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Analysis of general multi-channel planar waveguides.

Using the planar waveguide concept in surface acoustic wave (SAW) technology is often advantageous when the modeling of transversely distributed phenomena is indispensable for an accurate design of SAW devices. This is especially true when complex multi-track structures such as transversely coupled resonator filters (TCRFs) are under consideration where, e.g., transverse velocity and stiffness profiles have to be incorporated in the device simulation. The interdigital transducers (IDTs) and the reflector gratings composing those devices behave as planar waveguides, supporting, in principle, all kinds of modes such as bound, semi-bound, and radiation modes. Therefore, to model these SAW propagation effects, we subdivide the SAW structures in transverse direction into several parallel waveguiding channels (N regions), and take, as the wave-describing quantity, a two-dimensional scalar potential function. By doing so, we obtain a complete set of orthonormal modes into which an arbitrary transverse excitation function can be expanded to study its propagation. The general mode spectrum includes a discrete spectrum of bound modes and continuous spectra of semi-bound and radiation modes. We calculate all types of modes by making use of the stack matrix technique. The present work, which arose from the requirement of creating an efficient mathematical tool for the simulation of TCRFs, provides the complete analysis of general SAW multi-channel structures.

Journal Article↗

Are mineralized tissues open crystal foams reinforced by crosslinked collagen? Some energy arguments.

Which of the elementary components (hydroxyapatite (HA) crystals, collagen, non-collagenous organic matter, water) do significantly contribute to the ultrastructural elastic stiffness magnitude and anisotropy of mineralized tissues; and how, i.e. through which shapes and assemblages (which micromechanical morphology)? We suggest answers to these questions by analyzing stiffness-volume fraction relationships of wet and dry tissue specimens in the framework of strain energy considerations. Radial stiffness values of both isotropic and anisotropic tissues are found to depend linearly to quadratically on only the mineral volume fraction. This suggests the isotropic contribution of HA to the ultrastructural stiffness. An energy-based analysis of the difference between the axial and radial stiffness values of anisotropic, collagen-rich tissues allows us to assess the collagen elasticity contribution, which is found to depend linearly on the extra-collagenous mineral concentration. These results suggest that collagen and hydroxyapatite are the elementary components governing the ultrastructural elastic stiffness magnitude and anisotropy of bone and mineralized tendons. The elastic stiffness of water and non-collagenous organic matter does not play a significant role. As for the morphological issue, we suggest that mineralized tissues are isotropic open crystal foams; and that these foams are reinforced unidirectionally by collagen molecules which are mechanically activated through tight links between these molecules and HA-crystals. The HA crystals are mechanically activated through stretching and bending in long bone tissues, they are predominantly stretched in mineralized tendons, and bent in hyperpycnotic tissues.

Animals↗

A quantitative investigation of structure-function relationships in a tendon fascicle model.

These studies sought to investigate quantitative relationships between the complex composite structure and mechanical properties of tendon. The isolated mouse tail tendon fascicle was chosen as an appropriate model for these so-called "structure-function" investigations. Specifically, collagen fibril diameters and mechanical properties were measured in fascicles from immature (3 week) control, adult (8 week) control, and adult (8 week) MovI3 transgenic mice. Results demonstrated a moderate correlation between mean fibril diameter and fascicle stiffness (r = 0.73, p = 0.001) and maximum load (r = 0.75, p < 0.001), whereas a weak correlation with fascicle modulus (r = 0.39, p = 0.11) and maximum stress (r = 0.48, p = 0.04). An analysis of pooled within-group correlations revealed no strong structure-function trends evidenced at the local or group level, indicating that correlations observed in the general structure-function analyses were due primarily to having three different experimental groups, rather than significant correlations of parameters within the groups.

Animals↗

Viscoelastic and dynamic nonlinear properties of airway smooth muscle tissue: roles of mechanical force and the cytoskeleton.

The viscoelastic and dynamic nonlinear properties of guinea pig tracheal smooth muscle tissues were investigated by measuring the storage (G') and loss (G") moduli using pseudorandom small-amplitude length oscillations between 0.12 and 3.5 Hz superimposed on static strains of either 10 or 20% of initial length. The G" and G' spectra were interpreted using a linear viscoelastic model incorporating damping (G) and stiffness (H), respectively. Both G and H were elevated following an increase in strain from 10 to 20%. There was no change in harmonic distortion (K(d)), an index of dynamic nonlinearity, between 10 and 20% strains. Application of methacholine at 10% strain significantly increased G and H while it decreased K(d). Cytochalasin D, isoproterenol, and HA-1077, a Rho-kinase inhibitor, significantly decreased both G and H but increased K(d). Following cytochalasin D, G, H, and K(d) were all elevated when mean strain increased from 10 to 20%. There were no changes in hysteresivity, G/H, under any condition. We conclude that not all aspects of the viscoelastic properties of tracheal smooth muscle strips are similar to those previously observed in cultured cells. We attribute these differences to the contribution of the extracellular matrix. Additionally, using a network model, we show that the dynamic nonlinear behavior, which has not been observed in cell culture, is associated with the state of the contractile stress and may derive from active polymerization within the cytoskeleton.

Animals↗

Introducing a selectively biodegradable filament wound arterial prosthesis: a short-term implantation study.

This article introduces a new compliant and selectively biodegradable filament wound vascular graft and reports the findings of a short-term implantation study. A basic feature of filament winding is its ability to tailor and better control the mechanical properties of the prosthesis, so that a closer match with the anisotropic properties of native arteries is achieved. The elastomeric vascular grafts comprise poly(ether urethane urea) fibers (Lycra) embedded in a two-component matrix consisting of poly(ether urethane) (Pellethane) and a highly flexible poly(ethylene glycol)/poly(lactic acid) biodegradable segmented copolymer (PELA). Typical tensile modulus values fall in the few megapascals (MPa) range, this being comparable to that of natural arteries. The wound graft exhibits excellent handling and suturability characteristics as well as enhanced burst strength. Furthermore, due to its biodegradable constituent, the prosthesis combines minimal intraoperative blood loss and high healing porosity. The graft displays initially negligible in vitro water permeation, which increases gradually with time. In this short-term study, the prostheses were implanted in the canine carotid, and their biological performance was compared to that of expanded Gore-Tex. The luminal surface of the wound grafts was coated with a thin layer of pseudointima, strongly adhered to the prosthesis surface. Contrasting with the very stiff Gore-Tex grafts, the filament wound prostheses retained their high compliance, being highly pulsatile upon explanation. Histological studies fully corroborated these findings, underscoring the healing properties of these new filament wound vascular prostheses.

Animals↗

Heterogeneous mechanical response of rat knee menisci to thermomechanical stress.

Thermodilatometric, dynamic thermomechanical, and light-microscopic analyses were done on the anterior and posterior regions of the rat knee menisci to correlate regional differences in morphology and extracellular matrix composition with regional mechanical behavior. Following the administration of a general anesthetic, menisci were excised from 12 young female Sprague-Dawley rats. During thermodilatometric and thermomechanical testing, tissue temperature was increased at a constant rate of 3.5 degrees C/min from 30 to 100 degrees C. Light microscopy revealed regional differences in cell density and proteoglycan content. The anterior horn was significantly heavier (greater than 87%) and thicker (greater than 60%) than the posterior region. During thermal analyses, both the anterior and posterior horns decreased in tissue thickness as the temperature increased from 30 to 73 degrees C. After 73 degrees C, however, the posterior horn expanded significantly, whereas the anterior remained in a comparatively contracted state. The rates of linear contraction and expansion of the posterior horn were seven times those of the anterior horn, and the stiffness of the anterior horn was significantly greater than the posterior horn.

Analysis of Variance↗

Viscoelastic modelling of impacted morsellised bone accurately describes unloading behaviour: an experimental study of stiffness moduli and recoil properties.

Morsellised bone impaction grafting is commonly used for revision arthroplasty surgery. Several reports have described the mechanical behaviour of this bone material during impaction and loading. In this study we observed the unloading progress. The loose morsellised bone was modified by particle size, particle size distribution, water and fat content. Bone pellets were constructed using different impaction energies. After impaction, the pellets were loaded statically, after which their swelling was recorded at three unloading levels. We deduced two time-dependent recoil properties, the time resistant number (TRN) and the half total swelling time (HTST), and also one stiffness property, the unloading confined modulus of elasticity (UCME). In impacted morsellised bone, the progress of swelling is visco-elastic. Bone pellets with an even distribution of particle sizes have the most rapid recoil. Those with a high liquid content recoil more slowly, and to a significantly greater extent, than pellets with low liquid content. The recoil of pellets with low liquid content is instantaneous, i.e. unrecordable, and the displacement is significantly less than in other pellet samples.

Animals↗

Intracortical remodeling in adult rat long bones after fatigue loading.

Intracortical remodeling in the adult skeleton removes and replaces areas of compact bone that have sustained microdamage. Although studies have been performed in animal species in which there is an existing baseline of remodeling activity, laboratory rodents have been considered to have limited suitability as models for cortical bone turnover processes because of a lack of haversian remodeling activity. Supraphysiological cyclic axial loading of the ulna in vivo was used to induce bending with consequent fatigue and microdamage. Right ulnae of adult Sprague-Dawley rats were fatigue-loaded to a prefailure stopping point of 30% decrease in ulnae whole bone stiffness. Ten days after the first loading, left ulnae were fatigued in the same way. Ulnae were harvested immediately to allow comparison of the immediate response of the left ulna to the fatigue loads, and the biological response of the right leg to the fatigue challenge. Histomorphometry and confocal microscopy of basic fuchsin-stained bone sections were used to assess intracortical remodeling activity, microdamage, and osteocyte integrity. Bone microdamage (linear microcracks, as well as patches of diffuse basic fuchsin staining within the cortex) occurred in fatigue-loaded ulnar diaphyses. Ten days after fatigue loading, intracortical resorption was activated in ulnar cortices. Intracortical resorption occurred in preferential association with linear-type microcracks, with microcrack number density reduced almost 40% by 10 days after fatigue. Resorption spaces were also consistently observed within areas of the cortex in which no bone matrix damage could be detected. Confocal microscopy studies showed alterations of osteocyte and canalicular integrity around these resorption spaces. These studies reveal that: (1) rat bone undergoes intracortical remodeling in response to high levels of cyclic strain, which induce microdamage in the cortex; and (2) intracortical resorption is associated both with bone microdamage and with regions of altered osteocyte integrity. From these studies, we conclude that rats can initiate haversian remodeling in long bones in response to fatigue, and that osteocyte death or damage may provide one of the stimuli for this process.

Animals↗

Elastic proteins: biological roles and mechanical properties.

The term 'elastic protein' applies to many structural proteins with diverse functions and mechanical properties so there is room for confusion about its meaning. Elastic implies the property of elasticity, or the ability to deform reversibly without loss of energy; so elastic proteins should have high resilience. Another meaning for elastic is 'stretchy', or the ability to be deformed to large strains with little force. Thus, elastic proteins should have low stiffness. The combination of high resilience, large strains and low stiffness is characteristic of rubber-like proteins (e.g. resilin and elastin) that function in the storage of elastic-strain energy. Other elastic proteins play very different roles and have very different properties. Collagen fibres provide exceptional energy storage capacity but are not very stretchy. Mussel byssus threads and spider dragline silks are also elastic proteins because, in spite of their considerable strength and stiffness, they are remarkably stretchy. The combination of strength and extensibility, together with low resilience, gives these materials an impressive resistance to fracture (i.e. toughness), a property that allows mussels to survive crashing waves and spiders to build exquisite aerial filters. Given this range of properties and functions, it is probable that elastic proteins will provide a wealth of chemical structures and elastic mechanisms that can be exploited in novel structural materials through biotechnology.

Animals↗

Bone morphogenetic protein-2 application by a poly(D,L-lactide)-coated interbody cage: in vivo results of a new carrier for growth factors.

OBJECT: Growth factors such as bone morphogenetic protein-2 (BMP-2) have been proven to promote spine fusion and to overcome the disadvantages of an autologous bone graft. The optimum method to deliver such growth factors remains a matter of discussion. The purpose of this study was to determine the safety and efficacy of a new poly(D,L-lactide) (PDLLA) carrier system for BMP-2 and to compare this carrier system with a collagen sponge carrier in a sheep cervical spine interbody fusion model. METHODS: Thirty-two sheep underwent C3-4 discectomy and fusion: Group 1, titanium cage (eight animals); Group 2, titanium cage coated with a PDLLA carrier (eight animals); Group 3, titanium cage coated with a PDLLA carrier including BMP-2 (150 microg) (eight animals); and Group 4, titanium cage combined with a collagen sponge carrier including BMP-2 (150 microg) (eight animals). Blood samples, body weight, and temperature were assessed. Radiographs were obtained pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks. At the same time points, disc space height, intervertebral angle, and lordosis angle were measured. After the sheep were killed 12 weeks postoperatively, flexion-extension radiography was performed to evaluate fusion sites. Quantitative computerized tomography scans were obtained to assess bone mineral density (BMD), bone mineral content (BMC), and bone callus volume (BCV). Biomechanical testing was performed in flexion, extension, axial rotation, and lateral bending. Stiffness, range of motion, neutral, and elastic zone were determined. Histomorphological and -morphometrical analyses were performed, and polychrome sequential labeling was used to determine the timeframe of new bone formation. There were no differences among the groups concerning blood counts, body weight, and temperature. Compared with the noncoated cages, all PDLLA-coated cages showed significantly higher values for BMD of the callus, as well as slightly higher values for BMC, BCV, and the bone volume/total volume ratio. In comparison with the cage-alone group, the BMP-2 groups showed significantly higher values for BMD and biomechanical stiffness. Histomorphological, -morphometrical, and polychrome sequential labeling analyses demonstrated greater progression of callus formation in the BMP-2 groups than in any other group. Compared with BMP-2 delivered using a collagen sponge carrier, BMP-2 application with a PDLLA carrier resulted in a higher BCV and a greater progression of interbody callus formation in the histomorphometrical analysis. CONCLUSIONS: The use of cervical spine interbody fusion cages coated with PDLLA as a delivery system for growth factors was effective. In this 12-week follow-up study, the PDLLA coating showed no adverse effects. The slight but not significant positive effect of the PDLLA carrier on interbody fusion might be a result of the degradation process of the biodegradable carrier. Compared with collagen sponge delivery of BMP-2, the PDLLA-coated interbody cages significantly increased the results of interbody bone matrix formation. In this new combination (implant + PDLLA + growth factor) the cage represents a "real fusion" cage, because it not only serves as a mechanical device for spinal fixation but also as a local drug delivery system.

Animals↗

A review on the mechanical quality of articular cartilage - implications for the diagnosis of osteoarthritis.

The functional behaviour of articular cartilage in diarthrodial joints is determined by its morphological and biomechanical properties. Whereas morphological changes are mainly detectable in the progressed stages of osteoarthritis, biomechanical properties seem to be more sensitive to early degenerative variations since they are determined by the biochemical composition and structural arrangement of the extracellular matrix. The objective of this paper is to review studies focussing on variations in the mechanical compressive properties during the early pre-osteoarthritic stage. The aim is to quantify the requirements to detect the early cartilage degeneration in pre-osteoarthritis based on the mechanical parameters and to create an updated basis for a better understanding of inherent relationships between characteristic parameters in articular cartilage. Correlations between mechanical and biochemical parameters as well as magnetic resonance, ultrasonic, histological and structural parameters were observed. In early osteoarthritis, static moduli decrease below 80% of healthy controls and dynamic moduli below 30% of controls. To identify osteoarthritic changes of articular cartilage based on static or dynamic mechanical parameters in an early stage of the disease progression the accuracy of a mechanical testing method has to be adequate to detect changes of 10% in cartilage stiffness.

Biomechanical Phenomena↗

Measurement of intracellular strain on deformable substrates with texture correlation.

Mechanical stimuli are important factors that regulate cell proliferation, survival, metabolism and motility in a variety of cell types. The relationship between mechanical deformation of the extracellular matrix and intracellular deformation of cellular sub-regions and organelles has not been fully elucidated, but may provide new insight into the mechanisms involved in transducing mechanical stimuli to biological responses. In this study, a novel fluorescence microscopy and image analysis method was applied to examine the hypothesis that mechanical strains are fully transferred from a planar, deformable substrate to cytoplasmic and intranuclear regions within attached cells. Intracellular strains were measured in cells derived from the anulus fibrosus of the intervertebral disc when attached to an elastic silicone membrane that was subjected to tensile stretch. Measurements indicated cytoplasmic strains were similar to those of the underlying substrate, with a strain transfer ratio (STR) of 0.79. In contrast, nuclear strains were much smaller than those of the substrate, with an STR of 0.17. These findings are consistent with previous studies indicating nuclear stiffness is significantly greater than cytoplasmic stiffness, as measured using other methods. This study provides a novel method for the study of cellular mechanics, including a new technique for measuring intranuclear deformations, with evidence of differential magnitudes and patterns of strain transferred from the substrate to cell cytoplasm and nucleus.

Animals↗

Respective role of humoral factors and blood pressure in aortic remodeling of DOCA hypertensive rats.

Hypertension results in increased thickness and stiffness of large artery walls. The goal of our study was to assess the respective roles of humoral factors such as Ang II, endothelin and blood pressure in these aortic modifications. For this purpose, uninephrectomized rats received DOCA and high salt diet, and when hypertension was installed, they were treated for 5 weeks with either a long-acting calcium antagonist, mibefradil (30 mg/kg/day), an ACE inhibitor, enalapril (3 mg/kg/day), or a mixed ETA and ETB endothelin receptor antagonist, bosentan (100 mg/kg/day). A group of hypertensive rats was left untreated and a sham-operated group of normotensive rats was used for control. At the end of treatment, aortic medial thickness and elastin as well as collagen were evaluated by quantitative morphometry. DOCA-salt hypertensive rats exhibited a marked increase in medial thickness associated with no change in absolute content in extracellular matrix. Elastin relative density decreased in DOCA rats. Enalapril had no effect on arterial pressure. Bosentan decreased slightly (by 12 mm Hg), but not significantly, blood pressure. None of these drugs had an effect on medial thickness suggesting that in DOCA hypertensive rats neither Ang II nor endothelin play a significant role in the remodeling of the aorta. In contrast, mibefradil almost normalized arterial pressure, prevented medial hypertrophy and increased elastin density. Further studies are required in order to assess if this effect is directly linked to the blood pressure decrease or to another mechanism related to the calcium antagonistic property of mibefradil.

Angiotensin II↗

Long-term cardiovascular effects of high "osteoprotective" dose levels of 17 beta-estradiol in spontaneously hypertensive rats.

The effects of estrogen replacement therapy in menopausal women are more obvious on bones than on the cardiovascular system. The optimal estrogen dosage may differ in these different parts of the body. In hypertensive rats, low doses have been shown to reduce arterial collagen and stiffness, whereas higher dosages are required for osteoprotection. From 4 to 20 weeks of age, female spontaneously hypertensive rats (SHRs) were divided into four groups: without ovariectomy, under placebo or 17 beta-estradiol (10 micrograms/kg/day), and with ovariectomy under either placebo or 17 beta-estradiol (same dosage). Serial tail systolic blood pressure measurements were performed, and histomorphometry of the thoracic aorta was determined at the end of the study. Under estrogen, blood pressure was unchanged, whereas the aortic wall-to-lumen ratio was increased, particularly in the presence of ovariectomy. The elastin to collagen ratio was significantly decreased, due both to a decrease in elastin and an increase in collagen density, with no change in media thickness. The latter findings were not observed when ovariectomy was performed. Independent of changes in wall stress, high-dose estrogen increases the aortic extracellular matrix in female SHRs. This increase may be reversed in the presence of ovariectomy, suggesting that estrogen was not the only gonadal factor responsible for altered vascular structure and function.

Animals↗

Nuclear rupture in confined cell migration triggers nuclear actin polymerization to limit chromatin leakage.

Upon cell migration in confined space, such as during cancer metastasis, mechanical forces from the extracellular matrix act onto the nucleus leading to nuclear envelope (NE) rupture, chromatin leakage and genomic instability. Here we found that during confined migration, NE rupture triggers dynamic nuclear F-actin formation dependent on the formins DIAPH1 and DIAPH3. We show that DIAPH3 dynamically and transiently relocates to the nucleus upon NE rupture. Interfering with DIAPH1/3 or with nuclear actin polymerization resulted in nuclear instability during confined migration. Notably, nuclear formin activity or actin assembly limit NE rupture-induced chromatin leakage. Similarly, silencing of Ataxia Telangiectasia and Rad3-related protein (ATR) reduced NE rupture-triggered nuclear F-actin assembly and increased chromatin leakage. Consistent with this, ATR promotes the phosphorylation of DIAPH3 at S1072 adjacent to its autoregulatory domain to promote nuclear actin polymerization. Using atomic force microscopy, we found that nuclear actin assembly or nuclear DIAPH3 activity promotes nuclear stiffness in an ATR-dependent manner. Thus, our study identifies an ATR-formin module that regulates nuclear mechanical properties through induction of intranuclear actin scaffolding.

Formins↗

[Patophysiology of osteoarthritis].

Osteoarthritis (OA) is slowly evolving disease of articular cartilage degneration characterized by the gradual development of joint pain, stiffness and limitation of motion. Musculoskeletal diseases are growing medical, social and economic problem. OA among them takes leading position with incidence, morbidity and poor quality of life. In the last few decades there is increasing interest for better knowledge of all aspects of the disease, especially with regard to its pathophysiology. This paper focuses the recent aspects of patophysiology of OA, because knowledge of patophysiology means the challenge for the clinician to find a way to best prevent articular cartilage degradation, preserve joint function, treat joint pain and treat concurrent inflammation.

Cytokines↗

Mechanical functioning of peripheral nerves: linkage with the "mushrooming" effect.

Biomechanical properties of nerve have been studied extensively. All neural matrix tissues have been suggested to be the main load-bearing component. Based on the ultrastructure it has been proposed that the architecture of the epineurium allows some degree of extensibility of the nerve. A role of the perineurium could be to withstand the positive endoneurial pressure. The hypothesis is that the mechanical behaviour of nerves is dependent on an interaction between the core swelling pressure and restraint by the outer sheath. Loss of this balance will alter that behaviour. To test this, rat sciatic nerves were subjected to mechanical loading at in vivo and ex vivo tension. Retraction of nerve segments was measured after excision and after incubation at 37 degrees C or freezing. Swelling properties of the nerve were measured by immersion in water or PBS (phosphate buffer solution) with intact or opened epineurium. Results showed a significant decrease in strength and stiffness with an increase in strain of the nerve after excision, compared to in vivo. Retraction was on average 11%. Freezing or incubation at 37 degrees C did not alter retraction. The swelling properties of the nerve demonstrated a significant difference between intact and opened epineurium and similar results for water and PBS, indicating that epineurium is a constraint and that the nerves are underhydrated. The proposed model for the intact nerve is a continuous connective tissue tube surrounding and constraining an inner swelling pressure of the neural core. Loss of integrity of the nerve has detrimental effects on its biomechanical properties.

Animals↗

Muscle cell peeling from micropatterned collagen: direct probing of focal and molecular properties of matrix adhesion.

To quantitatively elucidate attributes of myocyte-matrix adhesion, muscle cells were controllably peeled from narrow strips of collagen-coated glass. Initial growth of primary quail myoblasts on collagen strips was followed by cell alignment, elongation and end-on fusion between neighbors. This geometric influence on differentiation minimized lateral cell contact and cell branching, enabling detailed study of myocyte-matrix adhesion. A micropipette was used to pull back one end of a quasi-cylindrical cell while observing in detail the non-equilibrium detachment process. Peeling velocities fluctuated as focal roughness, microm in scale, was encountered along the detachment front. Nonetheless, mean peeling velocity ( microm/second) generally increased with detachment force (nN), consistent with forced disruption of adhesion bonds. Immunofluorescence of beta1-integrins correlated with the focal roughness and appeared to be clustered in axially extended focal contacts. In addition, the peeling forces and rates were found to be moderately well described by a dynamical peeling model for receptor-based adhesion (Dembo, M., Torney, D. C., Saxman, K. and Hammer, D. (1988). Proc. R. Soc. Lond. B 234, 55-83). Estimates were thereby obtained for the spontaneous, molecular off-rate (kooff, (less than or equal to)10/seconds) and the receptor complex stiffness (kappa, approx. 10(-5)-10(-6) N/m) of adherent myocytes. Interestingly, the local stiffness is within the range of flexible proteins of the spectrin superfamily. The overall approach lends itself to elucidating the developing function of other structural and adhesive components of cells, particularly skeletal muscle cells with specialized components, such as the spectrin-homolog dystrophin and its membrane-linked receptor dystroglycan.

Animals↗