2009-11, Schuler, Martin, Hamilton, Douglas W., Kunzler, Tobias P., Sprecher, Christoph M., de Wild, Michael, Brunette, Donald M., Textor, Marcus, Tosatti, Samuele G. P.

Mimicking proteins found in the extracellular matrix (ECM) using specific peptide sequences is a well-known strategy for the design of biomimetic surfaces, but has not yet been widely exploited in the field of biomedical implants. This study investigated osteoblast and, as a control, fibroblast proliferation to novel consensus heparin-binding peptides sequences KRSR and FHRIKKA that were immobilized onto rough (particle-blasted and chemically etched) commercially pure titanium surfaces using a poly(L-lysine)-graft- poly(ethylene glycol) (PLL-g-PEG) molecular assembly system. This platform enabled a detailed study of specific cell-peptide interactions even in the presence of serum in the culture medium; thanks to the excellent nonfouling properties of the PLL-g-PEG surface. Cell-binding peptide sequence RGD in combination with KRSR or FHRRIKA was used to examine a potentially-enhanced or synergistic effect on osteoblast proliferation. Bare titanium and bioinactive surfaces (i.e., unfunctionalized PLL-g-PEG and scrambled KSSR, RFHARIK, and RDG) were used as control substrates. Additionally, in a newly developed experimental setup, freshly harvested bone chips from newborn rat calvariae were placed onto the same type of surfaces investigating size and pattern of osteoblast outgrowths. The findings of the current study demonstrated that the difference in osteoblast and fibroblast proliferation was influenced by surface topography more so than by the presence of surface-bound KRSR and FHRRIKA. On the other hand, in comparison with the control surfaces, osteoblast outgrowths from rat calvarial bone chips covered a significantly larger area on RGD, KRSR, and FHRRIKA surfaces after 8 days and also migrated in an isotropic way unlike cells on the bioinactive substrates. Furthermore, the stimulatory effect of 0.75 pmol cm-2 RGD on osteoblast migration pattern could be enhanced when applied in combination with 2.25 pmol cm-2 KRSR.

2006-06, Ferguson, S.J., Broggini, N., Wieland, M., de Wild, Michael, Rupp, F., Geis-Gerstorfer, J., Cochran, D.L., Buser, D.

The functional capacity of osseointegrated dental implants to bear load is largely dependent on the quality of the interface between the bone and implant. Sandblasted and acid-etched (SLA) surfaces have been previously shown to enhance bone apposition. In this study, the SLA has been compared with a chemically modified SLA (modSLA) surface. The increased wettability of the modSLA surface in a protein solution was verified by dynamic contact angle analysis. Using a well-established animal model with a splitmouth experimental design, implant removal torque testing was performed to determine the biomechanical properties of the bone-implant interface. All implants had an identical cylindrical shape with a standard thread configuration. Removal torque testing was performed after 2, 4, and 8 weeks of bone healing (n = 9 animals per healing period, three implants per surface type per animal) to evaluate the interfacial shear strength of each surface type. Results showed that the modSLA surface was more effective in enhancing the interfacial shear strength of implants in comparison with the conventional SLA surface during early stages of bone healing. Removal torque values of the modSLA-surfaced implants were 8-21% higher than those of the SLA implants (p = 0.003). The mean removal torque values for the modSLA implants were 1.485 N m at 2 weeks, 1.709 N m at 4 weeks, and 1.345 N m at 8 weeks; and correspondingly, 1.231 N m, 1.585 N m, and 1.143 N m for the SLA implants. The bone-implant interfacial stiffness calculated from the torque-rotation curve was on average 9-14% higher for the modSLA implants when compared with the SLA implants (p = 0.038). It can be concluded that the modSLA surface achieves a better bone anchorage during early stages of bone healing than the SLA surface; chemical modification of the standard SLA surface likely enhances bone apposition and this has a beneficial effect on the interfacial shear strength.

2002, de Wild, Michael, Berner, Simon, Suzuki, Hitoshi, Ramoino, Luca, Baratoff, Alexis, Jung, Thomas A.

In this review the emerging science of single molecules is discussed from the perspective of nanoscale molecular functions and devices. New methods for the controlled assembly of well-defined mo lecular nanostructures are presented: self assembly and single molecular positioning. The observation and selective modification of conformation, electronics, and molecular mechanics of individual molecules and molecular assemblies by scanning probes are demonstrated. To complement this scientific review, some of the possible consequences and visions for future developments are discussed, as far as they derive from the presented systems. Here, the prospects of nanoscale science to stimulate technological evolution are ex emplified.

2009-01, Schuler, Martin, Kunzler, Tobias P., de Wild, Michael, Sprecher, Christoph M., Trentin, Diana, Brunette, Donald M., Textor, Marcus, Tosatti, Samuele G. P.

The goal of this study was to reproducibly generate samples with complex surface topographies and chemistries identical to a "master surface" and to test their response in cell culture using rat calvarial cells. Negative replicas of dual-type topography were fabricated using dental impression material with half of the surface exhibiting smooth and rough topography, respectively. Positive epoxy resin replicas were cast from the same negative replica eight times consecutively and coated with a 60-nm thin film of titanium dioxide using a vapor deposition technique. Atomic force microscopy, scanning electron microscopy, confocal white light microscopy, and X-ray photoelectron spectroscopy indicated that TiO2-coated epoxy replicas had surface topographical features and surface compositions nearly indistinguishable from the original titanium master surfaces. The described technique showed high reproducibility over at least eight generations of replication using the same negative replica. Rat calvarial osteoblasts proliferated just as well on dual topography surfaces as on single topography surfaces. The advantage of the dual-type substrates is that they facilitate comparison within a single culture dish, thus eliminating dish-to-dish variation as well as saving material, time and costs compared to the usual method of evaluating surfaces in separate dishes.

2004-09-04, Bonifazi, Davide, Spillmann, Hannes, Kiebele, Andreas, de Wild, Michael, Seiler, Paul, Cheng, Fuyong, Güntherodt, Hans‐Joachim, Jung, Thomas, Diederich, François

Plenty of room on top: Unprecedented one- and two-dimensional fullerene patterns were obtained upon evaporation of pristine C60 onto pre-organized porphyrin monolayers on silver surfaces following a bottom-up approach. The arrangement of the fullerene molecules on the patterned layer can be controlled by the porphyrin structure (see scanning tunneling microscopy images).

2006-07, Schuler, Martin, Owen, Gethin Rh., Hamilton, Douglas W., de Wild, Michael, Textor, Marcus, Brunette, Donald M., Tosatti, Samuele G.P.

Surface topography and (bio)chemistry are key factors in determining cell response to an implant. We investigated cell adhesion and spreading patterns of epithelial cells, fibroblasts and osteoblasts on biomimetically modified, smooth and rough titanium surfaces. The RGD bioactive peptide sequence was immobilized via a non-fouling poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) molecular assembly system, which allowed exploitation of specific cell–peptide interactions even in the presence of serum. As control surfaces, bare titanium and bio-inactive surfaces (scrambled RDG and unfunctionalized PLL-g-PEG) were used. Our findings demonstrated that surface topography and chemistry directly influenced the attachment and morphology of all cell types tested. In general, an increase in cell number and more spread cells were observed on bioactive substrates (containing RGD) compared to bio-inactive surfaces. More fibroblasts were present on smooth than on rough topographies, whereas for osteoblasts the opposite tendency was observed. Epithelial cell attachment did not follow any regular pattern. Footprint areas for all cell types were significantly reduced on rough compared to smooth surfaces. Osteoblast attachment and footprint areas increased with increasing RGD-peptide surface density. However, no synergy (interaction) between RGD-peptide surface density and surface topography was observed for osteoblasts neither in terms of attachment nor footprint area.

2002-10-18, de Wild, Michael, Berner, Simon, Suzuki, Hitoshi, Yanagi, Hisao, Schlettwein, Derck, Ivan, Stanislav, Baratoff, Alexis, Guentherodt, Hans-Joachim, Jung, Thomas A.

The stars and stripes: A novel route to highly perfect molecular self-assembly is presented. Depending on the relative surface (Ag(111)) coverage of the two species, subphthalocyanine and C60 (green and yellow in the colored STM image) on an surface, well-ordered intermixed monolayers consisting of 1D chains with 1 nm width or 2D hexagonal patterns are formed. The structural parameters and schematic binary "phase diagram" of this system are deduced from detailed room-temperature STM studies. The most important underlying interactions and the relevant properties of the molecules are discussed qualitatively.