Speaker
Description
Introduction
Pulmonary fibrosis (PF) is a debilitating disease with a poor prognosis, often linked to long-term exposure to harmful substances. Understanding the role of pollutants in PF onset requires sophisticated in vitro models capable of replicating lung physiology and pathology. In this contribution we present the realisation of an innovative approach based on new materials and 3D bioprinting to create a bioengineered lung-on-chip (LOC) platform aiming at mimicking the microstructure and extracellular matrix function.
Methods
The 3D lung model was manufactured by using advanced bioprinting techniques. Embedded bioprinting was employed, exploiting microtissues precursors (μTPs), obtained by dynamic seeding of human lung fibroblasts inside biodegradable porous gelatin microcarriers, as previously reported (1,2).As sacrificial inks, a plethora of materials based on a poly(ethylene glycol)-based poly(ether urethane) (PEG-PEU) and α-cyclodextrins (a-CDs) was developed.(3) Different a-CD concentrations were tested, while keeping PEG-PEU concentration constant at 4% w/v and the hydrogels were characterized through rheology and stability tests. To further modulate their performances, the PEG-PEU-based support baths were enriched with a Pluronic®– based PEU (P407-PEU).
Results
Among the sacrificial ink formulations, the hydrogel with the highest proportion of P407-PEU exhibited superior mechanical and self-healing performances and was thus selected for further investigation as a support bath. Stability tests under culture-mimicking conditions demonstrated structural integrity for up to 7–10 days. To evaluate bioprinting potential, qualitative printing tests were performed using a 3D bioprinter (Dr. Invivo 4D6 - Rokit). The selected hydrogel demonstrated shear-thinning behavior and rapid structural recovery. Furthermore, it showed easy extrusion through an 18G needle while maintaining the filament shape (Fig. 1). These characteristics make it suitable not only as a support matrix but also as injectable biomaterial ink.
The ink demonstrated to be able to support μTPs dispersion to deliver lung tissue models, to be hosted in a microfluidic platform to test the toxicity of pollutants after aerosol exposure.
Discussion
This contribution aims at illustrating the collective use of discipline and expertise such as bioprinting, biomaterial science, customized polymer synthesis, biomaterial processing, in vitro model design, microfluidics, bioengineering, epidemiology and biostatistics (the latter to identify relevant pollutants to be tested) to develop a novel in vitro platform to evaluate the effect of inhaled harmful substances in respiratory disease onset, contributing to the progress of healthcare through advanced techniques and overcome existing challenges in health management.
References
(1) De Gregorio, V. (2022) Biomaterials, 121573
(2) Scalzone, A. (2024), Biofabrication, 10.1088/1758-5090/ad3aa5
(3) Torchio, A. et al. (2021) Materials Science and Engineering: C, 127, 112194.
Acknowledgment
Work performed within BREATH project (CUP E53D23016840001) – funded by European Union – Next Generation EU within the PNRR, Mission 4, Component 2, Investment 1.1, PRIN PNRR 2022 program (D.D. 1409 14/09/2022 MUR). This abstract reflects only the authors’ views and opinions and the Ministry cannot be considered responsible for them.
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