Journal
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Volume 62, Issue 1, Pages 14-22Publisher
AMER THORACIC SOC
DOI: 10.1165/rcmb.2019-0232MA
Keywords
precision-cut lung slice; hydrogel; biomaterial; three-dimensional printing; pulmonary disease modeling
Funding
- National Institutes of Health (NIH)/National Center for Advancing Translational Sciences Colorado Clinical and Translational Science Award [UL1 TR002535]
- NIH/National Heart Lung and Blood Institute [T32 HL007085-43]
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Maintaining the three-dimensional architecture and cellular complexity of lung tissue ex vivo can enable elucidation of the cellular and molecular pathways underlying chronic pulmonary diseases. Precision-cut lung slices (PCLS) are one human-lung model with the potential to support critical mechanistic studies and early drug discovery. However, many studies report short culture times of 7-10 days. Here, we systematically evaluated poly(ethylene glycol)-based hydrogel platforms for the encapsulation of PCLS. We demonstrated the ability to support ex vivo culture of embedded PCLS for at least 21 days compared with control PCLS floating in media. These customized hydrogels maintained PCLS architecture (no difference), viability (4.7-fold increase, P < 0.0001), and cellular phenotype as measured by SFTPC (1.8-fold increase, P < 0.0001) and vimentin expression (no change) compared with nonencapsulated controls. Collectively, these results demonstrate that hydrogel biomaterials support the extended culture times required to study chronic pulmonary diseases ex vivo using PCLS technology.
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