With rising ethical concerns of using animals for certain applications (such as testing skin irritants), research into non-animal models has become very popular leading to several innovative systems we’ll describe here. First however, let’s look at why we need skin models. For a recap on the structure and function of the skin, see our previous article.
What are skin models used for?
There are several applications:
- Dermal toxicity studies to measure the degree to which substances are toxic;
- Cosmetic claim substantiation to validate (or invalidate!) the statements made in association with cosmetic products (“makes you look 10 years younger!”);
- Pharmacology studies to test new pharmacologic agents;
- Absorption studies to measure skin permeation, irritation, phototoxicity, and corrosion.
Why don’t we test products on humans?
However, human testing isn’t always possible or ethical.
There are ethical, practical, and economic considerations, particularly in the early phases of development. A new drug must go through years of in vivo and in vitro testing before it can reach human testing.
In an effort to improve the usefulness of cell and tissue studies like those listed above, from testing a new skin lotion to a new topical ointment for psoriasis, and to decrease the need for animal models, there is a huge interest in creating accessible and reproducible surrogates for in vivo human skin.
In terms of practicality, when using living human skin as a model in vivo responses can be difficult to measure and interpret and subject to significant variability. For example, the skin on your back, arm, and foot all absorb substances differently. When testing a product, we need clear, reproducible, and reliable results.
What are examples of skin models?
1) Ex vivo human skin
Oh yes, cadaver skin…but also skin leftover from plastic surgeries! Kind of neat actually!
2) Ex vivo animal skin
When ex vivo human skin is not available, animal skin may be used. Pig skin is similar to human skin and is readily available, and as such is popular for skin studies. Among rodents, rat skin is most similar to human skin. However the use of animal models creates a major challenge: correlating results from ex vivo animal studies to in vivo or ex vivo human studies to predict human responses.
3) Artificial skin models
These vary in their complexity ranging from simple homogeneous polymer materials to lipid-based parallel artificial membrane-permeability assay (PAMPA) or phospholipid vesicle-based permeation-assay membranes. These are highly homogenous materials which may enhance the reproducibility of results. However this simplicity limits their usefulness in cases where a facsimile of human skin is needed.
4) Reconstructed skin models
Reconstructed skin models consist of layers of human cells cultured over a polymeric matrix to form a 3D matrix. This allows different cell types to be incorporated to achieve a structure of the a range of compositions and degrees of complexity. Generally, these are made commercially or in-house to simulate either the epidermis (known as reconstructed human epidermis [RHE] models) or the complete multilayer structure of the human skin (known as living skin equivalents [LSEs]). Commercially available RHE models include EpiSkin®, SkinEthic®, and EpiDerm® and LSE models include GraftSkin®, EpiDermFT®, and Pheninon®.
5) Skin cell models
Skin cell lines can be used to create monolayers of one cell type or mixed cell co-cultures depending. Skin cell lines are of particular interest where the diverse skin types from those that burn easily to those that are highly UV resistant can be studied in consumer ingredient research.
A popular cell type are keratinocytes which constitute around 90% of the human epidermis. Melanocytes are similarly popular skin models (although as our regular readers know melanocytes are not just found in the skin!) and are ideally suited to toxicity testing, phenotypic assays (e.g., expression of differentiation markers), mitochondrial dysfunction, and bioprinting.
Open Source Skin Models?
Since many skin models are either protected by patents and/or are made using proprietary tissue culture procedures there are concerns over their long term availability and global accessibility. As a consequence of this, some researchers are looking to open-source models. One example of this is the ALEXANDRA (Alternatives to Experiments on Animals Destined to Research Applications) Association.
Do you have a favorite skin model? Tweet us @TempoBioscience or tell us in the comments below.