Contents
Introduction
In the last decades, the study and development of mimetic skin models
have been a hot topic of discussion mainly due to the rising of ethical
questions and the establishment of new rules regarding the prohibition
of animal testes. The need of new and efficient skin mimetic models
remains crucial namely for pharmaceutical, cosmetic and toxicological
purposes.
The safety and toxicity of new products and formulations must be
assessed prior human application according to the European Union (EU)
guidelines and to the Organisation for Economic Cooperation and
Development (OECD) guidelines for testing dangerous ingredients for the
skin (Kandarova et al., 2004, OECD, 2015, Fentem, 1999, Fentem and
Botham, 2004, Worth et al., 1998).
Efficient methods for development and rationalization of drug
formulations aiming topical application demand specific skin models
capable of estimating the properties and the most suitable drug
formulation. After the identification of important penetration and
permeation properties (wanted and unwanted) for the drug formulations,
its optimization becomes achievable (Flaten et al., 2015).
In line with this facts, several mimetic skin models have been developed
and some are already available in the market, while the research
continues for further improvements in their quality, complexity and
mimetic properties. Different biomimetic materials have been used from
the silicone membranes or poly(dimethylsiloxane) (PDMS) models to human
cell cultures as well as different technologies to simulate the highly
complex and stratified structure of the human skin.
The big challenges in the development of skin substitutes are related
with: a) the need of reproducibility in the results obtained using these
models; b) their capacity to better mimic the multitude of human skin
structure and functions and c) the development of cost-effective skin
membrane models (Sarkiri et al., 2019, Flaten et al., 2015). The main
focus of the present review is to summarize the currently reported
healthy and disease skin mimetic models, discuss the characteristics and
applications of these proposals and to identify the new trends in skin
engineering.
Human skin – structure and functions
The skin is the major organ of the human body having a surface area ofat ca 2 m2, representing approximately 10% of
the body mass for adults (Lee et al., 2006, Ng and Lau, 2015, Sofia A.
Costa Lima., 2018). Skin is a physical barrier in the interface between
the body and the external environment and constitutes a first-line
defence entity for protection of the body, controlling what may enter
and exit in the body. Moreover, skin is composed by a network of cells
and matrix elements providing multifaceted functions such as the
prevention of the body´s dehydration, protection of the body against
infectious agents or ultraviolet radiation, thermoregulation, sensation
and synthesis of vitamin D (Prausnitz et al., 2012, Sofia A. Costa
Lima., 2018, Lee et al., 2006).
The organization of the skin consists of three major layers hypodermis,
dermis and epidermis. The type of structure, cellular composition and
major components of the three skin layers are summarized in Figure 1 (A
and B), and these topics are discussed in more detail on the following
subsections.