Engineering in vitro models of cystic fibrosis lung disease using neutrophil extracellular trap inspired biomaterials

Abstract

Cystic fibrosis (CF) is a muco-obstructive lung disease where inflammatory responses due to chronic infection result in the accumulation of neutrophil extracellular traps (NETs) in the airways. NETs are web-like...

Synthetic mucus barrier arrays as a nanoparticle formulation screening platform

“…Specifically, we developed a synthetic mucus barrier array (SMBA) platform containing mucin-based hydrogels which can be tailored to mimic the viscoelastic properties of native mucus in health and disease. [29][30][31] To confirm the validity of the SMBA system, we performed studies using polystyrene (PS) NP with size and surface chemistries previously evaluated in the literature. Based on the use of NAC as a mucolytic agent to enhance the penetration of NP through hyper-concentrated mucus produced in cystic fibrosis lung disease, 16,32 we then evaluated a newly identified mucolytic agent TCEP to determine its effectiveness as an NP permeation enhancer.…”

Synthetic mucus barrier arrays as a nanoparticle formulation screening platform

“…Specifically, we developed a synthetic mucus barrier array (SMBA) platform containing mucin-based hydrogels which can be tailored to mimic the viscoelastic properties of native mucus in health and disease. [29][30][31] To confirm the validity of the SMBA system, we performed studies using polystyrene (PS) NP with size and surface chemistries previously evaluated in the literature. Based on the use of NAC as a mucolytic agent to enhance the penetration of NP through hyper-concentrated mucus produced in cystic fibrosis lung disease, 16,32 we then evaluated a previously untested mucolytic agent TCEP to determine if it could potentially serve as an NP permeation enhancer.…”

Lack of correlation between in vitro and within patient measures of P. aeruginosa biofilms in cystic fibrosis

“…To mimic the conditions of the CF lung environment, adaptations of standardized in vitro models have also emerged, in which PA biofilms are cultivated on top of CF epithelial cell lines [ 5 ] in various formulations of synthetic [ 6 ] and pooled [ 7 , 8 ] CF sputa. Further advancements in biofilm modelling, including the use of bacteria-embedded gels [ [9] , [10] , [11] ] and encapsulating beads [ 12 , 13 ], have shown comparable imitation of PA biofilm structures to that described within pwCF ( i.e. , visualized in animal replicas, sputum smears and explanted lungs).…”