Biomaterials: reconstructing the skin

To accelerate the healing of chronic or acute wounds that struggle to heal naturally, scientists from Inserm and Besançon University Hospital are developing a biomaterial that reproduces the architecture and physical properties of human skin. Grafted to the patient, it will boost tissue regeneration.

Dans un laboratoire, une jeune femme réalise une observation à l’aide d’un microscope imposant. Sur une table à côté d’elle, un écran d’ordinateur présente une image qui correspond à la reconstitution en trois dimensions d’un tissu biologique.
Using a confocal microscope, Marion Tissot observes human skin cells cultured in the presence of the biomaterial being developed at the Besançon health campus © Inserm/François Guénet

Here we are at the heart of the Besançon health campus, the ground covered with the first autumn leaves that crunch under the feet of the bustling students. Researcher Gwenaël Rolin enthusiastically welcomes us to his laboratory. Today we are going to test the TissYou project that he has been developing for ten years now: a biomaterial capable of regenerating the skin. A type of intradermal dressing that accelerates the healing of chronic or acute wounds. How? ‘The biomaterial will be grafted to the patient’s wound so that their own cells can colonise it and regenerate the skin. As healing progresses, the biomaterial will break down until it disappears completely’, explains the researcher. To be effective, the biomaterial must be supple like human skin and provide a welcoming environment for the patient’s skin cells. Now let’s follow Rolin into the first part of the laboratory to take a look at its mechanical and biological properties.

Un homme tient un petit morceau de tissu blanc, fin et légèrement étirable, entre le pouce et l’index de chacune de ses mains gantées.

This is what the biomaterial looks like. White, like the human deep dermis, it has the same architecture and is slightly elastic, like the skin. Rolin is preparing to colonise skin cells in the biomaterial, as if it were deposited in the wound of a patient.

To do this, cells need to be recovered from human skin donations. These cells, concentrated in a test tube, are sorted and characterised one by one. A technique called « flow cytometry », which is performed here by PhD student Zélie Dirand.

Une jeune femme place un petit tube dans un gros appareil.
Une autre jeune femme place des petites boîtes de culture cellulaire rondes en plastique dans une étuve.

Once isolated, the skin cells are grown and observed in real time by a computer in this robotic microscope. 

The redder the cell nucleus, the more the gene that codes for collagen is expressed – a sign that the cell inoculated in the biomaterial is active and synthesising new skin components.

Un liquide rose est déposé à l’aide d’une longue pipette sur un petit carré de tissu blanc placé dans une boîte de culture en plastique.

Rolin deposits the culture fluid containing the skin cells onto the biomaterial. Will they distribute evenly?

Here is the 3D visualisation of a slice of the biomaterial eight days after cell inoculation, performed by laboratory technician Marion Tissot. Each blue disc is a cell nucleus. We can see that the skin cells are evenly distributed within the biomaterial, making the first test a success!

Une femme et un homme assis à un bureau sur lequel un écran d’ordinateur montre l’image d’un tissu biologique en trois dimensions.
À gauche, une jeune femme prépare une expérience sur une paillasse de laboratoire. À droite, zoom sur l’expérience : une lanière de tissu blanc, retenue à chaque extrémité par un système de pince, est étiré au maximum de sa résistance par l’appareil dans laquelle elle a été placée.

After biologically qualifying the product, we will measure its mechanical properties under the concentrated eye of Tiguida Kadiakhe, biomechanics PhD student at the CNRS FEMTO-ST institute. It is essential that the product is able to reproduce the human dermis by being both supple and resistant. The biomaterial is placed under considerable stress in order to test its elasticity and measure its various mechanical properties. It is essential that it can stretch in response to the bending of a phalanx or knee and boost healing. The data are compared with those of human skin. Verdict? Elasticity is as hoped!

The first clinical trials in humans are expected to start in 2025. For the moment, the product is intended for use in reconstructive surgery and chronic wounds, but could also one day be used in the management of severe burns.

A report produced with Gwenaël Rolin’s team at the Host-graft-tumour interactions and cell and gene engineering laboratory (unit 1098 Inserm/French National Blood Service (EFS)/Franche-Comté University) and at Clinical Investigation Centre 1431 (CIC 1431 Inserm/Besançon Regional University Hospital/Franche-Comté University)..

The TissYou project is the recipient of European Eurostars 2 funding, the consortium members of which are the Right Institute, Besançon University Hospital, the companies Straticell (Belgium) and Rescoll, and the Ludwig Boltzmann Research Institute (Austria).

Photos: Inserm/François Guénet
Author: L. A.