Minimal contraction for tissue-engineered skin substitutes when matured at the air–liquid interface

The structural stability of skin substitutes is critical to avoid aesthetic and functional problems after grafting, such as contractures and hypertrophic scars. The present study was designed to assess the production steps having an influence on the contractile behaviour of the tissue-engineered skin made by the self-assembly approach, where keratinocytes are cultured on tissue-engineered dermis comprised of fibroblasts and the endogenous extracellular matrix they organized. Thus, different aspects were investigated, such as the assembly method of the engineered dermis (various sizes and anchoring designs) and the impact of epithelial cell differentiation (culture submerged in the medium or at the air–liquid interface). To evaluate the structural stability at the end of the production, the substitutes were detached from their anchorages and deposited on a soft substrate, and contraction was monitored over 1 week. Collected data were analysed using a mathematical model to characterize contraction. We observed that the presence of a differentiated epidermis significantly reduced the amount of contraction experienced by the engineered tissues, independently of the assembly method used for their production. When the epidermis was terminally differentiated, the average contraction was only 24 4% and most of the contraction occurred within the first 12 h following deposition on the substrate. This is 2.2-fold less compared to when the epidermis was cultured under the submerged condition, or when tissue-engineered dermis was not overlaid with epithelial cells. This study highlights that the maturation at the air–liquid interface is a critical step in the reconstruction of a tissueengineered skin that possesses high structural stabilit

L'insertion socio-professionnelle transition majeure de l'existence

In this article, five theoretical models of integration into the labor market are at first presented. Each of these views this integration as a major life transition. Seven research projects, bearing on this topic, are then examined in terms of their goals and their relationships to some of the five models. The practical implications of these projects for psychological education and career counselling are also outlined.Dans cet article, nous présentons d'abord différentes conceptions de l'insertion socio-professionnelle abordées par cinq théoriciennes du développement de la personne, sous l'angle particulier d'une transition majeure de l'existence. Sept projets de recherche portant sur l'insertion socio-professionnelle sont ensuite analysés selon la perspective transitionnelle qui les particularise. Les objectifs et conceptions de la transition sur lesquels reposent chacune de ces recherches sont présentés. Des implications pratiques en matière d'éducation psychologique et de counseling de carrière auprès de populations en démarche d'insertion socio-professionnelle sont proposées

Therapeutic education in atopic dermatitis: A position paper from the International Eczema Council

International audienceBackgroundAtopic dermatitis (AD) is a chronic, inflammatory skin disease that affects as many as 12.5% of children aged 0-17 years and 3% of the adult population. In the United States, 31.6 million children and adults are estimated to be living with AD.ObjectiveTherapeutic patient education (TPE) has proven its value in the management of chronic diseases for which adherence to therapy is suboptimal. This article explores experts' opinions and treatment practices to determine if TPE is a recommended and effective method for treating AD.MethodsForty-two (51%) of 82 Councilors and Associates of the International Eczema Council (IEC), an international group with expertise in AD, responded to an electronic survey on TPE and AD.ResultsMost respondents (97.5%) agreed that TPE should play an important role in the management of AD. Many respondents (82.9%) believed that all patients with AD, regardless of disease severity, could benefit from TPE.LimitationsThe International Eczema Council survey lacks specific information on AD severity.ConclusionsPublications have shown the positive effect of TPE on the course of the disease, the prevention of complications, and the autonomy and quality of patient life. Survey respondents agreed that TPE can improve the quality of patient care and patient satisfaction with care

Dynamic mechanical stimulations induce anisotropy and improve the tensile properties of engineered tissues produced without exogenous scaffolding

Mechanical strength and the production of extracellular matrix (ECM) are essential characteristics for engineered tissues designed to repair and replace connective tissues that are subject to stress and strain. In this study, dynamic mechanical stimulation (DMS) was investigated as a method to improve the mechanical properties of engineered tissues produced without the use of an exogenous scaffold, referred to as the self-assembly approach. This method, based exclusively on the use of human cells without any exogenous scaffolding, allows for the production of a tissue sheet comprised of cells and ECM components synthesized by dermal fibroblasts in vitro. A bioreactor chamber was designed to apply cyclic strain to engineered tissues in order to determine if dynamic culture had an impact on their mechanical properties and ECM organization. Fibroblasts were cultured in the presence of ascorbic acid for 35 days to promote ECM production and allow the formation of a tissue sheet. This sheet was grown on a custom-built anchoring system allowing for easy manipulation and fixation of the tissue in the bioreactor. Following the 35 day period, tissues were maintained for 3 days in static culture (SC), or subjected either to a static mechanical stimulation of 10% strain, or a dynamic DMS with a duty cycle of 10% uniaxial cyclic strain at 1 Hz. ECM was characterized by histology, immunofluorescence labeling and Western blotting. Both static and dynamic mechanical stimulation induced the alignment of assessed cytoskeletal proteins and ECM components parallel to the axis of applied strain and increased the ECM content of the tissues compared to SC. Measurement of the tensile mechanical properties revealed that mechanical stimulation significantly increases both the ultimate tensile strength and tensile modulus of the engineered tissues when compared to the non-stimulated control. Moreover, we demonstrated that cyclic strain significantly increases these parameters when compared to a static-loading stimulation and that mechanical stimulation contributes to the establishment of anisotropy in the structural and mechanical properties of self-assembled tissue sheets

Mechanical Properties of Tissue-Engineered Vascular Constructs Produced Arterial or Venous Cells

There is a clinical need for better blood vessel substitutes, as current surgical procedures are limited by the availability of suitable autologous vessels and suboptimal behavior of synthetic grafts in small caliber arterial graft (<5 mm) applications. The aim of the present study was to compare the mechanical properties of arterial and venous tissue-engineered vascular constructs produced by the self-assembly approach using cells extracted from either the artery or vein harvested from the same human umbilical cord. The production of a vascular construct comprised of a media and an adventitia (TEVMA) was achieved by rolling a continuous tissue sheet containing both smooth muscle cells and adventitial fibroblasts grown contiguously in the same tissue culture plate. Histology and immunofluorescence staining were used to evaluate the structure and composition of the extracellular matrix of the vascular constructs. The mechanical strength was assessed by uniaxial tensile testing, whereas viscoelastic behavior was evaluated by stepwise stress-relaxation and by cyclic loading hysteresis analysis. Tensile testing showed that the use of arterial cells resulted in stronger and stiffer constructs when compared with those produced using venous cells. Moreover, cyclic loading demonstrated that constructs produced using arterial cells were able to bear higher loads for the same amount of strain when compared with venous constructs. These results indicate that cells isolated from umbilical cord can be used to produce vascular constructs. Arterial constructs possessed superior mechanical properties when compared with venous constructs produced using cells isolated from the same human donor. This study highlights the fact that smooth muscle cells and fibroblasts originating from different cell sources can potentially lead to distinct tissue properties when used in tissue engineering applications.Canadian Institutes of Health ResearchFonds de la recherche en santé du Québe

Sustained long-term efficacy and safety of adalimumab in paediatric patients with severe chronic plaque psoriasis from a randomized, double-blind, phase III study.

BACKGROUND: Adalimumab (ADA) (Humira® , AbbVie Inc., U.S.A.) is approved by the European Medicines Agency for children aged ≥ 4 years with severe plaque psoriasis. OBJECTIVES: To evaluate the long-term efficacy and safety of ADA in children with severe plaque psoriasis. METHODS: Results are presented from the 52-week long-term extension (LTE) of the randomized, double-blind, double-dummy, phase III trial, in children with severe plaque psoriasis (results from prior periods have been published). Patients aged ≥ 4 and < 18 years were randomized 1 : 1 : 1 to ADA 0·8 mg kg-1 (40 mg maximum) or 0·4 mg kg-1 (20 mg maximum) every other week or to methotrexate (MTX) 0·1-0·4 mg kg-1 (25 mg maximum) weekly. The 16-week initial treatment (IT) period was followed by a 36-week withdrawal period and a 16-week retreatment period. Patients could enter the LTE at prespecified time points to receive ADA 0·8 mg kg-1 (blinded or open label) or ADA 0·4 mg kg-1 (blinded), or to remain off treatment. Efficacy is reported for patient groups according to doses received in the IT and LTE periods. RESULTS: Of the 114 patients randomized in the IT period, 108 entered the LTE (n = 36 in each group); 93 received ADA 0·8 mg kg-1 . Efficacy (≥ 75% improvement from baseline in Psoriasis Area and Severity Index) was maintained or improved from entry to the end of the LTE: MTX(IT)/ADA 0·8(LTE) 31-86% of patients; ADA 0·4(IT)/0·4 or 0·8(LTE) 28-47%; ADA 0·8(IT)/0·8(LTE) 50-72%. No serious infections occurred in the LTE. CONCLUSIONS: After 52 weeks of long-term ADA treatment in children aged 4-18 years with severe plaque psoriasis, disease severity was reduced and maintained or further improved, as demonstrated by efficacy outcomes. No new safety risks were identified. What's already known about this topic? The results from the first three periods of this phase III trial in children aged 4-18 years with severe plaque psoriasis suggest that adalimumab is a safe and efficacious treatment option in this population. What does this study add? This is the first study to evaluate long-term treatment of adalimumab in children with severe psoriasis, and the first to evaluate switching from methotrexate to adalimumab in this population

Therapeutic patient education in atopic dermatitis:worldwide experiences

Therapeutic patient education (TPE) has proven effective in increasing treatment adherence and improving quality of life (QoL) for patients with numerous chronic diseases, especially atopic dermatitis (AD). This study was undertaken to identify worldwide TPE experiences in AD treatment. Experts from 23 hospitals, located in 11 countries, responded to a questionnaire on 10 major items. Patients in TPE programs were mainly children and adolescents with moderate to severe AD or markedly affected QoL. Individual and collective approaches were used. Depending on the center, the number of sessions varied from one to six (corresponding to 2 to 12 hours of education), and 20 to 200 patients were followed each year. Each center's education team comprised multidisciplinary professionals (e.g., doctors, nurses, psychologists). Evaluations were based on clinical assessment, QoL, a satisfaction index, or some combination of the three. When funding was obtained, it came from regional health authorities (France), insurance companies (Germany), donations (United States), or pharmaceutical firms (Japan, Italy). The role of patient associations was always highlighted, but their involvement in the TPE process varied from one country to another. Despite the nonexhaustive approach, our findings demonstrate the increasing interest in TPE for managing individuals with AD. In spite of the cultural and financial differences between countries, there is a consensus among experts to integrate education into the treatment of eczema