Tissue Engineering

Provital’s Tissue Engineering Know-How 

In the pursued of our strategic goal of acquiring independence, at Provital, we strongly invested in the development of 3D skin models reconstructed from scratch in our own laboratories, so that we are able to fine-tune our needs together with notably increase our in-house know-how of these techniques:

1. Reconstructed human epidermis. Our goal has been to develop an accurate 3D reconstructed human epidermis model mimicking the native human epidermis with the correct layer disposition of keratinocytes. Through our own independent research, we have advanced in developing efficient methods to create a human epidermis model which is highly reproducible and ensures repeatability and accuracy of results.

2. Reconstructed human pigmented epidermis. In our in vitro tests in reconstructed human pigmented epidermis (RHPE), the goal is to create a model that accurately responds to the treatment with compounds that reduce or increase melanin, leading to precise tests of our product’s efficacy. The process means we decided to move from in vitro tests using reconstructed epidermis made of only keratinocytes, to tests that will also include melanocytes. This is especially interesting because it allows to consider melanin measurements in its natural environment instead of employing mouse cells or isolated human melanocytes.

3. Particular non-invasive tests to measure the quality of the skin’s barrier function in our own lab.

4. In vitro histologies. We are now capable of independently performing all the steps needed in this regard, from paraffin inclusion and microtome cuts, to H&E or Fontana - Masson staining, performed in reconstructed skin models which, until very recently, could only be performed in biopsies.

5. Full-thickness models. We are in the process of developing in-house reconstructed full-thickness skin models, including fibroblasts and not only keratinocytes, so that the two compartments, epidermis and dermis, are present in the model.

6. We are able to analyze neuronal behavior thanks to our in-house know-how in tissue engineering and bioinformatic capabilities. In other words, due to our PBBP, we are able to further analyze the data by using cutting-egde immunofluorescence techniques as well as transcriptomics.

A revolutionary 3D skin model: Full Thickness (FT)

Thus, using a tissue engineering process, Provital became a global pioneer in the development of a stretch mark reconstructed skin model in 2019. 

For the first time, a 3D skin model with striae fibroblasts and normal keratinocytes was reconstructed in a way that recapitulates the physiology and morphology of the native skin, mimicking thus the hallmarks of stretch marks. So, thanks to our tissue engineering efforts to perform this human Full Thickness (FT) reconstructed skin model, we were able to gain unprecedented knowledge about stretch marks formation. 

We discovered, for the first time, that not only does this tissue produce less collagen and less growth factors, but also an atrophy of the epidermis caused by dermal fibroblasts, which indicates a direct influence of the dermis on the quality of the epidermis. This key finding led to the peer-reviewed publication in the International Journal of Cosmetic Science, “Striae reconstructed, a full thickness skin model that recapitulates the pathology behind stretch marks”, and the development of Striover™.

A better Melanin quantification thanks to advancements in RHPE 

As the classic melanin measurement is not very sensitive, and at Provital we are now able to customize the skin reconstruction conditions according to our needs, we have been working on a new quantification technique for melanin production in our own RHPE model. 

This in-house model is part of our Industrial Doctoral Thesis program, focused on the reconstruction of human skin models.

In this new method, we have applied image quantification using machine learning, within the PBBP. So we have been able to improve the sensitivity of the technique, along with being able to adjust the conditions.

Our reinforce leadership in ethical cosmetic testing

We have also identified immunohistochemistry, immunofluorescence and confocal microscopy key strategic partnerships to further analyze our reconstructed skin models, thus consolidating our commitment to state-of-the-art cosmetic scientific research, and positioning Provital as a global leader on in vitro testing.

Besides, investing in an industrial PhD specialized in Tissue Engineering has also been a key strategic step towards promoting Provital’s in-house research capacities and expanding the limits of cosmetics ethical testing for many of our Careactives™.