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

Area of Science:

• Computational biology
• Dermatology
• Pharmacokinetics

Background:

• Traditional skin permeability models often assume fixed geometry and homogeneity, limiting their application to adult skin.
• Infant skin possesses distinct structural and functional properties, particularly concerning its barrier function, compared to adult skin.

Purpose of the Study:

• To develop a sophisticated, self-organizing multicellular epidermis model capable of simulating barrier formation with realistic cell morphology.
• To differentiate computational models for adult and infant skin by adjusting cell turnover parameters.
• To simulate and predict the permeation of topically applied substances, like caffeine, across different skin types.

Main Methods:

• A self-organizing multicellular epidermis model was created with realistic cell morphology.
• Model parameters were modulated to reflect adult and infant skin cell turnover rates, generating distinct models.
• Caffeine diffusion was simulated via molecular exchange between model agents (cells and extracellular space) to recapitulate experimental permeability data.

Main Results:

• The models generated distinct epidermal and stratum corneum thicknesses matching experimental measurements.
• Adjusting surface concentration and intercellular exchange rates allowed the model to replicate experimental permeability data.
• The infant skin model successfully predicted caffeine concentration profiles, closely aligning with experimental results.

Conclusions:

• This computational approach provides a robust platform for understanding skin physiology and barrier function, especially in infants.
• The developed model offers a valuable tool for predicting substance permeation in infant skin, crucial for pediatric dermatology and drug development.
• This work advances the comprehension of skin barrier development and function during the critical early years of life.