Application of biophysics and bioengineering to the assessment of skin barrier function

Abstract

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. The cause of AD is multifactoral and it is affected by both genetic and environmental factors. Of all the causes of potential barrier defects, the lowered amino-acid derived natural moisturizing factor (NMF) in the stratum corneum (SC), especially associated with a known filaggrin mutation, shows the strongest link to AD. As a result, quantification of NMF in the SC in both healthy and compromised SC is the principal aim of this thesis. Because tape stripping is a key technique used to harvest the SC, a novel imaging method to measure the amount of SC per tape strip was validated. This method offers rapid, simple and reproducible SC quantification. It shows good correlation with existing gravimetric and infrared absorption methods and may provide a better standard method in the future.The tape-stripping extraction of NMF showed an abundant SC ‘reservoir’ of the constituents in healthy skin. Iontophoretic extraction of NMF was highly dependant upon molecular properties, particularly charge and concentration. In general, charged NMF constituents were easily extracted by reverse iontophoresis, whereas iontophoresis only offered modest enhancement of zwitterionic species.Quantification of NMF at different body sites, specifically forehead and forearm, showed similar profiles. However, forehead SC was thinner, and in general contained a lower total amount of NMF and less-ordered lipids. Forehead SC may therefore be considered a less competent barrier.A 3-week application of 0.1% w/v sodium lauryl sulphate (SLS) to healthy volunteers was used to model damaged skin similar to that in AD and chronic irritant contact dermatitis. The SC barrier post-treatment showed significantly reduced NMF, substantial lipid disordering, and the presence of immature corneocytes. The methods employed were sufficiently sensitive to detect these changes. In particular, the NMF components present at high levels in the SC may be useful, potential markers for skin ‘health’ and for its resistance to irritant chemicals.

Date of Award	1 Sep 2011
Original language	English
Awarding Institution	University of Bath
Supervisor	Richard Guy (Supervisor)