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4D Human Tissue Modeling: Pushing the Boundaries of In Vitro Testing

In recent years, there has been rapid progress in the development of novel technologies for cost-effective screening of chemicals, ingredients, drugs, and cosmetic formulations that strive to replace animal models and generate human-relevant data. Scientists are not only increasingly acknowledging the limitations of those “golden standards” for safety and efficacy testing that involve animals, they are also showing greater interest in ethical innovation.

Two-dimensional (2D) cultures have been traditionally used for the routine screening and discovery of active ingredients and therapeutics. In the last decades, three-dimensional (3D) cell culture approaches have gained significant attention because they can combine multiple cell types to more closely resemble the architecture and function of human organs. This enables a higher degree of insights.

However, there are still significant limitations associated with these 2D & 3D static culture techniques. One of those key challenges is the in vitro simulation of blood circulation: in static culture models, cells are not getting a steady flow of nutrients and oxygen as they would in the human body, nor are metabolic by-products removed. This makes it harder to capture the relevant complexity of the in vivo natural microenvironments and get reliable & representative data that further bridges the gap between initial candidates screening and human trials. With better human-relevant insights, there is no need to resort to animal models.


3D Skin Cultures & Microfluidics – Better Together

At Revivo Biosystems, the R&D team has tirelessly searched for better solutions to more closely replicate the natural skin microenvironment, and help clients deliver more accurate and faster testing results.

To overcome the above mentioned challenges, we have developed a unique organ-on-a-chip platform that allows mimicking the function of the blood flow and engineer what we call a REVSkin™ - a 4D full thickness skin model grown under dynamic, in vivo-like conditions.

These microtissues are based on living human cells, continuously nourished with nutrients from the dermal side (like blood vessels do in our body), while the epidermal side is exposed to the external environment. As a result, our sophisticated system can produce the currently most realistic solution on the market by recreating an in vivo-like micro-environment without involving animals.

“Traditional technology is static: it is like black-and-white photography. Because of the mimicking of the blood flow, REVIVO’s technology is dynamic: it is like taking a video in colors!” explains Dr. Massimo Alberti, the CEO and Founder of Revivo Biosystems. “We can recreate physiological and cell-level processes outside the body, such as delivering nutrients and removing cell metabolites. Therefore our tech adds more depth to the research our clients do.”

Static 3D cultures Our organ-on-a-chip approach

Top advantages of REVSkin™:

1. More realistic model means more reliable data

The mimicking of the blood flow in our 3D microtissues creates an environment closer to the one of real skin tissue in our bodies. This, in turn, makes sure that our 4D skin models show great morphological and chemical similarities to human skin so that you can obtain more accurate results, and avoid rework & retesting linked to false negatives and false positives. This saves time and resources.

2. Cost-effective & faster experiments without involving humans or animals

The ingenuity of the REVIn™ microfluidic device in which our REVSkin™ tissues are grown, is that it can be easily integrated into our RELEGO™ platform. This enables in situ permeability, toxicity and efficacy testing for chemicals, drugs and cosmetic ingredients.

This sophisticated system is amenable to the complete automation of testing protocols, which saves you hours of work and money. So, no more long manual sampling nights with our automated fraction collector!

3. Superior barrier function compared to static models

The development of well-characterized full-thickness skin models have important implications in both academic and industrial R&D settings.

Our dynamic flow system and culturing technique improves epithelial morphology and differentiation of full-thickness human skin and oral mucosa equivalents, leading to the enhanced synthesis of basement membrane proteins and improved barrier function.

Click here to learn more about our REVSkin™ Case study

4. Our tissues are based on human primary cells

The development of innovative skincare products starts when tests are conducted on human skin cells instead of animals. The cells that make up our REVSkin™ tissues are human fibroblasts and human keratinocytes cultured to form a full-thickness model consisting of dermis and epidermis.

5. We choose serum-free media to grow our skin

One more important fact about our tissue models is that we use culture media that is devoid of animal serum. We top this up by avoiding the use of animals and animal tissues. This enables us to be compatible with any project requiring animal-free experiments!

6. No more worries about collagen-based matrix contraction

Most reconstructed full-thickness skin models rely on animal collagen for their dermal matrix. A very problematic limitation of collagen-based matrices is that they contract during the culturing process as a result of fibroblast metabolism. This causes dishomogeneous keratinocytes seeding and ultimately a reconstructed skin model that is not fully keratinized and does not have a reliable exposure area for topical applications. Such issues can make permeation and efficacy testing impossible without the risk of having unreliable results.

To overcome these limitations we engineered our skin equivalents using a fibrin-based dermal matrix. Thus all collagen that is present in our REVSkin™ tissues is naturally produced by the human fibroblasts that compose them, and not animal-derived.

This is very useful for our clients who want to observe the early markers of efficacy of their dermo-cosmetic ingredients on collagen production, at the different stages of skin development.

We are also happy to speak with you and help you find the right protocol and pricing for your project needs. If you haven’t already, please follow us on LinkedIn for weekly updates about our release schedules, new products and services.


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