{"doi":"10.1101/2022.12.23.521822","title":"Biomimetic human lung alveolar interstitium chip with extended longevity","abstract":"Abstract Determining the mechanistic causes of lung diseases, developing new treatments thereof, and assessing toxicity whether from chemical exposures or engineered nanomaterials would benefit significantly from a preclinical human lung alveolar interstitium model of physiological relevance. The existing preclinical models have limitations because they fail to replicate the key anatomical and physiological characteristics of human alveoli. Thus, a human lung alveolar interstitium chip was developed to imitate key alveolar microenvironmental factors including: an electrospun nanofibrous membrane as the analogue of the basement membrane for co-culture of epithelial cells with fibroblasts embedded in 3D collagenous gels; physiologically relevant interstitial matrix stiffness; interstitial fluid flow; and 3D breathing-like mechanical stretch. The biomimetic chip substantially improved epithelial barrier function compared to transwell models. Moreover, the chip having a gel made of a collagen I-fibrin blend as the interstitial matrix sustained the interstitium integrity and further enhanced the epithelial barrier resulting in a longevity that extended beyond eight weeks. The assessment of multiwalled carbon nanotube toxicity on the chip was in line with the animal study.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313875,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9179,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":697641,"name":"Jiafeng Liu","orcid":null,"position":1,"is_corresponding":false},{"id":1012901,"name":"Cindy Liang","orcid":null,"position":2,"is_corresponding":false},{"id":1012902,"name":"Christopher Corona","orcid":null,"position":3,"is_corresponding":false},{"id":542380,"name":"Michael D. Story","orcid":"0000-0001-6522-4169","position":4,"is_corresponding":false},{"id":897318,"name":"Brian Meckes","orcid":"0000-0002-8389-4622","position":5,"is_corresponding":false},{"id":697087,"name":"Yong Yang","orcid":"0000-0003-4305-8029","position":6,"is_corresponding":false},{"id":1012574,"name":"Kun Man","orcid":"0000-0002-3764-3312","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T00:33:48.490749Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}