Tissue engineering is a dichotomy of scaffold-based and scaffold-free cultures. Scaffold-based cultures form highly organotypic structures but with low consistency and throughput. On the other hand, scaffold-free cultures create consistently sized and shaped cell aggregates but have been limited to spheroid-like structure and function thus restricting their use in accurate disease modeling. Here, we show that scaffold-free, suspension cultures could be improved by using a soluble non-gelling concentration of basement membrane (BM) in the creation of an organotypic lung model from three stable cells representing the epithelial, vascular, and stromal cell populations. We observed that soluble BM promotes the emergence of lumina comparable to mammalian lung airspaces. Moreover, we also found evidence of the formation of a branching, perfusable vasculature in the aggregates supplemented with soluble BM. Aside from these structural traits, we observed increased proliferation, survival, and 3D growth of the aggregates. As proof of concept, we applied this technology in the modeling of lung fibrosis via TGFb induction and testing of two potential antifibrotic drugs. Our results demonstrate a novel 3D culture method that could be applied in the creation of organotypic models from stable cells. We anticipate this technology to pioneer the creation of novel suspension-based organoids which could foster consistent, expedited 3D culture. Furthermore, this technology could be applied in patient-derived organoids for personalized drug screening.

Soluble basement membrane promotes organotypic growth of a lung triculture

ACS Fall 2021

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