Personne : Beaudoin-Cloutier, Chanel
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Beaudoin-Cloutier
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Chanel
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Université Laval. Faculté de médecine
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Publication Restreint Production of a bilayered self-assembled skin substitute using a tissue-engineered acellular dermal matrix(Mary Ann Liebert, 2015-09-28) Beaudoin-Cloutier, Chanel; Bernard, Geneviève; Germain, Lucie; Larouche, Danielle; Auger, François A.; Gauvin, Robert; Guignard, Rina; Lacroix, Dan.; Moulin, Véronique; Lavoie, AmélieOur bilayered self-assembled skin substitutes (SASS) are skin substitutes showing a structure and functionality very similar to native human skin. These constructs are used, in life-threatening burn wounds, as permanent autologous grafts for the treatment of such affected patients even though their production is exacting. We thus intended to shorten their current production time to improve their clinical applicability. A self-assembled decellularized dermal matrix (DM) was used. It allowed the production of an autologous skin substitute from patient's cells. The characterization of SASS reconstructed using a decellularized dermal matrix (SASS-DM) was performed by histology, immunofluorescence, transmission electron microscopy, and uniaxial tensile analysis. Using the SASS-DM, it was possible to reduce the standard production time from about 8 to 4 and a half weeks. The structure, cell differentiation, and mechanical properties of the new skin substitutes were shown to be similar to the SASS. The decellularization process had no influence on the final microstructure and mechanical properties of the DM. This model, by enabling the production of a skin substitute in a shorter time frame without compromising its intrinsic tissue properties, represents a promising addition to the currently available burn and wound treatments.Publication Accès libre Développement préclinique d'une méthode plus rapide de production par génie tissulaire d'un substitut cutané bilamellaire autologue(2016) Beaudoin-Cloutier, Chanel; Germain, Lucie; Auger, François A.; Gauvin, RobertIntroduction: Le Laboratoire d’Organogenèse Expérimentale (LOEX) utilise une technique de production de substituts cutanés bilamellaires autologues auto-assemblés (SASS) unique. Cette méthode permet la génération d’équivalents cutanés permanents avec une structure et une fonction similaire à la peau normale humaine. Problématique et objectifs: Cette thèse présente d’abord les premiers résultats d’essais cliniques pour le traitement de plaies chroniques complexes traitées avec SASS. Ces résultats démontrent une efficacité et une sécurité d’utilisation de ces SASS. Toutefois, il y a un intérêt de développer une méthode de production plus rapide de ces substituts cutanés afin d’améliorer l’accessibilité clinique et le pronostic des patients grands brûlés, lors de leur utilisation en phase aiguë. En effet, le délai de couverture cutanée définitive essentielle à la thermorégulation et à l’effet de barrière est directement en lien avec les pronostics vital et morbide de cette population. Le délai actuel de 8 semaines pour la production des greffons aurait avantage à être réduit pour améliorer leur utilité quant aux soins des patients. Méthode: Dans un premier temps, le développement et la mise au point d’une méthode de production plus rapide de SASS à partir de matrices dermiques décellularisées (SASS-DM), générant des peaux reconstruites en seulement 4 semaines et demie est présenté. Par la suite, l’équivalence de la méthode de production rapide de ces peaux est d’abord vérifiée in vitro et comparée à la méthode standard quant à ses caractéristiques histologiques, de différenciation cellulaire et la présence d’une membrane basale fonctionnelle. La méthode rapide est finalement comparée in vivo à la méthode standard quant à l’évolution de ces peaux greffées sur les vivants, de façon à compléter le développement préclinique de cette nouvelle méthode innovatrice. Résultats: La méthode rapide de production des peaux bilamellaires autologues auto-assemblées s’est montrée équivalente à la méthode de production standard et ce, autant in vitro qu’in vivo. Conclusion: Ce travail présente d’abord l’utilisation clinique des peaux reconstruites bilamellaires pour le traitement de plaies variqueuses chronique, qui s’avère efficace et sécuritaire. Puis, le développement préclinique d’une méthode plus rapide de production de peaux reconstruites bilamellaires autologues est présenté, permettant de générer des greffons en 4 semaines et demie plutôt que 8 semaines, et ce avec une qualité équivalente à la méthode standard. Cette innovation représente un ajout majeur aux modes de traitement des grands brûlés puisqu’elle a le potentiel de changer la planification chirurgicale et leur pronostic de survie.Publication Accès libre Health utilities in burn injury survivors : a systematic review(Science Direct, 2021-09-17) Synodinou, Dafni; Beaudoin-Cloutier, Chanel; Savoie-White, Félix H.; Guertin, Jason Robert; Sangone, Alassane; Chang, Sue-Ling; Bergeron, FrédéricBackground An estimated 11 million burn injuries with medical attention occur every year worldwide. Although potentially deadly, burn injuries are now considered a chronic disease with multiple lifetime physical and psychological sequelae. However, it remains unclear how these events affect patients’ utility scores. We aimed to conduct a systematic review to summarize the utility scores of burn injury survivors. Methods We conducted on March 18th, 2020 a systematic review of the published literature using a search strategy designed in collaboration with a research librarian. Our search strategy aimed to identify studies that provided burn injury survivors’ utility scores via a standardized indirect instrument. Results We identified 15 studies that reported burn injury survivors’ utility scores. Most studies used the EQ-5D instruments to assess patients’ utility scores. Results varied substantially between studies, ranging from a low of 0.06 to a high of 0.972. Our review identified two key trends. First, utility scores seem to be negatively correlated with the severity of the burn injury. Second, utility scores in adults tend to increase in function of the time since injury. Conclusion Unfortunately, due to differences in study design and settings, patient populations and instruments used to assess patients’ utility scores, we were unable to combine all study results into a single value. In spite of this limit, results we identified support previous trends identified by others regarding the relationship between utility scores and the burn injury severity and/or the time since injury.Publication Restreint In vivo evaluation and imaging of a bilayered self-assembled skin substitute using a decellularized dermal matrix grafted on mice(Mary Ann Liebert, Inc, 2016-12-13) Beaudoin-Cloutier, Chanel; Perron, Cindy; Germain, Lucie; Goyer, Benjamin; Larouche, Danielle; Auger, François A.; Gauvin, Robert; Guignard, Rina; Moulin, VéroniqueAs time to final coverage is the essence for better survival outcome in severely burned patients, we have continuously strived to reduce the duration for the preparation of our bilayered self-assembled skin substitutes (SASS). These SASS produced in vitro by the self-assembly approach have a structure and functionality very similar to native skin. Recently, we have shown that a decellularized dermal matrix preproduced by the self-assembly approach could be used as a template to further obtain self-assembled skin substitute using a decellularized dermal template (SASS-DM) in vitro. Thus, the production period with patient cells was then reduced to about 1 month. Herein, preclinical animal experiments have been performed to confirm the integration and evolution of such a graft and compare the maturation of SASS and SASS-DM in vivo. Both tissues, reconstructed from adult or newborn cells, were grafted on athymic mice. Green fluorescent protein-transfected keratinocytes were also used to follow grafted tissues weekly for 6 weeks using an in vivo imaging system (IVIS). Cell architecture and differentiation were studied with histological and immunofluorescence analyses at each time point. Graft integration, macroscopic evolution, histological analyses, and expression of skin differentiation markers were similar between both skin substitutes reconstructed from either newborn or adult cells, and IVIS observations confirmed the efficient engraftment of SASS-DM. In conclusion, our in vivo graft experiments on a mouse model demonstrated that the SASS-DM had equivalent macroscopic, histological, and differentiation evolution over a 6-week period, when compared with the SASS. The tissue-engineered SASS-DM could improve clinical availability and advantageously shorten the time necessary for the definitive wound coverage of severely burned patients.Publication Accès libre Pro-angiogenic capacities of microvesicles produced by skin wound myofibroblasts(Kluwer, 2017-04-08) Beaudoin-Cloutier, Chanel; Merjaneh, Mays; Langlois, Amélie; Larochelle, Sébastien; Ricard-Blum, Sylvie; Moulin, VéroniqueWound healing is a very highly organized process where numerous cell types are tightly regulated to restore injured tissue. Myofibroblasts are cells that produce new extracellular matrix and contract wound edges. We previously reported that the human myofibroblasts isolated from normal wound (WMyos) produced microvesicles (MVs) in the presence of the serum. In this study, MVs were further characterized using a proteomic strategy and potential functions of the MVs were determined. MV proteins isolated from six WMyo populations were separated using two-dimensional differential gel electrophoresis. Highly conserved spots were selected and analyzed using mass spectrometry resulting in the identification of 381 different human proteins. Using the DAVID database, clusters of proteins involved in cell motion, apoptosis and adhesion, but also in extracellular matrix production (21 proteins, enrichment score: 3.32) and in blood vessel development/angiogenesis (19 proteins, enrichment score: 2.66) were identified. Another analysis using the functional enrichment analysis tool FunRich was consistent with these results. While the action of the myofibroblasts on extracellular matrix formation is well known, their angiogenic potential is less studied. To further characterize the angiogenic activity of the MVs, they were added to cultured microvascular endothelial cells to evaluate their influence on cell growth and migration using scratch test and capillary-like structure formation in Matrigel®. The addition of a MV-enriched preparation significantly increased endothelial cell growth, migration and capillary formation compared with controls. The release of microvesicles by the wound myofibroblasts brings new perspectives to the field of communication between cells during the normal healing process.Publication Restreint Prospective study on the treatment of lower-extremity chronic venous and mixed ulcers using tissue-engineered skin substitute made by the self-assembly approach(Lippincott Williams & Wilkins, 2013-09-01) Beaudoin-Cloutier, Chanel; Germain, Lucie; Larouche, Danielle; Labbé, Raymond; Rochon, Marie-Hélène; Roy, Michel A.; Genest, Hervé; Soucy, Jacques; Dubé, Nathalie; Auger, François A.; Ospina, Carlos E.; Arsenault, Frédéric; Rodrigue, Bertrand; Boa, Olivier; Moulin, VéroniqueBACKGROUND: Despite present optimal standard treatment of lower-extremity ulceration, a high incidence of recurrence and treatment failure is observed. The objective of this project was to evaluate the effect of a self-assembled skin substitute (SASS) made by tissue engineering as a temporary cutaneous dressing in the treatment of hard-to-heal chronic ulcers. PATIENTS AND METHODS: The prospective uncontrolled case study includes patients suffering from venous or mixed ulcers lasting more than 6 months and unresponsive to compression therapy, with an Ankle Brachial Index greater than 0.5. Compression therapy was combined with the weekly application of SASS, produced from the patient’s own skin cells, until healing. A weekly follow-up recorded wound size, skin aspect, pain, drainage, and percentage of wound healing. Photographs were also taken to assess ulcer evolution. RESULTS: Fourteen ulcers present on 5 patients were treated. A mean of 6.7 SASS depositions by ulcer was required for healing. Two ulcers developed a minor wound infection, which was treated with oral antibiotics; another 2 ulcers recurred, and 1 healed with a second course of treatment, whereas 1 ulcer had a small recurrence treated with local wound care. CONCLUSION: The authors’ study suggests that the SASS used as a biological dressing is a promising treatment for hard-to-heal chronic venous and mixed ulcers that are unresponsive to compression therapy.