Anti-inflammatory properties of micropatterned titanium coatings.

Prolonged inflammation and reactive oxygen species (ROS) generated around an implanted biosensor are the primary causes of the foreign body response, including encapsulation of biosensor membranes. We have previously demonstrated that TiO2 surfaces reduce ROS. Here we investigated the potential of using the anti-inflammatory properties of TiO2 in the design of biosensor membranes with improved long-term in vivo transport properties. Micropatterned Ti films were sputtered onto quartz surfaces in a series of hexagonally distributed dots with identical coverage area of 23% and dot size ranging from 5 to 100 microm. The antioxidant effect of the surfaces was investigated using a cell-free peroxynitrite donor assay and assays of superoxide released from stimulated surface-adhering neutrophils and macrophages. In all three assays, the amount of ROS was monitored using luminol-amplified chemiluminescence. Patterned surfaces in all experimental models significantly decreased ROS compared to the etched surfaces. In the cell-free experiment, the ROS reduction was only dependent on fractional surface coverage. In the cell experiments, however, a dot-size-dependent ROS reduction was seen, with the largest reduction at the smallest dot-size surfaces. These results indicate that micropatterned surfaces with small dots covering only 23% of the surface area exhibit similar antioxidative effect as fully covered surfaces.

[1]  J. A. Hubbell,et al.  Photo-crosslinked copolymers of 2-hydroxyethyl methacrylate, poly(ethylene glycol) tetra-acrylate and ethylene dimethacrylate for improving biocompatibility of biosensors. , 1995, Biomaterials.

[2]  L. Bjursten,et al.  Optimized density gradient separation of leukocyte fractions from whole blood by adjustment of osmolarity. , 1986, Journal of immunological methods.

[3]  K. Ishihara,et al.  Development of a ferrocene-mediated needle-type glucose sensor covered with newly designed biocompatible membrane, 2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate. , 1995, Medical progress through technology.

[4]  P. Tengvall,et al.  Titanium-hydrogen peroxide interaction: model studies of the influence of the inflammatory response on titanium implants. , 1989, Biomaterials.

[5]  J S Beckman,et al.  Peroxynitrite-induced luminol chemiluminescence. , 1993, The Biochemical journal.

[6]  K. Van Dyke,et al.  A new screening method to detect water-soluble antioxidants: acetaminophen (Tylenol) and other phenols react as antioxidants and destroy peroxynitrite-based luminol-dependent chemiluminescence. , 1998, Journal of bioluminescence and chemiluminescence.

[7]  C. Pascual,et al.  Effect of antioxidants on induction time of luminol luminescence elicited by 3-morpholinosydnonimine (SIN-1). , 1999, Luminescence : the journal of biological and chemical luminescence.

[8]  Richard Skalak,et al.  The interface zone of inorganic implantsIn vivo: Titanium implants in bone , 2006, Annals of Biomedical Engineering.

[9]  P. Tengvall,et al.  Anti-inflammatory effects of a titanium-peroxy gel: role of oxygen metabolites and apoptosis. , 2004, Journal of biomedical materials research. Part A.

[10]  J. Frangos,et al.  Inhibition of Inflammatory Species by Titanium Surfaces , 2000, Clinical orthopaedics and related research.

[11]  H. Nygren,et al.  Polymorphonuclear leukocytes in coagulating whole blood recognize hydrophilic and hydrophobic titanium surfaces by different adhesion receptors and show different patterns of receptor expression. , 2001, The Journal of laboratory and clinical medicine.

[12]  J. Frangos,et al.  Reactive oxygen species inhibited by titanium oxide coatings. , 2003, Journal of biomedical materials research. Part A.

[13]  N Wisniewski,et al.  Characterization of implantable biosensor membrane biofouling , 2000, Fresenius' journal of analytical chemistry.

[14]  I Lundström,et al.  Physico-chemical considerations of titanium as a biomaterial. , 1992, Clinical materials.

[15]  Ingemar Lundström,et al.  Auger electron spectroscopic studies of the interface between human tissue and implants of titanium and stainless steel , 1986 .

[16]  W. Saltzman,et al.  Micron-scale positioning of features influences the rate of polymorphonuclear leukocyte migration. , 2001, Biophysical journal.

[17]  P. Tengvall,et al.  Interaction between hydrogen peroxide and titanium: a possible role in the biocompatibility of titanium. , 1989, Biomaterials.

[18]  L. Bjursten,et al.  Implants in the abdominal wall of the rat. , 1986, Scandinavian journal of plastic and reconstructive surgery.

[19]  James M. Anderson,et al.  Chapter 4 Mechanisms of inflammation and infection with implanted devices , 1993 .

[20]  D. Scharnweber,et al.  Electrochemical behavior of titanium-based materials – are there relations to biocompatibility? , 2002, Journal of materials science. Materials in medicine.

[21]  A Curtis,et al.  Topographical control of cells. , 1997, Biomaterials.

[22]  W M Reichert,et al.  In vitro characterization of vascular endothelial growth factor and dexamethasone releasing hydrogels for implantable probe coatings. , 2005, Biomaterials.

[23]  M Ferrari,et al.  Nanoporous anti-fouling silicon membranes for biosensor applications. , 2000, Biosensors & bioelectronics.

[24]  L. Hench,et al.  Biocompatibility of silicates for medical use. , 2007, Ciba Foundation symposium.

[25]  Y. Chen,et al.  In vivo investigation of blood compatibility of titanium oxide films. , 1998, Journal of biomedical materials research.

[26]  M. Textor,et al.  Surface characterization of implant materials c.p. Ti, Ti-6Al-7Nb and Ti-6Al-4V with different pretreatments. , 1999, Journal of materials science. Materials in medicine.

[27]  J. Ragai Trapped radicals in titania gels , 1987, Nature.

[28]  C. S. Chen,et al.  Geometric control of cell life and death. , 1997, Science.