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1.
J R Soc Interface ; 21(213): 20230592, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38593841

RESUMO

The mechanical characterization of the oesophagus is essential for applications such as medical device design, surgical simulations and tissue engineering, as well as for investigating the organ's pathophysiology. However, the material response of the oesophagus has not been established ex vivo in regard to the more complex aspects of its mechanical behaviour using fresh, human tissue: as of yet, in the literature, only the hyperelastic response of the intact wall has been studied. Therefore, in this study, the layer-dependent, anisotropic, visco-hyperelastic behaviour of the human oesophagus was investigated through various mechanical tests. For this, cyclic tests, with increasing stretch levels, were conducted on the layers of the human oesophagus in the longitudinal and circumferential directions and at two different strain rates. Additionally, stress-relaxation tests on the oesophageal layers were carried out in both directions. Overall, the results show discrete properties in each layer and direction, highlighting the importance of treating the oesophagus as a multi-layered composite material with direction-dependent behaviour. Previously, the authors conducted layer-dependent cyclic experimentation on formalin-embalmed human oesophagi. A comparison between the fresh and embalmed tissue response was carried out and revealed surprising similarities in terms of anisotropy, strain-rate dependency, stress-softening and hysteresis, with the main difference between the two preservation states being the magnitude of these properties. As formalin fixation is known to notably affect the formation of cross-links between the collagen of biological materials, the differences may reveal the influence of cross-links on the mechanical behaviour of soft tissues.


Assuntos
Esôfago , Projetos de Pesquisa , Humanos , Estresse Mecânico , Esôfago/fisiologia , Anisotropia , Fenômenos Biomecânicos , Resistência à Tração
2.
Biomech Model Mechanobiol ; 23(1): 23-59, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37935880

RESUMO

The gastrointestinal (GI) organs of the human body are responsible for transporting and extracting nutrients from food and drink, as well as excreting solid waste. Biomechanical experimentation of the GI organs provides insight into the mechanisms involved in their normal physiological functions, as well as understanding of how diseases can cause disruption to these. Additionally, experimental findings form the basis of all finite element (FE) modelling of these organs, which have a wide array of applications within medicine and engineering. This systematic review summarises the experimental studies that are currently in the literature (n = 247) and outlines the areas in which experimentation is lacking, highlighting what is still required in order to more fully understand the mechanical behaviour of the GI organs. These include (i) more human data, allowing for more accurate modelling for applications within medicine, (ii) an increase in time-dependent studies, and (iii) more sophisticated in vivo testing methods which allow for both the layer- and direction-dependent characterisation of the GI organs. The findings of this review can also be used to identify experimental data for the readers' own constitutive or FE modelling as the experimental studies have been grouped in terms of organ (oesophagus, stomach, small intestine, large intestine or rectum), test condition (ex vivo or in vivo), number of directions studied (isotropic or anisotropic), species family (human, porcine, feline etc.), tissue condition (intact wall or layer-dependent) and the type of test performed (biaxial tension, inflation-extension, distension (pressure-diameter), etc.). Furthermore, the studies that investigated the time-dependent (viscoelastic) behaviour of the tissues have been presented.


Assuntos
Trato Gastrointestinal , Estômago , Animais , Gatos , Humanos , Suínos , Trato Gastrointestinal/fisiologia , Fenômenos Biomecânicos , Estresse Mecânico , Análise de Elementos Finitos
3.
Int J Biol Macromol ; 251: 126287, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37573913

RESUMO

Cellulose nanocrystals (CNCs) have gained significant attraction from both industrial and academic sectors, thanks to their biodegradability, non-toxicity, and renewability with remarkable mechanical characteristics. Desirable mechanical characteristics of CNCs include high stiffness, high strength, excellent flexibility, and large surface-to-volume ratio. Additionally, the mechanical properties of CNCs can be tailored through chemical modifications for high-end applications including tissue engineering, actuating, and biomedical. Modern manufacturing methods including 3D/4D printing are highly advantageous for developing sophisticated and intricate geometries. This review highlights the major developments of additive manufactured CNCs, which promote sustainable solutions across a wide range of applications. Additionally, this contribution also presents current challenges and future research directions of CNC-based composites developed through 3D/4D printing techniques for myriad engineering sectors including tissue engineering, wound healing, wearable electronics, robotics, and anti-counterfeiting applications. Overall, this review will greatly help research scientists from chemistry, materials, biomedicine, and other disciplines to comprehend the underlying principles, mechanical properties, and applications of additively manufactured CNC-based structures.

4.
Asian J Pharm Sci ; 18(3): 100812, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37274921

RESUMO

Biopolymers are promising environmentally benign materials applicable in multifarious applications. They are especially favorable in implantable biomedical devices thanks to their excellent unique properties, including bioactivity, renewability, bioresorbability, biocompatibility, biodegradability and hydrophilicity. Additive manufacturing (AM) is a flexible and intricate manufacturing technology, which is widely used to fabricate biopolymer-based customized products and structures for advanced healthcare systems. Three-dimensional (3D) printing of these sustainable materials is applied in functional clinical settings including wound dressing, drug delivery systems, medical implants and tissue engineering. The present review highlights recent advancements in different types of biopolymers, such as proteins and polysaccharides, which are employed to develop different biomedical products by using extrusion, vat polymerization, laser and inkjet 3D printing techniques in addition to normal bioprinting and four-dimensional (4D) bioprinting techniques. This review also incorporates the influence of nanoparticles on the biological and mechanical performances of 3D-printed tissue scaffolds. This work also addresses current challenges as well as future developments of environmentally friendly polymeric materials manufactured through the AM techniques. Ideally, there is a need for more focused research on the adequate blending of these biodegradable biopolymers for achieving useful results in targeted biomedical areas. We envision that biopolymer-based 3D-printed composites have the potential to revolutionize the biomedical sector in the near future.

5.
Colloid Polym Sci ; : 1-19, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37360022

RESUMO

The AC electrical properties of EVA- and NBR-based composites filled with different conductive fillers were investigated. Result shows several magnitudes of increment in AC electrical conductivity and dielectric permittivity after the addition of these conductive fillers, indicating that these materials can be used as supercapacitors. The magnitude of increment was varied according to polymer and filler types. Herein, we also have tested the applicability of different sigmoidal models to find out the percolation threshold value of permittivity for these binary polymer composite systems. It is observed that except sigmoidal-Boltzmann and sigmoidal-dose-response models, other sigmoidal models exhibit different values of percolation threshold when considered for any particular polymer composite system. The paper discusses the variation in results of percolation threshold with an emphasis on the advantages, disadvantages and limitations of these models. We also have applied the classical percolation theory to predict the percolation threshold of permittivity and compared with all the reported sigmoidal models. To judge the unanimous acceptability of these models, they tested vis-à-vis the permittivity results of various polymer composites reported in published literature. To comprehend, all the models except the sigmoidal-logistic-1 model were successfully applicable for predicting the percolation threshold of permittivity for polymer composites. Supplementary Information: The online version contains supplementary material available at 10.1007/s00396-023-05120-2.

6.
Biomech Model Mechanobiol ; 21(6): 1685-1702, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36030514

RESUMO

Mechanical characterisation of the layer-specific, viscoelastic properties of the human oesophagus is crucial in furthering the development of devices emerging in the field, such as robotic endoscopic biopsy devices, as well as in enhancing the realism, and therefore effectiveness, of surgical simulations. In this study, the viscoelastic and stress-softening behaviour of the passive human oesophagus was investigated through ex vivo cyclic mechanical tests. Due to restrictions placed on the laboratory as a result of COVID-19, only oesophagi from cadavers fixed in formalin were allowed for testing. Three oesophagi in total were separated into their two main layers and the mucosa-submucosa layer was investigated. A series of uniaxial tensile tests were conducted in the form of increasing stretch level cyclic tests at two different strain rates: 1% s[Formula: see text] and 10% s[Formula: see text]. Rectangular samples in both the longitudinal and circumferential directions were tested to observe any anisotropy. Histological analysis was also performed through a variety of staining methods. Overall, the longitudinal direction was found to be much stiffer than the circumferential direction. Stress-softening was observed in both directions, as well as permanent set and hysteresis. Strain rate-dependent behaviour was also apparent in the two directions, with an increase in strain rate resulting in an increase in stiffness. This strain rate dependency was more pronounced in the longitudinal direction than the circumferential direction. Finally, the results were discussed in regard to the histological content of the layer, and the behaviour was modelled and validated using a visco-hyperelastic matrix-fibre model.


Assuntos
COVID-19 , Humanos , Anisotropia , Estresse Mecânico , Esôfago , Mucosa , Fenômenos Biomecânicos
7.
Nat Commun ; 13(1): 4406, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35906202

RESUMO

Emerging evidence suggests that resident macrophages within tissues are enablers of tumor growth. However, a second population of resident macrophages surrounds all visceral organs within the cavities and nothing is known about these GATA6+ large peritoneal macrophages (GLPMs) despite their ability to invade injured visceral organs by sensing danger signals. Here, we show that GLPMs invade growing metastases that breach the visceral mesothelium of the liver via the "find me signal", ATP. Depleting GLPMs either by pharmacological or genetic tools, reduces metastases growth. Apoptotic bodies from tumor cells induces programmed cell death ligand 1 (PD-L1) upregulation on GLPMs which block CD8+ T cell function. Direct targeting of GLPMs by intraperitoneal but not intravenous administration of anti-PD-L1 reduces tumor growth. Thermal ablation of liver metastases recruits huge numbers of GLPMs and enables rapid regrowth of tumors. GLPMs contribute to metastatic growth and tumor recurrence.


Assuntos
Neoplasias Hepáticas , Macrófagos Peritoneais , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Fator de Transcrição GATA6/genética , Humanos , Macrófagos/metabolismo , Macrófagos Peritoneais/metabolismo , Recidiva Local de Neoplasia
8.
Int J Biol Macromol ; 218: 930-968, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35896130

RESUMO

The three-dimensional printing (3DP) also known as the additive manufacturing (AM), a novel and futuristic technology that facilitates the printing of multiscale, biomimetic, intricate cytoarchitecture, function-structure hierarchy, multi-cellular tissues in the complicated micro-environment, patient-specific scaffolds, and medical devices. There is an increasing demand for developing 3D-printed products that can be utilized for organ transplantations due to the organ shortage. Nowadays, the 3DP has gained considerable interest in the tissue engineering (TE) field. Polylactide (PLA) and polycaprolactone (PCL) are exemplary biomaterials with excellent physicochemical properties and biocompatibility, which have drawn notable attraction in tissue regeneration. Herein, the recent advancements in the PLA and PCL biodegradable polymer-based composites as well as their reinforcement with hydrogels and bio-ceramics scaffolds manufactured through 3DP are systematically summarized and the applications of bone, cardiac, neural, vascularized and skin tissue regeneration are thoroughly elucidated. The interaction between implanted biodegradable polymers, in-vivo and in-vitro testing models for possible evaluation of degradation and biological properties are also illustrated. The final section of this review incorporates the current challenges and future opportunities in the 3DP of PCL- and PLA-based composites that will prove helpful for biomedical engineers to fulfill the demands of the clinical field.


Assuntos
Materiais Biocompatíveis , Engenharia Tecidual , Materiais Biocompatíveis/química , Humanos , Poliésteres/química , Polímeros , Impressão Tridimensional , Engenharia Tecidual/métodos , Alicerces Teciduais/química
9.
Polymers (Basel) ; 14(9)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35566884

RESUMO

In this work, graphite nanoplatelets (GNP) were incorporated into poly (ethylene terephthalate) (PET) matrix to prepare PET-GNP nanocomposites using a melt compounding followed by compression moulding and then quenching process. Both static and dynamic mechanical properties of these quenched materials were characterized as a function of GNP contents using dynamic mechanical thermal analysis (DMTA) and tensile machine, respectively. The results demonstrated that the addition of GNP improved the stiffness of PET significantly. Additionally, the maximum increase in the storage modulus of 72% at 6 wt.% GNP. The incorporation of GNP beyond 6 wt.% into PET decreases the storage moduli, but they remain higher than pure PET. The observed reduction could be due to agglomeration, resulting in poorer dispersion and distribution of higher levels of GNP into the PET matrix. In contrast to the results for moduli, tensile strength and elongations at break reduce with increasing the GNP content. For example, tensile strength reduced from ∼46 MPa (neat PET) to ∼39 MPa (-15%) for the nanocomposites containing 2 wt.% GNP. This reduction is accompanied by a decline in elongation at break from ∼6.3 (neat PET) to ∼3.4 (-46%) for the same nanocomposites. Such reductions are followed by a gradual decrease in upon further addition of GNP. These reductions indicate that increasing GNP loadings, results in brittleness in nanocomposites. In addition, it was found that quenched PET and composite samples were not fully crystallized after processing and therefore (cold) crystallized during the first heating cycle DMTA, as indicated by a rise in storage moduli above the glass transition temperature during the DMTA first heat. Furthermore, mathematical models based on non-linear theories are developed to capture the experimental data. For this, a set of mechanical stress-strain data is used for model parameters' identification. Another set of data is used for the model validation that demonstrates good agreements with the experimental study.

10.
Biomech Model Mechanobiol ; 21(4): 1169-1186, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35477829

RESUMO

The oesophagus is a primarily mechanical organ whose material characterisation would aid in the investigation of its pathophysiology, help in the field of tissue engineering, and improve surgical simulations and the design of medical devices. However, the layer-dependent, anisotropic properties of the organ have not been investigated using human tissue, particularly in regard to its viscoelastic and stress-softening behaviour. Restrictions caused by the COVID-19 pandemic meant that fresh human tissue was not available for dissection. Therefore, in this study, the layer-specific material properties of the human oesophagus were investigated through ex vivo experimentation of the embalmed muscularis propria layer. For this, a series of uniaxial tension cyclic tests with increasing stretch levels were conducted at two different strain rates. The muscular layers from three different cadaveric specimens were tested in both the longitudinal and circumferential directions. The results displayed highly nonlinear and anisotropic behaviour, with both time- and history-dependent stress-softening. The longitudinal direction was found to be stiffer than the circumferential direction at both strain rates. Strain rate-dependent behaviour was apparent, with an increase in strain rate resulting in an increase in stiffness in both directions. Histological analysis was carried out via various staining methods; the results of which were discussed with regard to the experimentally observed stress-stretch response. Finally, the behaviour of the muscularis propria was simulated using a matrix-fibre model able to capture the various mechanical phenomena exhibited, the fibre orientation of which was driven by the histological findings of the study.


Assuntos
COVID-19 , Pandemias , Anisotropia , Fenômenos Biomecânicos , Esôfago , Humanos , Estresse Mecânico
11.
Luminescence ; 36(8): 2004-2013, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34453772

RESUMO

A smart photoluminescent nanocomposite surface coating was prepared for simple industrial production of long-persisting phosphorescence and superhydrophobic wood. The photoluminescent nanocomposite coatings were capable of continuing to emit light in the dark for prolonged time periods that could reach 1.5 h. Lanthanide-doped aluminium strontium oxide (LASO) nanoparticles at different ratios were immobilized in polystyrene (PS) and developed as a nanocomposite coating for wood substrates. To produce transparency in the prepared nanocomposite coating, LASO was efficiently dispersed in the form of nanoscaled particles to ensure homogeneous dispersion without agglomeration in the PS matrix. The coated wood showed an absorption band at 374 nm and two emission bands at 434 nm and 518 nm. The luminescence spectra showed both long-persisting phosphorescence as well as photochromic fluorescence relying on the LASO ratio. The improved superhydrophobicity and resistance to scratching of the coated wood could be attributed to the LASO NPs incorporated in the polystyrene matrix. Compared with the uncoated wood substrate, the coated LASO-PS nanocomposite film also displayed photostability and high durability. The current study demonstrated the potential high-scale manufacturing of smart wood for some applications such as safety directional signs in buildings, household products, and smart windows.


Assuntos
Nanocompostos , Madeira , Interações Hidrofóbicas e Hidrofílicas , Luminescência , Estrôncio
12.
Luminescence ; 36(8): 1922-1932, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34323352

RESUMO

Transparent wood with multifunctional properties has recently attracted more attention as an efficient building product. Here, we describe the development of transparent wood with long-persistent phosphorescence, tough surface, high durability, photostability, and reversibility without fatigue, and with ultraviolet shielding, superhydrophobicity, and flame-retardant activity. This long-persistent phosphorescent, or glow-in-the-dark, smart wood exhibited an ability to continue emitting light for prolonged periods of time. The photoluminescent translucent wooden substrate was prepared by immobilizing lignin-modulated wooden bulk with an admixture of methylmethacrylate (MMA), ammonium polyphosphate (APP), and lanthanide-doped strontium aluminate (LSA; SrAl2 O4 :Eu2+ ,Dy3+ ) phosphor nanoparticles. The photoluminescent transparent wood displayed a colour switch from colourless to bright white beneath ultraviolet (UV) light and greenish-yellow in the dark as reported by Commission Internationale de l'Éclairage laboratory colorimetric space coordinates. The generated phosphorescent wooden substrates demonstrated an absorbance band at 365 nm and an emission band at 516 nm. The phosphorescent transparent wood was improved flame-retardant properties, ultraviolet shielding, and superhydrophobic properties, as well as a reversible long-persistent phosphorescent responsiveness to UV light without fatigue. The current approach demonstrated a potential large-scale production strategy for multifunctional transparent wooden substrates for a range of applications such as smart windows, gentle indoor and outdoor lighting, and safety directional signs in buildings.


Assuntos
Retardadores de Chama , Madeira , Interações Hidrofóbicas e Hidrofílicas , Luminescência , Estrôncio
13.
J Manuf Syst ; 60: 787-798, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33897085

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly achieved global pandemic status. The pandemic created huge demand for relevant medical and personal protective equipment (PPE) and put unprecedented pressure on the healthcare system within a very short span of time. Moreover, the supply chain system faced extreme disruption as a result of the frequent and severe lockdowns across the globe. In such a situation, additive manufacturing (AM) becomes a supplementary manufacturing process to meet the explosive demands and to ease the health disaster worldwide. Providing the extensive design customization, a rapid manufacturing route, eliminating lengthy assembly lines and ensuring low manufacturing lead times, the AM route could plug the immediate supply chain gap, whilst mass production routes restarted again. The AM community joined the fight against COVID-19 by producing components for medical equipment such as ventilators, nasopharyngeal swabs and PPE such as face masks and face shields. The aim of this article is to systematically summarize and to critically analyze all major efforts put forward by the AM industry, academics, researchers, users, and individuals. A step-by-step account is given summarizing all major additively manufactured products that were designed, invented, used, and produced during the pandemic in addition to highlighting some of the potential challenges. Such a review will become a historical document for the future as well as a stimulus for the next generation AM community.

14.
Nat Commun ; 11(1): 2385, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404937

RESUMO

Upon tissue injury or microbial invasion, a large number of neutrophils converge from blood to the sites of injury or infection in a short time. The migration through a limited number of paths through tissues and capillary networks seems efficient and 'traffic jams' are generally avoided. However, the mechanisms that guide efficient trafficking of large numbers of neutrophils through capillary networks are not well understood. Here we show that pairs of neutrophils arriving closely one after another at capillary bifurcations migrate to alternating branches in vivo and in vitro. Perturbation of chemoattractant gradients and the increased hydraulic resistance induced by the first neutrophil in one branch biases the migration of the following neutrophil towards the other branch. These mechanisms guide neutrophils to efficiently navigate through capillary networks and outline the effect of inter-neutrophil interactions during migration on overall lymphocyte trafficking patterns in confined environments.


Assuntos
Movimento Celular/fisiologia , Fatores Quimiotáticos/metabolismo , Quimiotaxia/fisiologia , Técnicas Analíticas Microfluídicas/métodos , Neutrófilos/fisiologia , Algoritmos , Células Cultivadas , Humanos , Modelos Biológicos , Neutrófilos/citologia , Transdução de Sinais/fisiologia
15.
J Clin Invest ; 129(11): 4643-4656, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31545300

RESUMO

Essentially all Staphylococcus aureus (S. aureus) bacteria that gain access to the circulation are plucked out of the bloodstream by the intravascular macrophages of the liver - the Kupffer cells. It is also thought that these bacteria are disseminated via the bloodstream to other organs. Our data show that S. aureus inside Kupffer cells grew and escaped across the mesothelium into the peritoneal cavity and immediately infected GATA-binding factor 6-positive (GATA6+) peritoneal cavity macrophages. These macrophages provided a haven for S. aureus, thereby delaying the neutrophilic response in the peritoneum by 48 hours and allowing dissemination to various peritoneal and retroperitoneal organs including the kidneys. In mice deficient in GATA6+ peritoneal macrophages, neutrophils infiltrated more robustly and reduced S. aureus dissemination. Antibiotics administered i.v. did not prevent dissemination into the peritoneum or to the kidneys, whereas peritoneal administration of vancomycin (particularly liposomal vancomycin with optimized intracellular penetrance capacity) reduced kidney infection and mortality, even when administered 24 hours after infection. These data indicate that GATA6+ macrophages within the peritoneal cavity are a conduit of dissemination for i.v. S. aureus, and changing the route of antibiotic delivery could provide a more effective treatment for patients with peritonitis-associated bacterial sepsis.


Assuntos
Fator de Transcrição GATA6/imunologia , Macrófagos Peritoneais/imunologia , Peritonite/imunologia , Sepse/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Animais , Feminino , Macrófagos Peritoneais/microbiologia , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Peritonite/microbiologia , Peritonite/patologia , Sepse/microbiologia , Sepse/patologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/patologia , Vancomicina/farmacologia
16.
Polymers (Basel) ; 11(9)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466258

RESUMO

Poly(ethylene terephthalate)/graphite (PET/G) micro-composites were fabricated by the melt compounding method using a minilab extruder. The carbon fillers were found to act as nucleating agents for the PET matrix and hence accelerated crystallization and increased the degree of crystallinity. TGA showed that carbon fillers improved the resistance to thermal and thermo-oxidative degradation under both air and nitrogen atmospheres. However, a poor agreement was observed at higher loadings of the filler where the composites displayed reduced reinforcement efficiency. The results demonstrate that the addition of graphite at loading >14.5 wt.% made electrically conductive composites. It was calculated that the electric conductivities of PET/graphite micro-composites were enhanced, above the percolation threshold values by two orders of magnitudes compared to the PET matrix. The minimum value of conductivity required to avoid electrostatic charge application of an insulating polymer was achieved, just above the threshold values. The addition of graphite also improved thermal stability of PET, accelerated its crystallization process and increased the degree of crystallinity. Microscopic results exhibit no indication of aggregations at 2 wt.% graphite, whereas more agglomeration and rolling up could be seen as the graphite content was increased in the PET matrix (in particular, above the percolation threshold value). Furthermore, based on the mechanical experimental characterization of the PET/graphite micro-composites, a large deformation-based mathematical model is proposed for material behavior predictions. The model fits well the experimental data and predicts other mechanical data that are not included in the parameter identification.

17.
Eur J Immunol ; 49(6): 831-841, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31001813

RESUMO

There is a close association between inflammation and sterile injury, however not all sterile injuries are the same. While a regulated inflammatory response is crucial for proper healing, a dysregulated or nonterminating response leads to disrepair. While immune cells are thought to contribute to the disrepair, they may also be critical for proper healing and as such, their actions may dictate the end result. In all forms of sterile injury, release of damage-associated molecular patterns from necrotic cells causes robust recruitment of innate immune cells. The subsequent release of toxic mediators from immune cells is thought to be damaging in non-resolving sterile injuries in which the dysregulated immune response leads to chronic inflammatory disease. While similar mediators may be released from immune cells in resolution of acute injury, the spatial localization, timing, and self-termination may all be critical. In this review, we summarize the recent advances in our understanding of the temporal and spatial recruitment of various innate immune cells that beget appropriate healing of acute injuries. Where possible we try to compare this appropriate response to dysregulated sterile injuries in an attempt to identify novel therapeutic targets.


Assuntos
Imunidade Inata/imunologia , Fígado/imunologia , Fígado/lesões , Animais , Humanos , Inflamação/imunologia , Cicatrização/imunologia
18.
Int J Mol Sci ; 18(10)2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-29039777

RESUMO

Mitogen-activated protein kinase (MAPK) signaling is involved in a variety of cellular functions. MAPK-dependent functions rely on phosphorylation of target proteins such as mitogen- and stress-activated protein kinase 1 (MSK1). MSK1 participates in the early gene expression and in the production of pro- and anti-inflammatory cytokines. However, the role of MSK1 in neutrophil recruitment remains elusive. Here, we show that chemokine macrophage inflammatory protein-2 (CXCL2) enhances neutrophil MSK1 expression. Using intravital microscopy and time-lapsed video analysis of cremasteric microvasculature in mice, we studied the effect of pharmacological suppression of MSK1 by SB-747651A on CXCL2-elicited neutrophil recruitment. SB-747651A treatment enhanced CXCL2-induced neutrophil adhesion while temporally attenuating neutrophil emigration. CXCL2-induced intraluminal crawling was reduced following SB-747651A treatment. Fluorescence-activated cell sorting analysis of integrin expression revealed that SB-747651A treatment attenuated neutrophil integrin αMß2 (Mac-1) expression following CXCL2 stimulation. Both the transmigration time and detachment time of neutrophils from the venule were increased following SB-747651A treatment. It also decreased the velocity of neutrophil migration in cremasteric tissue in CXCL2 chemotactic gradient. SB-747651A treatment enhanced the extravasation of neutrophils in mouse peritoneal cavity not at 1-2 h but at 3-4 h following CXCL2 stimulation. Collectively, our data suggest that inhibition of MSK1 by SB-747651A treatment affects CXCL2-induced neutrophil recruitment by modulating various steps of the recruitment cascade in vivo.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Quimiocinas/metabolismo , Quimiotaxia de Leucócito/efeitos dos fármacos , Neutrófilos/fisiologia , Oxidiazóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Animais , Biomarcadores , Rastreamento de Células , Quimiocinas/farmacologia , Imunofenotipagem , Masculino , Camundongos , Neutrófilos/efeitos dos fármacos , Peritonite/etiologia , Peritonite/metabolismo , Peritonite/patologia
19.
Science ; 358(6359): 111-116, 2017 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-28983053

RESUMO

Neutrophils have been implicated as harmful cells in a variety of inappropriate inflammatory conditions where they injure the host, leading to the death of the neutrophils and their subsequent phagocytosis by monocytes and macrophages. Here we show that in a fully repairing sterile thermal hepatic injury, neutrophils also penetrate the injury site and perform the critical tasks of dismantling injured vessels and creating channels for new vascular regrowth. Upon completion of these tasks, they neither die at the injury site nor are phagocytosed. Instead, many of these neutrophils reenter the vasculature and have a preprogrammed journey that entails a sojourn in the lungs to up-regulate CXCR4 (C-X-C motif chemokine receptor 4) before entering the bone marrow, where they undergo apoptosis.


Assuntos
Neovascularização Fisiológica/imunologia , Neutrófilos/imunologia , Cicatrização/imunologia , Animais , Apoptose/imunologia , Medula Óssea/imunologia , Movimento Celular/imunologia , Fígado/irrigação sanguínea , Fígado/lesões , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores CXCR4/metabolismo , Regulação para Cima
20.
Proc Math Phys Eng Sci ; 472(2190): 20160170, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27436985

RESUMO

Electro-active polymers (EAPs) for large actuations are nowadays well-known and promising candidates for producing sensors, actuators and generators. In general, polymeric materials are sensitive to differential temperature histories. During experimental characterizations of EAPs under electro-mechanically coupled loads, it is difficult to maintain constant temperature not only because of an external differential temperature history but also because of the changes in internal temperature caused by the application of high electric loads. In this contribution, a thermo-electro-mechanically coupled constitutive framework is proposed based on the total energy approach. Departing from relevant laws of thermodynamics, thermodynamically consistent constitutive equations are formulated. To demonstrate the performance of the proposed thermo-electro-mechanically coupled framework, a frequently used non-homogeneous boundary-value problem, i.e. the extension and inflation of a cylindrical tube, is solved analytically. The results illustrate the influence of various thermo-electro-mechanical couplings.

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