Koria1, P., Brazeau2, D., Kirkwood3, K., Hayden4, P., Klausner4, M., Andreadis1, S. 1Department of Chemical Engineering, University at Buffalo, State University of New York, Amherst, NY, 2Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY, 3Department of Periodontics and Endodontics, University at Buffalo, State University of New York, Amhert, NY, 4MatTek Corportation, Ashland, MA.

The main function of the skin is to protect the body from infection, dehydration, and other environmental insults by creating an impermeable barrier of cornified cell layers, the stratum corneum. In contrast to cells in culture, tissue-engineeried skin equivalents contain well-developed basal, spinous, granular, and cornified cell layers providing an excellent model to study the tissue response to barrier disruption. Afer 7 d of culture at the air-liquid interface the barrier of the tissues was disrupted by short exposure to acetone and the global gene expression profile of the tissues was evaluated using DNA microarrays. We found that tissue-engineered skin responds to barrier disruption by a two-wave dynamic response. Early on, the cells upregulate signal transducing, stress, proliferation, and inflammation genes to protect the tissue and possibly to communicate the damage to the immune system and neighboring tissues. At later times, pro-inflammatory cytokines and some growth-related genes are signifcantly reduced but enzymes that participate in lipid synthesis increase, suggesting that the epidermal cells attempt to restore the lost barrier. Quantitative immunostaining for the proliferation antigen Ki67 revealed that barrier disruption by acetone increased proliferation by 4-fold in agreement with the microarray data and previous in vivo studies. Our work suggests that functional genomics may be used in tissue engineering to understand tissue development, wound regeneration, and response to environmental mental stimuli. A better understanding of engineered tissues at the molecular level may facilitate their application in the clinic and as biosensors for toxicologic testing.


ALI, Acetone, Acute barrier disruption, Air-liquid interface, Antigen Ki67, Barrier disruption, Biosensors, Cornified cell layers, DNA microarrays, Engineered tissues, Environmental stimuli, EpiDerm, Functional genomics, Gene expression, Global gene expression profile, Growth-related genes, Immunostaining, Impermeable barrier, Lipid synthesis, Microarray, Pro-inflammatory cytokines, Stratum corneum, Tissue development, Tissue engineering, Tissue-engineered skin, Toxicologic testing, Two-wave dynamic response, Wound regeneration

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