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Biomedical subjects

Patrick J Prendergast

Publications and source records attributed to Patrick J Prendergast.

14 recordsLinked to original sources
PubMed2006

Cement mantle fatigue failure in total hip replacement: experimental and computational testing.

One possible loosening mechanism of the femoral component in total hip replacement is fatigue cracking of the cement mantle. A computational method capable of simulating this process may therefore be a useful tool in the preclinical evaluation of prospective implants. In this study, we investigated the ability of a computational method to predict fatigue cracking in experimental models of the implanted femur construct. Experimental specimens were fabricated such that cement mantle visualisation was possible throughout the test. Two different implant surface finishes were considered: grit blasted and polished. Loading was applied to represent level gait for two million cycles. Computational (finite element) models were generated to the same geometry as the experimental specimens, with residual stress and porosity simulated in the cement mantle. Cement fatigue and creep were modelled over a simulated two million cycles. For the polished stem surface finish, the predicted fracture locations in the finite element models closely matched those on the experimental specimens, and the recorded stem displacements were also comparable. For the grit blasted stem surface finish, no cement mantle fractures were predicted by the computational method, which was again in agreement with the experimental results. It was concluded that the computational method was capable of predicting cement mantle fracture and subsequent stem displacement for the structure considered.

Arthroplasty, Replacement, Hip↗
PubMed2006

Bone remodelling algorithms incorporating both strain and microdamage stimuli.

Biomechanical theories to predict bone remodelling have used either mechanical strain or microdamage as the stimulus driving cellular responses. Even though experimental data have implicated both stimuli in bone cell regulation, a mechano-regulatory system incorporating both stimuli has not yet been proposed. In this paper, we test the hypothesis that bone remodelling may be regulated by signals due to both strain and microdamage. Four mechano-regulation algorithms are studied where the stimulus is: strain, damage, combined strain/damage, and either strain or damage with damage-adaptive remodelling prioritised when damage is above a critical level. Each algorithm is implemented with both bone lining cell (surface) sensors and osteocyte cell (internal) sensors. Each algorithm is applied to prediction of a bone multicellular unit (BMU) remodelling on the surface of a bone trabecula. It is predicted that a regulatory system capable of responding to changes in either strain or microdamage but which prioritises removal of damaged bone when damage is above a critical level, is the only one that provides a plausible prediction of BMU behaviour. A mechanism for this may be that, below a certain damage threshold, osteocyte processes can sense changes in strain and fluid flow but above the threshold damage interferes with the signalling mechanism, or causes osteocyte apoptosis so that a remodelling response occurs to remove the dead osteocytes.

Animals↗
PubMed2006

Prediction of the optimal mechanical properties for a scaffold used in osteochondral defect repair.

The optimal mechanical properties of a scaffold to promote cartilage generation in osteochondral defects in vivo are not known. During normal daily activities cartilage is subjected to large cyclic loads that not only facilitate nutrient transport and waste removal through the dense tissue but also act as a stimulus to the chondrocytes. In contrast, cartilage tissue is commonly engineered in vitro in a static culture; hence, in many cases, the properties of scaffolds have been tailored to suit this in vitro environment. In this study, a mechanoregulation algorithm for tissue differentiation was used to determine the influence of scaffold material properties on chondrogenesis in a finite element model of an osteochondral defect. It is predicted that increasing the stiffness of the scaffold increases the amount of cartilage formation and reduces the amount of fibrous tissue formation in the defect, but this only holds true up to a certain threshold stiffness above which the amount of cartilage formed is reduced. Reducing the permeability of the scaffold was also predicted to be beneficial. Considering a nonhomogeneous scaffold, an optimal design was determined by parametrically varying the mechanical properties of the scaffold through its depth. The Young's modulus reduced nonlinearly from the superficial region through the depth of the scaffold, while the permeability of the scaffold was lowest in the superficial region. As tissue engineering moves from a science toward a product, engineering design becomes more relevant, and predictive models such as that presented here can provide a scientific basis for design choices.

Animals↗
PubMed2006

A collagen-glycosaminoglycan scaffold supports adult rat mesenchymal stem cell differentiation along osteogenic and chondrogenic routes.

Adult mesenchymal stem cells have the proclivity to differentiate along multiple lineages giving rise to new bone, cartilage, muscle, or fat. Collagen, a normal constituent of bone, provides strength and structural stability and is therefore a potential candidate for use as a substrate on which to engineer bone and cartilage from their respective mesenchymal-derived precursors. In this study, a collagen- glycosaminoglycan scaffold was used to provide a suitable three-dimensional (3-D) environment on which to culture adult rat mesenchymal stem cells and induce differentiation along the osteogenic and chondrogenic lineages. The results demonstrate that adult rat mesenchymal stem cells can undergo osteogenesis when grown on the collagen-glycosaminoglycan scaffold and stimulated with osteogenic factors (dexamethasone, ascorbic acid, beta-glycerophosphate), as evaluated by the temporal induction of the bone-specific proteins, collagen I and osteocalcin, and subsequent matrix mineralization. The osteogenic factors were coupled to activation of the extracellular-regulated protein kinase (ERK), and this kinase was found to play a role in the osteogenic process. As well as supporting osteogenesis, when the cell-seeded scaffold was exposed to chondrogenic factors (dexamethasone and TGF-1beta), collagen II immunoreactivity was increased, providing evidence that the scaffold can also provide a suitable 3-D environment that supports chondrogenesis.

Animals↗
PubMed2005

The effect of cytoskeletal disruption on pulsatile fluid flow-induced nitric oxide and prostaglandin E2 release in osteocytes and osteoblasts.

Fluid flowing through the bone porosity might be a primary stimulus for functional adaptation of bone. Osteoblasts, and osteocytes in particular, respond to fluid flow in vitro with enhanced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) release; both of these signaling molecules mediate mechanically-induced bone formation. Because the cell cytoskeleton is involved in signal transduction, we hypothesized that the pulsatile fluid flow-induced release of NO and PGE(2) in both osteoblastic and osteocytic cells involves the actin and microtubule cytoskeleton. In testing this hypothesis we found that fluid flow-induced NO response in osteoblasts was accompanied by parallel alignment of stress fibers, whereas PGE(2) response was related to fluid flow stimulation of focal adhesions formed after cytoskeletal disruption. Fluid flow-induced PGE(2) response in osteocytes was inhibited by cytoskeletal disruption, whereas in osteoblasts it was enhanced. These opposite PGE(2) responses are likely related to differences in cytoskeletal composition (osteocyte structure was more dependent on actin), but may occur via cytoskeletal modulation of shear/stretch-sensitive ion channels that are known to be dominant in osteocyte (and not osteoblast) response to mechanical loading.

3T3 Cells↗
PubMed2005

Evolution of mechanoregulation of bone growth will lead to non-optimal bone phenotypes.

Mechanical forces acting on the bones during growth affect their final shape and strength. Mechanoregulation of bone growth may be recognized in embryogenesis, and also in the adaptation of the adult skeleton to changes in mechanical loading. Mechanoregulatory responses for tissues have arisen during evolution, but does evolution give rise to responses that produce optimal skeletal phenotypes? In this paper, we investigate the emergence of an optimal mechanoregulation response in a population. By combining equations describing long bone growth with a genetic algorithm to describe evolutionary change, we created a computational model to simulate the evolution of mechanoregulation in bone growth. A population of individuals is created where each individual is assigned a diploid gene set which controls the growth and remodelling of the bone. At maturity, each bone is assessed and its 'fitness' calculated; fitness is quantified as bone strength relative to bone mass. The simulation continues for many generations, and includes mutations and a varying environment. The genes present in the population are tracked and the evolution of parameters governing mechanoregulation is calculated. The results indicate that a population may converge to one bone growth algorithm but, more usually, a range of mechanoregulation algorithms for different individuals will persist after many generations. Even if the population converges to one mechanoregulation law, convergence to the 'optimum' bone was never found. Although many researchers propose that natural selection has pushed skeletal structure towards an optimum, our computational model suggests that this is unlikely to be the case.

Adaptation, Physiological↗
PubMed2005

Acromion-fixation of glenoid components in total shoulder arthroplasty.

Successful design of components for total shoulder arthroplasty has proven to be challenging. This is because of the difficulties in maintaining fixation of the component that inserts into the scapula; i.e., the glenoid component. Glenoid components that are fixated to both the glenoid and acromion (a long process extending medially on the dorsal aspect of the scapula) have the possible advantage of greater stability over those that are fixated to the glenoid alone. In this study, a finite element analysis is used to investigate whether or not acromion fixation is advantageous for glenoid components. Full muscle loading and joint reaction forces are included in the finite element model. Reflective photoelasticity of five scapulae is used to obtain experimental data to compare with results from the finite element analysis, and it confirms the structural behaviour of the finite element model. When implanted with an acromion-fixated prosthesis, it is found that high unphysiological stresses occur in the scapula bone, and that stresses in the fixation are not reduced. Very high stresses are predicted in that part of the prosthesis which connects the acromion to the glenoid. It is found that the very high stresses are partly in response to the muscle and joint reaction forces acting at the acromion. It is concluded that, because of the relatively high forces acting at the acromion, fixation to it may not be the way forward in glenoid component design.

Acromion↗
PubMed2005

Preclinical testing of femoral hip components: an experimental investigation with four prostheses.

Existing standards for the preclinical testing of femoral hip implants have been successful in the objective of guaranteeing the implant's fatigue strength. There is a need for an experimental test which could ensure prostheses were not susceptible to aseptic loosening. In this study we measure the relative movement between the prosthesis and the bone of four different cemented femoral component designs in in vitro tests. The aim is to determine if differences can be distinguished and whether the differences correlate with clinical performance. The four designs are the Charnley (DePuy International Ltd., UK), the Exeter (Stryker Osteonics Howmedica Corp., USA), the Lubinus SPII (Waldemar-Link GmbH, Germany), and the Miiller Curved (JRI Ltd, UK). Five tests were carried out for each femoral component type, giving a total of 20 tests, and their permanent relative displacement (termed migration) and recoverable (i.e., elastic) relative displacement (termed inducible displacement) monitored over one million loading cycles. Considerable variation occurred in the tests. Nonetheless, most femoral components migrated medially, posteriorly, and distally. Most also rotated into varus. Translations of the Charnley (64 microns) and Lubinus (67 microns) implants were less than the Müller (72 microns) and Exeter (94 microns) implants, but this difference is not statistically significant. Most of the femoral components had rapid early migration followed by slower steady-state migration. With regard to the steady state inducible displacements of the prostheses, those of the Charnley, Exeter, and Lubinus decreased or were stable with respect to time, whilst those of the Müller typically increased with respect to time. It is concluded that migration is not a suitable basis for in vitro comparison of prosthesis designs. However inducible displacement trends provide a clinically comparable performance ranking.

Arthroplasty, Replacement, Hip↗
PubMed2004

A comparison of strain and fluid shear stress in stimulating bone cell responses--a computational and experimental study.

Bone undergoes continuous remodeling in response to mechanical loading. However, the underlying mechanisms by which bone cells respond to their changing mechanical environment, that is, strain in the load-bearing matrix or fluid flow through the canalicular network, are not well understood. It has been established in vitro that bone cells respond differently to substrate strain and fluid shear stress treatments. Uncovering the mechanical basis of these differences represents a significant challenge to our understanding of cellular mechanotransduction and bone remodeling. To investigate this problem, we developed a biomechanical model of an adherent cell, to test the hypothesis that bone cells respond differently to 0.6 Pa fluid shear stress and 1,000 mu(epsilon) substrate strain stimulation because of qualitative and quantitative differences in the cellular deformation caused. Fluid shear stress loading conditions resulted in maximum displacements at the apical surface of the cell approximately 8 times higher than those due to strain at the cell-substrate interface and also caused higher stressing of all parts of the cell. Significantly, this shows that the deforming effects of fluid shear stress and strain on a cellular level are qualitatively different, which may provide a basis for explaining differences in bone cell responses to both stimuli as reported in several studies. Although our approach to modeling the morphology and complex physical environment of an adherent cell is certainly simplified, our results do show independent roles for fluid flow and strain as mechanical stimuli and highlight the importance of deformation on a cellular level in bone physiology.

Adolescent↗
PubMed2003

Can finite element models detect clinically inferior cemented hip implants?

Rigorous preclinical testing of cemented hip prostheses against the damage accumulation failure scenario will reduce the incidence of aseptic loosening. For that purpose, a finite element simulation is proposed that predicts damage accumulation in the cement mantle and prosthetic migration. If the simulation is to become a convincing preclinical test, it should be able to distinguish between implants in a clinically relevant way, based on accurate predictions of long-term failure mechanisms of cemented hip prostheses. The algorithm was used to simulate long-term fatigue experiments on femoral reconstructions with Mueller Curved and Lubinus SPII stems. Clinically, the Mueller Curved system performs inferior to the Lubinus SPII system. The finite element simulation predicted much more cement damage around the Mueller Curved stem and showed that the entire cement mantle was involved in the failure process, which was not the case around the Lubinus SPII stem. In addition, the Mueller Curved stem was predicted to migrate more than the Lubinus SPII. The predictions showed excellent agreement with the experimental findings: similar damage locations in the cement, more damage for the Mueller Curved, similar prosthetic migration directions, and more migration for the Mueller Curved stem. This is the first time that a finite element simulation is able to differentiate between a clinically superior and an inferior implant, based on accurate simulation of the long-term failure mechanisms in a cemented reconstruction. Its use for preclinical testing purposes is corroborated.

Cementation↗
PubMedDate not supplied

Perforation of cancellous bone trabeculae by damage-stimulated remodelling at resorption pits: a computational analysis.

Loss of trabeculae in cancellous bone is often attributed to a general decline in the bone mass leading to fracture of the thin trabeculae. It has never been investigated whether trabecular perforation may have any other biomechanical mechanism. In this paper, an alternative hypothesis is proposed and tested using a computational model. Taking it as given that osteoclastic resorption is targeted to microdamage, it is hypothesised that the creation of a resorption cavity during normal bone remodelling could cause a stress-concentration in the bone tissue. If the resorption cavities were excessively deep, as is seen during osteoporosis, then this stress concentration may be sufficient to generate more microdamage so that osteoclasts "chase" newly formed damage leading to perforation. If this were true then we should find that, for a given trabecular thickness, there is a critical depth of resorption cavity such that smaller cavities refill whereas deeper cavities cause microdamage accumulation, continued osteoclast activity, and eventual trabecular perforation. Computer simulation is used to test this hypothesis. Using a remodelling stimulus calculated from both strain and damage and a simplified finite element model of a trabeculum with cavities of different sizes, it is predicted that such a critical depth of resorption cavity does indeed exist. Therefore we suggest that an increase in resorption depth relative to the thickness of trabeculae may be responsible for trabecular perforation during osteoporosis, rather than simply trabecular fracture due to insufficient strength.

Algorithms↗
PubMedDate not supplied

Tracking the changes in unloaded bone: Morphology and gene expression.

Bone formation and growth are controlled by genetic, hormonal and biomechanical factors. In this study, an established rat disuse osteoporosis model, hindlimb-suspension (HLS), was used to relate morphological change and gene expression to altered mechanical load in the underloaded femora and the ostensibly normally loaded humeri of the suspended rats (39 days old at onset; 1, 3, 7 and 14 days suspension). Morphological change was measured by labelling new bone formation with fluorescent agents during the experimental period and subsequent histological analysis of bone sections post-sacrifice. Hindlimb suspension reduced both the total amount of bone present, assessed as cross-sectional area, and the bone formation rate at the mid-diaphysis of the unloaded femora while no significant effect was found in the loaded humeri. In addition, the femora of the suspended animals were found to have a markedly increased circularity as a result of unloading. A sensitive semi-quantitative method of gene expression analysis, involving the creation of SMART cDNA arrays, was successfully implemented. This technique amplified all populations of mRNA to levels where they could be assessed using standard molecular biology protocols. Gene expression patterns of two candidate genes, c-fos and osteocalcin were assessed in periosteal tissue. Altered gene expression patterns were identified and tracked over the suspension period. The altered levels of both candidate genes were found to be consistent with the changes observed in the histological analysis.

Animals↗
PubMedDate not supplied

Effects of in vitro preculture on in vivo development of human engineered cartilage in an ectopic model.

We investigated whether, and under which conditions (i.e., cell-seeding density, medium supplements), in vitro preculture enhances in vivo development of human engineered cartilage in an ectopic nude mouse model. Monolayer-expanded adult human articular chondrocytes (AHACs) were seeded into Hyalograft C disks at 1.3 x 10(7) cells/cm3 (low density) or 7.6 x 10(7) cells/cm3 (high density). Constructs were directly implanted subcutaneously in nude mice for up to 8 weeks or precultured for 2 weeks before implantation. Preculture medium contained either transforming growth factor-beta1 (TGF-beta1, 1 ng/mL), fibroblast growth factor-2, and platelet-derived growth factor (proliferating medium) or TGF-beta1 (10 ng/mL) and insulin (differentiating medium). Both in vitro and after in vivo implantation, constructs derived by cell seeding at high versus low density and precultured in differentiating versus proliferating medium generated more cartilaginous tissues containing higher amounts of glycosaminoglycan and collagen type II and lower amounts of collagen type I, and with higher equilibrium moduli. As compared with direct implantation of freshly seeded scaffolds, preculture of AHAC-Hyalograft C constructs in differentiating medium, but not in proliferating medium, supported enhanced in vivo development of engineered cartilage. The effect of preculture was more pronounced when constructs were seeded at low density as compared with high density. This study indicates that preculture of human engineered cartilage in differentiating medium has the potential to provide grafts with higher equilibrium moduli and enhanced in vivo developmental capacity than freshly seeded scaffolds. These findings need to be validated in an orthotopic model system.

Animals↗