A Quantum Leap for Sensitive Skin: 3D Bioprinted Tissue Model Could Drive Future Development of Customized Cosmetic Ingredients
Interview with Colin McGuckin, Founding Director & Chief Scientific Officer at CTIBIOTECH and Sébastien Cadau, Cell Culture & Tissue Engineering Manager at BASF
CTIBIOTECH, BASF Beauty Care Solutions
3D tissue models are a powerful tool to quickly and reliably test cosmetic products for skincare applications. In the past years, CTIBIOTECH and BASF have jointly made important progress in this field. Recently, they teamed up to develop an immune skin model containing human macrophages that is suitable to screen drugs and cosmetic ingredients for normal and inflamed skin. Colin McGuckin, Founding Director & Chief Scientific Officer at CTIBIOTECH, and Sébastien Cadau, Cell Culture & Tissue Engineering Manager at BASF, share insights into their research findings.
You developed the world’s first 3D full-size bioprinted immune skin model including human macrophages. How did this come about?
McGuckin: Skin is our first line of defense against the bacteria and viruses that we touch every day. Without the immunology of the skin, we would not survive very long. But the sensitive balance that exists in the skin can easily be disrupted and lead to skin irritations like atopic dermatitis and acne. We believe that sophisticated models are required for testing and screening advanced chemicals and cosmetics. We created our model to give a more accurate window into the way in which products react on skin in order to avoid problems in humans later and to help improve sensitive skin signs.
How does the model work?
McGuckin: We created a full-thickness skin model into which we added a variety of human macrophages – one of the most important infection-fighting killers in the skin. The model is 3D bioprinted for two reasons: firstly, to distribute the immune function in the model accurately, and secondly, to industrialize the model so that it can be produced many times. We can print over 100 models per hour, which gives many options for chemical companies to test their products. Combining advanced engineering with biomedicine is the future!
How does this skin model help you to develop innovative active ingredients for skincare applications?
Cadau: The 3D model provides a powerful platform for us to study the function of macrophages in fully reconstructed skin. Compared to current in vitro methods, it allows analysis that is more in line with human physiology. As macrophages are key players in skin immunity, the bioprinted tissue can help us to provide efficient solutions that assist in promoting or recovering a healthy skin by interrupting the chronical loop of inflammation.
There is a growing consumer demand for soothing ingredients. In particular, people are looking for cosmetics that help face environmental factors such as stressful urban lifestyle, multilight exposure, or extreme temperatures, and for dermocosmetic applications that help to strengthen reactive and sensitive skin.
Which results have you gained so far?
Cadau: The macrophages in our models reach a suitable maturity, which has been demonstrated by their specificity of cytokine release during the challenge phases of our experiments with good response to lipopolysaccharide and dexamethasone.
In addition, the modern technology convergence of bioprinting with modern flow cytometric bead array has been a particular advantage in the reproducibility and speed of testing.
Combining these two technologies, it is possible to print many such models in the space of a few hours and having them matured and analyzed within three weeks. This gives hope for more automated screening with immunized skin equivalents.
The model generated a lot of interest in the cosmetics industry when we presented it in a paper at IFSCC 2020, and we won the Henry Maso Award for the related publication.
Fig. 1 3D bioprinted skin models maturing in 12-well plates. © CTIBIOTECH
What should we expect next?
McGuckin: Macrophages have a high degree of plasticity that promotes or suppresses inflammation to maintain skin homeostasis. The protocol used in the current model allows a perfect assessment of the first pro-inflammatory phase thanks to the detected functional macrophage M1 subpopulation. Moreover, this model has already been further advanced to measure phagocytosis following bacterial exposure, which has led to promising results.
These are great successes, but we want to go one step further. To better address the recovery phase of inflammation, we are currently working on protocol optimizations to improve the anti-inflammatory answer of the more fragile macrophage M2 subpopulation.
BASF and CTIBIOTECH started their cooperation back in 2011. What other projects have you worked on together?
Cadau: We successfully used a 3D human sebaceous gland model developed by CTIBIOTECH to produce physiological sebum ex vivo in a long-term culture. It allows to study the function of sebaceous glands in relation to a range of age-related, microbial and inflammatory skin disorders. This technology has contributed significantly to the development of our innovative active ingredient Bix’Activ®. It reduces sebum production by restraining the proliferation of sebocytes in sebaceous glands. Results like this show the great potential of 3D bioprinting for the research and development of cosmetic ingredients.
Cell Culture & Tissue Engineering Manager
BASF Beauty Care Solutions
Sébastien Cadau has a master’s degree in biology and a PhD in development & oncology from Joseph Fournier University (Grenoble, France).
After a post-doc in tissue engineering to develop an innervated and endothelialized skin model at LOEX, Laval University (Quebec, Canada), he joined the BASF Beauty Care Solutions research team to lead the tissue engineering platform, establish the skin model portfolio and evaluate the efficacies of new cosmetic ingredients.
Founding Director & Chief Scientific Officer
Colin McGuckin was the UK’s first full professor of regenerative medicine, before founding CTIBIOTECH to create not only organ-based models for drug screening and efficacy testing, but also to create cell and organ therapies of the future. Coming from a background of hematology/oncology his work expanded in the 1990’s to stem cells and his academic group were first in the world to create neural and hepatic tissues from adult stem cells. Now at CTIBIOTECH they are leaders in 3D bioprinting models of the human body, with a lot of success in complex skin, tumors and liver systems.