Bioprinted Four-Cell-Type Lung Model for Viral Infection Studies Under Air-Liquid Interface Conditions.

Area of Science:

• Biotechnology
• Tissue Engineering
• Respiratory Medicine

Background:

• Viral lung infections pose a significant public health challenge, exacerbated by new variants and seasonal patterns.
• Current research models like 2D cell cultures and animal studies have limitations in fully replicating human lung physiology.
• There is a critical need for advanced in vitro models to study viral pathogenesis and develop effective antiviral therapies.

Purpose of the Study:

• To engineer a 3D human lung model using microextrusion bioprinting.
• To assess the viability, cell marker expression, and potential for viral infection of the engineered lung model.
• To establish a more physiologically relevant platform for studying viral lung infections.

Main Methods:

• Utilized microextrusion bioprinting to create 3D lung constructs with endothelial, fibroblast, macrophage, and epithelial cells (A549 and Calu-3).
• Encapsulated cells within a specialized hydrogel (alginate, gelatin, hyaluronic acid, collagen, laminin-521).
• Cultured constructs under air-liquid interface (ALI) conditions and analyzed cell viability and marker expression over 21 days.

Main Results:

• Successfully generated viable 3D lung models with distinct cell types.
• Demonstrated sustained cell viability and metabolic activity for up to 21 days.
• The 3D lung models were susceptible to infection by both influenza A virus (IAV) and SARS-CoV-2 omicron variant.

Conclusions:

• The bioprinted 3D lung model provides a robust and physiologically relevant platform for studying viral respiratory infections.
• This advanced model holds significant potential for preclinical testing of antiviral drugs and understanding host-pathogen interactions.
• Tissue engineering approaches, like this bioprinted lung model, represent a promising future direction for infectious disease research.