Artificial skin in perspective: concepts and applications

Abstract

Skin, the largest organ of the human body, is organized into an elaborate layered structure consisting mainly of the outermost epidermis and the underlying dermis. A subcutaneous adipose-storing hypodermis layer and various appendages such as hair follicles, sweat glands, sebaceous glands, nerves, lymphatics, and blood vessels are also present in the skin. These multiple components of the skin ensure survival by carrying out critical functions such as protection, thermoregulation, excretion, absorption, metabolic functions, sensation, evaporation management, and aesthetics. The study of how these biological functions are performed is critical to our understanding of basic skin biology such as regulation of pigmentation and wound repair. Impairment of any of these functions may lead to pathogenic alterations, including skin cancers. Therefore, the development of genetically controlled and well characterized skin models can have important implications, not only for scientists and physicians, but also for manufacturers, consumers, governing regulatory boards and animal welfare organizations. As cells making up human skin tissue grow within an organized three-dimensional (3D) matrix surrounded by neighboring cells, standard monolayer (2D) cell cultures do not recapitulate the physiological architecture of the skin. Several types of human skin recombinants, also called artificial skin, that provide this critical 3D structure have now been reconstructed in vitro. This review contemplates the use of these organotypic skin models in different applications, including substitutes to animal testing.

Figure 1

Skin draw showing skin components and layers. Epidermis: containing melanocytes and keratinocytes that are able to differentiate and form the different strata (Corneum, Lucidum, Granulosum and Germinativum). Dermis: formed by fibroblasts embedded in a matrix. Hypodermis: containing the adipose tissue.

Figure 2

Optical microscopy showing the differences between human and mouse skin. Note that the murine dermis is thin and the epidermis is comprised of typically only 3 layers, while human dermis is quite thick and epidermis is generally 6-10 layers thick. HE staining. 60x magnification.

Figure 3

Optical microscopy of human facial skin and human artificial skin. Note that epidermis and dermis thickness is very similar. Also that human artificial skin presents all epidermal layers, showing the differentiation of this epithelium. HE staining. 60x magnification.

Figure 4

Preparation model of artificial skin. First step is the preparation of the dermal equivalent, consisting of type I collagen and fibroblasts. After polymerization of this layer, there is the plating of keratinocytes (K) and melanocytes (M). 24 hrs after plating and after the contraction of collagen gel, this whole structure is passed to a steel grid to form the air-liquid interface. After 2 weeks on the interface there is the formation of artificial skin. HE staining. 40x magnification