In vitro comparison of mechanical and degradation properties of equivalent absorbable suture materials from two different manufacturers.

OBJECTIVE: To compare the mechanical, knotting, and absorption properties of 3 synthetic absorbable suture materials (polyglactin 910, polydioxanone, poliglecaprone 25) from 2 different manufacturers (Huaiyin Medical Instruments Co. Ltd. and Ethicon Inc.). SAMPLE POPULATION: Suture material samples from the same manufacturing lot for each suture type and manufacturer. METHODS: Part 1: 10 samples of each suture were incubated in bovine serum and tested for ultimate load and stiffness at days 0, 1, 7, 14, 21, and 28. Part 2: 10 knotted samples were similarly evaluated, without incubation. RESULTS: Huaiyin polydioxanone had a greater (P<.001) ultimate load on days 0, 1, and 7; and a consistently greater stiffness for the duration of the study, compared with the Ethicon polydioxanone. Ethicon poliglecaprone 25 had a greater ultimate load on days 0, 1, 7 (P<.001); on day 21 Huaiyin had a greater ultimate load. Ethicon poliglecaprone had greater stiffness on days 0, 1, 7 (P<.001). Ethicon polyglactin 910 had a greater (P<.001) ultimate load at all times and a greater stiffness (P<.001) at days 0, 1, 7, and 14 compared with Huaiyin polyglactin 910. Huaiyin polydioxanone and polyglactin 910 had greater knot breaking strengths than Ethicon equivalents (P<.001). CONCLUSION: Differences in mechanical properties exist between nominally identical suture materials from different manufacturers.

Dse1 may control cross talk between the pheromone and filamentation pathways in yeast.

The filamentous/invasive growth pathway is activated by nutrient limitation in the haploid form of the yeast Saccharomyces cerevisiae, whereas exposure to mating-pheromone causes cells to differentiate into gametes. Although these two pathways respond to very different stimuli and generate very different responses, they utilize many of the same signaling components. This implies the need for robust mechanisms to maintain signal fidelity. Dse1 was identified in an allele-specific suppressor screen for proteins that interact with the pheromone-responsive Gbetagamma, and found to bind both to a Gbetagamma-affinity column, and to the shared MEKK, Ste11. Although overexpression of Dse1 stimulated invasive growth and transcription of both filamentation and mating-specific transcriptional reporters, deletion of DSE1 had no effect on these outputs. In contrast, pheromone hyper-induced transcription of the filamentation reporter in cells lacking Dse1 and in cells expressing a mutant form of Gbeta that exhibits diminished interaction with Dse1. Thus, the interaction of Dse1 with both Gbeta and Ste11 may be designed to control cross talk between the pheromone and filamentation pathways.

Aging enhances a mechanically-induced reduction in tendon strength by an active process involving matrix metalloproteinase activity.

Age-associated and degenerative loss of functional integrity in soft tissues develops from effects of cumulative and subtle changes in their extracellular matrix (ECM). The highly ordered tendon ECM provides the tissue with its tensile strength during loading. As age and exercise collide in the high incidence of tendinopathies, we hypothesized that aged tendons fail due to cumulative damage resulting from a combination of diminished matrix repair and fragmentation of ECM proteins induced by prolonged cyclical loading, and that this is an active cell-mediated process. We developed an equine tendon explant model to examine the effect of age on the influence of prolonged cyclical loading at physiologically relevant strain rates (5% strain, 1 Hz for 24 h) on tissue mechanical properties, loss of ECM protein and matrix metalloproteinase (MMP) expression. We show significantly diminished mechanical strength of cyclically loaded tissue compared to controls (39.7 +/- 12%, P

Regional load bearing of the canine acetabulum.

OBJECTIVE: To determine the load bearing areas of the canine acetabulum. MATERIALS AND METHODS: A kinematic study of four healthy dogs was used to determine the orientation of the femur to the pelvis at mid-stance. Femora and pelves from 10 canine cadavers were loaded with the physiological canine hip reaction force and angle being replicated. Impression material placed within the acetabulum was extruded from areas of load bearing. Digital images before and after loading were used to assess if six different regions of the acetabulum were fully, partially or non-load bearing. RESULTS: All areas of the acetabulum were partially or fully load bearing. The cranial and caudal thirds of the acetabulum were 7.9 and 13.1 times more likely to be fully load bearing than the central third, respectively. There was a significant difference in load bearing between the axial, middle and abaxial thirds of the acetabulum in all tests, with the middle and abaxial thirds 72.4 and 351 times more likely to be fully load bearing than the axial third, respectively. CONCLUSION: The cranial and caudal thirds and the middle and abaxial thirds of the canine acetabulum are fully load bearing. CLINICAL RELEVANCE: The caudal third of the canine acetabulum is loaded and therefore recommendations that fractures in this area be managed conservatively need to be reconsidered.

Noninvasive Raman spectroscopy of human tissue in vivo.

We report the first transcutaneous Raman spectrum of human bone in vivo obtained at skin-safe laser illumination levels. The spectrum of thumb distal phalanx was obtained using spatially offset Raman spectroscopy (SORS), which provides chemically specific information on deep layers of human tissue, well beyond the reach of existing comparative approaches. The spectroscopy is based on collecting Raman spectra away from the point of laser illumination using concentric rings of optical fibers. As a generic analytical tool this approach paves the way for a range of uses including disease diagnosis, noninvasive probing of pharmaceutical products, biofilms, catalysts, paints, and in dermatological applications.

Novel assessment of bone using time-resolved transcutaneous Raman spectroscopy.

UNLABELLED: With fragility fractures increasing as the population ages, there is a need for improved means to estimate risk of fracture. We recorded Raman spectra of both the mineral and organic phases of bone transcutaneously, a technology with potential to enhance bone quality and fracture risk assessment. INTRODUCTION: The current "gold standard" assessment of bone quality is BMD determined by DXA. However, this accounts for only 60-70% of bone strength. X-rays are absorbed by the mineral phase of bone, whereas the organic phase remains essentially invisible; however, bone strength is critically dependent on both phases. We report, for the first time, a Raman spectroscopic technique that analyses both phases of bone beneath unbroken skin by eliminating spectral components of overlying tissues. MATERIALS AND METHODS: We used an 800-nm laser (1-kHz, 1-ps pulses) with a synchronized 4-ps Kerr gate with variable picosecond delay that effectively shuttered out photons from overlying tissues. We measured bone Raman spectra at a point 2 mm above the carpus from two mouse genotypes with extreme differences in bone matrix quality: wildtype and oim/oim (matched for age, sex, and weight). Typical depth was 1.1 mm. We repeated the measurements with overlying tissues removed down to bone. Oim/oim mice produce only homotrimeric collagen, which results in poorly mineralized bone tissue. RESULTS: The main spectral features were present from both bone phases. The spectral bands were in similar ratios when measured through the skin or directly from bone (in both genotypes). The band of the mineral phase (phosphate nu1) was smaller in oim/oim mice when measured directly from bone and through skin. The band associated with a particular vibrational mode of organic phase collagen (CH2 wag) showed a frequency shift between the genotypes. CONCLUSIONS: This novel technique allowed us, for the first time, to make objective transcutaneous spectral measurements of both the mineral and the organic phases of bones and distinguish between normal and unhealthy bone tissue. After further optimization, this technology may help improve fracture risk assessments and open opportunities for screening in anticipation of the predicted increase in fragility fractures.

Kerr-gated time-resolved Raman spectroscopy of equine cortical bone tissue.

Picosecond time-resolved Raman spectroscopy in equine cortical bone tissue is demonstrated. Using 400-nm pulsed laser excitation (1 ps at 1 kHz) it is shown that Kerr cell gating with a 4-ps window provides simultaneously time-resolved rejection of fluorescence and time-resolved Raman scatter enabling depth profiling through tissue. The Raman shifts are the same as those observed by conventional cw Raman spectroscopy using deep-red or near-infrared lasers. The time decay of Raman photons is shown to fit an inverse square root of time function, suggesting propagation by a diffusive mechanism. Using polystyrene behind a bone specimen, it is shown that the 400-nm laser light penetrates at least 0.31 mm below the surface of a fully mineralized bone tissue specimen and generates observable bone Raman scatter (approximately 415 to 430 nm) through most of this depth. These novel results demonstrate great promise for in vivo applications for studying diseased bone tissue, and ways to optimize the setup are discussed.

Regional load bearing of the feline acetabulum.

OBJECTIVE: To test if the caudal acetabulum of the cat is unloaded at mid-stance as has been asserted. MATERIALS AND METHODS: A kinematic study of five healthy cats was performed to ascertain the mid-stance angle of the hip joint, and the orientation of the pelvis and femur. Femora and pelves from 10 feline cadavers were loaded at physiological load at the mid-stance angle. Impression material placed within the acetabulum was extruded from areas of load bearing. Digital images before and after loading were used to assess whether three areas of the acetabulum, cranial, central and caudal, were fully, partially or non-load bearing. RESULTS: There was a significant difference in load bearing in the three regions (p < 0.001, Kruskal-Wallis test), with a significant difference in load bearing between the cranial and central thirds (p < 0.001) and the cranial and caudal thirds (p < 0.001) but no difference between the central and caudal thirds of the acetabulum (Mann-Whitney-U test). CONCLUSIONS: The load bearing areas of the feline acetabula are the caudal and central thirds. CLINICAL RELEVANCE: The caudal acetabulum of the cat is loaded, therefore the recommendations for simple fractures being treated conservatively needs to be reconsidered.

Inter-subject variability effects on the primary stability of a short cementless femoral stem.

This paper is concerned with the primary stability of the Furlong Evolution(®) cementless short stem across a spectrum of patient morphology. A computational tool is developed that automatically selects and positions the most suitable stem from an implant system made of a total of 48 collarless stems to best match a 3D model based on a library of CT femur scans (75 males and 34 females). Finite Element contact models of reconstructed hips, subjected to physiologically-based boundary constraints and peak loads of walking mode, were simulated using a coefficient of friction of 0.4 and an interference-fit of 50 µm. Maximum and average implant micromotions across the subpopulation were predicted to be 100±7 µm and 7±5 µm with ranges [15 µm, 350 µm] and [1 µm, 25 µm], respectively. The computed percentage of implant area with micromotions greater than reported critical values of 50 µm, 100 µm and 150 µm never exceeded 14%, 8% and 7%, respectively. To explore the possible correlations between anatomy and implant performance, response surface models for micromotion metrics were constructed. Detailed morphological analyses were conducted and a clear nonlinear decreasing trend was observed between implant average micromotion and both the metaphyseal canal flare indices and average densities in Gruen zones. The present study demonstrates that the primary stability and tolerance of the short stem to variability in patient anatomy were high, reducing the need for patient stratification. In addition, the developed tool could be utilised to support implant design and planning of femoral reconstructive surgery.

A novel technique for four-point bending of small bone samples with semi-automatic analysis.

The design of this system takes into account the following parameters: the effects of excessive strain; specimen depth and width; span-depth ratio; overhang; rate of loading; measuring displacement from the crosshead position; radius of contact points; and the distance between the contacts. The contacts are radius edges rather than cylinders, although this is not to be recommended for multiple cycles because of wear problems, it does make the system as stiff as possible (allowance is made for this compliance). Equations are presented that allow the surface stress and strain to be calculated for each time point semi-automatically. The combination of stiff contacts and strain equations based on crosshead position not mid-span displacement is novel, this allows rapid analysis with minimum intervention from the user and gives results that are in agreement with those in the literature.

Template-assisted electrohydrodynamic atomization of polycaprolactone for orthopedic patterning applications.

This paper presents the development of the novel deposition of biodegradable polycaprolactone (PCL) polymer patterns on a metallic substrate using a jet spraying technique, template-assisted electrohydrodynamic atomization (TAEA), at ambient temperature. The structure of patterns was controlled by systematically varying the polymer concentration (2-15 wt.%) and the flow rate (1-25 µl min(-1)). Polymer deposition was carried out in the stable cone-jet mode to precisely control the surface structure and morphology. The patterns were studied by optical microscopy, scanning electron microscopy and profilometry, and a high degree of control over the pattern geometry and thickness was achieved by varying the spraying time. The hardness and the effective elastic modulus of the polymer patterns were estimated using nanoindentation. The effect of load, loading rate and the holding time on the hardness and effective elastic modulus was derived. Optimal results were obtained with 5 wt.% PCL in DMAC solution sprayed within the stable cone-jet mode operating window at a flow rate of 15 µl min(-1) for 300 s at 11.1 kV with a working distance of 60mm. Hexagonal patterns were well-defined and repeatable with thickness of ~34 µm. The hardness is 1.6 MPa at a loading rate of 0.1 µN/s and nearly halved when the load rate was increased to 1 µN/s. The effective elastic modulus of ~12 MPa is obtained for a load rate of 0.1 µN/s.

Polarization of the yeast pheromone receptor requires its internalization but not actin-dependent secretion.

In the best understood models of eukaryotic directional sensing, chemotactic cells maintain a uniform distribution of surface receptors even when responding to chemical gradients. The yeast pheromone receptor is also uniformly distributed on the plasma membrane of vegetative cells, but pheromone induces its polarization into "crescents" that cap the future mating projection. Here, we find that in pheromone-treated cells, receptor crescents are visible before detectable polarization of actin cables and that the receptor can polarize in the absence of actin-dependent directed secretion. Receptor internalization, in contrast, seems to be essential for the generation of receptor polarity, and mutations that deregulate this process confer dramatic defects in directional sensing. We also show that pheromone induces the internalization and subsequent polarization of the mating-specific Galpha and Gbeta proteins and that the changes in G protein localization depend on receptor internalization and receptor-Galpha coupling. Our data suggest that the polarization of the receptor and its G protein precedes actin polarization and is important for gradient sensing. We propose that the establishment of receptor/G protein polarity depends on a novel mechanism involving differential internalization and that this serves to amplify the shallow gradient of activated receptor across the cell.

The mating-specific Galpha interacts with a kinesin-14 and regulates pheromone-induced nuclear migration in budding yeast.

As a budding yeast cell elongates toward its mating partner, cytoplasmic microtubules connect the nucleus to the cell cortex at the growth tip. The Kar3 kinesin-like motor protein is then thought to stimulate plus-end depolymerization of these microtubules, thus drawing the nucleus closer to the site where cell fusion and karyogamy will occur. Here, we show that pheromone stimulates a microtubule-independent interaction between Kar3 and the mating-specific Galpha protein Gpa1 and that Gpa1 affects both microtubule orientation and cortical contact. The membrane localization of Gpa1 was found to polarize early in the mating response, at about the same time that the microtubules begin to attach to the incipient growth site. In the absence of Gpa1, microtubules lose contact with the cortex upon shrinking and Kar3 is improperly localized, suggesting that Gpa1 is a cortical anchor for Kar3. We infer that Gpa1 serves as a positional determinant for Kar3-bound microtubule plus ends during mating.

Mechanical testing of human cardiac tissue: some implications for MRI safety.

PURPOSE: The effects of aging on tissue strength and its ability to withstand forces associated with MRI have not been investigated. This study aimed to determine the forces required to cause partial or total detachment of a heart valve prosthesis in patients with age-related degenerative diseases exposed to MRI. METHODS: Eighteen tissue samples excised during routine heart valve replacement surgery were subjected to a suture pull-out test using a tensile materials testing machine. Five preconditioning cycles were applied before commencing the final destructive test. The test was complete when the sample ruptured and the suture was pulled completely free from the tissue. Results were compared with previously calculated magnetically induced forces at 4.7 T. RESULTS: All tissue samples displayed a basic failure pattern. Mean forces required to cause initial yield and total rupture were 4.0 N (+/- 3.3 N) and 4.9 N (+/- 3.6 N), respectively. Significant factors determining initial yield were stenosed calcific tissue (p < .01), calcific degeneration (single pathology) (p < .04) and tissue stiffness (p < .01). Calcific degeneration (p < .03) and tissue stiffness (p < .03) were also significant in determining maximum force required to cause total rupture. CONCLUSION: Specific age-related degenerative cardiac diseases stiffen and strengthen tissue resulting in significant forces being required to pull a suture through valve annulus tissue. These forces are significantly greater than magnetically induced < 4.7 T. Therefore, patients with degenerative valvular diseases are unlikely to be at risk of valve dehiscence during exposure to static magnetic field < or = 4.7 T.

Early experience with a new technique and technology designed for the study of pulsatile cardiopulmonary bypass in the rat.

The benefits of pulsatile flow during the period of cardiopulmonary bypass (CPB) applied during open-heart surgery remains controversial. We have developed a rodent (rat) model of CBP that has been designed to functionally mimic the clinical setting, principally, but not solely, for the study of pulsatile CPB. The successful development of this model centres on the design of the bypass circuitry and the surgical approach employed. The entire circuit is similar to clinical equipment in terms of its construction, configuration, performance, material surface area to blood volume ratio, and priming volume to blood volume ratio. The overall priming volume of the perfusion circuitry is less than 12 ml. Early studies confirm that the pumping technology functions well, gas exchange was adequate at all times, and blood pressure exhibited a normal CPB profile and haemodynanmic response to pulsatile blood flow. We conclude that this is an effective tool for investigating the pathophysiology of pulsatile blood flow during CPB.