418 A Novel Automated Solution to Study Biotherapeutics Infusion and Pharmacokinetics Within Human Skin

Predicting response to biotherapeutics remains a significant challenge in bioengineering, especially since the diffusion process of high molecular weight molecules in human tissue remains largely unknown. This study presents an innovative microfluidic system to study the diffusion of therapeutic formulations in ex vivo human skin explants. The FlowSkin® model is based on the implantation of a custom-made porous catheter into a human skin biopsy embedded in a proprietary matrix to keep skin cells and appendages functional. Exchanges between the flow and the tissue were maintained via an automated fluidic system for 10 days without detectable alteration of tissue viability while preserving physiological levels of structural cell proliferation. A combination of X-ray tomography and molecular analyses was used to examine the model’s relevance in studying the diffusion of molecules with different molecular weights. The obtained results position the FlowSkin® model as a relevant tool to study directly in human skin the efficacy, toxicity, and pharmacokinetics of systemically and subcutaneously administered drugs.