Biomedical subjects

P J Prendergast

Publications and source records attributed to P J Prendergast.

At least 19 recordsLinked to original sources

PubMed2006

Random-walk models of cell dispersal included in mechanobiological simulations of tissue differentiation.

Computational models have shown that biophysical stimuli can be correlated with observed patterns of tissue differentiation, and simulations have been performed that predict the time course of tissue differentiation in, for example, long bone fracture healing. Some simulations have used a diffusion model to simulate the migration and proliferation of cells with the differentiating tissue. However, despite the convenience of the diffusion model, diffusion is not the mechanism of cell dispersal: cells disperse by crawling or proliferation, or are transported in a moving fluid. In this paper, a random-walk model (i.e., a stochastic model), with and without a preferred direction, is studied as an approach to simulate cell proliferation/migration in differentiating tissues and it is compared with the diffusion model. A simulation of tissue differentiation of gap tissue in a two-dimensional model of a bone/implant interface was performed to demonstrate the differences between diffusion vs. random walk with a preferred direction. Results of diffusion and random-walk models are similar with respect to the change in the stiffness of the gap tissue but rather different results are obtained regarding tissue patterning in the differentiating tissues; the diffusion approach predicted continuous patterns of tissue differentiation whereas the random-walk model showed a more discontinuous pattern-histological results are not available that can unequivocally establish which is most similar to experimental observation. Comparing isotropic to anisotropic random walk (preferred direction of proliferation and cell migration), a more rapid reduction of the relative displacement between implant and bone is predicted. In conclusion, we have shown how random-walk models of cell dispersal and proliferation can be implemented, and shown where differences between them exist. Further study of the random-walk model is warranted, given the importance of cell seeding and cell dispersal/proliferation in many mechanobiological problems.

Animals↗

PubMed2006

A collagen-based interface construct for the assessment of cell-dependent mechanical integration of tissue surfaces.

The interface between any newly engineered tissue and pre-existing tissue is of great importance to tissue engineering; however, this process has so far been largely ignored, with few reports regarding the mechanical strength of newly integrated connective tissues surfaces. A new model system has been developed to generate a well-defined interface between two collagen lattices: one pre-contracted by resident fibroblasts and the other a cell-free wrapping gel. This construct can be cultured for prolonged periods (>2 weeks) and can also be fitted onto a mechanical testing system to measure the interface adhesive strength at the end of the culture time. Interface adhesive strength shows a six-fold increase after 1 week in culture, compared with the time-zero baseline. Observations of cell migration across the interface suggest that cell translocation in the three-dimensional matrix might play an important role in the integration process. In this new controlled geometry, normal and shear stresses at the interface can be analysed by finite element modelling and the areas at which debonding starts can be defined. The current experimental design permits solid multiple (homogeneous or heterogeneous) interface formation in vitro with a well-defined geometry and the possibility of measuring mechanical linkage. This design should enable many other factors affecting cell-driven interface strengthening to be investigated.

Animals↗

PubMed2006

Strength of cancellous bone trabecular tissue from normal, ovariectomized and drug-treated rats over the course of ageing.

Hormone therapy (HT) drugs and bisphosphonates prevent osteoporosis by inhibiting osteoclastic bone resorption. However, the effects of osteoporosis and anti-resorptive drugs on the mechanical behavior of the bone tissue constituting individual trabeculae have not yet been quantified. In this study, we test the hypothesis that the mechanical properties of bone trabecular tissue will differ for normal, ovariectomized and drug-treated rat bones over the course of ageing. Microtensile testing is carried on individual trabeculae from tibial bone of ovariectomized (OVX) rats, OVX rats treated with tibolone and placebo-treated controls. The method developed minimizes errors due to misalignment and stress concentrations at the grips. The local mineralization of single trabeculae is compared using micro-CT images calibrated for bone mineral content assessment. Our results indicate that ovariectomy in rats increases the stiffness, yield strength, yield strain and ultimate stress of the mineralized tissue constituting trabecular bone relative to normal; we found significant differences (P < 0.05) at 14, 34 and 54 weeks of treatment. These increases are complemented by a significant increase in the mineral content at the tissue level, although overall bone mineral density and mass are reduced. With drug treatment, the properties remain at, or slightly below, the placebo-treated controls levels for 54 weeks. The higher bone strength in the OVX group may cause the trabecular architecture to adapt as seen during osteopenia/osteoporosis, or alternately it may compensate for loss of trabecular architecture. These findings suggest that, in addition to the effects of osteoporosis and subsequent treatment on bone architecture, there are also more subtle processes ongoing to alter bone strength at the tissue level.

Aging↗

PubMed2006

Influence of strong static magnetic fields on primary cortical neurons.

Intense uniform magnetic fields, such as those used in magnetic resonance imaging (MRI), are thought to exert little influence at the cellular level. Here we report modifications of the signaling cascades in rat cortical neurons cultured for 1 h in magnetic fields of up to 5 Tesla. The activation of c-Jun N-terminal kinase (JNK) increases monotonically with field strength, with a maximal activation of approximately 10% at 5 T, whereas the activation of extra cellular-regulated kinase (ERK) shows a maximum at 0.75 T ( approximately 10%). Since ERK is involved in cellular differentiation, these results indicate a magnetic induction of the signaling events associated with differentiation. However, the cells respond to further increases in field strength by evoking a stress response, since JNK is a stress-activated protein kinase. Three possible mechanisms are discussed and of these, the most plausible is magnetic field induced change in the membrane rest potential, a microscale magnetohydrodynamic effect. This mechanism most likely involves the activation of voltage dependent Ca(2+) channel opening; since intracellular Ca(2+) concentration was also found to be modified by the static magnetic field.

Animals↗

PubMed2006

Stress-concentrating effect of resorption lacunae in trabecular bone.

Analyses of the distributions of stress and strain within individual bone trabeculae have not yet been reported. In this study, four trabeculae were imaged and finite elements models were generated in an attempt to quantify the variability of stress/strain in real trabeculae. In three of these trabeculae, cavities were identified with depths comparable to values reported for resorption lacunae ( approximately 50 microm)-although we cannot be certain, it is most probable that they are indeed resorption lacunae. A tensile load was applied to each trabeculum to simulate physiological loading and to ensure that bending was minimized. The force carried by each trabecula was calculated from this value using the average cross sectional area of each trabecula. The analyses predict that very high stresses (>100 MPa) existed within bone trabecular tissue. Stress and strain distributions were highly heterogeneous in all cases, more so in trabeculae with the presumptive resorption lacunae where at least 30% of the tissue had a strain greater than 4000 micoepsilon in all cases. Stresses were elevated at the pit of the lacunae, and peak stress concentrations were located in the longitudinal direction ahead of the lacunae. Given these high strains, we suggest that microdamage is inevitable around resorption lacunae in trabecular bone, and may cause the bone multicellular unit to proceed to resorb a packet of bone in the trabeculum rather than just resorb whatever localized area was initially targeted.

Animals↗

PubMed2005

Bone ingrowth simulation for a concept glenoid component design.

Glenoid component loosening is the major problem of total shoulder arthroplasty. It is possible that uncemented component may be able to achieve superior fixation relative to cemented component. One option for uncemented glenoid is to use porous tantalum backing. Bone ingrowth into the porous backing requires a degree of stability to be achieved directly post-operatively. This paper investigates the feasibility of bone ingrowth with respect to the influence of primary fixation, elastic properties of the backing and friction at the bone prosthesis interface. Finite element models of three glenoid components with different primary fixation configurations are created. Bone ingrowth into the porous backing is modelled based on the magnitude of the relative interface micromotions and mechanoregulation of the mesenchymal stem cells that migrated via the bonded part of the interface. Primary fixation had the most influence on bone ingrowth. The simulation showed that its major role was not to firmly interlock the prosthesis, but rather provide such a distribution of load, that would result in reduction of the peak interface micromotions. Should primary fixation be provided, friction has a secondary importance with respect to bone ingrowth while the influence of stiffness was counter intuitive: a less stiff backing material inhibits bone ingrowth by higher interface micromotions and stimulation of fibrous tissue formation within the backing.

Cell Differentiation↗

PubMed2005

Cardiovascular stent design and vessel stresses: a finite element analysis.

Intravascular stents of various designs are currently in use to restore patency in atherosclerotic coronary arteries and it has been found that different stents have different in-stent restenosis rates. It has been hypothesized that the level of vascular injury caused to a vessel by a stent determines the level of restenosis. Computational studies may be used to investigate the mechanical behaviour of stents and to determine the biomechanical interaction between the stent and the artery in a stenting procedure. In this paper, we test the hypothesis that two different stent designs will provoke different levels of stress within an atherosclerotic artery and hence cause different levels of vascular injury. The stents analysed using the finite-element method were the S7 (Medtronic AVE) and the NIR (Boston Scientific) stent designs. An analysis of the arterial wall stresses in the stented arteries indicates that the modular S7 stent design causes lower stress to an atherosclerotic vessel with a localized stenotic lesion compared to the slotted tube NIR design. These results correlate with observed clinical restenosis rates, which have found higher restenosis rates in the NIR compared with the S7 stent design. Therefore, the testing methodology outlined here is proposed as a pre-clinical testing tool, which could be used to compare and contrast existing stent designs and to develop novel stent designs.

Blood Vessel Prosthesis↗

PubMed2004

Mechano-regulation of stem cell differentiation and tissue regeneration in osteochondral defects.

Cartilage defects that penetrate the subchondral bone can undergo spontaneous repair through the formation of a fibrous or cartilaginous tissue mediated primarily by mesenchymal stem cells from the bone marrow. This tissue is biomechanically inferior to normal articular cartilage, and is often observed to degrade over time. Whether or not biomechanical factors control the type and quality of the repair tissue, and its subsequent degradation, have yet to be elucidated. In this paper, we hypothesise a relationship between the mechanical environment of mesenchymal stem cells and their subsequent dispersal, proliferation, differentiation and death. The mechano-regulation stimulus is hypothesised to be a function of strain and fluid flow; these quantities are calculated using biphasic poroelastic finite element analysis. A finite element model of an osteochondral defect in the knee was created, and used to simulate the spontaneous repair process. The model predicts bone formation through both endochondral and direct intramembranous ossification in the base of the defect, cartilage formation in the centre of the defect and fibrous tissue formation superficially. Greater amounts of fibrous tissue formation are predicted as the size of the defect is increased. Large strains are predicted within the fibrous tissue at the articular surface, resulting in significant cell apoptosis. This result leads to the conclusion that repair tissue degradation is initiated in the fibrous tissue that forms at the articular surface. The success of the mechano-regulation model in predicting many of the cellular events that occur during osteochondral defect healing suggest that in the future it could be used as a tool for optimising scaffolds for tissue engineering.

Animals↗

PubMed2004

A three-dimensional finite element model of an adherent eukaryotic cell.

Mechanical stimulation is known to cause alterations in the behaviour of cells adhering to a substrate. The mechanisms by which forces are transduced into biological responses within the cell remain largely unknown. Since cellular deformation is likely involved, further understanding of the biomechanical origins of alterations in cellular response can be aided by the use of computational models in describing cellular structural behaviour and in determining cellular deformation due to imposed loads of various magnitudes. In this paper, a finite element modelling approach that can describe the biomechanical behaviour of adherent eukaryotic cells is presented. It fuses two previous modelling approaches by incorporating, in an idealised geometry, all cellular components considered structurally significant, i.e. prestressed cytoskeleton, cytoplasm, nucleus and membrane components. The aim is to determine if we can use this model to describe the non-linear structural behaviour of an adherent cell and to determine the contribution of the various cellular components to cellular stability. Results obtained by applying forces (in the picoNewton range) to the model membrane nodes suggest a key role for the cytoskeleton in determining cellular stiffness. The model captures non-linear structural behaviours such as strain hardening and prestress effects (in the region of receptor sites), and variable compliance along the cell surface. The role of the cytoskeleton in stiffening a cell during the process of cell spreading is investigated by applying forces to five increasingly spread cell geometries. Parameter studies reveal that material properties of the cytoplasm (elasticity and compressibility) also have a large influence on cellular stiffness. The computational model of a single cell developed here is proposed as one that is sufficiently complex to capture the non-linear behaviours of the cell response to forces whilst not being so complex that the parameters cannot be specified. The model could be very useful in computing cellular structural behaviour in response to various in vitro mechanical stimuli (e.g. fluid flow, substrate strain), or for use in algorithms that attempt to simulate mechanobiological processes.

Actin Cytoskeleton↗

PubMed2004

Effect of a degraded core on the mechanical behaviour of tissue-engineered cartilage constructs: a poro-elastic finite element analysis.

The structure and functionality of tissue-engineered cartilage is determined by the tissue culture conditions and mechanical conditioning during growth. The quality of tissue-engineered cartilage can be evaluated using tests such as the confined compression test. Tissue-engineered cartilage constructs usually consist of an outer layer of cartilage and an inner core of either undeveloped cartilage or degrading scaffold material. A biphasic poro-elastic finite element model was used to demonstrate how such a core influences the reaction force-time curve obtained from a confined compression test. The finite element model predicted that higher volumes of degraded scaffold in the inner core would reduce the aggregate modulus calculated from the confined compression test and raised the estimate of tissue permeability. The predicted aggregate modulus reduced from 0.135 MPa, for a homogenous construct, to 0.068 MPa, for a construct that was only 70% cartilaginous. It was found that biphasic poro-elastic finite modelling should be used in preference to a one-dimensional model that assumed homogeneity in estimating the properties of tissue-engineered cartilage.

Biomechanical Phenomena↗

PubMed2004

Endothelial cell alignment on cyclically-stretched silicone surfaces.

Endothelial cells at the interface between the bloodstream and the vessel wall are continuously subjected to mechanical stimulation in vivo, and it widely recognised that such stimulation plays an important role in cardiovascular physiology. Cell deformation is induced by mechanical forces such as cyclic stretch, fluid shear stress, and transmural pressure. Although much of the work in this field has dealt with the effect of fluid shear stress, very little is known about how cyclic forces modulate and alter the morphology of single endothelial cells, and thereafter, how they effect the confluent layer of endothelial cells lining the vessel wall. The aim of this study is to investigate the response of endothelial cells when subjected to substrate deformation of similar magnitude to those experienced in vivo. Human umbilical vein endothelial cells (HUVEC) were cultured on plasma-treated silicone strips and uni-axially cyclically stretched using a custom made mechanical device. Results showed that endothelial cells subject to 10% deformation for as little as 4 h reoriented perpendicular to the stretch direction. In addition, although no integrin coating was applied to the substrate, it was found that plasma-treated silicone provided a cell adhesion substrate comparable to the commonly used collagen type I. Thus the results show that the stretch stimulus alone affects the morphology of endothelial cells. Further studies are required to establish the relative importance of substrate strain vs. fluid flow stimuli.

Biocompatible Materials↗

PubMed2004

Elastic behavior of porcine coronary artery tissue under uniaxial and equibiaxial tension.

The aim of this study was to characterize the nonlinear anisotropic elastic behavior of healthy porcine coronary arteries under uniaxial and equibiaxial tension. Porcine coronary tissue was chosen for its availability and similarity to human arterial tissue. A biaxial test device previously used to test human femoral arterial tissue samples (Prendergast, P. J., C. Lally, S. Daly, A. J. Reid, T. C. Lee, D. Quinn, and F. Dolan. ASME J. Biomech. Eng., Vol. 125, pp. 692-699, 2003) was further developed to test porcine coronary tissue specimens. The device applies an equal force to the four sides of a square specimen and therefore creates a biaxial stretch that demonstrates the anisotropy of arterial tissue. The nonlinear elastic behavior was marked in both uniaxial and biaxial tests. The tissue demonstrated higher stiffness in the circumferential direction in four out of eight cases subjected to biaxial tension. Even though anisotropy is demonstrated it is proposed that an isotropic hyperelastic model may adequately represent the properties of an artery, provided that an axial stretch is applied to the vessel to simulate the in vivo longitudinal tethering on the vessel. Isotropic hyperelastic models based on the Mooney-Rivlin constitutive equation were derived from the test data by averaging the longitudinal and circumferential equibiaxial data. Three different hyperelastic models were established to represent the test specimens that exhibited a high stiffness, an average stiffness, and a low stiffness response; these three models allow the analyst to account for the variability in the arterial tissue mechanical properties. These models, which take account of the nonlinear elastic behavior of coronary tissue, may be implemented in finite element models and used to carry out preclinical tests of intravascular devices. The errors associated with the hyperelastic models when fitting to both the uniaxial and equibiaxial data for the low stiffness, average stiffness, and high stiffness models were found to be 0.836, 5.206, and 2.980, respectively.

Animals↗

PubMed2003

Mechanical simulation of muscle loading on the proximal femur: analysis of cemented femoral component migration with and without muscle loading.

OBJECTIVE: This study examines the effect of including muscle forces in fatigue tests of cemented total hip arthroplasty reconstructions. DESIGN: An experimental device capable of applying the joint reaction force, the abductor force, the vastus lateralis force, and the tensor fasciae latae force to the implanted femur is described. BACKGROUND: Current in vitro fatigue tests of cemented total hip arthroplasty reconstructions do not apply physiological muscle loads. Experimental and numerical studies report significant differences in stresses obtained in the cement mantle depending on the loads applied. The differing stresses may alter the outcome of an in vitro test. METHODS: Ten femoral components were reproducibly implanted into proximal composite femurs. Five of these femoral components were tested using a loadprofile which included muscle loading, five were tested without muscle loading. The migration of each femoral component was monitored continuously during dynamic fatigue tests. RESULTS: Clinically comparable migration amounts were found for both sets of femoral components, with the femoral components tested with muscle loading experiencing lower mean migration, lower mean inducible displacement, and less experimental scatter. CONCLUSIONS: The inclusion of muscle forces seems to stabilise the femoral component during the test. In vitro fatigue tests of cemented total hip arthroplasty reconstructions should include muscle loading to provide increased confidence in the results obtained. RELEVANCE: This study examines how the migration of cemented femoral hip prostheses is influenced by muscle forces. Hip prostheses are one of the few medical devices for which pre-clinical testing protocols have emerged, and this study ascertains whether or not the inclusion of muscle forces is necessary for pre-clinical tests. The conclusion that muscle loading should be included, and that it is important for the development of a new generation of standardised tests to provide enhanced patient protection against functionally poor prostheses.

Arthroplasty, Replacement, Hip↗

PubMed2003

The relationship between cement fatigue damage and implant surface finish in proximal femoral prostheses.

The majority of cemented femoral hip replacements fail as a consequence of loosening. One design feature that may affect loosening rates is implant surface finish. To determine whether or not surface finish effects fatigue damage accumulation in a bone cement mantle, we developed an experimental model of the implanted proximal femur that allows visualisation of damage growth in the cement layer. Five matte surface and five polished surface stems were tested. Pre-load damage and damage after two million cycles was measured. Levels of pre-load (shrinkage) damage were the same for both matte and polished stems; furthermore damage for matte vs. polished stems was not significantly different after two million cycles. This was due to the large variability in damage accumulation rates. Finite element analysis showed that the stress is higher for the polished (assumed debonded) stem, and therefore we must conclude that either the magnitude of the stress increase is not enough to appreciably increase the damage accumulation rate or, alternatively, the polished stem does not debond immediately from the cement. Significantly (P=0.05) more damage was initiated in the lateral cement compared to the medial cement for both kinds of surface finish. It was concluded that, despite the higher cement stresses with debonded stems, polished prostheses do not provoke the damage accumulation failure scenario.

Arthroplasty, Replacement, Hip↗

PubMed2003

Multi-axial fatigue failure of orthopedic bone cement - experiments with tubular specimens.

Bone cement is subjected to multi-axial cyclic loading when used to fixate orthopedic prostheses for joint arthroplasty. In this study, tubular specimens of poly(methylmethacrylate) (PMMA) bone cement are subjected to internal pressure and cyclic axial loading to ascertain the influence of multi-axial loading on fatigue life. As expected, it was found that the probability of survival of specimens under multi-axial loading was very much reduced relative to specimens loaded uniaxially. Furthermore, the variability of the fatigue life was increased by multi-axial loading. In conclusion, the results point to the importance of characterizing the behavior of bone cements under the multi-axial fatigue experienced in vivo, and of the importance of accounting for the multi-axial stress state when predicting implant longevity.

Journal Article↗

PubMed2003

The effect of prosthesis design on vibration of the reconstructed ossicular chain: a comparative finite element analysis of four prostheses.

HYPOTHESIS: It was hypothesized that the differences in the bioacoustic performance of ossicular replacement prosthesis designs, and insertion positions, could be quantified using finite element analysis. BACKGROUND: Many designs of prosthesis are available for middle ear surgery. The materials used, and the shape of the implants, differ widely. Advances in computer simulation technologies offer the possibility of replicating the in vivo behavior of the different prostheses. If this can be achieved, insight into the design attributes required for improved biofunctionality may be gained. METHODS: Micro-computed tomography and nuclear magnetic resonance imaging were used to obtain geometric information that was translated into a finite element model of the outer and middle ear. The forced frequency response across the hearing range of the normal middle ear was compared with the middle ear reconstructed with partial and total ossicular replacement prostheses. RESULTS: The amplitude of vibration of the footplate was more similar to that of the normal ear when a Kurz total ossicular replacement prosthesis was implanted than when a Xomed total ossicular replacement prosthesis was implanted. This may be attributed to the latter's titanium link. Partial ossicular replacement prostheses were stiffest and had lower umbo vibrations and higher stapedial footplate vibrations. In all cases but one, the vibration of the prostheses had resonances that caused the vibration of the stapes footplate to be noticeably different from normal. CONCLUSION: The authors confirmed the hypothesis that finite element modeling can be used to predict the differences in the response of ossicular replacement prostheses. This study shows that computer simulation can potentially be used to test or optimize the vibroacoustic characteristics of middle ear implants.

Acoustic Impedance Tests↗

PubMed2003

Comparative locomotory behavior of T lymphocytes versus T lymphoma cells on flat and grooved surfaces.

Locomotion is a characteristic of many cell types, including malignant cells. It is driven by a combination of interacting factors, one of which is recognized to be the surface microtopography. In this study, an in vitro analysis of cell migration was carried out to observe and quantify the differences in locomotion of two types of lymphoid cell on both flat and grooved surfaces. The cells studied were peripheral blood T lymphocytes (PBTL) and a malignant T lymphoma cell line (HUT78). It was found that, on the grooved pattern, the lymphoma HUT78 cells were more diffusive in their migration than the T lymphocyte PBTL cells whereas, on the flat surface, the T lymphocyte PBTL cells had a more diffusive response than the T lymphoma HUT78 cells. It was also found that malignant T lymphoma cells are significantly slower and less diffusive when exposed to a plane substrate than when subjected to a grooved substrate. On the contrary, PBTL cells showed only a moderate drop in cell speed and diffusion on the grooved compared to the flat substrate. PBTL cells did, however, show a general alignment to the direction of the grooves whereas HUT78 did not. Therefore, we have found that the surface topography can influence the motile response of the two different T cell types in different ways, and this can be quantified in terms of motility parameters. This difference may have exploitable applications for cell sorting.

Cell Adhesion↗

PubMed2003

Analysis of prolapse in cardiovascular stents: a constitutive equation for vascular tissue and finite-element modelling.

The effectiveness of a cardiovascular stent depends on many factors, such as its ability to sustain the compression applied by the vessel wall, minimal longitudinal contraction when it is expanded, and its ability to flex when navigating tortuous blood vessels. The long-term reaction of the tissue to the stent is also device dependant; in particular some designs provoke in-stent restenosis (i.e., regrowth of the occlusion around the stent). The mechanism of restenosis is thought to involve injury or damage to the vessel wall due to the high stresses generated around the stent when it expands. Because of this, the deflection of the tissue between the struts of the stent (called prolapse or "draping") has been used as a measure of the potential of a stent to cause restenosis. In this paper, uniaxial and biaxial experiments on human femoral artery and porcine aortic vascular tissue are used to develop a hyperelastic constitive model of vascular tissue suitable for implementation in finite-element analysis. To analyze prolapse, four stent designs (BeStent 2, Medtronic AVE; NIROYAL, Boston Scientific; VELOCITY, Cordis; TETRA, Guidant) were expanded in vitro to determine their repeating-unit dimensions. This geometric data was used to generate a finite element model of the vascular tissue supported within a repeating-unit of the stent. Under a pressure of 450 mm Hg (representing the radial compression of the vessel wall), maximum radial deflection of 0.253 mm, 0.279 mm, 0.348 mm and 0.48 mm were calculated for each of the four stents. Stresses in the vascular wall were highest for the VELOCITY stent. The method is proposed as a way to compare stents relative to their potential for restenosis and as a basis for a biomechanical design of a stent repeating-unit that would minimize restenosis.

Animals↗