title: Titanium surface characteristics, including topography and wettability, alter macrophage activation.
abstract: Biomaterial surface properties including chemistry, topography, and wettability regulate cell response. Previous studies have shown that increasing surface roughness of metallic orthopaedic and dental implants improved bone formation around the implant. Little is known about how implant surface properties can affect immune cells that generate a wound healing microenvironment. The aim of our study was to examine the effect of surface modifications on macrophage activation and cytokine production. Macrophages were cultured on seven surfaces: tissue culture polystyrene (TCPS) control; hydrophobic and hydrophilic smooth Ti (PT and oxygen-plasma-treated (plasma) PT); hydrophobic and hydrophilic microrough Ti (SLA and plasma SLA), and hydrophobic and hydrophilic nano-and micro-rough Ti (aged modSLA and modSLA). Smooth Ti induced inflammatory macrophage (M1-like) activation, as indicated by increased levels of interleukins IL-1β, IL-6, and TNFα. In contrast, hydrophilic rough titanium induced macrophage activation similar to the anti-inflammatory M2-like state, increasing levels of interleukins IL-4 and IL-10. These results demonstrate that macrophages cultured on high surface wettability materials produce an anti-inflammatory microenvironment, and this property may be used to improve the healing response to biomaterials.
  
  
  CONCLUSIONS
  Metals like titanium (Ti) are common in orthopaedics and dentistry due to their ability to integrate with surrounding tissue and good biocompatibility. Roughness- and wettability-increasing surface modifications promote osteogenic differentiation of stem cells on Ti. While these modifications increase production of osteoblastic factors and bone formation, little is known about their effect on immune cells. The initial host response to a biomaterial is controlled primarily by macrophages and the factors they secrete in response to the injury caused by surgery and the material cues. Here we demonstrate the effect of surface roughness and wettability on the activation and production of inflammatory factors by macrophages. Control of inflammation will inform the design of surface modification procedures to direct the immune response and enhance the success of implanted materials.
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Hotchkiss
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Gireesh B
authors.initials: GB
authors.lastname: Reddy
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hyzy
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Schwartz
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA, USA; Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, Georgia Institute of Technology, GA, USA.
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Boyan
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: ronavarrete@vcu.edu.
authors.forename: Rene
authors.initials: R
authors.lastname: Olivares-Navarrete
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry*; D002454:Cell Differentiation; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D016348:Osseointegration; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis; D011137:Polystyrenes / Q000737:chemistry; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017155:Wettability
chemical_list: D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; C508609:IL10 protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D011137:Polystyrenes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014025:Titanium
keywords: Immune response; M1 activation; M2 activation; Macrophages; Surface roughness; Titanium; Wettability