PT  - JOURNAL ARTICLE
AU  - Briana R. Dye
AU  - Richard L. Youngblood
AU  - Robert S. Oakes
AU  - Tadas Kasputis
AU  - Daniel W. Clough
AU  - Melinda S. Nagy
AU  - Jason R. Spence
AU  - Lonnie D. Shea
TI  - Human lung organoids develop into adult airway-like structures directed by physico-chemical biomaterial properties
AID  - 10.1101/564252
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 564252
4099  - http://biorxiv.org/content/early/2019/02/28/564252.short
4100  - http://biorxiv.org/content/early/2019/02/28/564252.full
AB  - Tissues derived from human pluripotent stem cell (hPSC) often represent early developmental time points. Yet, when transplanted into immunocompromised mice, these hPSC-derived tissues further mature, which has been enhanced with biomaterial scaffolds, gaining tissue structure and cell types similar to the native adult lung. Our goal was to define the physico-chemical biomaterial properties, including the polymer type, degradation, and pore interconnectivity of the scaffolds. Transplantation of human lung organoids (HLOs) on microporous poly(lactide-co-glycolide) (PLG) scaffolds or polycaprolactone (PCL) produced organoids that formed tube-like structures that resembled both the structure and cellular diversity of an adult lung airway. Microporous scaffolds formed from poly(ethylene glycol) (PEG) hydrogel scaffolds inhibit maturation and the HLOs remain as lung progenitors. The structures formed from cells that occupy multiple pores within the scaffold, and pore interconnectivity and polymer degradation contributed to the maturation. Finally, the overall size of the generated airway structure and the total size of the tissue was influenced by the material degradation rate. Collectively, these biomaterial platforms provide a set of tools to promote maturation of the tissues and to control the size and structure of the organoids.