title: Osteogenic potential of human adipose-tissue-derived mesenchymal stromal cells cultured on 3D-printed porous structured titanium.
abstract: Integration of porous metal prosthetics, which restore form and function of irreversibly damaged joints, into remaining healthy bone is critical for implant success. We investigated the biological properties of adipose-tissue-derived mesenchymal stromal/stem cells (AMSCs) and addressed their potential to alter the in vitro microenvironment of implants. We employed human AMSCs as a practical source for musculoskeletal applications because these cells can be obtained in large quantities, are multipotent, and have trophic paracrine functions. AMSCs were cultured on surgical-grade porous titanium disks as a model for orthopedic implants. We monitored cell/substrate attachment, cell proliferation, multipotency, and differentiation phenotypes of AMSCs upon osteogenic induction. High-resolution scanning electron microscopy and histology revealed that AMSCs adhere to the porous metallic surface. Compared to standard tissue culture plastic, AMSCs grown in the porous titanium microenvironment showed differences in temporal expression for genes involved in cell cycle progression (CCNB2, HIST2H4), extracellular matrix production (COL1A1, COL3A1), mesenchymal lineage identity (ACTA2, CD248, CD44), osteoblastic transcription factors (DLX3, DLX5, ID3), and epigenetic regulators (EZH1, EZH2). We conclude that metal orthopedic implants can be effectively seeded with clinical-grade stem/stromal cells to create a pre-conditioned implant.
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Lewallen
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA; Department of Biomedical Engineering and Physiology, Mayo Graduate School, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Dakota L
authors.initials: DL
authors.lastname: Jones
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Amel
authors.initials: A
authors.lastname: Dudakovic
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Roman
authors.initials: R
authors.lastname: Thaler
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Paradise
authors.affiliation: Department of Health Sciences Research, College of Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Hilal M
authors.initials: HM
authors.lastname: Kremers
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Abdel
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kakar
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St. SW Rochester, MN 55905, USA.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Dietz
authors.affiliation: Stryker Orthopedics, 325 Corporate Drive, Mahwah, NJ 07430, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Cohen
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. Electronic address: lewallen.david@mayo.edu.
authors.forename: David G
authors.initials: DG
authors.lastname: Lewallen
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA; Department of Biomedical Engineering and Physiology, Mayo Graduate School, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA. Electronic address: vanwijnen.andre@mayo.edu.
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D066330:Printing, Three-Dimensional; D046509:Tissue Culture Techniques / Q000379:methods*; D014025:Titanium / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D014025:Titanium
keywords: Biomaterial; Extracellular matrix; Gene expression; Mesenchymal stem cell; Scanning electron microscopy