A Predictive Self-Organizing Multicellular Computational Model of Infant Skin Permeability to Topically Applied Substances

Abstract

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Skin Barrier Function in Infants: Update and Outlook

“…The middle of the ventral side of volar forearm was chosen for the measurements. The results obtained using the computational model compared very well with the experimental data [160]. This technique clearly has potential for evaluation of chemical permeation following repeated use of baby wipes and other infant skin care products.…”

“…The authors used CRS to measure skin hydration and NMF concentrations in infants. Recently, Stamatas et al (2021) proposed a computational model for estimation of permeation of actives in infant skin [160]. Briefly, skin permeation of a marker compound (caffeine) in infants and adults was determined using CRS.…”

Computational modelling predicts impaired barrier function and higher sensitivity to skin inflammation following pH elevation

“…This model builds on a previously presented model that considers explicitly keratinocyte proliferation, differentiation and desquamation processes and can recapitulate skin structure, water barrier function and penetration kinetics of an external substance introduced at the skin surface at a given time of the simulation. 13 This model is modified here by the introduction of KLK production, auto-activation (KLK*) and inhibition by LEKTI, processes which affect the rate of corneocyte desquamation at the skin surface. 20,21 The mathematical model first described by Tanaka et al 10 is adapted and integrated at the agent-level programming of the corneocytes, present only in the SC.…”

“…The agent-based model also allows for the simulation of permeation of a topically applied substance, as described by Stamatas et al 13 Here, we consider that the externally applied substance is an irritant, which can trigger skin inflammation depending on its . 15 (II) KLK and its inhibitor, LEKTI are released at the interface of SG and SC and interact in the SC.…”

“…(III) The irritant substance is introduced at the surface and diffuses through the epidermis according to its concentration gradient and the inter-agent exchange rates specific to the SC or the VE, reflecting the compositional difference of the two layers (lipophilic SC compared to hydrophilic VE). 13 (IV) When the intra-cellular irritant concentration of VE cells rises above a predefined threshold, it triggers the release of inflammatory cytokines. The cells are coloured according to their differentiation status on the left part (dark blue for stem cells, light blue for transient amplifying cells, light green for basal cells, light pink for spinous cells, dark pink for granular cells and tan for corneocytes), the intra-cellular irritant concentration in the middle (the greener, the higher the irritant concentration) and the intra-cellular inflammatory cytokines concentration on the right (the redder, the higher the inflammatory cytokines concentration in skin pH at tissue level through the study of the system's emerging properties.…”