Accueil du site > Equipes > Fonctionnalité et dynamique du tissu cutané (D. Sigaudo-Roussel) > Thématiques > Réparation tissulaire et propriétés fonctionnelles de la peau > Tissue repair and functional properties of the skin
Project leaders : P. Sommer, D. Sigaudo-Roussel
Persons involved in the project : M-S. Nguyen Tu, J. Boizot, G. Aimond, J. Vial, R. Debret, A. Josset-Lamaugarny, B. Fromy, D. Vital-Durand, J.L. Saumet.
Wound healing is a complex phenomenon in which the dermal and epidermal events are closely involved and is not, as was long believed, a simple linear process in which growth factors are synthesized to activate cell proliferation and migration. Tissue repair helps to restore skin functional quality in a healthy body. However, this repair ability may be compromised or weakened by different medical conditions and can lead to the formation of a scar tissue, which is often vulnerable and unstable, limiting further a functional skin restoration and leading to an increased incidence of skin lesions.
Repair of the elastic network
We are interested in improving healing through re-induction of the synthesis of elastic fibers in the wounds. One of the limiting factors in regenerative medicine is the lack of neo-synthesis of elastic fibers in the neo-tissue. Several approaches can be considered : the influence of growth factors, pharmacological modulation by a duly certified molecule and the addition of a synthetic matrix providing macro and microenvironment favorable to elastogenesis.
This program will seek to identify and address the mechanisms that inhibit the formation of elastic fibers in wounds or during tissue reconstruction. Furthermore, it aims as well to understand the mechanisms providing the dill extract with elastogenic pro-activity in different models (reconstructed skin, chronic scar in animal tissue regeneration therapeutic), by identifying the molecules involved and their mode of action. This project is conducted with the company Urgo, specialist in manufacturing bandages for wound healing, resulting in a CIFRE scholarship (PhD J. Boizot, 2011-2013), around modeling healing via hypoxia and the effect on the elastogenesis.
As part of the team dynamics, the elastogenic potential of tissues with their ability to neo-vascularization and innervation will be studied in parallel. The idea is to consider the quality of the repaired tissue as a whole.
Physiological and molecular characteristics of the fragile skin
Research in this theme will aim to better understand how tissue repair affects the functional quality of the skin. The study design and therapeutic target is the bedsore. This is a serious clinical complication that impairs quality of life and leads to very high socio-economic complications (overload nursing, expensive treatments, extended stay). Sloughs can also lead to other diseases through the resulting open wounds. It is therefore essential to implement a policy of prevention.
A functional skin is protected from damages by mechanical, thermal and chemical resistance but this feature is lost during aging or when under stress.
It is recognized that the functional elastogenesis is not done or poorly during tissue repair or ulcerative wounds. Mechanisms that may be affected are not known, although it is a crucial step in tissue repair. As a constant chronic wounds is hypoxia, we study the effect of hypoxia on the elastogenesis.
A model of in vitro hypoxia was developed by engineering a reconstructed human skin, and by using a model of pressure-induced ulceration in mice to create localized hypoxic conditions. We investigate whether the activation of genes is inhibited or if hypoxia / ischemia induces improper assembly. This program will be closely linked to studies on the control of elastogenesis by epigenetic gene regulation.
This research program being funded by Urgo, the matrices developed in industry to reduce the deleterious effects caused by hypoxia matrices will be tested in our conditions. The utmost pharmacological interest would be to activate these matrices with active molecules strengthening elastogenesis.
This interface program will be performed along with the development of organotypic models and in synergy with the study of bedsores in in vivo models and in humans.
Obesity and diabetes are associated with skin complications, especially dermal functions involved in maintaining skin strength. However, the mechanisms by which obese diabetes causes skin fragility are little understood. Previous studies have shown that the accumulation of subcutaneous adipose tissue and increased BMI are negatively correlated with skin thickness in mice and patients.
Among the many pathological conditions associated with skin fragility, bedsores are one of the most common problems in clinic and are caused by the application of pressure or shear force.
In diabetes and obesity, the project is to study the relationship between the network of elastic fibers and neurovascular network in response to external pressure and hypoxia, and their involvement in the fragile skin ; the healing process after hypoxic pressure injuries ; and finally the quality of the scar tissue in term of elastic fiber, vascular and nervous network structures and functionality.
We seek to understand and optimize the healing process and thereby maximize the functional quality of the scar tissue.
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