Abstract

Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery) and/or the body (transdermal delivery). In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening. Several academic laboratories have developed their own human skin equivalent models and applied these models for studying skin permeation, corrosivity and irritation, compound toxicity, biochemistry, metabolism and cellular pharmacology. Various aspects of the state of the art of human skin equivalents are reviewed and discussed.

Highlights

  • Human skin serves as an important barrier against the penetration of exogenous substances into the body, and provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin and/or the body

  • As the basal keratinocytes proliferate, the “daughter” cells migrate superficially and differentiate, forming the stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum, respectively

  • Human skin equivalents (HSEs) are bioengineered substitutes composed of primary human skin cells and components of extracellular matrices (ECM)

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Summary

Human Skin and Skin Barrier

As the largest organ in the body, is an anatomical barrier between the internal and external environment; it protects the body from toxic substances, pathogens, and organisms. The stratum corneum has been proposed to possess a “bricks and mortar” structure, in which the corneocytes represent the “bricks” and the intercellular lamellar lipid bilayers represent the “mortar”; this layer provides the most significant contribution to the permeation barrier properties of human skin [2]. Associated with the epidermis and dermis are skin appendages possessing different functions such as sweat glands that regulate body temperature by secreting sweat onto the surface of the skin; sebaceous glands that secrete sebum to moisturize the skin and hair; hair follicles that play an important role in wound healing, as they are a source of keratinocyte proliferation during reepithelialization [4]; arrector pilli muscles that pull hairs straight; and nails that protect distal phalanx and the fingertip. Roberts and his group proposed a solute structure-skin transport model for aqueous solutions in which permeation rates depend on both partitioning and diffusivity: Partitioning is related to octanol-water partition coefficient, and diffusivity to solute size and hydrogen bonding [6]

Tissue Engineering and Regenerative Medicine
Need and Criteria for Human Skin Equivalents
Clinical skin replacements and grafts
In Vitro Permeation and Toxicity Screening Models
Commercially Available Human Skin Equivalents for in Vivo Applications
Epidermal Models
Dermal Models
Full-Thickness Models
Commercially Available Human Skin Equivalents for in Vitro Applications
Development of Non-Commercial Human Skin Equivalents
Perspectives
24. Tissue Engineering and Cell Transplantation
Findings
Methods

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