Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds

Human skin wounds (66) inflicted between 20 h and 7 months prior to biopsy were studied. In order to identify the type of cellular differentiation of the fibroblastic cells in the granulation tissue, alpha-smooth muscle actin and desmin were immunohistochemically localized. The value of any presumed time-dependent appearance and/or disappearance of positively stained cells was tested for the estimation of wound age. In skin specimens with a wound age less than 5 days (n =15) no typical granulation tissue had developed and no alpha-actin-positive myofibroblasts could be detected. The first appearance of positively reacting myofibroblasts was noted in a 5-day-old wound. In 57% of the lesions with a wound age between 5 and 31 days (25 out of 44 cases) typical granulation tissue formation was present and myofibroblasts with positive reaction for alpha-smooth muscle actin could be identified. Numerous positively reacting cells could generally be found in wounds aged between 16 and 31 days, but also in wounds less than 16 days old. In 29% of the cases with a wound age of more than 31 days (2 out of 7 cases) alpha-sma-positive myofibroblasts also occured. Fibroblastic cells positive for desmin could not be seen at all in our series. Our results demonstrate the appearance of alpha-sma-positive myofibroblasts with the initial formation of typical granulation tissue in human skin lesions as early as approximately 5 days after wounding. In contrast to recent experimental results these cells remained detectable in wounds aged more than 2 months in some cases. The immunohistochemical detection of actin-positive cells, therefore, demonstrates whether an unknown skin wound is aged approximately 5 days or more. Even though a time-dependent decrease of myofibroblasts in human granulation tissue after 31 days in human wounds seems probable, the extended presence (up to about 2 months) of these cells allows no further exact age determination of older wounds

Intervertebral disc characterisation by elastography: a preliminary study.

BiomecAM chai

Experimental validation of a patient-specific model of orthotic action in adolescent idiopathic scoliosis

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.PURPOSE: Personalized modeling of brace action has potential in improving brace efficacy in adolescent idiopathic scoliosis (AIS). Model validation and simulation uncertainty are rarely addressed, limiting the clinical implementation of personalized models. We hypothesized that a thorough validation of a personalized finite element model (FEM) of brace action would highlight potential means of improving the model. METHODS: Forty-two AIS patients were included retrospectively and prospectively. Personalized FEMs of pelvis, spine and ribcage were built from stereoradiographies. Brace action was simulated through soft cylindrical pads acting on the ribcage and through displacements applied to key vertebrae. Simulation root mean squared errors (RMSEs) were calculated by comparison with the actual brace action (quantified through clinical indices, vertebral positions and orientations) observed in in-brace stereoradiographies. RESULTS: Simulation RMSEs of Cobb angle and vertebral apical axial rotation was lower than measurement uncertainty in 79 % of the patients. Pooling all patients and clinical indices, 87 % of the indices had lower RMSEs than the measurement uncertainty. CONCLUSIONS: In-depth analysis suggests that personalization of spinal functional units mechanical properties could improve the simulation's accuracy, but the model gave good results, thus justifying further research on its clinical application

THE TRUNK ORIENTATION DURING SPRINT START ESTIMATED USING A SINGLE INERTIAL SENSOR

Sprint start and block acceleration are two very important phases which could determine the result of a sprint. Tellez & Doolittle (1984) showed that these two phases account for 64% of the total result for a 100m sprint. Sprinters have to move from a crouch to a standing position, trying to reach their maximal velocity as fast as possible. Many authors have delved into the biomechanical factors concerning both phases (Fortier et al., 2005; Harland & Steele, 1997; Schot & Knutzen, 1992). Trunk orientation is considered by coaches one of the key elements in moving from the crouch to the upright position, however only a few studies focused specifically on this parameter (Čoh et al., 1998; Čoh et al., 2006; Natta et al., 2006). Moreover, the experimental setups used in the latter studies are quite cumbersome and limited in terms of acquisition volume (motion capture systems, high-speed cameras or optical contact time meters), therefore, they are hardly usable during everyday training sessions. Wearable inertial measurement units (IMU), that embed 3D linear acceleration and angular rate sensors (accelerometers and gyroscopes), can be effectively used to perform in-field biomechanical analysis of sprint running, providing information useful for performance optimisation and injury prevention. In particular, IMUs provide an estimate of body segment rotations relative to an inertia system of reference with one axis oriented as the gravitational field. The aim of this pilot study is to validate the use of a single IMU to estimate the trunk orientation angle in the progression plane during a sprint start from the blocks

Non-invasive biomechanical characterization of intervertebral discs by shear wave ultrasound elastography: a feasibility study.

PublishedJournal ArticleThe final publication is available at Springer via http://dx.doi.org/10.1007/s00330-014-3382-8OBJECTIVES: Although magnetic resonance is widely spread to assess qualitatively disc morphology, a simple method to determine reliably intervertebral disc status is still lacking. Shear wave elastography is a novel technique that allows quantitative evaluation of soft-tissues' mechanical properties. The aim of this study was to assess preliminary the feasibility and reliability of mechanical characterization of cervical intervertebral discs by elastography and to provide first reference values for asymptomatic subjects. METHODS: Elastographic measurements were performed to determine shear wave speed (SWS) in C6-C7 or C7-T1 disc of 47 subjects; repeatability and inter-operator reproducibility were assessed. RESULTS: Global average shear wave speed (SWS) was 3.0 ± 0.4 m/s; measurement repeatability and inter-user reproducibility were 7 and 10%, respectively. SWS was correlated with both subject's age (p = 1.3 × 10(-5)) and body mass index (p = 0.008). CONCLUSIONS: Shear wave elastography in intervertebral discs proved reliable and allowed stratification of subjects according to age and BMI. Applications could be relevant, for instance, in early detection of disc degeneration or in follow-up after trauma; these results open the way to larger cohort studies to define the place of this technique in routine intervertebral disc assessment. KEY POINTS: A simple method to obtain objectively intervertebral disc status is still lacking. Shear wave elastography was applied in vivo to assess intervertebral discs. Elastography showed promising results in biomechanical disc evaluation. Elastography could be relevant in clinical routine for intervertebral disc assessment.ParisTech BiomecAM chair programParisTechYves Cotrel FoundationsSociété GénéraleProteorCove

Intervertebral disc characterization by shear wave elastography: An in vitro preliminary study.

Published onlineJOURNAL ARTICLEAuthor's accepted (post-print) manuscriptThe final version of record is available at http://dx.doi.org/10.1177/0954411914540279Patient-specific numerical simulation of the spine is a useful tool both in clinic and research. While geometrical personalization of the spine is no more an issue, thanks to recent technological advances, non-invasive personalization of soft tissue's mechanical properties remains a challenge. Ultrasound elastography is a relatively recent measurement technique allowing the evaluation of soft tissue's elastic modulus through the measurement of shear wave speed. The aim of this study was to determine the feasibility of elastographic measurements in intervertebral disc. An in vitro approach was chosen to test the hypothesis that shear wave speed can be used to evaluate intervertebral disc mechanical properties and to assess measurement repeatability. In total, 11 oxtail intervertebral discs were tested in compression to determine their stiffness and apparent elastic modulus at rest and at 400 N. Elastographic measurements were performed in these two conditions and compared to these mechanical parameters. The protocol was repeated six times to determine elastographic measurement repeatability. Average shear wave speed over all samples was 5.3 ± 1.0 m/s, with a repeatability of 7% at rest and 4.6% at 400 N; stiffness and apparent elastic modulus were 266.3 ± 70.5 N/mm and 5.4 ± 1.1 MPa at rest, respectively, while at 400 N they were 781.0 ± 153.8 N/mm and 13.2 ± 2.4 MPa, respectively. Correlations were found between elastographic measurements and intervertebral disc mechanical properties; these preliminary results are promising for further in vivo application.ParisTech BiomecAM chair programProteorParisTechYves Cotrel Foundation

In vivo cervical intervertebral disc characterisation by elastography.

PublishedJournal ArticleThis is an Accepted Manuscript of an article published by Taylor & Francis in Computer Methods in Biomechanics and Biomedical Engineering on 30/07/2014, available online: http://www.tandfonline.com/10.1080/10255842.2014.931515Not availableParisTech BiomecAM chair programProteorSociété GénéraleCoveaParisTechYves Cotrel Foundation

Evaluation of a patient-specific finite-element model to simulate conservative treatment in adolescent idiopathic scoliosis

PublishedJournal ArticleAuthor's accepted manuscript.Study design: Retrospective validation study. Objectives: To propose a method to evaluate, from a clinical standpoint, the ability of a finite-element model (FEM) of the trunk to simulate orthotic correction of spinal deformity and to apply it to validate a previously described FEM. Summary of background data: Several FEMs of the scoliotic spine have been described in the literature. These models can prove useful in understanding the mechanisms of scoliosis progression and in optimizing its treatment, but their validation has often been lacking or incomplete. Methods: Three-dimensional (3D) geometries of 10 patients before and during conservative treatment were reconstructed from biplanar radiographs. The effect of bracing was simulated by modeling displacements induced by the brace pads. Simulated clinical indices (Cobb angle, T1-T12 and T4-T12 kyphosis, L1-L5 lordosis, apical vertebral rotation, torsion, rib hump) and vertebral orientations and positions were compared to those measured in the patients' 3D geometries. Results: Errors in clinical indices were of the same order of magnitude as the uncertainties due to 3D reconstruction; for instance, Cobb angle was simulated with a root mean square error of 5.7°, and rib hump error was 5.6°. Vertebral orientation was simulated with a root mean square error of 4.8° and vertebral position with an error of 2.5 mm. Conclusions: The methodology proposed here allowed in-depth evaluation of subject-specific simulations, confirming that FEMs of the trunk have the potential to accurately simulate brace action. These promising results provide a basis for ongoing 3D model development, toward the design of more efficient orthoses.ParisTech BiomecAM chair programProteorParisTechYves Cotrel Foundation

A mathematical model for fibro-proliferative wound healing disorders

The normal process of dermal wound healing fails in some cases, due to fibro-proliferative disorders such as keloid and hypertrophic scars. These types of abnormal healing may be regarded as pathologically excessive responses to wounding in terms of fibroblastic cell profiles and their inflammatory growth-factor mediators. Biologically, these conditions are poorly understood and current medical treatments are thus unreliable. In this paper, the authors apply an existing deterministic mathematical model for fibroplasia and wound contraction in adult mammalian dermis (Olsenet al., J. theor. Biol. 177, 113–128, 1995) to investigate key clinical problems concerning these healing disorders. A caricature model is proposed which retains the fundamental cellular and chemical components of the full model, in order to analyse the spatiotemporal dynamics of the initiation, progression, cessation and regression of fibro-contractive diseases in relation to normal healing. This model accounts for fibroblastic cell migration, proliferation and death and growth-factor diffusion, production by cells and tissue removal/decay. Explicit results are obtained in terms of the model processes and parameters. The rate of cellular production of the chemical is shown to be critical to the development of a stable pathological state. Further, cessation and/or regression of the disease depend on appropriate spatiotemporally varying forms for this production rate, which can be understood in terms of the bistability of the normal dermal and pathological steady states—a central property of the model, which is evident from stability and bifurcation analyses. The work predicts novel, biologically realistic and testable pathogenic and control mechanisms, the understanding of which will lead toward more effective strategies for clinical therapy of fibro-proliferative disorders

Biomechanical comparison of a new stand-alone anterior lumbar interbody fusion cage with established fixation techniques – a three-dimensional finite element analysis

<p>Abstract</p> <p>Background</p> <p>Initial promise of a stand-alone interbody fusion cage to treat chronic back pain and restore disc height has not been realized. In some instances, a posterior spinal fixation has been used to enhance stability and increase fusion rate. In this manuscript, a new stand-alone cage is compared with conventional fixation methods based on the finite element analysis, with a focus on investigating cage-bone interface mechanics and stress distribution on the adjacent tissues.</p> <p>Methods</p> <p>Three trapezoid 8° interbody fusion cage models (dual paralleled cages, a single large cage, or a two-part cage consisting of a trapezoid box and threaded cylinder) were created with or without pedicle screws fixation to investigate the relative importance of the screws on the spinal segmental response. The contact stress on the facet joint, slip displacement of the cage on the endplate, and rotational angle of the upper vertebra were measured under different loading conditions.</p> <p>Results</p> <p>Simulation results demonstrated less facet stress and slip displacement with the maximal contact on the cage-bone interface. A stand-alone two-part cage had good slip behavior under compression, flexion, extension, lateral bending and torsion, as compared with the other two interbody cages, even with the additional posterior fixation. However, the two-part cage had the lowest rotational angles under flexion and torsion, but had no differences under extension and lateral bending.</p> <p>Conclusion</p> <p>The biomechanical benefit of a stand-alone two-part fusion cage can be justified. This device provided the stability required for interbody fusion, which supports clinical trials of the cage as an alternative to circumferential fixations.</p