Precise In Vitro Recapitulation of Pathological Acute Lung Injury Induced by Modern Fire Smoke Using a Lung-on-a-Chip-Organoid Integrated Model

Jiyan Bio’s Standardized Organoid Culture System (OCM-010) Facilitates COMT Target Discovery and Drug Combination Strategy Validation

Burn Injury Combined with Smoke Inhalation-Induced Acute Lung Injury (SI-ALI) is a critical clinical condition. Epidemiological data indicate that mortality rates in burn patients with SI-ALI are 40% higher than those with burns alone. The pathophysiological mechanisms involve alveolar-capillary barrier disruption, inflammatory cytokine cascades, and oxidative stress. Current clinical treatments remain largely supportive, with a lack of targeted therapies, partly due to the absence of reliable research models.

Recently, Prof. Wan Xiaojian’s team from the Critical Care Medicine Center of Changhai Hospital, Naval Medical University, in collaboration with Prof. Fang Jingjing’s team from the Naval Specialty Medical Center, published a groundbreaking study titled "Modeling fire-related smoke inhalation injury using the human lung-on-a-chip and organoid platform: Pathogenesis insights and therapeutic evaluation" in the journal VIEW (Q1, IF 9.7). This study utilized Jiyan Bio’s Lung Organoid Culture Medium (Product Code: OCM-010) and other products to innovatively integrate lung-on-a-chip technology and lung organoid culture systems, successfully establishing an in vitro model that closely mimics acute lung injury caused by modern fire smoke. Through proteomics and molecular docking, the study identified novel pathogenic molecules such as catechol-O-methyltransferase (COMT) and potential therapeutic agents. The model further validated the efficacy of a combined therapy (intravenous vitamin C + nebulized budesonide) using a microfluidic platform, providing a new research framework for understanding SI-ALI pathogenesis and evaluating drug efficacy.

Why a New Lung Injury Model?

Modern fire smoke contains toxic gases (e.g., hydrogen cyanide, carbon monoxide) and complex compounds from burning materials, which disrupt the alveolar-vascular barrier and trigger oxidative stress and inflammatory cascades. Existing models face two major limitations:

✦Animal models: Limited by physiological differences, high costs, and ethical concerns.
✦Monolayer cell models: Fail to replicate multi-cellular interactions or direct gas exposure.
This study overcame these challenges by combining lung-on-a-chip and organoid technologies to create a human-relevant in vitro model.

Technical Highlights: Replicating Real Lung Injury

1.Lung-on-a-Chip Design - Tri-layer Architecture Mimicking Alveolar-Capillary Barrier:
✦Upper Layer: Human umbilical vein endothelial cells (HUVECs) simulating hemodynamic conditions
✦Middle Layer: Porous membrane creating physiological alveolar-capillary interface

✦Lower Layer: Alveolar epithelial cells (A549 cell line or lung organoids) for direct smoke exposure

The gravity-driven fluidic system (rocking tilt mechanism) replicates respiratory and hemodynamic forces while eliminating contamination risks and bubble interference inherent to conventional pump systems.(Fig. 1-2).

Fig. 1
Fig. 2

2.Smoke Generation System: Precision Simulation of Modern Building Material Combustion
✦Material Selection: Non-metallic materials commonly used in yachts (e.g., polyimide foam, nitrile rubber) were proportioned according to real cabin volume ratios.
✦Controlled Pyrolysis: Materials underwent thermal decomposition at precisely maintained 600°C (core fire temperature), replicating authentic fire conditions.
✦Quality Control: Fourier-transform infrared spectroscopy (FTIR) enabled real-time smoke composition monitoring to ensure batch-to-batch consistency.

3.Lung organoid culture:
✦Cell source: Distal non-cancerous lung tissue from surgical patients.
✦Process: Enzymatic digestion → cell isolation → 3D culture in Matrigel.
✦Validation: High expression of alveolar markers (SFTPC, E-cadherin) and exclusion of airway basal cell contamination (KRT5-negative)(Fig. 3).
Fig. 3

Organoid-Chip Model: Decoding Smoke-Induced Cellular Damage

1.Lung-on-a-chip Simulation of SI-ALI:
✦Dynamic co-culture of dual cell types: Pulmonary epithelial cells and endothelial cells were seeded in the upper and lower layers of the chip respectively.
✦Smoke exposure: Smoke was directly infused into the alveolar channel chamber to simulate authentic inhalation injury.
✦Real-time monitoring: Fluorescent labeling (e.g., FITC-dextran) was employed to track alveolar barrier permeability changes (Fig. 4).

Fig. 4

2.Pathological features:

Oxidative stress (↑ ROS), mitochondrial damage (abnormal ultrastructure), inflammatory storms (↑ IL-6, TNF-α), and immune cell infiltration (↑ THP-1 adhesion).(Fig. 5)
Fig. 5

3.Molecular mechanism:

✦COMT upregulation: Linked to oxidative stress and inflammatory pathways.
✦Drug screening: Identified FDA-approved candidates (e.g., Ractopamine HCl, Bimatoprost) via molecular docking.

Drug Testing: Bridging Chips to Clinics

The model validated the synergistic effects of nebulized budesonide + intravenous vitamin C, highlighting its potential for evaluating cell-specific drug mechanisms in near-physiological conditions.

Future Directions

✦Long-term pathology modeling: Incorporate late-stage fibrosis.
✦Mechanical stretch: Simulate breathing-induced alveolar stress.
✦Multi-organ chip linkage: Study systemic impacts of smoke injury.

Conclusion

This study establishes a transformative platform for SI-ALI research, advancing in vitro models as "human surrogates." Jiyan Bio’s organoid and organ-chip technologies promise to accelerate drug discovery and precision medicine.

Reference: Li J, et al. VIEW. 2025;20240114. DOI:10.1002/VJW.20240114

Scientific Review: The technical details in this article have been cross-validated against the Materials and Methods section of the original paper to ensure accurate presentation.

Cited Jiyan Products

OCK010 Lung Organoid Kit

OCM010 Lung Organoid Complete Medium

SE-Gel(S-001)

Collagen I

About Jiyan Biotech

Suzhou Jiyan Biotech Co., Ltd. focuses on tumor precision medicine, specializing in tumor organoid models and organ-on-a-chip platforms for drug sensitivity testing, drug evaluation, target discovery, and disease mechanism research.

As a national high-tech enterprise, Jiyan Bio has developed 50+ organoid models and offers a comprehensive product line, including "all-in-one" organoid kits and high-throughput screening solutions. With 26 patents (14 granted), we are committed to advancing innovative tools for personalized therapy and drug development.

Jiyan's founding mission—"Empowering Global Endeavors, Advancing Precision Research"—drives our relentless pursuit of innovation. As research and development fuel our progress, we remain dedicated to delivering more reliable products and superior services. Let’s grow and progress together—we look forward to collaborating with you!