MECHANOBIOLOGY… REJUVENATING SKIN

Mechanobiology: how cells react to mechanical forces
As its name indicates, mechanobiology consists of placing biological cells under pressure, i.e. submitting them to mechanical stress to observe how they behave. Stress can mean pressure, twisting or pulling. This discipline of biology is looking at modifications to biological tissues and cells subjected to physical forces that can promote their development, influence
their physiology or cause illness. The underlying mechanisms, i.e. the relations between the physical stimulus and the molecular response, are far from being understood.

Yet for 20 years, this discipline has been on the rise, with applications in the fight against cancer, tissue engineering, embryo development and healing (1). The impact of a massage on the temperature of the human body, blood circulation, muscle strength and the nervous system have all been explored, but very little work has been done on the impact of a massage on the structure or biology of the skin, and none at all on skin aging.

This is exactly what L’Oréal R&I undertook to do as it was established that cells are sensitive to forces and convert mechanical signals into a biochemical response (mechanotransduction). However, cells use a variety of mechanisms to respond to mechanical forces, depending on their type, their environment, tissue aging, etc., and these mechanisms have not yet been
fully identified.

Given its locations, scientists at L'Oréal contacted teams in their region and fostered collaborations with centres of excellence such as the Mechanobiology Institute, Singapore for systemic biology (2), and in France the Institut Langevin for elastography and the Denis Diderot university for cell adhesion and tissue mechanics. Mechanobiology has a privileged field of application in L'Oréal: skin ageing.

Skin mechanobiology
The signs of aging we know well concern different compartments of the skin: the epidermis, the dermis and the hypodermis. Skin aging is a complex biological process affected by internal and external factors. It mainly impacts the production of proteins in the extracellular matrix leading to damage to the network of elastic fibres in the dermal-epidermal junction (DEJ).

These fibres give their elastic properties to the skin tissues and also enable them to modulate their proliferation and differentiation. In adults (20 years old), the gradual deterioration in the elastic fibres is not counterbalanced by the renewal of functional fibres. Visually, the most marked sign of this deterioration is without doubt the appearance of lines on the skin, but there are numerous clinical and histological modifications. This knowledge led L'Oréal scientists to develop a massage instrument, for routine use by consumers, with or without a cream. First though, they needed to understand the biological effects of mechanical stimulation on the skin and prove that rejuvenation was possible.

They did this in two stages:
1- Firstly an ex vivo study, i.e. on skin maintained alive. We tried to identify the frequencies and amplitudes of external mechanical stimulation that would enhance the expression of proteins in the extracellular matrix and the dermal-epidermal
junction. The skin was treated twice daily for 1 minute over 10 days. The results: strengthening of the dermal-epidermal junction and an increase in the extracellular matrix for a frequency of 75 Hz.

Based on these results, they designed a prototype skin massage device and optimized it to define the best combination: the frequency, the head, the movement and the ergonomics.

2- A second randomized in vivo clinical trial on 42 women aged from 65 to 75 divided into two groups: G1 (22 volunteers using a cream) and G2 (20 volunteers, using a cream and the device), for 8 weeks, twice a day.

The evaluation was done by an independent expert in a double-blind study using a global aging atlas (lines and texture) and per zone (cheeks, lip contours, neck and décolleté). The results were completed by an instrumental evaluation and an evaluation of efficacy perceived by the volunteers.

3- Everything converges on a visible improvement in the signs of aging and in particular: firmness, slackening of the face and the neck.This work was presented twice at congresses and published in PlosOne in 2017 (3).

Clarisonic launches Smart Profile Uplift
This is a perfect illustration of L'Oréal’s model for innovation “transforming science into beauty”. Initial work on mechanobiology started in Advanced Research in Singapore in 2008. The massage head was designed and optimized by engineers and designers at Clarisonic. The Smart Profile Uplift massage device was launched on the US market and is set to conquer the world in 2017.

Skin mechanobiology: a story with a promising future
The teams are continuing on several fronts: fibroblasts and tissue engineering to reconstruct more functionalized, older skin, that would be an extraordinary prediction tool for the efficacy of some substances. There are many skin models currently sold around the world, mainly developed from collagens. However, all these skin substitutes have the same limit: it is impossible to reproduce a tissue with elastic properties similar to the tissues sought. This is due to a lack of understanding of the biological parameters driving the synthesis of functional elastic fibres in adult tissue and the absence of suitable substrates to create the microenvironment that has the right ratio of elastic and viscoelastic components in the tissues and their matrix.