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Auger, François A.

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Auger

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François A.

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Université Laval. Département chirurgie

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ncf11847160

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Voici les éléments 1 - 10 sur 27
  • PublicationRestreint
    Tissue-engineered human skin substitutes developed from collagen-populated hydrated gels : clinical and fundamental applications
    (Springer, 1998-11-01) Germain, Lucie; Auger, François A.; Rouabhia, Mahmoud; Berthod, François; Goulet, Francine; Moulin, Véronique
    The field of tissue engineering has opened several avenues in biomedical sciences, through ongoing progress. Skin substitutes are currently optimised for clinical as well as fundamental applications. The paper reviews the development of collagen-populated hydrated gels for their eventual use as a therapeutic option for the treatment of burn patients or chronic wounds: tools for pharmacological and toxicological studies, and cutaneous models for in vitro studies. These skin substitutes are produced by culturing keratinocytes on a matured dermal equivalent composed of fibroblasts included in a collagen gel. New biotechnological approaches have been developed to prevent contraction (anchoring devices) and promote epithelial cell differentiation. The impact of dermo-epidermal interactions on the differentiation and organisation of bio-engineered skin tissues has been demonstrated with human skin cells. Human skin substitutes have been adapted for percutaneous absorption studies and toxicity assessment. The evolution of these human skin substitutes has been monitored in vivo in preclinical studies showing promising results. These substitutes could also serve as in vitro models for better understanding of the immunological response and healing mechanism in human skin. Thus, such human skin substitutes present various advantages and are leading to the development of other bio-engineered tissues, such as blood vessels, ligaments and bronchi.
  • PublicationRestreint
    A novel approach for studying angiogenesis : a human skin equivalent with a capillary-like network
    (Princeton Scientific Publishers, 1999-04-01) Hudon, Valérie.; Germain, Lucie; Black, Annie.; Auger, François A.
    Angiogenesis results from an ordered set of events that can be modulated in vivo by a variety of angiogenesis-enhancing or inhibiting agents. We review in vitro angiogenesis models and the agents that enhance or inhibit angiogenesis. We also discuss a new in vitro angiogenesis model created within a skin equivalent. Briefly, endothelial cells were combined with the cutaneous cells of a standard skin equivalent and cultured in a chitosan cross-linked collagen-glycosaminoglycan scaffold of this endothelialized skin. This model enables the formation of capillary-like structures in a coculture environment containing newly synthesized extracellular matrix by fibroblasts and keratinocytes. Several morphological characteristics associated with the microvasculature in vivo were observed in the endothelialized skin equivalent such as histotypic organization of tubular structures, basement membrane deposition, and intercellular junction formation.
  • PublicationRestreint
    Minimal contraction for tissue-engineered skin substitutes when matured at the air–liquid interface
    (John Wiley & Sons, 2013-06-03) Germain, Lucie; Larouche, Danielle; Auger, François A.; Marcoux, Hugo-Bastien; Gauvin, Robert; Guignard, Rina
    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 tissue engineered skin that possesses high structural stability
  • PublicationRestreint
    Skin equivalent produced with human collagen
    (Society for In Vitro Biology, 1995-06-01) Noël, Bernard; Tremblay, Nathalie; Germain, Lucie; Auger, François A.; López Valle, Carlos Antonio; Guignard, Rina; Goulet, Francine
    Several studies have recently been conducted on cultured skin equivalent (SE), prepared using human keratinocytes seeded on various types of dermal equivalents (DE). We previously showed the advantages of our anchorage method in preventing the severe surface reduction of DE due to fibroblast contractile properties in vitro. A new anchored human SE was established in our laboratory in order to obtain a bioengineered tissue that would possess the appropriate histological and biological properties. In order to compare the effects of different collagen origins on the evolution of SE in vitro, human keratinocytes were seeded on three types of anchored DE. A comparative study was carried out between bovine SE (bSE), human SE (hSE), and human skin equivalent containing additional dermal matrix components (hSE +). Immunohistological analysis showed that hSE and hSE+ presented good structural organization, including the deposition of several basement membrane constituents. Higher amounts of transglutaminase, ceramides, and keratin 1 were detected in the epidermal layers of all SE when cultured at the air-liquid interface. However, a 92 kDa gelatinase activity was higher in bovine skin equivalent (bSE) compared to hSE cultures. The use of human collagens comparatively to bovine collagen as SE matricial component delayed the degradation of the dermal layer in culture.
  • PublicationRestreint
    Skin Substitutes and Wound Healing
    (Karger, 2009-02-04) Germain, Lucie; Auger, François A.; Lacroix, Dan.
    Medical science has vastly improved on the means and methods available for the treatment of wounds in the clinic. The production and use of various types of skin substitutes has led to dramatic improvements in the odds of survival for severely burned patients, but they have also shown promise for many other applications, including cases involving chronic wounds that are not life threatening. Nowadays, more than 20 products are commercially available, more are undergoing clinical trials and a large number of new models are being investigated in various research laboratories worldwide. Many of the current products do not contain any living cells and vary in their capacity to harness the innate capacity of the body to heal itself. Others include living cells, of allogeneic or autologous origin, and are often referred to as ‘cellular therapy’ or ‘tissue-engineered’ products. Modifications and improvements are currently investigated that aim at improving the healing potential of those products through the use of recombinant growth factors and additional features such as microvascularization. Fundamental research into wound healing and scar-free regeneration raises the hope that we will eventually be able to restore almost completely the appearance and function of skin after the healing of wounds.
  • PublicationAccès libre
    Electric potential across epidermis and its role during wound healing can be studied by using an in vitro reconstructed human skin
    (S-N Publications, 2012-02-28) Plante, Michel; Germain, Lucie; Roberge, Charles; Auger, François A.; Gauvin, Robert; Dubé, Jean; Rochette-Drouin, Olivier; Goulet, Daniel; Lévesque, Philippe; Bourdages, Michel; Moulin, Véronique
    Background : After human epidermis wounding, transepithelial potential (TEP) present in nonlesional epidermis decreases and induces an endogenous direct current epithelial electric field (EEF) that could be implicated in the wound re-epithelialization. Some studies suggest that exogenous electric stimulation of wounds can stimulate healing, although the mechanisms remain to be determined. The Problem : Little is known concerning the exact action of the EEF during healing. The mechanism responsible for TEP and EEF is unknown due to the lack of an in vitro model to study this phenomenon. Basic Science Advances : We carried out studies by using a wound created in a human tissue-engineered skin and determined that TEP undergoes ascending and decreasing phases during the epithelium formation. The in vitro TEP measurements over time in the wound were corroborated with histological changes and with in vivo TEP variations during porcine skin wound healing. The expression of a crucial element implicated in Na+ transport, Na+/K+ ATPase pumps, was also evaluated at the same time points during the re-epithelialization process. The ascending and decreasing TEP values were correlated with changes in the expression of these pumps. The distribution of Na+/K+ ATPase pumps also varied according to epidermal differentiation. Further, inhibition of the pump activity induced a significant decrease of the TEP and of the re-epithelization rate. Clinical Care Relevance : A better comprehension of the role of EEF could have important future medical applications regarding the treatment of chronic wound healing. Conclusion : This study brings a new perspective to understand the formation and restoration of TEP during the cutaneous wound healing process.
  • PublicationRestreint
    Reconstructed human skin produced in vitro and grafted on athymic mice
    (Ovid, 2002-06-15) Li, Hui; Germain, Lucie; Xu, Wen; Larouche, Danielle; Juhász, Julianna; Auger, François A.; Pouliot, Roxane
    Background. The best alternative to a split-thickness graft for the wound coverage of patients with extensive burns should be in vitro reconstructed autologous skin made of both dermis and epidermis and devoid of exogenous extracellular matrix proteins and synthetic material. We have designed such a reconstructed human skin (rHS) and present here its first in vivo grafting on athymic mice. Methods. The rHS was made by culturing newborn or adult keratinocytes on superimposed fibrous sheets obtained after culturing human fibroblasts with ascorbic acid. Ten days after keratinocyte seeding, reconstructed skins were either cultured at the air-liquid interface or grafted on athymic mice. We present the macroscopic, histologic, and phenotypic properties of such tissues in vitro and in vivo after grafting on nude mice. Results. After maturation in vitro, the reconstructed skin exhibited a well-developed human epidermis that expressed differentiated markers and basement membrane proteins. Four days after grafting, a complete take of all grafts was obtained. Histological analysis revealed that the newly generated epidermis of newborn rHS was thicker than that of adult rHS after 4 days but similar 21 days after grafting. The basement membrane components (bullous pemphigoid antigens, laminin, and type IV and VII collagens) were detected at the dermo-epidermal junction, showing a continuous line 4 days after grafting. Ultrastructural studies revealed that the basement membrane was continuous and well organized 21 days after transplantation. The macroscopic aspect of the reconstructed skin revealed a resistant, supple, and elastic tissue. Elastin staining and elastic fibers were detected as a complex network in the rHS that contributes to the good elasticity of this new reconstructed tissue. Conclusions. This new rHS model gives supple and easy to handle skins while demonstrating an adequate wound healing on mice. These results are promising for the development of this skin substitute for permanent coverage of burn wounds.
  • PublicationRestreint
    Anchored skin equivalent cultured in vitro: a new tool for percutaneous absorption studies
    (Tissue Culture Association, 1993-11-01) Michel, Martine; Germain, Lucie; Auger, François A.
    Dear Editor: The recent awareness that skin plays many important roles, such as a physical and immunological semi-permeable membrane which protects the whole body surface from water loss and selectively controls the rate of molecule penetration in the circulatory system, has fostered a keen interest in percutaneous absorption studies. The development of transdermal therapeutic system has concretely shown that skin bioabsorption properties are of major interest in the pharmaceutical industry (7). Moreover, in the field of toxicology, potentially harmful compounds that come in contact with the body surface must be tested. Different models have been designed to evaluate this important biological skin function using fresh or frozen skin (7,10,12,18). A major drawback of these models is the constant need of a human or animal skin supply which may lead to technical and ethical problems. Human cadaver skin is not easily available for most investigators. Moreover, an important and unavoidable variability in the skin absorption properties has been observed between samples from different individuals (21). Therefore, the present study was undertaken to set up an in vitro cultured skin equivalent for percutaneous absorption studies which could remedy these drawbacks. Recent progress in cell and tissue culture lead to the production of skin equivalents composed of a keratinocyte layer growing on a dermal equivalent. Various dermal equivalents have been proposed upon which keratinocytes can be seeded (1,15,19,20). These epidermal cells will remain in an undifferentiated state when the three-dimensional culture is kept immersed in the culture medium. However, an improved epidermal cell differentiation, characterized by the formation of the stratum corneum, is obtained when these skin equivalents were cultured at the air-liquid interface (13). In order to produce a skin equivalent suitable for the measurement of in vitro percutaneous absorption, we have adapted our previous design described for dermal equivalent anchorage (8) to the culture of skin equivalent. This technique allows these skin equivalents to be easily mounted on Franz diffusion cells. In the present study, human keratinocytes and dermal fibroblasts were isolated from normal adult skin specimens removed during plastic surgery and cultured as previously described (2,6,16). Dermal equivalents were prepared according to the method of Bell (1), with some modifications as described by Rompr~ et at. (17). The collagen/fibroblasts mixture was poured into a petri dish (35 mm in diameter) containing a ring of filter paper, accordingly to the method developed by L5pez Valle et at. (8), to prevent the collagen lattice contraction. In the present study, this anchorage was not glued to the bottom of the dish, to facilitate the subsequent technical manipulations of the skin equivalent. After keratinocyte addition, such a system led to the production of a skin equivalent presenting a constant surface area (Fig. 1). These skin equivalents, when raised at the air-liquid interface using conventional systems i.e. deposition
  • PublicationRestreint
    From newborn to adult : phenotypic and functional properties of skin equivalent and human skin as a function of donor age
    (Liss, 1997-05-01) Michel, Martine; Germain, Lucie; L'Heureux, Nicolas; Auger, François A.
    The skin's most important function is to act as a barrier against fluid loss, microorganism infections, and percutaneous absorption. To fulfill this role, keratinocytes proliferate and differentiate to produce a protective layer: the stratum corneum. Because stem cells are responsible for the production of differentiated progeny and stem cells (K19-expressing cells) are less abundant in skin from older donors, the purpose of this study was to establish whether histological and functional properties of differentiating skin is influenced by donor age. The in vitro model developed for the evaluation of skin properties (Michel et al., 1995) was used to produce skin equivalents from newborn, child, and adult keratinocytes. Throughout maturation, skin equivalents were compared with corresponding skin biopsies for keratin, filaggrin, and transglutaminase expression. Percutaneous absorptions of hydrocortisone also were measured and correlated with lipid content. After 1 wk of immersed culture, the epidermal layer of newborn skin equivalents was thicker than child and adult epidermis. As expected, a greater proportion of cutaneous stem cells was present in newborn compared with children and adult skin equivalents. No age-related difference was observed for differentiation markers. When skin equivalents were cultured at the air-liquid interface, cell differentiation and stratum corneum formation were induced, and the age-related variation in the thickness of the epidermal layer disappeared. Percutaneous absorption through these matured skin equivalents did not vary with age. Their lipid density and profile were similar. Accordingly, skin biopsies exhibited comparable percutaneous absorption profiles independently of donor age. In conclusion, although newborn skin equivalents, or skin biopsies, contained more stem cells than child and adult counterparts, no age-related histological difference was observed in the differentiated tissues. Moreover, the functional barrier property of skins and matured skin equivalents did not vary with age. Therefore, both newborn and adult keratinocytes produce useful in vitro models to study epidermal differentiation processes involved in both normal and pathological states.
  • PublicationAccès libre
    Improved methods to produce tissue-engineered skin substitutes suitable for the permanent closure of full-thickness skin injuries
    (Mary Ann Liebert, 2016-11-01) Germain, Lucie; Larouche, Danielle; Auger, François A.; Martel, Israël; Cantin-Warren, Laurence; Ayoub, Akram; Gauvin, Robert; Guignard, Rina; Desgagné, Maxime; Moulin, Véronique; Lavoie, Amélie
    There is a clinical need for skin substitutes to replace full-thickness skin loss. Our group has developed a bilayered skin substitute produced from the patient’s own fibroblasts and keratinocytes referred to as Self-Assembled Skin Substitute (SASS). After cell isolation and expansion, the current time required to produce SASS is 45 days. We aimed to optimize the manufacturing process to standardize the production of SASS and to reduce production time. The new approach consisted in seeding keratinocytes on a fibroblast-derived tissue sheet before its detachment from the culture plate. Four days following keratinocyte seeding, the resulting tissue was stacked on two fibroblast-derived tissue sheets and cultured at the air–liquid interface for 10 days. The resulting total production time was 31 days. An alternative method adapted to more contractile fibroblasts was also developed. It consisted in adding a peripheral frame before seeding fibroblasts in the culture plate. SASSs produced by both new methods shared similar histology, contractile behavior in vitro and in vivo evolution after grafting onto mice when compared with SASSs produced by the 45-day standard method. In conclusion, the new approach for the production of high-quality human skin substitutes should allow an earlier autologous grafting for the treatment of severely burned patients.