Intratumoral Heterogeneity Assessment of the Extracellular Bone Matrix and Immune Microenvironment in Osteosarcoma Using Digital Imaging to Predict Therapeutic Response.

The assessment of chemotherapy response in osteosarcoma (OS) based on the average percentage of viable cells is limited, as it overlooks the spatial heterogeneity of tumor cell response (foci of resistant cells), immune microenvironment, and bone microarchitecture. Despite the resulting positive classification for response to chemotherapy, some patients experience early metastatic recurrence, demonstrating that our conventional tools for evaluating treatment response are insufficient. We studied the interactions between tumor cells, immune cells (lymphocytes, histiocytes, and osteoclasts), and bone extracellular matrix (ECM) in 18 surgical resection samples of OS using multiplex and conventional immunohistochemistry (IHC: CD8, CD163, CD68, and SATB2), combined with multiscale characterization approaches in territories of good and poor response (GRT/PRT) to treatment. GRT and PRT were defined as subregions with <10% and ≥10% of viable tumor cells, respectively. Local correlations between bone ECM porosity and density of immune cells were assessed in these territories. Immune cell density was then correlated to overall patient survival. Two patterns were identified for histiocytes and osteoclasts. In poor responder patients, CD68 osteoclast density exceeded that of CD163 histiocytes but was not related to bone ECM load. Conversely, in good responder patients, CD163 histiocytes were more numerous than CD68 osteoclasts. For both of them, a significant negative local correlation with bone ECM porosity was found (P < .01). Moreover, in PRT, multinucleated osteoclasts were rounded and intermingled with tumor cells, whereas in GRT, they were elongated and found in close contact with bone trabeculae. CD8 levels were always low in metastatic patients, and those initially considered good responders rapidly died from their disease. The specific recruitment of histiocytes and osteoclasts within the bone ECM, and the level of CD8 represent new features of OS response to treatment. The associated prognostic signatures should be integrated into the therapeutic stratification algorithm of patients after surgery.

Mechanobiology of bacterial biofilms: Implications for orthopedic infection.

Postoperative bacterial infections are prevalent complications in both human and veterinary orthopedic surgery, particularly when a biofilm develops. These infections often result in delayed healing, early revision, permanent functional loss, and, in severe cases, amputation. The diagnosis and treatment pose significant challenges, and bacterial biofilm further amplifies the therapeutic difficulty as it confers protection against the host immune system and against antibiotics which are usually administered as a first-line therapeutic option. However, the inappropriate use of antibiotics has led to the emergence of numerous multidrug-resistant organisms, which largely compromise the already imperfect treatment efficiency. In this context, the study of bacterial biofilm formation allows to better target antibiotic use and to evaluate alternative therapeutic strategies. Exploration of the roles played by mechanical factors on biofilm development is of particular interest, especially because cartilage and bone tissues are reactive environments that are subjected to mechanical load. This review delves into the current landscape of biofilm mechanobiology, exploring the role of mechanical factors on biofilm development through a multiscale prism starting from bacterial microscopic scale to reach biofilm mesoscopic size and finally the macroscopic scale of the fracture site or bone-implant interface.

A versatile micromodel technology to explore biofilm development in porous media flows.

Bacterial biofilms that grow in porous media are critical to ecosystem processes and applications ranging from soil bioremediation to bioreactors for treating wastewater or producing value-added products. However, understanding and engineering the complex phenomena that drive the development of biofilms in such systems remains a challenge. Here we present a novel micromodel technology to explore bacterial biofilm development in porous media flows. The technology consists of a set of modules that can be combined as required for any given experiment and conveniently tuned for specific requirements. The core module is a 3D-printed micromodel where biofilm is grown into a perfusable porous substrate. High-precision additive manufacturing, in particular stereolithography, is used to fabricate porous scaffolds with precisely controlled architectures integrating flow channels with diameters down to several hundreds of micrometers. The system is instrumented with: ultraviolet-C light-emitting diodes; on-line measurements of oxygen consumption and pressure drop across the porous medium; camera and spectrophotometric cells for the detection of biofilm detachment events at the outlet. We demonstrate how this technology can be used to study the development of Pseudomonas aeruginosa biofilm for several days within a network of flow channels. We find complex dynamics whereby oxygen consumption reaches a steady-state but not the pressure drop, which instead features a permanent regime with large fluctuations. We further use X-ray computed microtomography to image the spatial distribution of biofilms and computational fluid dynamics to link biofilm development with local flow properties. By combining the advantages of additive manufacturing for the creation of reproducible 3D porous microarchitectures with the flow control and instrumentation accuracy of microfluidics, our system provides a platform to study the dynamics of biofilm development in 3D porous media and to rapidly test new concepts in process engineering.

Diffusion properties of asymptomatic lumbar intervertebral discs in a pediatric cohort: a preliminary study of apparent diffusion coefficient.

PURPOSE: To explore the apparent diffusion coefficients of intervertebral discs in an asymptomatic pediatric cohort. METHODS: We conducted a prospective MRI study of the lumbar spine from below the thoracolumbar junction to the lumbosacral junction on 12 subjects (mean age 13 y.o.) with no spinal pathology or spinal posture disorder. MRI was carried out using a 1.5 T machine with acquisitions realized both in sagittal and coronal planes. First, disc hydration was determined, and then, diffusion-weighted images were obtained using an SE single-shot echo-planar sequence. Apparent diffusion coefficients (ADC) of anterior annulus fibrosus (AAF), nucleus pulposus (NP) and posterior annulus fibrosus (PAF) were measured in the sagittal plane. RESULTS: Averaged hydration of 0.27 SD 0.03 confirmed the asymptomatic nature of discs. Average scaled values of ADC were 0.46 SD 0.01, 0.22 SD 0.09 and 0.18 SD 0.03 for NP, AAF and PAF, respectively. ADC of NP were almost constant along the spine; PAF values show a slight increase in the thorax-sacrum direction, while AAF values showed a pronounced decrease. Locally, ADC of AAF was higher compared to ADC PAF values below the thoracolumbar junction and it reversed for subjacent discs. CONCLUSIONS: In our knowledge, our study provided the first diffusive properties of asymptomatic intervertebral discs in an adolescent cohort. ADC of NP was slightly higher than adults'. ADC evolutions of AAF were correlated with lordosis concavity which pointed out the role of compressive strain on fluid transport properties. This study could furnish information about segment homeostasis for exploration of pediatric spinal pathologies.

Biomechanical Comparison of Use of Two Screws versus Three Screws Per Fragment with Locking Plate Constructs under Cyclic Loading in Compression in a Fracture Gap Model.

OBJECTIVES: The aim of this study was to measure and compare the stiffness and cyclic fatigue of two plate-bone model constructs, with either two or three locking screws per fragment, under cyclic compression. METHODS: A 10-hole 3.5 mm stainless steel locking compression plate (LCP) was fixed 1 mm from a synthetic bone model in which the fracture gap was 47 mm. Two groups of 10 constructs, prepared with either two or three bicortical locking screws placed at the extremities of each fragment, were tested in a load-controlled compression test until failure. RESULTS: The three-screw constructs were stiffer than the two-screw constructs (196.75 ± 50.48 N/mm and 102.43 ± 22.93 N/mm, respectively) and the actuator displacements of the two-screw constructs were higher (18.02 ± 1.07 mm) than those of the three-screw constructs (14.48 ± 2.25 mm). The number of cycles to failure of the two-screw constructs was significantly lower (38,337.50 ± 2,196.98) than the that of the three-screw constructs (44,224.00 ± 1,515.24). Load at irreversible deformation was significantly lower in the two-screw constructs (140.93 ± 13.39 N) than in the three-screw constructs (184.27 ± 13.17 N). All constructs failed by plate bending at the gap between the two cylinders. CLINICAL SIGNIFICANCE: Omission of the third innermost locking screw during bridging osteosynthesis subjected to compression forces led to a 13.3% reduction in the number of cycles to failure and a 23.5% reduction of the load withstood by the plate before plastic deformation occurred.

Does a combined screw and dowel construct improve tibial fixation during anterior cruciate ligament reconstruction?

PURPOSE: The aims of the present study were to compare the biomechanical properties of tibial fixation in hamstring-graft ACL reconstruction using interference screw and a novel combination interference screw and dowel construct. MATERIAL AND METHODS: We compared the fixation of 30 (2- and 4-stranded gracilis and semitendinosis tendons) in 15 fresh-frozen porcine tibiae with a biocomposite resorbable interference screw (Group 1) and a screw and dowel construct (Group 2). Each graft was subjected to load-to-failure testing (50 mm/min) to determine maximum load, displacement at failure and pullout strength. RESULTS: There were no significant differences between the biomechanical properties of the constructs. Multivariate analysis demonstrated that combination constructs (ß = 140.20, p = 0.043), screw diameter (ß = 185, p = 0.006) and 4-strand grafts (ß = 51, p = 0.050) were associated with a significant increase in load at failure. Larger screw diameter was associated with increased construct stiffness (ß = 20.15, p = 0.020). CONCLUSION: The screw and dowel construct led to significantly increased fixation properties compared to interference screws alone in a porcine model. Increased screw diameter and utilization of 4-strand ACL grafts also led to improvement in load-to-failure of the construct. However, this is an in vitro study and additional investigations are needed to determine whether the results are reproducible in vivo. LEVEL OF EVIDENCE: Level V; Biomechanical study.

An energy approach describes spine equilibrium in adolescent idiopathic scoliosis.

The adolescent idiopathic scoliosis (AIS) is a 3D deformity of the spine whose origin is unknown and clinical evolution unpredictable. In this work, a mixed theoretical and numerical approach based on energetic considerations is proposed to study the global spine deformations. The introduced mechanical model aims at overcoming the limitations of computational cost and high variability in physical parameters. The model is constituted of rigid vertebral bodies associated with 3D effective stiffness tensors. The spine equilibrium is found using minimization methods of the mechanical total energy which circumvents forces and loading calculation. The values of the model parameters exhibited in the stiffness tensor are retrieved using a combination of clinical images post-processing and inverse algorithms implementation. Energy distribution patterns can then be evaluated at the global spine scale to investigate given time patient-specific features. To verify the reliability of the numerical methods, a simplified model of spine was implemented. The methodology was then applied to a clinical case of AIS (13-year-old girl, Lenke 1A). Comparisons of the numerical spine geometry with clinical data equilibria showed numerical calculations were performed with great accuracy. The patient follow-up allowed us to highlight the energetic role of the apical and junctional zones of the deformed spine, the repercussion of sagittal bending in sacro-illiac junctions and the significant role of torsion with scoliosis aggravation. Tangible comparisons of output measures with clinical pathology knowledge provided a reliable basis for further use of those numerical developments in AIS classification, scoliosis evolution prediction and potentially surgical planning.

MRI evaluation of the hydration status of non-pathological lumbar intervertebral discs in a pediatric population.

INTRODUCTION: The intervertebral disc (IVD) is made up of the annulus fibrosus (AF) and the nucleus pulposus (NP) - an inert hydrated complex. The ability of the IVD to deform is correlated to that of the NP and depends on its hydration. As the IVD ages, its hydration decreases along with its ability to deform. In adolescent idiopathic scoliosis, one of the etiological hypotheses pertains to the IVD, thus making its condition relevant for the diagnosis and monitoring of this pathology. HYPOTHESIS: IVD hydration depends on sex, age and spine level in an asymptomatic pediatric population. The corollary is data on a control group of healthy subjects. MATERIAL AND METHODS: A cohort of 98 subjects with normal spine MRI was enrolled; their mean age was 13.3 years. The disc volume and hydration of each IVD was evaluated on T2-weighted MRI sequences, using previously validated image processing software. This evaluation focused on the lumbar spine, from the thoracolumbar junction to the lumbosacral junction. It was assumed that IVD hydration was related to the ratio of NP and AF volumes. A mixed multivariate linear analysis was used to explore the impact of age, sex and spinal level on disc hydration. RESULTS: Disc hydration was higher overall in boys than in girls, but this difference was not significant. Hydration increased with age by +0.005 for each additional year (p=0.0213). Disc hydration appears to be higher at the thoracolumbar junction than the lumbar spine, although this difference was not significant. CONCLUSION: Through this MRI study, we established a database of non-pathological lumbar disc hydration as a function of age, sex and spinal segment along with 95% confidence intervals. LEVEL OF EVIDENCE: IV.

Mechanical behavior of screw versus Endobutton for coracoid bone-block fixation.

INTRODUCTION: Arthroscopic coracoid bone-block fixation by Endobutton was developed to avoid the complications associated with screwing. However, few studies have assessed the mechanical characteristics of the two. The aim of the present study was to assess and compare fixation rigidity by screw versus Endobutton. The study hypothesis was that rigidity is lower with Endobutton than with screws. MATERIAL AND METHOD: 3D print-outs of a glenoid and a coracoid process were obtained from CT scans of a patient showing anterior shoulder instability with significant bone defect. Four types of coracoid fixation were implemented: 1 or 2 4.5mm malleolar screws, and 1 or 2 Endobuttons. Three specimens per assembly were placed on a specific test bench. Lateromedial bone-block compression was exerted at 0.1mm/sec at 3 points: superior, central, inferior. The resultant force and bone-block displacement were recorded. RESULTS: Mean fixation rigidity with 1 screw, 2 screws, 1 Endobutton and 2 Endobuttons was respectively 158N/mm (range, 133-179), 249N/mm (241-259), 10N/mm (5-13) and 14N/mm (13-15), with significant difference between the screw and Endobutton groups (p<0.001). Displacement was greater with 1 than 2 Endobuttons under superior or inferior force, while the difference was non-significant under central force (7.45 vs 6.93mm; p=0.53) CONCLUSIONS: Screw fixation showed greater rigidity, while the Endobutton assembly showed less tension, leading to greater bone-block mobilization. The interest of using two Endobuttons is to reduce displacement under polar pressure. the present biomechanical study confirmed the mechanical vulnerability of bone-blocks fixed by endobutton until consolidation is achieved. LEVEL OF EVIDENCE: Biomechanical study.

Foot and ankle compensation for anterior cruciate ligament deficiency during gait in children.

BACKGROUND: Anterior cruciate ligament (ACL) injuries are common in adults and cause knee instability, pain, and an increased risk of osteoarthritis. Previous studies demonstrated changed gait patterns in adult patients with ACL deficiency. In paediatric patients, ACL injuries were once thought to be rare but are being increasingly diagnosed due to greater involvement of children in contact sports and to the introduction of more effective diagnostic tools such as magnetic resonance imaging (MRI). However, little is known about gait adaptation in children with ACL deficiency. The objective of this study was to look for compensatory foot and ankle behaviours during gait in paediatric patients with symptomatic ACL deficiency. HYPOTHESIS: Compensation for ACL deficiency during gait occurs at the foot and ankle in children, because compensation at the hip and pelvis would require greater energy expenditure. MATERIAL AND METHODS: We included 47 patients, 33 males and 14 females, ranging in age from 9 to 17 years (mean, 14.1 years). The patients had a history of unilateral ACL injury documented by MRI and initially treated by immobilisation and physical therapy. They were allowed to walk with full weight-bearing on the affected limb and were not taking medications at the time of the study. All patients had pain, knee instability, or functional limitation. The physical examination showed joint laxity indicating surgical ACL reconstruction. None had neurological conditions, congenital musculoskeletal abnormalities, or a history of knee surgery. Gait analysis (GA) was performed using a Vicon 460 system. Kinematic data for the ankle and foot were compared to those in a control group of 37 healthy children. Ankle angular positions were calculated for each group at the following stance time points: initial contact (0% of gait cycle [GC]), mid-stance (25% GC), terminal stance (60% GC), and swing (83% GC). Foot progression data were recorded at mid-stance (25% GC) and swing (70% GC). Student's t test was applied to compare the results to reference values obtained at our laboratory and to data from the control group. RESULTS: Compared to the reference values, the ankle was in plantar flexion at initial contact in 41 patients, and ankle dorsiflexion during the stance phase was diminished in 39 patients. The external foot progression angle was increased in 23 patients during the stance phase and 38 patients during the swing phase. Compared to the control group (mean age, 9.1 years), the patients had plantar flexion of the ankle at initial contact (3.43°±3.5° vs. 0.74°±3.6°, p<0.05) and decreased dorsiflexion during the stance phase (3.43°±3.5° vs. 0.74°±3.6°, p<0.05). No significant differences were found for any of the other parameters. DISCUSSION: Children with ACL deficiency developed compensatory foot and ankle behaviours during gait that improved knee stability. Understanding these compensations may guide treatment optimisation. LEVEL OF EVIDENCE: III, retrospective comparative study.

Biomechanical Comparison of Two Locking Plate Constructs Under Cyclic Loading in Four-Point Bending in a Fracture Gap Model: Two Screws versus Three Screws Per Fragment.

OBJECTIVES: The number of locking screws required per fragment during bridging osteosynthesis has not been fully determined in the dog. The purpose of this study was to assess the survival of two constructs, with either two or three screws per fragment, under cyclic bending. METHODS: A 10-hole, 3.5-mm stainless steel locking compression plate was fixed 1 mm away from a bone surrogate in which the fracture gap was 47 mm. Two groups of 10 constructs, prepared with either two or three bicortical locking screws placed at the extremities of each fragment, were tested in a load-controlled 4-point bending test (range 0.7 to + 7 Nm) until failure. RESULTS: The 3-screw constructs were stiffer than the 2-screw constructs (19.73 ± 0.68 N/mm vs. 15.52 ± 0.51 N/mm respectively) and the interfragmentary relative displacements were higher for the 2-screw constructs (11.17 ± 0.88%) than for the 3-screw constructs (8.00 ± 0.45%). The difference between the number of cycles to failure for the 3-screw constructs (162,448 ± 30,073 cycles) and the 2-screw constructs (143,786 ± 10,103 cycles) was not significant. Failure in all constructs was due to plate fracture at the level of the compression holes. CLINICAL SIGNIFICANCE: Omission of the third innermost locking screw during bridging osteosynthesis subjected to bending forces led to a 20% reduction in construct stiffness and increased relative displacement (+39.6%) but did not change fatigue life.

Results of arthroscopic Bankart repair with Hill-Sachs remplissage for anterior shoulder instability.

PURPOSE: The aim of this study was to evaluate mid-term outcomes of Bankart repair with Hill-Sachs remplissage (BHSR) and to highlight prognostic factors of failure. METHODS: Thirty-four patients operated on for anterior shoulder instability with BHSR were enrolled in a prospective non-randomised study. Clinical and radiographic evaluation was performed at 1.5, three, six months and yearly thereafter. Outcome measures included Rowe and Walch-Duplay score. RESULTS: At mean follow-up of 35 months (24-63), the Rowe and Walch-Duplay scores reached respectively 92.7 and 88.2 points. The mean deficit in external rotation was 6° in ER1 and 1° in ER2 (p = 0.4, p = 0.9 respectively). Five patients (14.7%) had a recurrence of instability and three others had a persistent anterior apprehension. In the failure group, the Hill-Sachs lesion was deeper (26% vs 19% of the humeral diameter; p = 0.04) and range of motion at 1.5 months postoperatively was greater. Age at surgery, pre-operative instability severity index score (ISIS), hyperlaxity, type and level of sport, amount of glenoid bone loss had no correlation with failure rate. CONCLUSIONS: The rate of failure at mid-term follow-up of BHSR was higher than commonly reported. The premature recovery of range of motion seems to be a clinical sign of failure at follow-up. Moreover, in case of deep Hill-Sachs lesion (>20%) an alternative procedure should be considered. LEVEL OF EVIDENCE: Level IV.

BMI-related microstructural changes in the tibial subchondral trabecular bone of patients with knee osteoarthritis.

Overweight is a risk factor for osteoarthritis on the knees. Subchondral trabecular bone (SCTB) densification has been shown to be associated with cartilage degeneration. This study analyzed the microarchitectural changes in the SCTB of tibial plateaus to validate the hypothesis that the degree of remodeling is correlated with a patient's body weight. Twenty-one tibial plateaus were collected during total knee arthroplasty from 21 patients (15 women and 6 men). These patients had a mean age of 70.4 years (49-81), mean weight of 74.7 kg (57-93) and mean body mass index (BMI) of 28.4 kg/m2 (21.3-40.8). One cylindrical plug was harvested in the center of each tibial plateau (medial and lateral). Micro-CT parameters (7.4 µm resolution) were determined to describe the SCTB structure. On the medial plateau, there were significant correlations between BMI and bone volume fraction BV/TV (r = 0.595, p = 0.004), structure model index SMI (r = -0.704 p = 0.0002), trabecular space Tb.Sp (r = 0.600, p = 0.04) and trabecular number Tb.N (r = 0.549, p = 0.01). SCTB densification during osteoarthritis is associated with a reduction in its elastic modulus, which could increase cartilage stress, and accelerate cartilage loss. SCTB densification has been shown to precede cartilage degeneration. The correlation of SCTB microarchitecture and body weight may explain why knee osteoarthritis is more common in overweight or obese patients. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1653-1660, 2017.

Characterisation of Supra- and Infratentorial ICP Profiles.

In pathophysiology and clinical practice, the intracranial pressure (ICP) profiles in the supratentorial and infratentorial compartments are unclear. We know that the pressure within the skull is unevenly distributed, with demonstrated ICP gradients. We recorded and characterised the supra- and infratentorial ICP patterns to understand what drives the transtentorial ICP gradient.A 70-year-old man was operated on for acute cerebellar infarction. One supratentorial probe and one cerebellar probe were implanted. Both signals were recorded concurrently and analysed off-line. We calculated mean ICP, ICP pulse amplitude, respiratory waves, slow waves and the RAP index of supra- and infratentorial ICP signals. Then, we measured transtentorial difference and performed correlation analysis for every index.Supratentorial ICP mean was 8.5 mmHg lower than infratentorial ICP, but the difference lessens for higher values. Both signals across the tentorium showed close correlation. Supra- and infratentorial pulse amplitude, respiratory waves and slow waves also showed a high degree of correlation. The compensatory reserve (RAP) showed good correlation. In this case report, we demonstrate that the mean value of ICP is higher in the posterior fossa, with a strong correlation across the tentorium. All other ICP-derived parameters display a symmetrical profile.

Bernoulli's Principle Applied to Brain Fluids: Intracranial Pressure Does Not Drive Cerebral Perfusion or CSF Flow.

In line with the first law of thermodynamics, Bernoulli's principle states that the total energy in a fluid is the same at all points. We applied Bernoulli's principle to understand the relationship between intracranial pressure (ICP) and intracranial fluids. We analyzed simple fluid physics along a tube to describe the interplay between pressure and velocity. Bernoulli's equation demonstrates that a fluid does not flow along a gradient of pressure or velocity; a fluid flows along a gradient of energy from a high-energy region to a low-energy region. A fluid can even flow against a pressure gradient or a velocity gradient. Pressure and velocity represent part of the total energy. Cerebral blood perfusion is not driven by pressure but by energy: the blood flows from high-energy to lower-energy regions. Hydrocephalus is related to increased cerebrospinal fluid (CSF) resistance (i.e., energy transfer) at various points. Identification of the energy transfer within the CSF circuit is important in understanding and treating CSF-related disorders. Bernoulli's principle is not an abstract concept far from clinical practice. We should be aware that pressure is easy to measure, but it does not induce resumption of fluid flow. Even at the bedside, energy is the key to understanding ICP and fluid dynamics.

Cadaveric Study Comparing the Biomechanical Properties of Grafts Used for Knee Anterolateral Ligament Reconstruction.

PURPOSE: To measure the biomechanical properties (maximum load, stiffness, and elongation) of the anterolateral ligament (ALL), gracilis, and iliotibial band (ITB) within the same subject. METHODS: Thirteen unpaired knees were used (7 women, 6 men). The donors had a mean age at death of 54 years (range: 37 to 70 years). The mechanical properties of two types of ALL grafts were evaluated: ITB and two-strand gracilis. The mechanical properties of ALL were also measured. Validated methods were used to perform the tensile tests to failure and to record the results. Student's t-test was used to compare the various samples. RESULTS: The maximum load to failure was 141 N (±40.6) for the ALL, 200.7 N (±48.7) for the gracilis, and 161.1 N (±27.1) for the ITB. Only the gracilis had a significantly higher failure load than ITB and ALL (P = .001 and P = .03). The stiffness was 21 N mm-1 (±8.2) for the ALL, 131.7 N mm-1 (±43.7) for the gracilis, and 39.9 N mm-1 (±6) for the ITB. The elongation at failure was 6.2 mm (±3.2) for the ALL, 19.9 mm (±6.5) for the gracilis, and 20.8 mm (±14.7) for the ITB. CONCLUSIONS: The gracilis had the highest maximum load to failure. The ITB's mechanical properties most closely resemble those of the ALL. CLINICAL RELEVANCE: The biomechanical properties of each potential ALL graft can be factored in when deciding which type of graft to use.

Adipose stromal cells improve healing of vocal fold scar: Morphological and functional evidences.

OBJECTIVES/HYPOTHESIS: Adipose derived stromal cells (ASCs) are abundant and easy to prepare. Such cells may be useful for treating severe vocal disturbance caused by acute vocal fold scars. STUDY DESIGN: Prospective animal experiments with controls. METHODS: Twenty New-Zealand white rabbits were used in the present study. We evaluated vocal fold healing, with or without injection of autologous ASCs, after acute scarring. A defined lesion was created and the ASCs were immediately injected. Vocal fold regeneration was evaluated histomorphometrically and via viscoelastic analysis using an electrodynamic shaker. RESULTS: Six weeks after ASC injection, vocal folds exhibited significantly less inflammation than control folds (P < 0.005). In addition, hypertrophy of the lamina propria and fibrosis were significantly reduced upon ASC injection (P < 0.02). The decrease in viscoelastic parameters was less important in the ASC injected group compared to the noninjected group (P = 0.08). CONCLUSION: Injection of autologous ASCs improved vocal fold healing in our preclinical model. Further studies are needed, but this method may be useful in humans. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:E278-E285, 2016.

Experimental and Numerical Models of Complex Clinical Scenarios; Strategies to Improve Relevance and Reproducibility of Joint Replacement Research.

This research review aims to focus attention on the effect of specific surgical and host factors on implant fixation, and the importance of accounting for them in experimental and numerical models. These factors affect (a) eventual clinical applicability and (b) reproducibility of findings across research groups. Proper function and longevity for orthopedic joint replacement implants relies on secure fixation to the surrounding bone. Technology and surgical technique has improved over the last 50 years, and robust ingrowth and decades of implant survival is now routinely achieved for healthy patients and first-time (primary) implantation. Second-time (revision) implantation presents with bone loss with interfacial bone gaps in areas vital for secure mechanical fixation. Patients with medical comorbidities such as infection, smoking, congestive heart failure, kidney disease, and diabetes have a diminished healing response, poorer implant fixation, and greater revision risk. It is these more difficult clinical scenarios that require research to evaluate more advanced treatment approaches. Such treatments can include osteogenic or antimicrobial implant coatings, allo- or autogenous cellular or tissue-based approaches, local and systemic drug delivery, surgical approaches. Regarding implant-related approaches, most experimental and numerical models do not generally impose conditions that represent mechanical instability at the implant interface, or recalcitrant healing. Many treatments will work well in forgiving settings, but fail in complex human settings with disease, bone loss, or previous surgery. Ethical considerations mandate that we justify and limit the number of animals tested, which restricts experimental permutations of treatments. Numerical models provide flexibility to evaluate multiple parameters and combinations, but generally need to employ simplifying assumptions. The objectives of this paper are to (a) to highlight the importance of mechanical, material, and surgical features to influence implant-bone healing, using a selection of results from two decades of coordinated experimental and numerical work and (b) discuss limitations of such models and the implications for research reproducibility. Focusing model conditions toward the clinical scenario to be studied, and limiting conclusions to the conditions of a particular model can increase clinical relevance and research reproducibility.

Can the gracilis replace the anterior cruciate ligament in the knee? A biomechanical study.

PURPOSE: The purpose of this study was to determine whether a four-strand gracilis-only construct possesses the biomechanical properties needed to act as an anterior cruciate ligament (ACL) reconstruction graft. METHODS: This was a pilot study with 32 cadaver specimens. The biomechanical properties of three types of grafts were determined using validated tensile testing methods: patellar tendon (BTB), both hamstring tendons together (GST4) and gracilis alone (G4). RESULTS: The maximum load at failure of the G4 was 416.4 N (±187.7). The GST4 and BTB had a maximum load at failure of 473.5 N (±176.9) and 413.3 N (±120.4), respectively. The three groups had similar mean maximum load and stiffness values. The patellar tendon had significantly less elongation at failure than the other two graft types. CONCLUSIONS: The biomechanical properties of a four-strand gracilis construct are comparable to the ones of standard grafts. This type of graft would be useful in the reconstruction of the anteromedial bundle in patients with partial ACL ruptures.

Spino-pelvic alignment influences disc hydration properties after AIS surgery: a prospective MRI-based study.

PURPOSE: To analyze the disc hydration and volumetric changes of the intervertebral disc after scoliosis surgery depending on the sagittal spino-pelvic organization. METHODS: We conducted a prospective MRI study in 45 patients with surgically treated adolescent idiopathic scoliosis (AIS) with a minimum 2-year follow-up. Fusion ended at L1 (n = 13), L2 (n = 14), L3 (n = 11) or L4 (n = 7). Total disc (Vd) and nucleus volumes (Vn) were extrapolated from 3D reconstruction using a custom-made image processing software (Biomechlab, Toulouse, France). Nucleus and external disc contours were semi-automatically detected on turbo spin echo T2-weighted sequence joined 3-mm sagittal cuts. Disc hydration was extrapolated from the nucleus-disc volume ratio (Vn/Vd). Radiographic sagittal parameters were measured pre- and post-operatively on full spine standing views (pelvic incidence, sacral slope, L1S1 lumbar lordosis). Lumbo-pelvic congruity was calculated by the ratio LL/SS according to Stagnara. RESULTS: Mean PI of the cohort was 55° (34°-85°). After surgical correction, lumbar lordosis was slightly increased by 3° (p = 0.02) decreasing lumbo-pelvic congruity from 1.37 to 1.27 (p < 0.01). When pelvic incidence was less than 55° (mean PI 46°), nucleus volumes have increased on average by 30 % compared to the preoperative status in the unfused lumbar discs, while the total disc volumes has remained stable. Five-year follow-up (n = 13) confirmed the constant improvement of the disc hydration ratio. When PI was high (mean PI 64°), volumetric changes were very mild and significant changes in nucleus volumes and disc hydration ratio concerned only the intermediate lumbar levels (L2L3, L3L4 and L4L5). CONCLUSIONS: This prospective MRI study showed a significant and sustainable improvement in T2 hypersignal of the disc, indirectly indicating improvement of disc hydration content after AIS surgery. Analysis of disc volumetric changes according to the pelvic incidence suggests that these changes are under the influence of the sagittal spino-pelvic alignment. PI seems to play a key role in the homeostasis of the discs under fusion and should be taken into account for preoperative planning. The restoration of the lumbo-pelvic congruence may help to limit early degenerative changes in the free-motion segment discs after AIS surgery. Hydration content was less sensitive to surgery when PI was high, suggesting higher shear stress in the lower discs. Longer follow-up is required to confirm this hypothesis.