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Cadau S.,Center Loex Of Luniversite Laval | Cadau S.,Laval University | Leoty-Okombi S.,BASF | Pain S.,BASF | And 4 more authors.
Biomaterials | Year: 2015

Glycation is one of the major processes responsible for skin aging through induction of the detrimental formation of advanced glycation end-products (AGEs). We developed an innovative tissue-engineered skin combining both a capillary-like and a nerve networks and designed a protocol to induce continuous AGEs formation by a treatment with glyoxal. We determined the optimal concentration of glyoxal to induce AGEs formation identified by carboxymethyl-lysin expression while keeping their toxic effects low. We showed that our tissue-engineered skin cultured for 44 days and treated with 200μ. m glyoxal for 31 days displayed high carboxymethyl-lysine expression, which induced a progressively increased alteration of its capillary and nerve networks between 28 and 44 days. Moreover, it produced an epidermal differentiation defect evidenced by the lack of loricrin and filaggrin expression in the epidermis. These effects were almost completely prevented by addition of aminoguanidine 1.5m. m, an anti-glycation compound, and only slightly decreased by alagebrium 500μ. m, an AGE-breaker molecule. This tissue-engineered skin model is the first one to combine a capillary and nerve network and to enable a continuous glycation over a long-term culture period. It is a unique tool to investigate the effects of glycation on skin and to screen new molecules that could prevent AGEs formation. © 2015 Elsevier Ltd. Source


Dubois Declercq S.,Center Loex Of Luniversite Laval | Dubois Declercq S.,Laval University | Pouliot R.,Center Loex Of Luniversite Laval | Pouliot R.,Laval University
The Scientific World Journal | Year: 2013

Psoriasis is a chronic, proliferative, and inflammatory skin disease affecting 2-3% of the population and is characterized by red plaques with white scales. Psoriasis is a disease that can affect many aspects of professional and social life. Currently, several treatments are available to help control psoriasis such as methotrexate, ciclosporin, and oral retinoids. However, the available treatments are only able to relieve the symptoms and lives of individuals. The discovery of new immunological factors and a better understanding of psoriasis have turned to the use of immunological pathways and could develop new biological drugs against specific immunological elements that cause psoriasis. Biological drugs are less toxic to the body and more effective than traditional therapies. Thus, they should improve the quality of life of patients with psoriasis. This review describes new psoriasis treatments, which are on the market or currently in clinical trials that are being used to treat moderate-to-severe plaque psoriasis. In addition, this paper describes the characteristics and mechanisms in detail. In general, biological drugs are well tolerated and appear to be an effective alternative to conventional therapies. However, their effectiveness and long-term side effects need to be further researched. © 2013 Sarah Dubois Declercq and Roxane Pouliot. Source


Clafshenkel W.P.,Carnegie Mellon University | Clafshenkel W.P.,Center Loex Of Luniversite Laval | Murata H.,Carnegie Mellon University | Andersen J.,Carnegie Mellon University | And 3 more authors.
PLoS ONE | Year: 2016

Erythrocytes have been described as advantageous drug delivery vehicles. In order to ensure an adequate circulation half-life, erythrocytes may benefit from protective enhancements that maintain membrane integrity and neutralize oxidative damage of membrane proteins that otherwise facilitate their premature clearance from circulation. Surface modification of erythrocytes using rationally designed polymers, synthesized via atomtransfer radical polymerization (ATRP), may further expand the field of membrane-engineered red blood cells. This study describes the fate of ATRP-synthesized polymers that were covalently attached to human erythrocytes as well as the effect of membrane engineering on cell stability under physiological and oxidative conditions in vitro. The biocompatible, membrane-reactive polymers were homogenously retained on the periphery of modified erythrocytes for at least 24 hours. Membrane engineering stabilized the erythrocyte membrane and effectively neutralized oxidative species, even in the absence of freeradical scavenger-containing polymers. The targeted functionalization of Band 3 protein by NHS-pDMAA-Cy3 polymers stabilized its monomeric form preventing aggregation in the presence of the crosslinking reagent, bis(sulfosuccinimidyl)suberate (BS3 ). A free radical scavenging polymer, NHS-pDMAA-TEMPO-, provided additional protection of surface modified erythrocytes in an in vitro model of oxidative stress. Preserving or augmenting cytoprotective mechanisms that extend circulation half-life is an important consideration for the use of red blood cells for drug delivery in various pathologies, as they are likely to encounter areas of imbalanced oxidative stress as they circuit the vascular system. © 2016 Clafshenkel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source


Moulin V.J.,Center Loex Of Luniversite Laval | Moulin V.J.,University of Quebec | Moulin V.J.,Laval University
Methods in Molecular Biology | Year: 2013

Skin fibrosis is involved in several pathologies as hypertrophic scar or scleroderma. The determination of the mechanisms at the origin of these problems is however difficult due to the low number of in vivo models. To bypass this absence of animal models, studies typically use human pathological cells cultured in a monolayer way on plastic. However, cell behavior is different according to the fact that cells are on plastic or embedded in matrix. Using a tissue engineering method, we have developed new in vitro models to study these pathologies of the skin. Human pathological cells are used to reconstitute a three dimensional fibrotic tissue comprising the dermal and the epidermal parts of the skin. This method is called the selfassembly approach and is based on the cell capacity to reconstitute in vitro their own environment as in vivo. In this chapter, protocols generating reconstructed pathological skin using this approach are detailed. The methods include extraction and culture of human skin keratinocytes and fibroblasts from very small cutaneous biopsies. In addition, a description of the protocols for the production of fibrotic dermal sheets can be found to obtain a model of fibrotic dermis that can be associated or not with a fully differentiated epidermis. © Springer Science+Business Media, LLC 2013. Source


Auger F.A.,Center Loex Of Luniversite Laval | Auger F.A.,Laval University | Gibot L.,CNRS Institute of Pharmacology and Structural Biology | Gibot L.,Toulouse 1 University Capitole | Lacroix D.,Center Loex Of Luniversite Laval
Annual Review of Biomedical Engineering | Year: 2013

Vascularization is one of the great challenges that tissue engineering faces in order to achieve sizeable tissue and organ substitutes that contain living cells. There are instances, such as skin replacement, in which a tissue-engineered substitute does not absolutely need a preexisting vascularization. However, tissue or organ substitutes in which any dimension, such as thickness, exceeds 400 ?mu?m need to be vascularized to ensure cellular survival. Consistent with the wide spectrum of approaches to tissue engineering itself, which vary from acellular synthetic biomaterials to purely biological living constructs, approaches to tissue-engineered vascularization cover numerous techniques. Those techniques range from micropatterns engineered in biomaterials to microvascular networks created by endothelial cells. In this review, we strive to provide a critical overview of the elements that must be considered in the pursuit of this goal and the major approaches that are investigated in hopes of achieving it. Copyright © 2013 by Annual Reviews. Source

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