3D-bioprinted respiratory disease model: Exploring the importance of culture conditions and controlled release in modeling infection
Year: 2024
Type: article
Abstract: The burden of respiratory illnesses is substantial, significantly impacting healthcare systems worldwide. As researchers work to better understand chronic diseases, as well as newly emerging respiratory viruses, the need for improved respiratory models has become evident. While 3D bioprinting has been illustrated as a feasible method to create complex cellularized constructs or respiratory models, it remains to be determined whether incorporating relevant biomechanical stimuli and/ or relevant growth factors significantly impacts the response of these models to infection. In this study, an alginate/gelatin/collagen solution was synthesized and characterized in terms of rheology, printability, degradation, mechanical properties, and biocompatibility. The bioink, which incorporated primary human pulmonary fibroblasts and THP-1 cells, was bioprinted to form hierarchical 3D constructs and subsequently seeded with primary human bronchial epithelial cells to form the respiratory tissue model. To explore the importance of growth factors and culture conditions in modeling infection, we strategically developed a hepatocyte-growth-factor-loaded nanoparticle system and incorporated them into the bioink for bioprinting the respiratory tissue model, followed by culturing under dynamic conditions in a breath-mimicking bioreactor. The effect of incorporating growth factors and dynamic culture conditions was examined over 28 days, followed by the infection of these constructs with the influenza A virus. It was determined that these constructs support infection, demonstrating a more clinically relevant infection pattern than 2D models. It was further determined that the inclusion of hepatocyte growth factor aids in epithelial cell growth, while the inclusion of biomechanical stimulus increases cellular metabolism and has a moderating effect on response to infection.
DOI: 10.36922/ijb.3895
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: diamond
OpenAlex ID: W4402547004