FeMn and FeMnAg biodegradable alloys : an in vitro and in vivo investigation

Iron-based biodegradable metal bone graft substitutes are in their infancy but promise to fill bone defects that arise after incidents such as trauma and revision arthroplasty surgery. Before clinical use however, a better understanding of their in vivo biodegradability, potential cytotoxicity and biocompatibility is required. In addition, these implants must ideally be able to resist infection, a complication of any implant surgery. In this study there was significant in vitro cytotoxicity caused by pure Fe, FeMn, FeMn1Ag and FeMn5Ag on both human foetal osteoblast (hFOB) and mouse pre-osteoblast (MC3T3-E1) cell lines. In vivo experiments on the other hand showed no signs of ill-effect on GAERS rats with the implanted FeMn, FeMn1Ag and FeMn5Ag pins being removed largely uncorroded. All Fe-alloys showed anti-bacterial performance but most markedly so in the Ag-containing alloys, there is significant bacterial resistance in vitro.peer-reviewe

Negative Poisson's ratios in tendons: An unexpected mechanical response.

UNLABELLED Tendons are visco-elastic structures that connect bones to muscles and perform the basic function of force transfer to and from the skeleton. They are essential for positioning as well as energy storing when involved in more abrupt movements such as jumping. Unfortunately, they are also prone to damage, and when injuries occur, they may have dilapidating consequences. For instance, there is consensus that injuries of tendons such as Achilles tendinopathies, which are common in athletes, are difficult to treat. Here we show, through in vivo and ex vivo tests, that healthy tendons are highly anisotropic and behave in a very unconventional manner when stretched, and exhibit a negative Poisson's ratio (auxeticity) in some planes when stretched up to 2% along their length, i.e. within their normal range of motion. Furthermore, since the Poisson's ratio is highly dependent on the material's microstructure, which may be lost if tendons are damaged or diseased, this property may provide a suitable diagnostic tool to assess tendon health. STATEMENT OF SIGNIFICANCE We report that human tendons including the Achilles tendons exhibits the very unusual mechanical property of a negative Poisson's ratio (auxetic) meaning that they get fatter rather than thinner when stretched. This report is backed by in vivo and ex vivo experiments we performed which clearly confirm auxeticity in this living material for strains which correspond to those experienced during most normal everyday activities. We also show that this property is not limited to the human Achilles tendon, as it was also found in tendons taken from sheep and pigs. This new information about tendons can form the scientific basis for a test for tendon health as well as enable the design of better tendon prosthesis which could replace damaged tendons

Frequency drift in MR spectroscopy at 3T

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B-0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p &lt; 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.</p

FeMn and FeMnAg biodegradable alloys: An in vitro and in vivo investigation

Iron-based biodegradable metal bone graft substitutes are in their infancy but promise to fill bone defects that arise after incidents such as trauma and revision arthroplasty surgery. Before clinical use however, a better understanding of their in vivo biodegradability, potential cytotoxicity and biocompatibility is required. In addition, these implants must ideally be able to resist infection, a complication of any implant surgery. In this study there was significant in vitro cytotoxicity caused by pure Fe, FeMn, FeMn1Ag and FeMn5Ag on both human foetal osteoblast (hFOB) and mouse pre-osteoblast (MC3T3-E1) cell lines. In vivo experiments on the other hand showed no signs of ill-effect on GAERS rats with the implanted FeMn, FeMn1Ag and FeMn5Ag pins being removed largely uncorroded. All Fe-alloys showed anti-bacterial performance but most markedly so in the Ag-containing alloys, there is significant bacterial resistance in vitro

Negative Poisson's ratios in tendons: An unexpected mechanical response.

UNLABELLED Tendons are visco-elastic structures that connect bones to muscles and perform the basic function of force transfer to and from the skeleton. They are essential for positioning as well as energy storing when involved in more abrupt movements such as jumping. Unfortunately, they are also prone to damage, and when injuries occur, they may have dilapidating consequences. For instance, there is consensus that injuries of tendons such as Achilles tendinopathies, which are common in athletes, are difficult to treat. Here we show, through in vivo and ex vivo tests, that healthy tendons are highly anisotropic and behave in a very unconventional manner when stretched, and exhibit a negative Poisson's ratio (auxeticity) in some planes when stretched up to 2% along their length, i.e. within their normal range of motion. Furthermore, since the Poisson's ratio is highly dependent on the material's microstructure, which may be lost if tendons are damaged or diseased, this property may provide a suitable diagnostic tool to assess tendon health. STATEMENT OF SIGNIFICANCE We report that human tendons including the Achilles tendons exhibits the very unusual mechanical property of a negative Poisson's ratio (auxetic) meaning that they get fatter rather than thinner when stretched. This report is backed by in vivo and ex vivo experiments we performed which clearly confirm auxeticity in this living material for strains which correspond to those experienced during most normal everyday activities. We also show that this property is not limited to the human Achilles tendon, as it was also found in tendons taken from sheep and pigs. This new information about tendons can form the scientific basis for a test for tendon health as well as enable the design of better tendon prosthesis which could replace damaged tendons

FimH Forms Catch Bonds That Are Enhanced by Mechanical Force Due to Allosteric Regulation*S⃞

The bacterial adhesive protein, FimH, is the most common adhesin of Escherichia coli and mediates weak adhesion at low flow but strong adhesion at high flow. There is evidence that this occurs because FimH forms catch bonds, defined as bonds that are strengthened by tensile mechanical force. Here, we applied force to single isolated FimH bonds with an atomic force microscope in order to test this directly. If force was loaded slowly, most of the bonds broke up at low force (<60 piconewtons of rupture force). However, when force was loaded rapidly, all bonds survived until much higher force (140–180 piconewtons of rupture force), behavior that indicates a catch bond. Structural mutations or pretreatment with a monoclonal antibody, both of which allosterically stabilize a high affinity conformation of FimH, cause all bonds to survive until high forces regardless of the rate at which force is applied. Pretreatment of FimH bonds with intermediate force has the same strengthening effect on the bonds. This demonstrates that FimH forms catch bonds and that tensile force induces an allosteric switch to the high affinity, strong binding conformation of the adhesin. The catch bond behavior of FimH, the amount of force needed to regulate FimH, and the allosteric mechanism all provide insight into how bacteria bind and form biofilms in fluid flow. Additionally, these observations may provide a means for designing antiadhesive mechanisms

Regulation of type 1 fimbriae synthesis and biofilm formation by the transcriptional regulator LrhA of Escherichia coli

Type 1 fimbriae of Escherichia coli facilitate attachment to the host mucosa and promote biofilm formation on abiotic surfaces. The transcriptional regulator LrhA, which is known as a repressor of flagellar, motility and chemotaxis genes, regulates biofilm formation and expression of type 1 fimbriae. Whole-genome expression profiling revealed that inactivation of lrhA results in an increased expression of structural components of type 1 fimbriae. In vitro, LrhA bound to the promoter regions of the two fim recombinases (FimB and FimE) that catalyse the inversion of the fimA promoter, and to the invertible element itself. Translational lacZ fusions with these genes and quantification of fimE transcript levels by real-time PCR showed that LrhA influences type 1 fimbrial phase variation, primarily via activation of FimE, which is required for the ON-to-OFF transition of the fim switch. Enhanced type 1 fimbrial expression as a result of lrhA disruption was confirmed by mannose-sensitive agglutination of yeast cells. Biofilm formation was stimulated by lrhA inactivation and completely suppressed upon LrhA overproduction. The effects of LrhA on biofilm formation were exerted via the changed levels of surface molecules, most probably both flagella and type 1 fimbriae. Together, the data show a role for LrhA as a repressor of type 1 fimbrial expression, and thus as a regulator of the initial stages of biofilm development and, presumably, bacterial adherence to epithelial host cells also