FGF2 overrides key pro-fibrotic features of bone marrow stromal cells isolated from Modic type 1 change patients.

Extensive extracellular matrix production and increased cell-matrix adhesion by bone marrow stromal cells (BMSCs) are hallmarks of fibrotic alterations in the vertebral bone marrow known as Modic type 1 changes (MC1). MC1 are associated with non-specific chronic low-back pain. To identify treatment targets for MC1, in vitro studies using patient BMSCs are important to reveal pathological mechanisms. For the culture of BMSCs, fibroblast growth factor 2 (FGF2) is widely used. However, FGF2 has been shown to suppress matrix synthesis in various stromal cell populations. The aim of the present study was to investigate whether FGF2 affected the in vitro study of the fibrotic pathomechanisms of MC1-derived BMSCs. Transcriptomic changes and changes in cell-matrix adhesion of MC1-derived BMSCs were compared to intra-patient control BMSCs in response to FGF2. RNA sequencing and quantitative real-time polymerase chain reaction revealed that pro-fibrotic genes and pathways were not detectable in MC1-derived BMSCs when cultured in the presence of FGF2. In addition, significantly increased cell-matrix adhesion of MC1-derived BMSCs was abolished in the presence of FGF2. In conclusion, the data demonstrated that FGF2 overrides key pro-fibrotic features of MC1 BMSCs in vitro. Usage of FGF2-supplemented media in studies of fibrotic mechanisms should be critically evaluated as it could override normally dominant biological and biophysical cues.

Simulation and evaluation of 3D traction force microscopy.

Measuring cell-generated forces by Traction Force Microscopy (TFM) has become a standard tool in cell mechanobiology. Although widely used in two dimensional (2D) experiments, only a few methods exist to measure traction in three-dimensional (3D) cell culture, since 3D volumetric high-resolution microscopy and more demanding computational approaches are required. Although it is commonly known that the selected experimental and computational setup highly influence the quality and accuracy of the results, no existing methods can adequately assess the errors involved in this process. We present a fully integrated simulation and evaluation platform that allows one to simulate TFM images and quantify errors of an applied approach for traction stress reconstruction, in order to improve experiments that attempt to measure mechanical interaction in cellular systems. In this context, we show that a careful parameter selection can decrease the reconstructed traction error by up to 40%.

The lever arm ratio of the rotator cuff to deltoid muscle explains and predicts pseudoparalysis of the shoulder: the Shoulder Abduction Moment index.

AIMS: In patients with a rotator cuff tear, tear pattern and tendon involvement are known risk factors for the development of pseudoparalysis of the shoulder. It remains unclear, however, why similar tears often have very different functional consequences. The present study hypothesizes that individual shoulder anatomy, specifically the moment arms (MAs) of the rotator cuff (RC) and the deltoid muscle, as well as their relative recruitment during shoulder abduction, plays a central role in pseudoparalysis. MATERIALS AND METHODS: Biomechanical and clinical analyses of the pseudoparalytic shoulder were conducted based on the ratio of the RC/deltoid MAs, which were used to define a novel anatomical descriptor called the Shoulder Abduction Moment (SAM) index. The SAM index is the ratio of the radii of two concentric spheres based on the centre of rotation of the joint. One sphere captures the humeral head (numerator) and the other the deltoid origin of the acromion (denominator). A computational rigid body simulation was used to establish the functional link between the SAM index and a potential predisposition for pseudoparalysis. A retrospective radiological validation study based on these measures was also undertaken using two cohorts with and without pseudoparalysis and massive RC tears. RESULTS: Decreased RC activity and improved glenohumeral stability was predicted by simulations of SAM indices with larger diameters of the humeral head, being consequently beneficial for joint stability. Clinical investigation of the SAM index showed significant risk of pseudoparalysis in patients with massive tears and a SAM < 0.77 (odds ratio (OR) 11). CONCLUSION: The SAM index, which represents individual biomechanical characteristics of shoulder morphology, plays a determinant role in the presence or absence of pseudoparalysis in shoulders with massive RC tears.

Pull-out strength of patient-specific template-guided vs. free-hand fluoroscopically controlled thoracolumbar pedicle screws: a biomechanical analysis of a randomized cadaveric study.

PURPOSE: To assess the pull-out strength of thoracolumbar pedicle screws implanted via either a patient-specific template-guided or conventional free-hand fluoroscopically controlled technique in a randomized cadaveric study, and to evaluate the influence of local vertebral bone density, quantified by Hounsfield units (HU), on pedicle screw pull-out strength. METHODS: Thoracolumbar pedicles of three spine cadavers were instrumented using either a free-hand fluoroscopically controlled or a patient-specific template-guided technique. Preoperative bone density was quantified by HU measured on CT. Pedicle perforation was evaluated on postoperative CT scans by an independent and blinded radiologist. After dissected vertebrae were embedded in aluminum fixation devices, pull-out testing was initiated with a preload of 50 N and a constant displacement rate of 0.5 mm/s. Subgroup analyses were performed excluding pedicle screws with a pedicle breach (n = 47). RESULTS: Pull-out strength was significantly different with 549 ± 278 and 441 ± 289 N in the template-guided (n = 50) versus fluoroscopically controlled (n = 48) subgroups (p = 0.031), respectively. Subgroup analysis limited to screws with an intrapedicular trajectory revealed a tendency toward a higher pull-out strength in the template-guided (n = 30) versus fluoroscopically controlled screws (n = 21) with 587 ± 309 and 454 ± 269 N (p = 0.118), respectively. There was a trend toward a higher pull-out strength (709 ± 418 versus 420 ± 149 N) in vertebrae with a bone density of (>171 HU) versus (<133 HU), respectively (p = 0.061). CONCLUSIONS: There was a significantly higher pull-out strength of thoracolumbar pedicle screws when inserted via a patient-specific template-guided versus conventional free-hand fluoroscopically controlled technique, potentially associated with screw trajectory.

An actin length threshold regulates adhesion maturation at the lamellipodium/lamellum interface.

The mechanical coupling between adherent cells and their substrates is a major driver of downstream behavior. This coupling relies on the formation of adhesion sites and actin bundles. How cells generate these elements remains only partly understood. A potentially important mechanism, the length threshold maturation (LTM), has previously been proposed to regulate adhesion maturation and actin bundle stabilization tangential to the leading edge. The LTM describes the process by which cells integrate lamellar myosin forces to trigger adhesion maturation. These forces, cumulated over the length of an actin bundle, are balanced at the anchoring focal complexes. When the bundle length exceeds a certain threshold, the distributed lamellar forces become sufficient to trigger the stabilization of the bundle and its adhesions. In this continuing study, we experimentally challenge the LTM for the first time, by seeding cells on micropatterned substrates with various non-adhesive gaps designed to selectively trigger the LTM. While stable actin bundles were observed on all patterns, their lengths were almost exclusively above 3 µm or 4 µm depending on the cell type. Furthermore, the frequency with which gaps were bridged increased nearly as a step function with increasing gap width, indicating a substrate dependent behavioral switch. These combined observations point strongly to LTM with a threshold above 3 µm. We thus experimentally confirm with two cell types our previous theoretical work postulating the existence of a length dependent threshold mechanism that triggers adhesion maturation and actin bundle stabilization.

Further characterisation of an experimental model of tendinopathy in the horse.

REASONS FOR PERFORMING STUDY: Injuries in energy-storing tendons are common in both horses and man. The high prevalence of reinjury and the relatively poor prognosis for returning to preinjury performance levels warrant further research, for which well characterised models would be very helpful. OBJECTIVES: Given the clinical similarities in tendinopathy of energy-storing tendons, we hypothesised that a recently developed experimental model of equine tendon injury would display many of the characteristics of clinical tendinopathy and could therefore be of use for both species, thus providing comparative insight to the human condition and offering direct potential impact to equine medicine. STUDY DESIGN: In vivo experimental study. METHODS: Surgical lesions were created in the superficial digital flexor tendon (SDFT) of 6 horses. Clinical examination, as well as biochemistry, histology and immunohistochemistry were performed on the harvested samples at 6 weeks post surgery. RESULTS: Disrupted collagen fibres, increased glycosaminoglycan content, increased presence of tenocytes with plump nuclei, the scarcity of inflammatory cells, increased matrix metalloproteinase (MMP) activity and neovascularisation were observed and found to be consistent with clinical tendinopathy. CONCLUSION AND RELEVANCE: This model displays the key features of the most common human and equine degenerative tendon disorders and is therefore an appropriate, if still imperfect, model of tendinopathy.

Tendon glycosaminoglycan proteoglycan sidechains promote collagen fibril sliding-AFM observations at the nanoscale.

The extracellular matrix of tendon is mainly composed of discontinuous Type-I collagen fibrils and small leucine rich proteoglycans (PG). Macroscopic tendon behaviors like stiffness and strength are determined by the ultrastructural arrangement of these components. When a tendon is submitted to load, the collagen fibrils both elongate and slide relative to their neighboring fibrils. The role of PG glycosaminoglycan (GAG) sidechains in mediating inter-fibril load sharing remains controversial, with competing structure-function theories suggesting that PGs may mechanically couple neighboring collagen fibrils (cross-linking them to facilitate fibril stretch) or alternatively isolating them (promoting fibril gliding). In this study, we sought to clarify the functional role of GAGs in tensile tendon mechanics by directly investigating the mechanical response of individual collagen fibrils within their collagen network in both native and GAG depleted tendons. A control group of Achilles tendons from adult mice was compared with tendons in which GAGs were enzymatically depleted using chondroitinase ABC. Tendons were loaded to specific target strains, chemically fixed under constant load, and later sectioned for morphological analysis by an atomic force microscope (AFM). Increases in periodic banding of the collagen fibrils (D-period) or decreases in fibril diameter was considered to be representative of collagen fibril elongation and the mechanical contribution of GAGs at the ultrascale was quantified on this basis. At high levels of applied tendon strain (10%), GAG depleted tendons showed increased collagen stretch (less fibril sliding). We conclude that the hydrophilic GAGs seem thus not to act as mechanical crosslinks but rather act to promote collagen fibril sliding under tension.

Numerically bridging lamellipodial and filopodial activity during cell spreading reveals a potentially novel trigger of focal adhesion maturation.

We present a novel approach to modeling cell spreading, and use it to reveal a potentially central mechanism regulating focal adhesion maturation in various cell phenotypes. Actin bundles that span neighboring focal complexes at the lamellipodium-lamellum interface were assumed to be loaded by intracellular forces in proportion to bundle length. We hypothesized that the length of an actin bundle (with the corresponding accumulated force at its adhesions) may thus regulate adhesion maturation to ensure cell mechanical stability and morphological integrity. We developed a model to test this hypothesis, implementing a "top-down" approach to simplify certain cellular processes while explicitly incorporating complexity of other key subcellular mechanisms. Filopodial and lamellipodial activities were treated as modular processes with functional spatiotemporal interactions coordinated by rules regarding focal adhesion turnover and actin bundle dynamics. This theoretical framework was able to robustly predict temporal evolution of cell area and cytoskeletal organization as reported from a wide range of cell spreading experiments using micropatterned substrates. We conclude that a geometric/temporal modeling framework can capture the key functional aspects of the rapid spreading phase and resultant cytoskeletal complexity. Hence the model is used to reveal mechanistic insight into basic cell behavior essential for spreading. It demonstrates that actin bundles spanning nascent focal adhesions such that they are aligned to the leading edge may accumulate centripetal endogenous forces along their length, and could thus trigger focal adhesion maturation in a force-length dependent fashion. We suggest that this mechanism could be a central "integrating" factor that effectively coordinates force-mediated adhesion maturation at the lamellipodium-lamellum interface.

Mechanical response of individual collagen fibrils in loaded tendon as measured by atomic force microscopy.

A precise analysis of the mechanical response of collagen fibrils in tendon tissue is critical to understanding the ultrastructural mechanisms that underlie collagen fibril interactions (load transfer), and ultimately tendon structure-function. This study reports a novel experimental approach combining macroscopic mechanical loading of tendon with a morphometric ultrascale assessment of longitudinal and cross-sectional collagen fibril deformations. An atomic force microscope was used to characterize diameters and periodic banding (D-period) of individual type-I collagen fibrils within murine Achilles tendons that were loaded to 0%, 5%, or 10% macroscopic nominal strain, respectively. D-period banding of the collagen fibrils increased with increasing tendon strain (2.1% increase at 10% applied tendon strain, p<0.05), while fibril diameter decreased (8% reduction, p<0.05). No statistically significant differences between 0% and 5% applied strain were observed, indicating that the onset of fibril (D-period) straining lagged macroscopically applied tendon strains by at least 5%. This confirms previous reports of delayed onset of collagen fibril stretching and the role of collagen fibril kinematics in supporting physiological tendon loads. Fibril strains within the tissue were relatively tightly distributed in unloaded and highly strained tendons, but were more broadly distributed at 5% applied strain, indicating progressive recruitment of collagen fibrils. Using these techniques we also confirmed that collagen fibrils thin appreciably at higher levels of macroscopic tendon strain. Finally, in contrast to prevalent tendon structure-function concepts data revealed that loading of the collagen network is fairly homogenous, with no apparent predisposition for loading of collagen fibrils according to their diameter.

Biomechanical consequences of first metatarsal osteotomy in treating hallux valgus.

BACKGROUND: Among the numerous osteotomies for correction of hallux valgus, the modified chevron is known for its good intrinsic stability and the scarf for its large corrective potential. An intermediate design, the reversed-L osteotomy, has been developed to combine these competing biomechanical objectives. The purpose of this in vitro study was to compare the structural and local biomechanical performance of these three designs. METHODS: Stiffness, cortical bone strains (a factor relevant to bone remodeling), strength and failure mode of the scarf, modified chevron and reversed-L osteotomies were measured on human specimens in two different loading configurations. FINDINGS: The scarf osteotomy caused significant changes in stiffness and cortical bone strains with the proximal apex being at the origin of bone failure. The chevron and reversed-L had a generally comparable response to the intact bone. The chevron specimens failed by pivoting of the distal fragment, and the reversed-L by pivoting or fracture. INTERPRETATION: This is the first study to investigate the cortical bone strain changes induced by these invasive osteotomies. Alterations from the intact bone response could be directly related to the design of the osteotomy. Notably, the critical weakening proximal apex of the scarf is avoided in the reversed-L, leading to results comparable to the chevron. This study provides support in favor of the intermediate design of the reversed-L as an effective compromise between the competing biomechanical objectives of corrective potential and mechanical stability.

Cytoskeleton reorganization of spreading cells on micro-patterned islands: a functional model.

Predictive numerical models of cellular response to biophysical cues have emerged as a useful quantitative tool for cell biology research. Cellular experiments in silico can augment in vitro and in vivo investigations by filling gaps in what is possible to achieve through 'wet work'. Biophysics-based numerical models can be used to verify the plausibility of mechanisms regulating tissue homeostasis derived from experiments. They can also be used to explore potential targets for therapeutic intervention. In this perspective article we introduce a single cell model developed towards the design of novel biomaterials to elicit a regenerative cellular response for the repair of diseased tissues. The model is governed by basic mechanisms of cell spreading (lamellipodial and filopodial extension, formation of cell-matrix adhesions, actin reinforcement) and is developed in the context of cellular interaction with functionalized substrates that present defined points of potential adhesion. To provide adequate context, we first review the biophysical underpinnings of the model as well as reviewing existing cell spreading models. We then present preliminary benchmarking of the model against published experiments of cell spreading on micro-patterned substrates. Initial results indicate that our mechanistic model may represent a potentially useful approach in a better understanding of cell interactions with the extracellular matrix.

Misalignment of total ankle components can induce high joint contact pressures.

BACKGROUND: A major cause of the limited longevity of total ankle replacements is premature polyethylene component wear, which can be induced by high joint contact pressures. We implemented a computational model to parametrically explore the hypothesis that intercomponent positioning deviating from the manufacturer's recommendations can result in pressure distributions that may predispose to wear of the polyethylene insert. We also investigated the hypothesis that a modern mobile-bearing design may be able to better compensate for imposed misalignments compared with an early two-component design. METHODS: Two finite element models of total ankle replacement prostheses were built to quantify peak and average contact pressures on the polyethylene insert surfaces. Models were validated by biomechanical testing of the two implant designs with use of pressure-sensitive film. The validated models were configured to replicate three potential misalignments with the most CLINICAL RELEVANCE: version of the tibial component, version of the talar component, and relative component rotation of the two-component design. The misalignments were simulated with use of the computer model with physiologically relevant boundary loads. RESULTS: With use of the manufacturer's guidelines for positioning of the two-component design, the predicted average joint contact pressures exceeded the yield stress of polyethylene (18 to 20 MPa). Pressure magnitudes increased as implant alignment was systematically deviated from this reference position. The three-component design showed lower-magnitude contact pressures in the standard position (<10 MPa) and was generally less sensitive to misalignment. Both implant systems were sensitive to version misalignment. CONCLUSIONS: In the tested implants, a highly congruent mobile-bearing total ankle replacement design yields more evenly distributed and lower-magnitude joint contact pressures than a less congruent design. Although the mobile-bearing implant reduced susceptibility to aberrant joint contact characteristics that were induced by misalignment, predicted average contact stresses reached the yield stress of polyethylene for imposed version misalignments of >5 degrees.

Collagen fibril morphology and mechanical properties of the Achilles tendon in two inbred mouse strains.

The relationship between collagen fibril morphology and the functional behavior of tendon tissue has been investigated in numerous experimental studies. Several of these studies suggest that larger fibril radius is a primary determinant of higher tendon stiffness and strength; others have shown that factors apart from fibril radius (such as fibril-fibril interactions) may be critical to improved tendon strength. In the present study, we investigate these factors in two inbred mouse strains that are widely used in skeletal structure-function research: C57BL/6J (B6) and C3H/HeJ (C3H). The aim was to establish a quantitative baseline that will allow one to assess how regulation of tendon extracellular matrix architecture affects tensile mechanical properties. We specifically focused on collagen fibril structure and glycosaminoglycan (GAG) content--the two primary constituents of tendon by dry weight--and their potential functional interactions. For this purpose, Achilles tendons from both groups were tested to failure in tension. Tendon collagen morphology was analyzed from transmission electron microscopy images of tendon sections perpendicular to the longitudinal axis. Our results showed that the two inbred strains are macroscopically similar, but C3H mice have a higher elastic modulus (P < 0.05). Structurally, C3H mice showed a larger collagen fibril radius compared to B6 mice (96 +/- 7 nm and 80 +/- 10 nm respectively). Tendons from C3H mice also showed smaller specific fibril surface (0.015 +/- 0.001 nm nm(-2) vs. 0.017 +/- 0.003 nm nm(-2) in the B6 tendons, P < 0.05), and accordingly a lower concentration of GAGs (0.60 +/- 0.07 microg mg(-1) vs. 0.83 +/- 0.11 microg mg(-1), P < 0.05). As in other studies of tendon structure and function, larger collagen fibril radius appears to be associated with stiffer tendon, but this functional difference could also be attributed to reduced potential surface area exchange between fibrils and the surrounding proteoglycan-rich matrix, in which the hydrophilic GAG side chains may promote inter-fibril sliding. This study provides an architectural and functional baseline for a comparative murine model that can be used to investigate the genetic regulation of tendon biomechanics.

Local strain measurement reveals a varied regional dependence of tensile tendon mechanics on glycosaminoglycan content.

Proteoglycans (PG) and their associated glycosaminoglycan (GAG) side chains are known to play a key role in the bearing of compressive loads in cartilage and other skeletal connective tissues. In tendons and connective tissues that are primarily loaded in tension, the influence of proteoglycans on mechanical behavior is debated due to conflicting experimental evidence that alternately supports or controverts a functional role of proteoglycans in bearing tensile load. In this study we sought to better reconcile these conflicting data by investigating the possibility that GAG content is differentially related to tensile tendon mechanics depending upon the anatomical subregion one considers. To test this hypothesis, we quantified the mechanical consequences of proteoglycan disruption within specific tendon anatomical subregions using an optical-mechanical measurement approach. Achilles tendons from adult mice were treated with chondroitinase ABC to obtain two groups consisting of native tendons and GAG-depleted tendons. All the tendons were mechanically tested and imaged with high-resolution digital video in order to optically quantify tendon strains. Tendon surface strains were locally analyzed in three main subregions: the central midsubstance, and the proximal and distal midsubstance near the muscle and bone insertions, respectively. Upon GAG digestion, the tendon midsubstance softened appreciably near the bone insertion, while elastic modulus in the central and proximal thirds was unchanged. Thus the contribution of PGs to tensile tendon mechanics is not straightforward and points to a heterogeneous and complex structure-function relationship in tendon. This study further highlights the importance of performing local strain analysis with regard to tensile tendon mechanics.

An analytical model for elucidating tendon tissue structure and biomechanical function from in vivo cellular confocal microscopy images.

Fibered confocal laser scanning microscopes have given us the ability to image fluorescently labeled biological structures in vivo and at exceptionally high spatial resolutions. By coupling this powerful imaging modality with classic optical elastography methods, we have developed novel techniques that allow us to assess functional mechanical integrity of soft biological tissues by measuring the movements of cells in response to externally applied mechanical loads. Using these methods we can identify minute structural defects, monitor the progression of certain skeletal tissue disease states, and track subsequent healing following therapeutic intervention in the living animal. Development of these methods using a murine Achilles tendon model has revealed that the hierarchical and composite anatomical structure of the tendon presents various technical challenges that can confound a mechanical analysis of local material properties. Specifically, interfascicle gliding can yield complex cellular motions that must be interpreted within the context of an appropriate anatomical model. In this study, we explore the various classes of cellular images that may result from fibered confocal microscopy of the murine Achilles tendon, and introduce a simple two-fascicle model to interpret the images in terms of mechanical strains within the fascicles, as well as the relative gliding between fascicles.

Kidney injury: an experimental investigation of blunt renal trauma.

BACKGROUND: The abdomen ranks third with regard to injured body regions, and urogenital trauma accounts for up to 10% of all abdominal injuries. Predictive numerical models are evolving as important tools for the development of preventative measures and preliminary clinical diagnostics. Such models require accurate biomechanical input data that at present is not sufficiently available. METHOD: The purpose of the present study was to determine the biomechanical response of whole, perfused porcine kidneys to blunt impact. Specifically of interest were the force-displacement characteristics of the organs, as well as the injury thresholds. Thirty nine young, adult pig kidneys (kidney mass 0.17 +/- 0.02 kg) were infused with physiologic saline solution, and impacted on their dorsal surface by a freely swinging right cylindrical pendulum. Two impact masses (2.1 and 4.7 kg) were used at varying impact velocities and corresponding impact energies. Resulting injuries were graded according to the AAST injury scale, and injury was related to impact mass, impact velocity, and impact energy. RESULTS AND CONCLUSIONS: It was determined that injury was best predicted by impact energy, and that for a given impact energy the resulting injury severity was relatively independent of either impact mass or impact velocity. For a moderate to severe injury, an impact energy threshold of 4 J, or a corresponding strain energy density of 25 kJ/m, was established. This information is essential to the development and implementation of accurate, predictive computational trauma models.

Microstructural insight into pedestrian pelvic fracture as assessed by high-resolution computed tomography.

Pelvic and femoral neck bone surface strains were recorded in five full-body human cadaver vehicle-pedestrian impacts. Impacts were performed at 40 km/h using automotive front ends constructed to represent those used in previously reported finite element simulations. While experimental kinematics and bone strains closely matched model predictions, observed pelvic fractures did not consistently agree with the model, and could not be solely explained by vehicle geometry. In an attempt to reconcile injury outcome with factors apart from vehicle design, a proxy measure of subject skeletal health was assessed by high-resolution quantitative computed tomography (HRqCT) of the femoral neck. The incidence of hip/pelvis fracture was found to be consistent with low volumetric bone mineral density and low trabecular bone density. This finding lends quantitative support to the notion that healthy trabecular architecture is crucial in withstanding non-physiological impact loads. Furthermore, it is recommended that injury criteria used to assess vehicle safety with regard to pedestrians consider the increased susceptibility of elderly victims to pelvic fracture.

Strain energy density as a rupture criterion for the kidney: impact tests on porcine organs, finite element simulation, and a baseline comparison between human and porcine tissues.

High-velocity (up to 25 m/s) impact tests were performed on pig kidneys to characterize failure behavior at deformation rates associated with traumatic injury. Cylindrical tissue samples (n = 45) and whole perfused organs (n = 34) were impacted using both falling weights and a high-velocity pneumatic projectile impactor. Impact energy was incrementally increased until visible rupture occurred. The strain energy density failure threshold fell between 25 and 60 kJ/m3 for excised porcine tissue samples, and between 15 and 30 kJ/m3 for whole, perfused organs. The relationship between localized failure in whole organ impacts and tissue level failure thresholds observed in cylindrical tissue samples was explored using a detailed finite element model of the human kidney. The model showed good correlation between experimentally observed injury patterns and predicted strain energy density distributions within the renal parenchyma. Finally, to facilitate interpretation of the porcine renal impact results with regard to human trauma, quasi-static compression test results of freshly excised human kidney cortex samples (n = 30) were compared against similar tests on pig kidneys. Human tissues failed at Lagrange strain levels similar to porcine tissue (63+/-6.3%), but at 52% lower Lagrange stress (116+/-28 kPa), and 35% lower strain energy density (17.1+/-4.4 kJ/m3). Thus conservative interpretation of porcine test results is recommended.

Strain-rate dependent material properties of the porcine and human kidney capsule.

This study was performed to characterize the mechanical properties of the kidney capsular membrane at strain-rates associated with blunt abdominal trauma. Uniaxial quasi-static and dynamic tensile experiments were performed on fresh, unfrozen porcine and human renal capsules at deformation rates ranging from 0.0001 to 7 m/s (strain-rates of 0.005-250 s(-1)). Single stroke, dynamic tests were performed on samples of porcine renal capsule at strain-rates of 0.005 s(-1) (n = 33), 0.05 s(-1) (n = 17), 0.5 s(-1) (n = 38), 2 s(-1) (n = 10), 4 s(-1) (n = 10), 50 s(-1) (n = 21), 100 s(-1) (n = 18), 150 s(-1) (n = 17), 200 s(-1) (n = 10), and 250 s(-1) (n = 17). Due to limited availability of human tissues, only quasi-static tests were performed (0.005 s(-1), n = 25). Porcine renal capsule properties were found to match the material properties of human capsular tissue sufficiently well such that porcine tissue material can be used as a human test surrogate. The apparent elastic modulus and breaking stress of the porcine renal capsule were observed to increase significantly with increasing strain-rate (p < 0.01). Breaking strain was inversely related to strain-rate (p < 0.01). The effect of increasing strain-rate on material properties diminished appreciably at rates exceeding 150 s(-1). Empirically derived mathematical models of constitutive behavior were developed using a hyperelastic/viscoelastic Ogden formulation, as well as a Cowper-Symonds law material curve multiplication.