The Role of Surface Roughness for Implant Incorporation in Bone

A careful topographical characterization is important for reliable interpretation of the role of implant surface roughness in bone incorporation. In this paper, the currently available measuring instruments and evaluation techniques are described and discussed first, than literature on the role of surface roughness for cell and bone tissue reactions in vitro and, with special emphasis, the in vivo studies are reviewed. Finally, the results from a series of the authors own animal studies evaluating screw-shaped implants with different surface roughnesses are summarized. The results demonstrated firmer bone fixation for blasted implants than for turned ones. A blasted surface with an average height deviation (Sa) of 1.5 µm had a better bone fixation than a blasted surface with an average height deviation (Sa) of 1.2 µm. A tendency towards more bone in contact and higher removal torques was found for blasted implant surfaces with an average height deviation (Sa) of 1.2 µm than with blasted surfaces with 2.2 µm average height deviation (Sa)

Osseointegration effects of local release of strontium ranelate from implant surfaces in rats

BACKGROUND: Numerous studies have reported the beneficial effects of strontium on bone growth, particularly by stimulating osteoblast proliferation and differentiation. Thus, strontium release around implants has been suggested as one possible strategy to enhance implant osseointegration. AIM: This study aimed to evaluate whether the local release of strontium ranelate (Sr-ranelate) from implants coated with mesoporous titania could improve bone formation around implants in an animal model. MATERIALS AND METHODS: Mesoporous titania (MT) thin coatings were formed utilizing the evaporation induced self-assembly (EISA) method using Pluronic (P123) with or without the addition of poly propylene glycol (PPG) to create materials with two different pore sizes. The MT was deposited on disks and mini-screws, both made of cp Ti grade IV. Scanning electron microscopy (SEM) was performed to characterize the MT using a Leo Ultra55 FEG instrument (Zeiss, Oberkochen, Germany). The MT was loaded with Sr-ranelate using soaking and the drug uptake and release kinetics to and from the surfaces were evaluated using quartz crystal microbalance with dissipation monitoring (QCM-D) utilizing a Q-sense E4 instrument. For the in vivo experiment, 24 adult rats were analyzed at two time points of implant healing (2 and 6 weeks). Titanium implants shaped as mini screws were coated with MT films and divided into two groups; supplied with Sr-ranelate (test group) and without Sr-ranelate (control group). Four implants (both test and control) were inserted in the tibia of each rat. The in vivo study was evaluated using histomorphometric analyses of the implant/bone interphase using optical microscopy. RESULTS: SEM images showed the successful formation of evenly distributed MT films covering the entire surface with pore sizes of 6 and 7.2 nm, respectively. The QCM-D analysis revealed an absorption of 3300 ng/cm2 of Sr-ranelate on the 7.2 nm MT, which was about 3 times more than the observed amount on the 6 nm MT (1200 ng/cm2). Both groups showed sustained release of Sr-ranelate from MT coated disks. The histomorphometric analysis revealed no significant differences in bone implant contact (BIC) and bone area (BA) between the implants with Sr-ranelate and implants in the control groups after 2 and 6 weeks of healing (BIC with a p-value of 0.43 after 2 weeks and 0.172 after 6 weeks; BA with a p-value of 0.503 after 2 weeks, and 0.088 after 6 weeks). The mean BIC and BA values within the same group showed significant increase among all groups between 2 and 6 weeks. CONCLUSION: This study could not confirm any positive effects of Sr-ranelate on implant osseointegration

Identification of structural features in chemicals associated with cancer drug response : a systematic data-driven analysis

Peer reviewe

Effects of an Unusual Poison Identify a Lifespan Role for Topoisomerase 2 in Saccharomyces Cerevisiae

A progressive loss of genome maintenance has been implicated as both a cause and consequence of aging. Here we present evidence supporting the hypothesis that an age-associated decay in genome maintenance promotes aging in Saccharomyces cerevisiae (yeast) due to an inability to sense or repair DNA damage by topoisomerase 2 (yTop2). We describe the characterization of LS1, identified in a high throughput screen for small molecules that shorten the replicative lifespan of yeast. LS1 accelerates aging without affecting proliferative growth or viability. Genetic and biochemical criteria reveal LS1 to be a weak Top2 poison. Top2 poisons induce the accumulation of covalent Top2-linked DNA double strand breaks that, if left unrepaired, lead to genome instability and death. LS1 is toxic to cells deficient in homologous recombination, suggesting that the damage it induces is normally mitigated by genome maintenance systems. The essential roles of yTop2 in proliferating cells may come with a fitness trade-off in older cells that are less able to sense or repair yTop2-mediated DNA damage. Consistent with this idea, cells live longer when yTop2 expression levels are reduced. These results identify intrinsic yTop2-mediated DNA damage as a potentially manageable cause of aging

Integrin signaling to the actin cytoskeleton

Integrin engagement stimulates the activity of numerous signaling molecules, including the Rho family of GTPases, tyrosine phosphatases, cAMP-dependent protein kinase and protein kinase C, and stimulates production of PtdIns(4,5)P2. Integrins promote actin assembly via the recruitment of molecules that directly activate the actin polymerization machinery or physically link it to sites of cell adhesion

In vitro Candida albicans biofilm formation on different titanium surface topographies

Objectives To investigate if differences in titanium implant surface topography influence Candida albicans biofilm formation. Materials and Methods Titanium discs were prepared and characterized using a profilometer: Group A (R a 0.15 µm, smooth), Group B (R a 0.64 µm, minimally rough) and Group C (R a 1.3 µm, moderately rough). Contact angle and surface free energy (SFE) were determined for each group. Non-preconditioned titanium discs were incubated with C. albicans for 24 h. In additional experiments, the titanium discs were initially coated with human saliva, bovine serum albumin or phosphate-buffered saline for 2 h before incubation with C. albicans for 24 h. The amount of fungal biofilm formation was quantified using a colorimetric assay. Results C. albicans biofilm formation was significantly lower (p < 0.05) on the minimally rough titanium surface compared to smooth and moderately rough surfaces. The titanium surface displaying the lowest SFE (Group B) was associated with significantly lower (p < 0.05) C. albicans biofilm formation than the other two groups. Salivary coating resulted in greater adherence of C. albicans with increased surface roughness. Conclusions The minimally rough titanium discs displayed lowest SFE compared to smooth and moderately rough surfaces and showed the least C. albicans biofilm formation. This study demonstrated that C. albicans biofilm formation increased in a SFE-dependent manner. These findings suggest that SFE might be a more explanatory factor for C. albicans biofilm formation on titanium surfaces than roughness. The presence of a pellicle coating may negate the impact of SFE on C. albicans biofilm formation on titanium surfaces

A normalized drug response metric improves accuracy and consistency of anticancer drug sensitivity quantification in cell-based screening

Accurate quantification of drug effects is crucial for identifying pharmaceutically actionable cancer vulnerabilities. Current cell viability-based measurements often lead to biased response estimates due to varying growth rates and experimental artifacts that explain part of the inconsistency in high-throughput screening results. We developed an improved drug scoring model, normalized drug response (NDR), which makes use of both positive and negative control conditions to account for differences in cell growth rates, and experimental noise to better characterize drug-induced effects. We demonstrate an improved consistency and accuracy of NDR compared to existing metrics in assessing drug responses of cancer cells in various culture models and experimental setups. Notably, NDR reliably captures both toxicity and viability responses, and differentiates a wider spectrum of drug behavior, including lethal, growth-inhibitory and growth-stimulatory modes, based on a single viability readout. The method will therefore substantially reduce the time and resources required in cell-based drug sensitivity screening.Abhishekh Gupta et al. present a normalized drug response (NDR) metric for accurate quantification of drug sensitivity in cell-based high-throughput assays. They show that NDR captures both toxicity and viability responses to improve drug effect classification over existing methods