A Novel Perfused Full-Thickness Human Skin Microphysiological System for Modeling Injury, Regeneration, Tumor...

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Translational Research

Background:

• Preclinical research faces challenges translating findings to humans due to species differences.
• Current models like organ-on-a-chip lack full microenvironmental and anatomical complexity.
• There is a need for physiologically relevant human models to improve translational success and reduce animal testing.

Purpose of the Study:

• To develop and validate a novel ex vivo model for perfusing large human abdominal fasciocutaneous flaps.
• To establish a platform for studying human tissue responses to injury and disease.
• To provide a proof-of-concept for extended viability and diverse research applications of human skin tissue.

Main Methods:

• Refined surgical techniques, angiosome mapping, and bioreactor engineering.
• Optimized perfusion media and validated perfusion success using thermal and fluorescent angiography.
• Assessed tissue viability through histological analysis, TUNEL staining, gene expression, metabolic monitoring, and cell propagation.

Main Results:

• Successfully maintained viability of ex vivo perfused human fasciocutaneous flaps for up to three weeks.
• Demonstrated successful perfusion and metabolic activity monitoring (glucose consumption, lactate production).
• Validated tissue viability and functionality through comprehensive assessments.

Conclusions:

• This novel ex vivo human skin perfusion model offers extended viability and physiological relevance.
• The model serves as a powerful platform for investigating radiation/chemical injuries, adipose tissue metabolism, and cancer models (melanoma, breast cancer).
• This represents a significant advancement in human-centric preclinical research, reducing reliance on animal models.