DS04 - Vie, santé et bien-être

Electrostimulation of wound healing: toward a more effective therapy – WHEEL

Submission summary

Chronic wounds are a serious public health issue. In 2014, 3.6 million patients presented chronic wounds in France. This number is increasing each year because of population aging and the increasing prevalence of chronic disease such as diabetes and obesity. Classical options for wound treatments are chemical, biological or mechanical debridement, antibiotic therapy, compressing bandaging and wound dressing. However, some more innovative therapies are available. Among them, electrical stimulation is a promising technology, especially because it is based on a physical natural process and not on pharmacological drugs.
Why use electric field in this context? The rational behind this is that a cutaneous wound creates a break in the epithelium and its transepithelial potential which generates an endogenous electric field at the wound margins. In healthy context this endogenous electric field stimulate surrounding cell to achieve an optimal healing, but in chronic wounds, this endogenous electric field is lost. Thus, electrostimulation approach is based on technology that aims to mimic the body’s physiological electrical signal. Electrostimulation is clinically efficient in improving wound healing, even if electrical parameters applied are empirical and differs between each centers.
Moreover, it has to be mentioned that when the cell is exposed to high external electric field (far from endogenous electric field parameters mentioned above) the plasma membrane becomes permeable to ions, drugs and molecules as large as plasmid DNA, which are otherwise impermeable: this is electroporation phenomenon. A medical application of electroporation is gene electrotransfer (GET), which is highly promising in wound healing by transferring relevant therapeutic plasmid. Interestingly, in this context, some authors demonstrated that electric field applied alone significantly improved wound closure. Besides, the main clinical application of electroporation in medicine which has reached an established position in local cancer treatment is electrochemotherapy (ECT). In this case also, clinicians commonly observed, but cannot explain, aesthetic and functional wound healing of the treated sites. In brief, even if cellular mechanisms are not yet deciphered, there is a strong link between wound healing and electroporation.
The hypothesis of the WHEEL project is that electric parameters used in electrochemotherapy and gene electrotransfer stimulate cells and promote cutaneous wound healing via induction of keratinocyte proliferation, migration and differentiation, extracellular matrix deposition by fibroblasts and promotion of angiogenesis. Thus, the objectives are to understand, visualize and quantify cutaneous cell and tissue responses to this external electric field application. For this purpose, this project proposes a multiscale analysis for wound healing investigation: from tissue level, to cellular and molecular levels.
The innovation of the WHEEL project is that the study will be conducted on 3D human skin substitutes reconstructed by innovative tissue engineering technique, which is clearly in rupture with conventional approaches. Indeed, rodents are classically used in wound healing studies, however murine skin differs from human skin in its architecture, its cellular composition and mechanisms of healing. Furthermore, most in vitro studies are led onto cell cultivated in monolayer. However, 2D cell systems lose mechanical and biophysical signals, intercellular communication as well as the architecture of the tissue from which they originate. Thus, 3D tissue models mimic biological tissue better than classical cell culture. Besides, according to the 3R’s ethical rule, this approach is an efficient and ethical alternative to the use of laboratory animals.
In conclusion, in a societal and global economic point of view, this project proposes a very innovative concept in stimulating wound healing by controllable and tunable physical approach.

Project coordination

Laure GIBOT (Institut de pharmacologie et de biologie structurale)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IPBS UMR 5089 Institut de pharmacologie et de biologie structurale

Help of the ANR 296,460 euros
Beginning and duration of the scientific project: - 48 Months

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