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BACKGROUND: Chediak-Higashi syndrome (CHS) is a rare and potentially fatal autosomal recessive disease characterized by frequent bacterial infections, bleeding tendency, oculocutaneous albinism, photosensitivity and progressive neurologic dysfunction. Owing to the rarity of this condition, the objective of this study was to describe patients with CHS. METHODS: Retrospective evaluation of patients followed in a paediatric tertiary centre of Allergy and Immunology of São Paulo, Brazil, between 1986 and 2018 with a confirmed diagnosis of CHS. Data were obtained from medical records. Demographic aspects, family history, clinical findings, laboratory data, diagnosis, treatment and outcome were described. RESULTS: A total of 14 patients (five male) were included. Clinical manifestations were first recognized at a median age of two months (at birth-20 months). Median age at diagnosis was 1.7 years (0-5 years). All patients had recurrent infections. Albinism was present in 13 patients and silvery or light hair was present in 14. Seven patients developed hemophagocytic lymphohistiocytosis (HLH); the median age at the diagnosis of HLH was 5.7 years (2.6-6.7 years) and the median interval between the diagnosis of CHS and HLH was 3.3 years (0-5 years). Four of the most recently diagnosed patients underwent bone marrow transplantation (BMT). Nine patients are deceased, and one was lost to follow-up. The median age of death was 6.7 years (3.8-22 years). Five patients died of HLH, one of lymphoma, and three of infection. All the patients who had HLH before the year of 2000 died of HLH. The two most recently diagnosed patients with HLH were able to cure the HLH, although they died of other causes. Four patients are alive, three of them after successful BMT. CONCLUSION: Thirty years of follow up showed an improvement in the prognosis in patients with CHS. The better understanding of the underlying biological mechanisms of HLH allowed the standardization of management protocols, resulting in survival improvement. BMT is the only treatment that can change CHS prognosis, which emphasizes the need for early identification of the disease.
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Trasplante de Médula Ósea , Síndrome de Chediak-Higashi/diagnóstico , Adolescente , Albinismo , Brasil , Síndrome de Chediak-Higashi/mortalidad , Síndrome de Chediak-Higashi/terapia , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Infecciones , Linfohistiocitosis Hemofagocítica , Masculino , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Centros de Atención Terciaria , Adulto JovenRESUMEN
Schistosomiasis - caused by trematodes from the genus Schistosoma - affects more than 200 million people worldwide. Growing resistance to therapy with praziquantel (PZQ) has encouraged the search for novel treatments against this neglected disease. The compound 7-epiclusianone (7-epi) - isolated from 'bacupari' (the fruit of the Gracinia brasiliensis tree) - has promising activity against Schistosoma mansoni in vitro, damaging the parasite's tegument. However, the target and mechanism of action of 7-epi have not been identified. Here, we examined the possibility that 7-epi harms the tegument by inhibiting parasite superoxide dismutase (SOD), which protects the tegument from damage by reactive oxygen species produced by host immune cells. Molecular docking analysis in silico suggested strong interactions between 7-epi and S. mansoni cytosolic superoxide dismutase (SmCtSOD) at allosteric cavities. Schistosoma mansoni couples were cultivated ex vivo with 12.44-198.96 µm 7-epi for 24 h, and then parasite extracts were tested for lipid peroxidation (as a surrogate for oxidative stress), and SOD activity and expression. Lipid peroxidation levels increased after incubation with concentrations ≥99.48 µm 7-epi, and this compound reduced SOD activity at concentrations ≥24.87 µm. However, contact with 7-epi did not alter SOD expression, by quantitative real-time polymerase chain reaction (qRT-PCR). Our results show that the inhibition of SmCtSOD is partly responsible for the tegument detachment observed after incubation with 7-epi, but is not the only cause of the antiparasitic action of this compound in vitro.
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Benzofenonas/farmacología , Benzoquinonas/farmacología , Inhibidores Enzimáticos/farmacología , Schistosoma mansoni/enzimología , Superóxido Dismutasa/antagonistas & inhibidores , Animales , Benzofenonas/química , Benzoquinonas/química , Inhibidores Enzimáticos/química , Perfilación de la Expresión Génica , Integumento Común , Peroxidación de Lípido , Simulación del Acoplamiento Molecular , Reacción en Cadena en Tiempo Real de la Polimerasa , Schistosoma mansoni/efectos de los fármacos , Superóxido Dismutasa/biosíntesis , Superóxido Dismutasa/químicaRESUMEN
BACKGROUND: Determining whether patients with cow's milk allergy (CMA) can tolerate foods produced with baked milk could provide a better quality of life, a better prognosis, and an option for desensitization. OBJECTIVES: The aim of this study was to identify which patients over four years of age with persistent CMA could tolerate baked milk, to compare the clinical and laboratory characteristics of reactive and non-reactive groups and to describe their clinical evolution. MATERIALS AND METHODS: A cross-sectional study was conducted (January/13 to November/14) that included all the patients followed at a food allergy center who met the inclusion criteria. The patients underwent an oral food challenge (OFC) with a muffin (2.8g of cow's milk protein). To exclude cow's milk (CM) tolerance, the patients were subsequently challenged with unheated CM. RESULTS: Thirty patients met all the inclusion criteria. Fourteen patients (46.7%) were considered non-reactive to baked milk and reactive to unheated CM. When the groups that were reactive and non-reactive to baked milk were compared, no statistically significant differences in clinical features were found. The prick test for α-lactalbumin (p=0.01) and casein (p=0.004) and the serum specific IgE for casein (p=0.05) presented statistical differences. After one year, none of the patients who were reactive to baked milk were ingesting CM, while 28% of the tolerant patients were consuming fresh CM (p=0.037). CONCLUSIONS: Baked milk can be tolerated by patients with CMA, especially those with lower levels of casein and α-lactalbumin. This option can improve quality of life and accelerate tolerance.
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Culinaria , Hipersensibilidad a la Leche/epidemiología , Hipersensibilidad a la Leche/inmunología , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Tolerancia Inmunológica/inmunología , MasculinoRESUMEN
This work presents a combined experimental-numerical framework for the biomechanical characterization of highly hydrated collagen hydrogels, namely with 0.20, 0.30 and 0.40% (by weight) of collagen concentration. Collagen is the most abundant protein in the extracellular matrix of animals and humans. Its intrinsic biocompatibility makes collagen a promising substrate for embedding cells within a highly hydrated environment mimicking natural soft tissues. Cell behaviour is greatly influenced by the mechanical properties of the surrounding matrix, but the biomechanical characterization of collagen hydrogels has been challenging up to now, since they present non-linear poro-viscoelastic properties. Combining the stiffness outcomes from rheological experiments with relevant literature data on collagen permeability, poroelastic finite element (FE) models were developed. Comparison between experimental confined compression tests available in the literature and analogous FE stress relaxation curves showed a close agreement throughout the tests. This framework allowed establishing that the dynamic shear modulus of the collagen hydrogels is between 0.0097 ± 0.018 kPa for the 0.20% concentration and 0.0601 ± 0.044 kPa for the 0.40% concentration. The Poisson's ratio values for such conditions lie within the range of 0.495-0.485 for 0.20% and 0.480-0.470 for 0.40%, respectively, showing that rheology is sensitive enough to detect these small changes in collagen concentration and thus allowing to link rheology results with the confined compression tests. In conclusion, this integrated approach allows for accurate constitutive modelling of collagen hydrogels. This framework sets the grounds for the characterization of related hydrogels and to the use of this collagen parameterization in more complex multiscale models.
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Colágeno/química , Hidrogeles/química , Fenómenos Biomecánicos , Simulación por Computador , Análisis de Elementos Finitos , Modelos Biológicos , Reología , Ingeniería de TejidosRESUMEN
BACKGROUND: Cow's milk allergy diagnosis many times requires double-blind placebo-controlled food challenge (DBPCFC), which presents high accuracy but involves risks, specifically in infants and anaphylactic patients. The identification of the cut-off values for specific IgE to milk or its components would contribute to cow's milk allergy (CMA) diagnosis. The aim of this study was to compare discriminating concentration of a cow's milk specific IgE and its fractions (α-lactoalbumin, ß-lactoglobulin, casein) in children for the CMA diagnosis. METHODS: this study included 123 patients (M:F=1.3:1) median age at diagnosis=1.91 years, (3.5m to 13.21y) with CMA diagnosis via DBPCFC (n=26), proven anaphylaxis due to cow's milk (n=46) or a suggestive clinical history associated with a positive skin prick test (n=51) and open oral food challenge. The control group included 61 patients (1 male:1.1 female) ages ranging from 0.66 to 16.7 years (median=6.83 years). Receiver operator characteristics (ROC) curves were constructed to determine the best cut-offs that guarantees high specificity (>95%) for cow's milk and its components. RESULTS: considering 98% specificity, cut-off points were: 3.06 kU/L for cow's milk, 2.06 kU/L for α-lactalbumin, 1.85 kU/L for ß-lactoglobulin and 1.47kU/L for casein. The best ROC curve (area under the curve=0.929) was obtained evaluating cow's milk. CONCLUSION: this study showed that the cut-off point detected for whole cow's milk revealed a better discriminatory capacity for CMA diagnosis without the necessity of the milk components testing.
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Anafilaxia/prevención & control , Hipersensibilidad a la Leche/diagnóstico , Grupos de Población , Adolescente , Anafilaxia/etiología , Animales , Bovinos , Niño , Preescolar , Femenino , Humanos , Inmunización , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Lactante , Masculino , Leche/inmunología , Hipersensibilidad a la Leche/complicaciones , Estándares de Referencia , Valores de Referencia , Sensibilidad y EspecificidadRESUMEN
Although the richness of Bacteria and Fungi in Cerrado' soils has been reported, here we report, for the first time, the archaeal community in Cerrado's soils. DNA extracted from soil of two distinct vegetation types, a dense subtype of sensu strict (cerrado denso) and riverbank forest (mata de galeria), was used to amplify Archaea-specific 16S rRNA gene. All of the fragments sequenced were classified as Archaea into the phylum Thaumarchaeota, predominantly affiliated to groups I.1b and I.1c. Sequences affiliated to the group I.1a were found only in the soil from riverbank forest. Soils from 'cerrado denso' had greater Archaea richness than those from 'mata de galeria' based on the richness indexes and on the rarefaction curve. ß-Diversity analysis showed significant differences between the sequences from the two soil areas studied because of their different thaumarchaeal group composition. These results provide information about the third domain of life from Cerrado soils.
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Archaea/clasificación , Archaea/genética , Microbiología del Suelo , Archaea/aislamiento & purificación , Brasil , Genes Arqueales , Genes de ARNr , Metagenoma , Filogenia , ARN Ribosómico 16S/genética , Suelo/química , ÁrbolesRESUMEN
BACKGROUND: A double-blind, placebo-controlled food challenge (DBPCFC) is considered the gold standard for diagnosing food allergy, but because of methodological difficulties it is rarely conducted in clinical practice, especially in paediatric patients. The purpose of the study was to propose a DBPCFC protocol that is adapted to our conditions for the diagnosis of an IgE-mediated cow's milk allergy (CMA) in a Brazilian reference centre for paediatric allergies. METHODS: This study includes the experimental phase (choice of materials, adjustments made to protocols described in the literature) and the test execution phase. DBPCFCs were performed in 58 patients aged 1-15 years who were separated into two groups: Group 1 (n=39), sex 1.6 M:F, 5.3 years median age, suggestive history of IgE-mediated CMA; and Group 2 (n=19), sex 1.4 M:F, 8.3 years median age with symptoms not associated with milk ingestion and laboratory data not compatible with IgE-mediated CMA. RESULTS: The materials were standardised for testing: containers and disposable products, low-lactose cow's milk (CM) and vehicles, such as natural fruit juice, vegetable soup and soybean-based beverages. Each DBPCFC was performed in a single day with two blind, randomised phases with a 2-h interval between them. The milk doses were gradually increased and offered in regular intervals of 15-30 min. Following negative or inconclusive results, patients underwent an open oral challenge test with 200 mL of low-lactose CM. CONCLUSIONS: The proposed adaptation for the DBPCFC allowed to implement this important test for the diagnosis of IgE-mediated CMA in a reference centre for paediatric allergies. It was considered feasible and safe if performed in an appropriate setting with physician supervision.
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Inmunización , Hipersensibilidad a la Leche/diagnóstico , Proteínas de la Leche/inmunología , Leche/efectos adversos , Adolescente , Alérgenos/inmunología , Animales , Brasil , Bovinos , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Inmunoglobulina E/sangre , Pruebas Inmunológicas/métodos , Lactante , Masculino , Hipersensibilidad a la Leche/epidemiología , Proteínas de la Leche/efectos adversos , Efecto Placebo , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND AND OBJECTIVE: The present work had as its main objective the development of a method for localizing and automatically segmenting lumbar intervertebral discs (IVD) in 3D from magnetic resonance imaging (MRI), with the goal of supporting the generation of finite element (FE) models from actual lumbar spine anatomy, by providing accurate and personalized information on the shape of the patient's IVD. The extension of the method to allow performing separate segmentations of the IVD's two main structures - annulus fibrosus (AF) and nucleus pulposus (NP) - as well as automatically detecting degenerated IVD where this distinction is no longer possible was also an objective of the work. METHODS: The method presented here evolves from 2D segmentations in the sagittal profile using Gabor filters towards 3D segmentations. It works by detecting the spine curves and intensity regions corresponding to IVD. As so, the 2D method from Zhu et al. (2013) was partially implemented, modified and adapted to 3D use, and then tested with eight spines from two separated online datasets. The 3D adaptation was achieved by using vertebral body segmentation masks to approximate the shape of the vertebrae and to adjust the spine curves accordingly. RESULTS: The method showed average values of 85%, 83% and 96% for the Dice coefficient, sensitivity and specificity, respectively. The method correctly identified 65 of 68 (96%) IVD as either healthy or degenerated. The method's Dice coefficient is within the range of existing 3D IVD segmentation methods in the literature (81-92%). The method took on average 6-7 s to perform a full 3D segmentation, which is well within the range of the existing methods (2 s - 19 min). CONCLUSIONS: The developed method can be used to generate accurate 3D models of the IVD based on MRI, with AF/NP distinction and detection of marked degeneration by comparing each IVD with the remaining spine levels. Further work shall improve the method towards distinguishing between specific levels of degeneration for clinically oriented FE modeling.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Humanos , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Simulación por Computador , Imagen por Resonancia Magnética/métodos , ComputadoresAsunto(s)
ARN Viral/análisis , Saliva/virología , Infección por el Virus Zika/diagnóstico , Virus Zika/aislamiento & purificación , Adulto , Animales , Sangre/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Tiempo , Virus Zika/genéticaRESUMEN
Systemic lupus erythematosus (SLE) is an autoimmune disorder of the connective tissue with a wide and heterogeneous spectrum of manifestations, with renal and neurological involvement usually related to worse prognosis. SLE more frequently affects females of reproductive age, and a high prevalence and renal manifestation seem to be associated with non-European ethnicity. The present study aims to investigate candidate loci to SLE predisposition and evaluate the influence of ethnic ancestry in the disease risk and clinical phenotypic heterogeneity of lupus at onset. Samples represented by 111 patients and 345 controls, originated from the city of Belém, located in the Northern Region of Brazil, were investigated for polymorphisms in HLA-G, HLA-C, SLC11A1, MTHFR, CASP8 and 15 KIR genes, in addition to 89 Amerindian samples genotyped for SLC11A1. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. Predisposition to SLE was associated with GTGT deletion at the SLC11A1 3'UTR, presence of KIR2DS2 +/KIR2DS5 +/KIR3DS1 + profile, increased number of stimulatory KIR genes, and European and Amerindian ancestries. The ancestry analysis ruled out ethnic differences between controls and patients as the source of the observed associations. Moreover, the African ancestry was associated with renal manifestations.
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Proteínas de Transporte de Catión/genética , Etnicidad/genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Lupus Eritematoso Sistémico/genética , Polimorfismo Genético , Receptores KIR/genética , Adulto , Edad de Inicio , Brasil , Ciudades , Femenino , Frecuencia de los Genes , Humanos , Lupus Eritematoso Sistémico/etnología , Masculino , Receptores KIR3DS1/genéticaRESUMEN
This work deals with the finite element (FE) implementation of a biphasic poroelastic formulation specifically developed to address the intricate behaviour of the Intervertebral Disc (IVD) and other highly hydrated soft tissues. This formulation is implemented in custom FE solver V-Biomech, being the validation performed with a lumbar IVD model, which was compared against the analogous FE model of Williams et al. and the experiments of Tyrrell et al. Good agreement with these benchmarks was achieved, meaning that V-Biomech and its novel poroelastic formulation are a viable alternative for simulation of biphasic soft tissues.
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Elasticidad , Análisis de Elementos Finitos , Disco Intervertebral/fisiología , Análisis Numérico Asistido por Computador , Ósmosis , Anisotropía , Anillo Fibroso/anatomía & histología , Anillo Fibroso/fisiología , Fenómenos Biomecánicos , Fuerza Compresiva , Simulación por Computador , Humanos , Disco Intervertebral/anatomía & histología , Modelos Biológicos , Presión , Estrés Mecánico , ViscosidadRESUMEN
BACKGROUND: Advancing age and degeneration frequently lead to low back pain, which is the most prevalent musculoskeletal disorder worldwide. Degenerative changes in intervertebral discs and musculo-ligamentous incapacity to compensate sagittal imbalance are typically amongst the sources of instability, with spinal fusion techniques being the main treatment options to relieve pain. The aims of this work were to: (i) assess the link between ligament degeneration and spinal instability by determining the role of each ligament per movement, (ii) evaluate the impact of disc height reduction in degenerative changes, and (iii) unveil the most advantageous type of posterior fixation in Oblique Lumbar Interbody Fusion to prevent adjacent disc degeneration. METHODS: Two L3-L5 finite element models were developed, being the first in healthy condition and the second having reduced L4-L5 height. Different degrees of degeneration were tested, combined with different fixation configurations for Oblique Lumbar Interbody Fusion. FINDINGS: Facet capsular ligament and anterior longitudinal ligament were the most influential ligaments for spinal stability, particularly with increasing degeneration and disc height reduction. Pre-existent degeneration had lower influence than the fusion procedure for the risk of adjacent disc degeneration, being the highest stability and minimal degeneration achieved with bilateral fixation. Right unilateral fixation was more suited to reduce disc stress than left unilateral fixation. INTERPRETATION: Bilateral fixation is the best option to stabilize the spinal segment, but unilateral right fixation may suffice. This has direct implications for clinical practice, and the extension to a population-based study will allow for more efficient fusion surgeries.
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Degeneración del Disco Intervertebral , Disco Intervertebral , Fusión Vertebral , Simulación por Computador , Humanos , Disco Intervertebral/cirugía , Degeneración del Disco Intervertebral/cirugía , Vértebras Lumbares/cirugíaRESUMEN
In the name of the authors of the paper "Permeability versus Design in TPMS Scaffolds", published in Materials in 2019 and already counting six citations in Google Scholar to date, I would like to formally respond to the comment manuscript now entitled "Assessing Porous Media Permeability in Non-Darcy Flow: A Re-Evaluation Based on the Forchheimer Equation" [...].
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The combination of computational methods with 3D printing allows for the control of scaffolds microstructure. Lately, triply periodic minimal surfaces (TPMS) have been used to design porosity-controlled scaffolds for bone tissue engineering (TE). The goal of this work was to assess the mechanical properties of TPMS Gyroid structures with two porosity levels (50 and 70%). The scaffold stiffness function of porosity was determined by the asymptotic homogenisation method and confirmed by mechanical testing. Additionally, microCT analysis confirmed the quality of the printed parts. Thus, the potential of both design and manufacturing processes for bone TE applications is here demonstrated.
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Huesos/fisiología , Análisis Numérico Asistido por Computador , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Módulo de Elasticidad , Análisis de Elementos Finitos , Procesamiento de Imagen Asistido por Computador , Porosidad , Impresión Tridimensional , Microtomografía por Rayos XRESUMEN
Scaffolds for bone tissue engineering are porous structures that serve as support for cellular growth and, therefore, new tissue formation. The present work assessed the influence of the porous architecture of triply periodic minimal surface (TPMS) scaffolds on their macroscopic permeability behavior, combining numerical and experimental methods. The TPMS scaffolds considered were Schwartz D, Schwartz P, and Gyroid, which have been previously studied for bone tissue engineering, with 70% porosity. On the experimental side, these scaffolds were produced by MultiJet 3D printing and tested for fluid passage to calculate their permeability through Darcy's Law. On the numerical side, finite element (FE) models of the scaffolds were simulated on ABAQUS® for fluid passage under compression to assess potential fluid concentration spots. The outcomes revealed that the design of the unit cell had a noticeable effect on both calculated permeability and FE computed fluid flow velocity, regardless of the identical porosity, with the Gyroid scaffold having higher permeability and the Schwartz P a lower probability of fluid trapping. Schwartz D had the worst outcomes in both testing modalities, so these scaffolds would most likely be the last choice for promoting cell differentiation onto bone cells. Gyroid and Schwartz P would be up for selection depending on the application and targeted bone tissue.
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Bone finite element (FE) studies based on infant post-mortem computed tomography (CT) examinations are being developed to provide quantitative information to assist the differentiation between accidental and inflicted injury, and unsuspected underlying disease. As the growing skeleton contains non-ossified cartilaginous regions at the epiphyses, which are not well characterised on CT examinations, it is difficult to evaluate the mechanical behaviour of the developing whole bone. This study made use of paired paediatric post mortem femoral CT and magnetic resonance imaging (MRI) examinations at two different stages of development (4 and 7 months) to provide anatomical and constitutive information for both hard and soft tissues. The work aimed to evaluate the effect of epiphyseal ossification on the propensity to shaft fractures in infants. The outcomes suggest that the failure load of the femoral diaphysis in the models incorporating the non-ossified epiphysis is within the range of bone-only FE models. There may however be an effect on the metaphysis. Confirmation of these findings is required in a larger cohort of children.
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Huesos/diagnóstico por imagen , Fémur/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Autopsia , Huesos/fisiopatología , Diáfisis/diagnóstico por imagen , Diáfisis/crecimiento & desarrollo , Diáfisis/fisiopatología , Epífisis/diagnóstico por imagen , Epífisis/crecimiento & desarrollo , Epífisis/fisiopatología , Femenino , Fémur/crecimiento & desarrollo , Fémur/fisiopatología , Análisis de Elementos Finitos , Humanos , Lactante , Recién Nacido , Masculino , Modelos Biológicos , RadiografíaRESUMEN
Scaffolds are used in diverse tissue engineering applications as hosts for cell proliferation and extracellular matrix formation. One of the most used tissue engineering materials is collagen, which is well known to be a natural biomaterial, also frequently used as cell substrate, given its natural abundance and intrinsic biocompatibility. This study aims to evaluate how the macroscopic biomechanical stimuli applied on a construct made of polycaprolactone scaffold embedded in a collagen substrate translate into microscopic stimuli at the cell level. Eight poro-hyperelastic finite element models of 3D printed hybrid scaffolds from the same batch were created, along with an equivalent model of the idealized geometry of that scaffold. When applying an 8% confined compression at the macroscopic level, local fluid flow of up to 20 [Formula: see text]m/s and octahedral strain levels mostly under 20% were calculated in the collagen substrate. Conversely unconfined compression induced fluid flow of up to 10 [Formula: see text]m/s and octahedral strain from 10 to 35%. No relevant differences were found amongst the scaffold-specific models. Following the mechanoregulation theory based on Prendergast et al. (J Biomech 30:539-548, 1997. https://doi.org/10.1016/S0021-9290(96)00140-6 ), those results suggest that mainly cartilage or fibrous tissue formation would be expected to occur under unconfined or confined compression, respectively. This in silico study helps to quantify the microscopic stimuli that are present within the collagen substrate and that will affect cell response under in vitro bioreactor mechanical stimulation or even after implantation.