Bioprinted cell-instructive lung-dECM constructs for reconstructing an immuno-regenerative pulmonary microenvironment

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Pulmonary tissue engineering demands scaffolds with mechanical compliance and instructive cues.
• Soft biomaterials often compromise printing fidelity.
• Decellularized lung matrix (dLM) offers potential but requires optimized processing.

Purpose of the Study:

• To develop and characterize decellularized lung matrix (dLM) bioinks for pulmonary tissue engineering.
• To investigate the impact of processing strategies on dLM bioink properties and printability.
• To evaluate the regenerative potential of printed dLM scaffolds in directing cell fate and modulating immune responses.

Main Methods:

• Osmotic decellularization strategy to preserve extracellular matrix (ECM) components like sulfated glycosaminoglycans (sGAGs).
• Print-matched thixotropy testing to standardize extrusion conditions and predict post-extrusion recovery.
• Bioprinting of dLM hydrogels and assessment of cytocompatibility and cell differentiation (mesenchymal stem cells, macrophages).

Main Results:

• dLM bioinks reconciled print fidelity with lung parenchymal viscoelasticity.
• Collagen-dominant dLM inks showed superior layer stacking; sGAG-rich matrices exhibited rapid viscosity rebuild.
• Printed scaffolds directed mesenchymal stem cell differentiation and promoted anti-inflammatory macrophage polarization.

Conclusions:

• Strategic preservation of lung ECM components yields printed scaffolds with high fidelity and regenerative capacity.
• dLM bioinks provide a compositionally validated platform for engineering lung tissue.
• The developed bioinks support niche-specific cell responses and in vitro immunomodulation.