Application of MatTek In Vitro Reconstructed Human Skin Models for Safety, Efficacy Screening, and Basic Preclinical Research

During the past three decades, great progress has been achieved in the development of in vitro reconstructed human epidermal (RhE) tissue models. This technology is now available via various manufacturers of commercially available tissue models, and has provided opportunities for researchers worldwide to reduce or even completely avoid in vivo experimentation for screening and prediction of cutaneous toxic effects of substances and mixtures. A major step forward in recognition of RhE models as alternative tools in toxicology was their full regulatory acceptance for in vitro skin corrosion testing in 2004 as OECD Test Guideline 431. International multicenter validation studies performed during 2004–2008 under the auspices of European Centre for the Validation of Alternative Methods (ECVAM) provided further acceptance of RhE models for in vitro skin irritation testing (OECD TG 439). The use of RhE as alternatives to animal experimentation is also promoted in the new EU regulatory framework for the Registration, Evaluation, Authorization and restriction of Chemicals (REACH), the EU Cosmetics Directive and its amendments, and other important EU and U.S. regulatory documents. This review will focus on commercially available RhE models produced by MatTek (Ashland, MA, USA: Bratislava, SK), including partial-thickness epidermal, pigmented epidermal, and full-thickness (FT) skin models, and present the ‘‘state of the art’’ in applications for hazard and safety assessment of cosmetic and household product chemical ingredients, pharmaceuticals, and medical device extracts. Examples of specific applications reviewed include skin corrosion; skin irritation; medical device testing; skin lightening/melanogenesis; skin phototoxicity; cutaneous photoaging/ UV protection; percutaneous absorption/permeation testing; skin genotoxicity screening; skin metabolism; skin sensitization screening; cutaneous wound healing; chemical warfare agents; and cutaneous microbiology/infection.

OECD TG 431, OECD TG 439, skin corrosion, skin irritation, skin lightening, skin pigmentation, skin phototoxicity, photoaging, UV protection, percutaneous absorption, genotoxicity screening, skin metabolism, cutaneous wound healing, cutaneous infection, EpiDerm EPIT-200, EFT-500, MelanoDerm, skin sensitization