Sepsis modelling: current approaches and organ-on-chip perspectives

Area of Science:

• Biomedical Engineering
• Immunology
• Pathophysiology

Background:

• Sepsis is a life-threatening condition characterized by immune dysregulation, endothelial dysfunction, and multi-organ failure.
• Current in vitro, in vivo, and ex vivo models have advanced understanding but face challenges in complexity, reproducibility, and clinical translation.
• Limitations in existing models hinder the development of effective sepsis therapies.

Purpose of the Study:

• To review and evaluate current sepsis research systems based on biological complexity, reproducibility, ethical constraints, and clinical applicability.
• To discuss the potential of microfluidic technology, specifically organ-on-chip systems, in modeling human sepsis pathophysiology.
• To identify challenges in sepsis research and propose directions for integrated modeling approaches to improve translational outcomes.

Main Methods:

• Literature review of conventional and advanced sepsis models.
• Comparative analysis of different experimental systems.
• Exploration of organ-on-chip technology for sepsis research.

Main Results:

• Conventional sepsis models exhibit limitations in replicating human pathophysiology and ensuring reproducibility.
• Organ-on-chip technology offers potential for higher biological complexity and physiological relevance in sepsis modeling.
• A gap exists between preclinical findings and clinical success due to model limitations.

Conclusions:

• There is a critical need for improved sepsis models that better mimic human disease.
• Organ-on-chip systems represent a promising avenue for advancing sepsis research and therapeutic discovery.
• An integrated approach to sepsis modeling is essential for enhancing translational outcomes.