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A considerable number of women giving birth during COVID-19 pandemic reported being concerned about changes to their childbirth plans and experiences due to imposed restrictions. Research prior to the pandemic suggests that women may be more at risk of post-traumatic stress symptoms (PTSS) due to unmet expectations of their childbirth plans. Therefore, this study aimed to examine if the mismatch between women's planned birth and actual birth experiences during COVID-19 was associated with women's postpartum PTSS. Women in the postpartum period (up to 6 months after birth) across 11 countries reported on childbirth experiences, mental health, COVID-19-related factors, and PTSS (PTSD checklist DSM-5 version) using self-report questionnaires (ClinicalTrials.gov: NCT04595123). More than half (64%) of the 3532 postpartum women included in the analysis reported changes to their childbirth plans. All changes were significantly associated with PTSS scores. Participants with one and two changes to their childbirth plans had a 12% and 38% increase, respectively, in PTSS scores compared to those with no changes (Exp(ß) = 1.12; 95% CI [1.06-1.19]; p < 0.001 and Exp(ß) = 1.38; 95% CI [1.29-1.48]; p < 0.001). In addition, the effect of having one change in the childbirth plan on PTSS scores was stronger in primigravida than in multigravida (Exp(ß) = 0.86; 95% CI [0.77-0.97]; p = 0.014). Changes to women's childbirth plans during the COVID-19 pandemic were common and associated with women's postpartum PTSS score. Developing health policies that protect women from the negative consequences of unexpected or unintended birth experiences is important for perinatal mental health.
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COVID-19 , Parto , SARS-CoV-2 , Trastornos por Estrés Postraumático , Humanos , Femenino , COVID-19/epidemiología , COVID-19/psicología , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , Adulto , Parto/psicología , Embarazo , Periodo Posparto/psicología , Encuestas y Cuestionarios , Pandemias , Adulto Joven , Parto Obstétrico/psicologíaRESUMEN
This pilot randomised controlled study (RCT) aimed to assess the feasibility and acceptability of a progressive muscle relaxation with guided imagery intervention (experimental group [EG]) compared to a neutral guided imagery placebo (active control group [ACG]) and standard care to diabetic foot ulcer [DFU] treatment (passive control group [PCG]), to decide on the need for a definitive RCT. Diabetic foot patients with one or two chronic DFU and significant levels of stress/anxiety/depression were recruited and assessed during a period of 6 months, at three moments. Primary outcomes: feasibility rates and satisfaction with relaxation sessions. Secondary outcomes: DFU healing score, DFU-related quality of life (DFUQoL), physical and mental HRQoL, stress and emotional distress, DFU representations, arterial blood pressure, and heart rate. A total of 146 patients completed the baseline (T0) assessment with 54 participants presenting significant distress being randomised into three groups. Patients were assessed 2 months post-intervention (T1) and 4 months after T1 (T2). Feasibility rates showed reduced values on eligibility, recruitment and inclusion in the study, although with an acceptable rate of refusal lower than 10%. On average, participants reported being satisfied with relaxation sessions and recommended them to other patients. Differences between groups showed that, at T1, PCG participants reported higher levels of stress than those from EG and ACG. Within-group differences showed improvements in stress, distress, DFUQoL and DFU extent over time only in EG and ACG. Only EG showed significant changes in DFU representations at T1. The results suggest that relaxation may be a promising coping strategy to deal with DFU distress and an important adjuvant therapy for DFU healing, supporting the implementation of a definitive RCT.
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Diabetes Mellitus , Pie Diabético , Úlcera del Pie , Humanos , Proyectos Piloto , Cicatrización de Heridas , Calidad de VidaRESUMEN
PURPOSE: Postoperative complications after a colonic and rectal surgery are of significant concern to the surgical community. Although there are different techniques to perform anastomosis (i.e., handsewn, stapled, or compression), there is still no consensus on which technique provides the least number of postoperative problems. The objective of this study is to compare the different anastomotic techniques regarding the occurrence or duration of postoperative outcomes such as anastomotic dehiscence, mortality, reoperation, bleeding and stricture (as primary outcomes), and wound infection, intra-abdominal abscess, duration of surgery, and hospital stay (as secondary outcomes). METHODS: Clinical trials published between January 1, 2010, and December 31, 2021, reporting anastomotic complications with any of the anastomotic technique were identified using the MEDLINE database. Only articles that clearly defined the anastomotic technique used, and report at least two of the outcomes defined were included. RESULTS: This meta-analysis included 16 studies whose differences were related to the need of reoperation (p < 0.01) and the duration of surgery (p = 0.02), while for the anastomotic dehiscence, mortality, bleeding, stricture, wound infection, intra-abdominal abscess, and hospital stay, no significant differences were found. Compression anastomosis reported the lowest reoperation rate (3.64%) and the handsewn anastomosis the highest (9.49%). Despite this, more time to perform the surgery was required in compression anastomosis (183.47 min), with the handsewn being the fastest technique (139.92 min). CONCLUSIONS: The evidence found was not sufficient to demonstrate which technique is most suitable to perform colonic and rectal anastomosis, since the postoperative complications were similar between the handsewn, stapled, or compression techniques.
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Absceso Abdominal , Infecciones Intraabdominales , Humanos , Grapado Quirúrgico , Técnicas de Sutura , Constricción Patológica , Absceso , Anastomosis Quirúrgica/métodos , Complicaciones PosoperatoriasRESUMEN
Microcurrent therapy can increase lipolytic activity. However, it is unknown if the increased availability of lipids can influence the selection of energy substrates during a single session of aerobic exercise. We aimed to analyze the effect of microcurrent application to the abdominal region in the consumption of lipids and carbohydrates, and respiratory exchange ratio (RER) during a single session of moderate aerobic exercise in young adults. A pilot study was conducted in which participants were allocated to intervention (IG) or placebo (PG) groups. In both groups, 40 min of microcurrent application with two frequencies (25 and 10 Hz) followed by 50 min of moderate-intensity aerobic exercise (45−55% of heart rate reserve) on a cycloergometer were performed. The microcurrent application was performed without intensity in the PG. A portable gas analyzer (K4b2) was used during exercise in both groups. Thirty-eight participants (20.6 ± 1.8 years; 18 in IG and 20 in PG) were enrolled. There were no significant differences in the consumption of substrates or RER between the groups during exercise (p > 0.05). Microcurrent application seems to be insufficient to influence the consumption of energy substrates and RER during a single session of aerobic exercise in young adults.
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Platelet-rich fibrin (PRF) has been incorporated in surgical procedures to promote tissue and bone healing, particularly in human medicine. The rationale for the use of platelet-based products stems from the fact that platelets, after being activated, release growth factors (GFs) and other active molecules such as cytokines, that modulate inflammation and tissue repair. Although PRF has been advanced as a therapeutic treatment for veterinary use, namely in canine and feline patients (following human medicine developments), to our knowledge a full characterization of PRF therapeutic effectors has never been performed. Herein, we studied the biological properties and release profile of GFs and other cytokines throughout ten days in in vitro culture conditions, in order to investigate the potential therapeutic ability of PRF for canine and feline practice. A protocol for obtaining PRF from whole blood without anti-coagulant from both species was optimized, originating large and homogenous PRF clots. Then, PRF clots obtained from four dogs and four cats were incubated in culture medium to assess the temporal release of platelet-derived growth factor-BB (PDGF-BB), vascular endothelial factor-A (VEGF-A), transforming growth factor ß-1 (TGF-ß1), and interleukin-8 (IL-8). Furthermore, morphological characterization of PRF clots, fresh and after 10 days of incubation, was performed by histology and high-resolution field emission electron scanning microscopy. In standard culture conditions, PRF clots from both species released PDGF-BB, TGF- ß1 and VEGF-A, in a sustained manner, up to day 10. Moreover, PRF presents an initial burst release of IL-8, a mediator of inflammatory response which plays a key role in neutrophil recruitment and degranulation. Overall, our findings show that PRF clots may be an efficient therapeutic strategy in canine and feline clinical practice, accelerating the local healing mechanism, through the sustained delivery of signalling molecules involved in the healing cascade.
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Fibrina Rica en Plaquetas/metabolismo , Secretoma/química , Secretoma/metabolismo , Animales , Becaplermina/sangre , Becaplermina/metabolismo , Gatos , Perros , Femenino , Masculino , Proyectos Piloto , Estándares de Referencia , Factores de Tiempo , Factor de Crecimiento Transformador beta1/sangre , Factor de Crecimiento Transformador beta1/metabolismo , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Work-family conflict constitutes an important source of occupational stress predicting teachers' burnout, and cognitive variables have shown to be core structures in explaining human adaptation to stress. Nevertheless, the role of cognitive appraisal needs to be fully analysed to comprehend how it can mediate the relationship between stress and burnout. In order to understand the potential mediation of cognitive appraisal in the relationship between stress and burnout, we adopted conceptual models of stress that highlighted the value of cognitive appraisal on positive and negative reactions to work demands. Also, we analysed the potential moderation of sex and age in the relationship between work-family conflict, cognitive appraisal, and burnout due to inconsistent findings on how these personal variables can interfere on these relations. In this study, we used structural equation modelling (SEM) to test the mediating of cognitive appraisal in the relationship between work-family conflicts and burnout. A survey with measures of work-family conflicts, cognitive appraisal, and burnout was administered to the participants consisting of 438 Portuguese teachers from kindergarten through high school, aged between 28 and 67 years (M = 46.85; SD = 7.88), 304 of whom were females (69.41%). The results confirmed that cognitive appraisal partially mediated the relationship between work-family conflict and burnout. The mediation effect of cognitive appraisal on the relationship between work-family conflict and burnout was invariant regardless of teachers' sex or age. In sum, cognitive appraisal should be considered in order to understand teachers' adaptation to work.
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Agotamiento Profesional , Conflicto Familiar , Adulto , Anciano , Cognición , Femenino , Humanos , Análisis de Clases Latentes , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Callous-unemotional (CU) traits observed during childhood and adolescence are thought to be precursors of psychopathic traits in adulthood. Adults with high levels of psychopathic traits typically present antisocial behavior. Such behavior can be indicative of atypical moral processing. Evidence suggests that moral dysfunction in these individuals may stem from a disruption of affective components of moral processing rather than from an inability to compute moral judgments per se. No study to date has tested if the dissociation between affective and cognitive dimensions of moral processing linked to psychopathic traits in adulthood is also linked to CU traits during development. Here, 47 typically developing adolescents with varying levels of CU traits completed a novel, animated cartoon task depicting everyday moral transgressions and indicated how they would feel in such situations and how morally wrong the situations were. Adolescents with higher CU traits reported reduced anticipated guilt and wrongness appraisals of the transgressions. However, our key finding was a significant interaction between CU traits and anticipated guilt in predicting wrongness judgments. The strength of the association between anticipated guilt and wrongness judgement was significantly weaker for those with higher levels of CU traits. This evidence extends our knowledge on the cognitive-affective processing deficits that may underlie moral dysfunction in youth who are at heightened risk for antisocial behavior and psychopathy in adulthood. Future longitudinal research is required to elucidate whether there is an increased dissociation between different components of moral processing from adolescence to adulthood for those with high psychopathic traits.
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In this study, a logistic regression model is applied to credit scoring data from a given Portuguese financial institution to evaluate the default risk of consumer loans. It was found that the risk of default increases with the loan spread, loan term and age of the customer, but decreases if the customer owns more credit cards. Clients receiving the salary in the same banking institution of the loan have less chances of default than clients receiving their salary in another institution. We also found that clients in the lowest income tax echelon have more propensity to default. The model predicted default correctly in 89.79% of the cases.
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This study investigated how the internal psychological states (i.e., challenge-skill perception, positive and negative affect, and effortless attention) and contextual features (i.e., activity and company) of momentary experiences relate to optimal experience in adolescents' lives. Data were collected from 245 Portuguese adolescents (14-19 years old, 63% female) by using the experience sampling method. Multilevel modeling revealed that challenge-skill and positive affect were positively associated with optimal experience, while negative affect was negatively associated with optimal experience. Effortless attention mediated the associations between internal states and optimal experience, while activity and company only moderated some of these associations. These findings will inform practitioners about the factors that should be addressed in interventions with adolescents to promote optimal experiences in their lives.
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Conducta del Adolescente/psicología , Afecto , Control Interno-Externo , Adolescente , Evaluación Ecológica Momentánea , Femenino , Humanos , Masculino , Psicología del AdolescenteRESUMEN
Rheumatoid arthritis (RA) is an autoimmune disease that affects the synovial cavity of joints, and its pathogenesis is associated with an increased expression of pro-inflammatory cytokines, namely tumour necrosis factor-alpha (TNF-α). It has been clinically shown to have an adequate response to systemic administration of TNF-α inhibitors, although with many shortcomings. To overcome such limitations, the immobilization of a TNF-α antibody on a nanofibrous substrate to promote a localized action is herein proposed. By using this approach, the antibody has its maximum therapeutic efficacy and a prolonged therapeutic benefit, avoiding the systemic side-effects associated with conventional biological agents' therapies. To technically achieve such a purpose, the surface of electrospun nanofibers is initially activated and functionalized, allowing TNF-α antibody immobilization at a maximum concentration of 6 µg/mL. Experimental results evidence that the biofunctionalized nanofibrous substrate is effective in achieving a sustained capture of soluble TNF-α over time. Moreover, cell biology assays demonstrate that this system has no deleterious effect over human articular chondrocytes metabolism and activity. Therefore, the developed TNF-capturing system may represent a potential therapeutic approach for the local management of severely affected joints.
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Polymeric nanoparticles (NPs) are strong candidates for the development of systemic and targeted drug delivery applications. Their size is a determinant property since it defines the NP-cell interactions, drug loading capacity, and release kinetics. Herein, poly(d,l-lactic acid) (PDLA) NPs were produced by the nanoprecipitation method, in which the influence of type and concentration of surfactant as well as PDLA concentration were assessed. The adjustment of these parameters allowed the successful production of NPs with defined medium sizes, ranging from 80 to 460 nm. The surface charge of the different NPs populations was consistently negative. Prednisolone was effectively entrapped and released from NPs with statistically different medium sizes (i.e., 80 or 120 nm). Release profiles indicate that these systems were able to deliver appropriate amounts of drug with potential applicability in the treatment of inflammatory conditions. Both NPs populations were cytocompatible with human endothelial and fibroblastic cells, in the range of concentrations tested (0.187-0.784 mg/mL). However, confocal microscopy revealed that within the range of sizes tested in our experiments, NPs presenting a medium size of 120 nm were able to be internalized in endothelial cells. In summary, this study demonstrates the optimization of the processing conditions to obtain PDLA NPs with narrow size ranges, and with promising performance for the treatment of inflammatory diseases. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 482-493, 2019.
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Portadores de Fármacos , Células Endoteliales/metabolismo , Fibroblastos/metabolismo , Nanopartículas/química , Poliésteres , Prednisolona , Línea Celular , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Células Endoteliales/citología , Fibroblastos/citología , Humanos , Tamaño de la Partícula , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacología , Prednisolona/química , Prednisolona/farmacocinética , Prednisolona/farmacologíaRESUMEN
A better understanding of emotion regulation (ER) within daily life is a growing focus of research. This study evaluated the average use of two ER strategies (cognitive reappraisal and expressive suppression) and concurrent and lagged relationships between these two ER strategies and affect (positive and negative affect) in the daily lives of adolescents. We also investigated the role of the same strategies at the trait level on these within-person relationships. Thirty-three adolescents provided 1,258 reports of their daily life by using the Experience Sampling Method for one week. Regarding the relative use of ER strategies, cognitive reappraisal (M = 2.87, SD = 1.58) was used more often than expressive suppression (M = 2.42, SD = 1.21). While the use of both strategies was positively correlated when evaluated in daily life (p = .01), the same did not occur at the trait level (p = .37). Multilevel analysis found that ER strategies were concurrently related to affect (p < .01), with the exception of cognitive reappraisal-positive affect relationship (p = .11). However, cognitive reappraisal predicted higher positive affect at the subsequent sampling moment ( ß = 0.07, p = .03). The concurrent associations between cognitive reappraisal and negative affect vary as function of the use of this strategy at the trait level (ß = 0.05, p = .02). Our findings highlighted the complex associations between daily ER strategies and affect of a normative sample of adolescents.
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Conducta del Adolescente/fisiología , Emociones/fisiología , Autocontrol , Adolescente , Afecto/fisiología , Niño , Evaluación Ecológica Momentánea , Femenino , Humanos , MasculinoRESUMEN
Gold nanoparticles (AuNPs) enable the treatment and real-time monitoring of several diseases, providing an exciting and advantageous nanomedicine strategy. These NPs have therefore been adequately functionalized to enable them to carry growth factors (GF), namely basic fibroblastic (bF) GF, which play an essential role in different and important cellular processes including cellular proliferation, survival, migration and differentiation. The AuNPs were coated with natural polymers, chitosan and heparin, to enhance their physicochemical properties such as suspension stability. The polyelectrolyte coating was monitored using a quartz crystal microbalance with dissipation, size and zeta-potential analysis. The natural polymer-coated AuNPs have a spherical shape and a positive surface charge due to chitosan amino groups, enabling their biofunctionalization with monoclonal antibodies to target specific biomolecules. Additionally, cellular assays with the chondrocyte cell line ATDC5 show that the NPs are cytocompatible at relevant concentrations. As a proof of concept of their potential application in tissue regeneration, the natural polymer-coated AuNPs were further functionalized with an antibody to selectively bind the desired GF. The bFGF concentration reached in the NPs without compromising the cytocompatibility demonstrates the potential of this carrier for tissue regeneration.
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Many efforts are being directed worldwide to the treatment of OA-focal lesions. The majority of those efforts comprise either the refinement of surgical techniques or combinations of biomaterials with various autologous cells. Herein, we tested electrospun polycaprolactone (PCL) nanofibrous meshes for cartilage tissue engineering. For that, articular chondrocytes (hACs) isolated from human osteoarthritic joints and Wharton's Jelly Stem Cells (hWJSCs) are cultured on electrospun nanofiber meshes, without adding external growth factors. We observed higher glycosaminoglycans production and higher over-expression of cartilage-related genes from hWJSCs cultured with basal medium, when compared to hACs isolated from osteoarthritic joints. Moreover, the presence of sulfated proteoglycans and collagen type II is observed on both types of cell cultures. We believe that this effect is due to either the electrospun nanofibers topography or the intrinsic chondrogenic differentiation potential of hWJSCs. Therefore, we propose the electrospun nanofibrous scaffolds in combination with hWJSCs as a viable alternative to the commercial membranes used in autologous chondrogenic regeneration approaches.
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Cartílago/citología , Técnicas de Cultivo de Célula/métodos , Condrocitos/citología , Células Madre Mesenquimatosas/citología , Nanofibras/química , Ingeniería de Tejidos/métodos , Diferenciación Celular , Condrogénesis/fisiología , Humanos , Osteoartritis , Poliésteres/química , RegeneraciónRESUMEN
Injectable calcium phosphate cements have been used as a valid alternative to autologous bone grafts for bone augmentation with the additional advantage of enabling minimally invasive implantation procedures and for perfectly fitting the tissue defect. Nevertheless, they have low biodegradability and lack adequate biochemical signaling to promote bone healing and remodeling. In previous in vitro studies, we observed that the incorporation of platelet lysate directly into the cement paste or loaded in hyaluronic acid microspheres allowed to modulate the cement degradation and the in vitro expression of osteogenic markers in seeded human adipose derived stem cells. The present study aimed at investigating the possible effect of this system in new bone formation when implanted in calvarial bilateral defects in rats. Different formulations were assessed, namely plain calcium phosphate cements, calcium phosphate cements loaded with human platelet lysate, hybrid injectable formulations composed of the calcium phosphate cement incorporating hyaluronin acid non-loaded microparticles (20% hyaluronin acid) or with particles loaded with platelet lysate. The degradability and new bone regrowth were evaluated in terms of mineral volume in the defect, measured by micro-computed tomography and histomorphometric analysis upon 4, 8 and 12 weeks of implantation. We observed that the incorporation of hyaluronin acid microspheres induced an overly rapid cement degradation, impairing the osteoconductive properties of the cement composites. Moreover, the incorporation of platelet lysate induced higher bone healing than the materials without platelet lysate, up to four weeks after surgery. Nevertheless, this effect was not found to be significant when compared to the one observed in the sham-treated group.
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Implantes Absorbibles , Plaquetas/química , Cementos para Huesos/uso terapéutico , Regeneración Ósea/fisiología , Fosfatos de Calcio/uso terapéutico , Fracturas Craneales/fisiopatología , Fracturas Craneales/terapia , Animales , Regeneración Ósea/efectos de los fármacos , Fosfatos de Calcio/química , Células Cultivadas , Implantes de Medicamentos/administración & dosificación , Ratas , Ratas Wistar , Fracturas Craneales/patología , Resultado del TratamientoRESUMEN
This study tested the mediating role of primary (e.g., threat and challenge perceptions) and secondary (e.g., coping potential and control perception) cognitive appraisal in the relationship between occupational stress and psychological health. This mediation was tested using a cross-sectional study based on self-reported measures. The total sample consisted of 2,302 nurses, 1,895 females (82.3%) and 407 males (17.7%), who completed an evaluation protocol with measures of occupational stress, cognitive appraisal, and psychological health. To test the mediating role of cognitive appraisal in the relationship between cognitive appraisal and psychological health, we used Structural Equation Modeling (SEM). The results confirmed that primary and secondary cognitive appraisals partially mediated the relationship between occupational stress and psychological health; however, the direct effects of stress on psychological health cannot be ignored. The findings indicated that cognitive appraisal is an important underlying mechanism in explaining adaptation at work.
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Hierarchical structures, constituted by polymeric nano and microfibers, have been considered promising scaffolds for tissue engineering strategies, mainly because they mimic, in some way, the complexity and nanoscale detail observed in real organs. The chondrogenic potential of these scaffolds has been previously demonstrated, but their osteogenic potential is not yet corroborated. In order to assess if a hierarchical structure, with nanoscale details incorporated, is an improved scaffold for bone tissue regeneration, we evaluate cell adhesion, proliferation, and osteogenic differentiation of human Wharton's jelly derived stem cells (hWJSCs), seeded into hierarchical fibrous scaffolds. Biological data corroborates that hierarchical fibrous scaffolds show an enhanced cell entrapment when compared to rapid prototyped scaffolds without nanofibers. Furthermore, upregulation of bone specific genes and calcium phosphate deposition confirms the successful osteogenic differentiation of hWJSCs on these scaffolds. These results support our hypothesis that a scaffold with hierarchical structure, in conjugation with hWJSCs, represents a possible feasible strategy for bone tissue engineering applications.
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Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Diferenciación Celular/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Andamios del Tejido/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Técnicas Electroquímicas/métodos , Humanos , Células Madre Mesenquimatosas/metabolismo , Ingeniería de Tejidos/métodos , Gelatina de Wharton/citologíaRESUMEN
Stem cells have received considerable attention by the scientific community because of their potential for tissue engineering and regenerative medicine. The most frequently used method to promote their differentiation is supplementation of the in vitro culture medium with growth/differentiation factors (GDFs). The limitations of that strategy caused by the short half-life of GDFs limit its efficacy in vivo and consequently its clinical use. Thus, the development of new concepts that enable the bioactivity and bioavailability of GDFs to be protected, both in vitro and in vivo, is very relevant. Nanoparticle-based drug delivery systems can be injected, protect the GDFs and enable spatiotemporal release kinetics to be controlled. Liposomes are well-established nanodelivery devices presenting significant advantages, viz. a high load-carrying capacity, relative safety and easy production, and a versatile nature in terms of possible formulations and surface functionalization. The main objective of the present study was to optimize the formulation of liposomes to encapsulate dexamethasone (Dex). Our results showed that the optimized Dex-loaded liposomes do not have any cytotoxic effect on human bone marrow-derived mesenchymal stem cells (hBMSCs). More importantly, they were able to promote an earlier induction of differentiation of hBMSCs into the osteogenic lineage, as demonstrated by the expression of osteoblastic markers, both phenotypically and genotypically. We concluded that Dex-loaded liposomes represent a viable nanoparticle strategy with enhanced safety and efficacy for tissue engineering and regenerative medicine.
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Huesos/citología , Diferenciación Celular/efectos de los fármacos , Dexametasona/farmacología , Liposomas , Células Madre Mesenquimatosas/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Huesos/enzimología , Dexametasona/administración & dosificación , Genotipo , Humanos , Células Madre Mesenquimatosas/citología , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión de Rastreo , Fenotipo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Inducer molecules capable of regulating mesenchymal stem cell differentiation into specific lineages have proven effective in basic science and in preclinical studies. Runt-related transcription factor 2 (RUNX2) is considered to be the central gene involved in the osteoblast phenotype induction, which may be advantageous for inducing bone tissue regeneration. This work envisions the development of a platform for gene delivery, combining liposomes as gene delivery devices, with electrospun nanofiber mesh (NFM) as a tissue engineering scaffold. pDNA-loaded liposomes were immobilized at the surface of functionalized polycaprolactone (PCL) NFM. Human bone-marrow-derived mesenchymal stem cells (hBMSCs) cultured on RUNX2-loaded liposomes immobilized at the surface of electrospun PCL NFM showed enhanced levels of metabolic activity and total protein synthesis. RUNX2-loaded liposomes immobilized at the surface of electrospun PCL NFMs induce a long-term gene expression of eGFP and RUNX2 by cultured hBMSCs. Furthermore, osteogenic differentiation of hBMSCs was also achieved by the overexpression of other osteogenic markers in medium free of osteogenic supplementation. These findings demonstrate that surface immobilization of RUNX2 plasmid onto elestrospun PCL NFM can produce long-term gene expression in vitro, which may be employed to enhance the osteoinductive properties of scaffolds used for bone tissue engineering strategies.
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Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Huesos/citología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Nanofibras/química , Ingeniería de Tejidos , Andamios del Tejido/química , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/química , ADN/química , ADN/genética , Electricidad , Homeostasis/efectos de los fármacos , Humanos , Liposomas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Modelos Moleculares , Poliésteres/química , Conformación ProteicaRESUMEN
Electrospun nanofiber meshes (NFM), due to their morphology and fibrous structure, are extensively proposed as biomedical devices, for tissue engineering on scaffolds and also as drug delivery systems. Liposomes are nanoparticles prepared from a biologically derived material (phospholipid), which are already in clinical use as a drug release device. Liposomes may be combined with biomaterial scaffolds to promote a local and sustained delivery of loaded bioactive agents. The main objective of the present study is to evaluate the efficacy of dexamethasone (Dex)-loaded liposomes immobilized on the surface of electrospun polycaprolactone (PCL) NFM for promoting the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). The in vitro release profile demonstrates a sustained release of Dex over 21 days, after an initial burst release over 12 h. Biological assays show that Dex-loaded liposomes immobilized on the surface of electrospun PCL NFMs do not exhibit any cytotoxic effect, being able to successfully promote the osteogenic differentiation of hBMSCs. We herein validate the concept of using liposomes immobilized on the surface of a nanostructured fibrous system to be used as an advanced cell carrier device with autonomous release of growth/differentiation factors relevant for tissue engineering and regenerative medicine strategies.