Microvascular fluid flow in ex vivo and engineered lungs

Area of Science:

• Pulmonary physiology
• Biomedical engineering
• Mathematical modeling

Background:

• Ex vivo lung perfusion is crucial for transplantation and regenerative engineering, but its microvascular physiology is poorly understood.
• Current fluid-handling protocols for lung perfusion are not standardized, leading to variable outcomes.
• Existing models of pulmonary fluid flow do not adequately address microvascular leak or capillary recruitment in ex vivo settings.

Purpose of the Study:

• To develop a robust, noninvasive, mechanistic model for predicting microvascular resistance and permeability in perfused lungs.
• To gain insight into capillary recruitment dynamics during ex vivo lung perfusion.
• To apply the model to native, decellularized, and regenerating lungs under perfusion.

Main Methods:

• Development of a novel mathematical model for pulmonary microvascular fluid flow.
• Application of the model to experimental data from ex vivo perfused lungs (native, decellularized, regenerating).
• Analysis of microvascular pressure-flow mechanics and barrier properties.

Main Results:

• The model provides accurate predictions of microvascular resistance and permeability.
• Quantified tissue-specific capillary-alveolar hydraulic conductivity and microvascular recruitment.
• Demonstrated that decellularization alters microvascular mechanics, with re-endothelialization partially restoring function.

Conclusions:

• The developed model offers significant insight into ex vivo lung perfusion and microvascular dynamics.
• The model can guide regenerative engineering strategies for lung repair and transplantation.
• Decellularization impacts lung microvascular function, highlighting the importance of re-endothelialization.