Conclusions
In face to the strict legislation regarding human and animal tests and in particular to the urgent need of development of efficient skin mimetic models for the evaluation of new skin pharmaceutical drugs and cosmetics, without using animal models, many different skin substituents have been described in the literature. The numerous examples mentioned in the present review highlighted the many different types of models from the most simple non-lipid approaches to the lipid-based models or even cell-based in vitro systems or at least ex vivo human or animals skin mimetics. In a lesser extent, some skin disease models have been reported aiming to mimic the morphological and functional characteristics of compromised skin, namely for psoriasis, atopic dermatitis or melanoma diseases.
Several improvements in the quality, complexity and mimetic properties of the skin mimetic models have been accomplished as well as the use of different technologies to produce the models and to simulate the highly complex and stratified structure of the human skin. Yet, some big challenges persist such as: a) the need of reproducibility in the results obtained using these models; b) the capacity of the models to better mimic the multitude of human skin structure and functions; c) the applicability of the use of that models to the evaluation of drugs exhibiting distinct physicochemical properties d) the improvement of storage conditions and shelf time and e) to guarantee the production of cost-effective skin membrane models.
With the last advances promoted by the use of advanced skin engineering technologies, the incorporation of various skin highly complex components such as vascularization, innervation, pigments and immune cells and other complex structures like glands or hairs in these models is started to be possible.
In the future it is expected that the models can evolve towards the “perfect” skin mimetic model, overcoming the drawbacks of the already described and allowing the efficient screening of new drugs and cosmetics, in a heathy skin or in a disease scenario. However, the selection of the most useful and adequate model(s) will probably be always a crucial point in the design of a study to test skin agents since the nature and complexity of the different described systems can be largely distinct. In the selection process of the best skin mimetic model several aspects may be considered as for example the main aim of the case study, the physicochemical properties of the drugs of interest, the type of biological effect expected for the compounds, amongst other important factors, namely those regarding the characteristics of the existent mimetic skin models such as their availability in the market, quality, complexity, stability, price and mimetic properties of each skin alternative.
In sum, perhaps the concomitant use of different skin mimetic models can allow a superior understanding of each case of study, thus revealing many different conclusions which probably cannot be obtained if a unique skin mimetic model was considered.