With a surface area of between 1.5 and 2.0 m2, the skin is the largest and most versatile organ of the human body, forming an effective barrier between the organism and the environment. It has a complex three-layer architecture, with the epidermis on the outside, the dermis in the middle and the subcutis on the bottom. Keratinocytes with Merkel cells, melanocytes and Langerhans cells form the tightly interconnected network of the epidermis, and are essential for protecting the body from environmental pathogens, ultraviolet rays and dehydration.
The dermis contains hair follicles, sweat glands, sebaceous glands, apocrine glands, lymphatic vessels and blood vessels, as well as protein fibers, which are essential for skin’s strength and elasticity. The subcutaneous layer is made up of adipocytes, fibroblasts, macrophages, and connective tissue that binds the skin to muscles and bones. The human skin accomplishes many essential functions, reacts to a wide range of sensory stimuli, regulates body temperature, and acts as a storage center for lipids and water (Kanitakis, 2002). Cell culture studies are essential for improving our knowledge of the structures and functions of the epidermal barrier, as well as the changes that can lead to dermatological disorders (Proksch et al., 2008).
The loss of a functional epidermis has profound biological and clinical consequences. The potentially disfiguring appearance of many skin diseases influences the psychological well-being of the patients, and makes the development of well tolerated treatments a high priority (Barankin and DeKoven, 2002). Burns, traumata, as well as several inherited and acquired diseases, can induce the failure of the epidermal barrier, resulting in life-threatening conditions. Traditional treatments for psoriasis and other inflammatory skin diseases are well established and continue to play a major role, however, biological therapies offer a more direct approach by improving symptom control and reducing associated co-morbidities (Constantin et al., 2014; Han, 2014).
Cell-based therapies with cultured cells or bioengineered skin products exploit the great regenerative capacities of keratinocytes and fibroblasts, which are essential for wound healing, inflammation, and immune responses. Stem cells of different origins also hold great promise for future therapeutic approaches (Petrof et al., 2014). Skin dendritic cells are essential for maintaining immune homeostasis, and could represent an interesting target when treating inflammatory skin diseases (Chu et al., 2011).
The development of 3D skin models provides an essential tool for various applications ranging from basic research to disease modeling and regenerative medicine (Mathes et al., 2014). Three-dimensional skin equivalents have allowed researchers to better understand the pathways leading to progression of melanoma (Levesque et al., 2017). There is also a growing interest in building physiological skin for human-relevant drug testing that incorporates different components, such as vasculature, appendages, pigment, innervation, and adipose tissue (Abaci et al., 2017). In 2009, the European Community introduced a ban on animal testing for all new cosmetics, and their ingredients, sold in Europe. Since then, several in vitro methods including cytotoxicity, cell proliferation, and angiogenesis assays have been developed and validated, providing reliable insight into the safety of new products (Bhattacharya et al., 2011; Adler et al., 2011).
Wound healing is a vital process for human survival. When scientists know more about the intrinsic cellular and molecular processes, as well as the role of keratinocytes, resident epithelial stem cells, fibroblasts, macrophages and adipocytes, they may be able to influence and accelerate the repair and regeneration of damaged or lost skin structures. The redevelopment of fully functional skin is critical following extensive tissue loss and scarring (Takeo et al., 2015). Particularly patients with severe burns could benefit from skin grafts using cultured keratinocytes (Mcheik et al., 2014).
Because skin cells exert signals to hair follicles, advancements in the field of regenerative medicine may generate novel therapeutic alternatives for promoting hair growth (Talavera-Adame et al., 2017), and for counteracting the chronological and environmental factors that induce aging of the skin (Newton et al., 2015).