Advanced Online Monitoring of In Vitro Human 3D Full-Thickness Skin Equivalents

Area of Science:

• Pharmacology
• Biomedical Engineering
• Dermatology

Background:

• Skin equivalents and explants are crucial for dermal penetration studies in drug development.
• Current methods lack direct measurement of in-tissue environmental conditions, limiting experimental relevance.
• Franz diffusion chambers measure only the receiving medium, not cellular conditions.

Purpose of the Study:

• To develop and validate a novel system for simultaneous in-tissue monitoring of environmental parameters and drug concentrations.
• To improve the accuracy and relevance of dermal penetration studies using skin models.
• To compare drug penetration and microenvironment in skin equivalents versus explants.

Main Methods:

• Integration of open flow microperfusion (OFM) for direct in-tissue sampling.
• Utilization of microfluidic biosensors for online monitoring of oxygen, glucose, lactate, and pH.
• Testing with full-thickness skin equivalents and explants for acyclovir, lidocaine, and diclofenac penetration.

Main Results:

• Demonstrated real-time measurement of key environmental parameters directly within skin models.
• Observed significant differences in oxygen, glucose, and drug concentrations in skin equivalents compared to culture medium and explants.
• Provided direct evidence of altered microenvironments affecting drug penetration in skin models.

Conclusions:

• The developed OFM and biosensor system offers a more accurate method for assessing dermal penetration and in-tissue conditions.
• This technology enhances the predictive value of skin models for pharmacological drug development.
• Real-time monitoring reveals critical differences between in-tissue and external measurements, impacting study outcomes.