, Portugal. Electronic address: nuno@dep.uminho.pt.
authors.forename: Nuno M
authors.initials: NM
authors.lastname: Neves
mesh_terms: D000368:Aged; D001672:Biocompatible Materials; D002454:Cell Differentiation; D003470:Culture Media; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis; D011091:Polyesters / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D001672:Biocompatible Materials; D003470:Culture Media; D011091:Polyesters; C016240:polycaprolactone
keywords: Biomaterials; High-throughput screening (gradient); Mesenchymal stem cells; Microstructures; Osteogenesis