Journal article
Characterization of human airway-derived decellularized extracellulr matrix hydrogels and their effects on airway epithelial cell growth, organization and differentiation
Biomaterials, Vol.336, 124420
01/01/2027
DOI: 10.1016/j.biomaterials.2026.124420
PMID: 42419184
Abstract
Three-dimensional human airway models are useful tools to study respiratory development, disease and regeneration. However, commonly used substrates such as Matrigel™ differ substantially from native airway ECM, and effects on cell behavior remain incompletely characterized. Human airway-derived decellularized ECM (AW-dECM) hydrogels represent a potentially more physiological alternative, but their properties relative to conventional matrices are undefined.
We performed a comprehensive characterization of AW-dECM and Matrigel™ hydrogels by assessing ECM composition, stiffness and viscoelasticity and evaluated effects on primary human bronchial epithelial cell behavior at air-liquid interface. AW-dECM (15 mg/mL; 30 mg/mL) exhibited lower stiffness and greater similarity to native airway tissue than standard concentration (SC; 8 mg/mL) or high concentration (HC; 19 mg/mL) Matrigel™. All hydrogels displayed typical viscoelastic behavior. Proteomic analysis revealed collagen I and VI enrichment in AW-dECM that was absent in Matrigel™. These differences lead to distinct cellular organization: SC Matrigel™ promoted organoid formation, HC Matrigel™ supported tubule-like structures/monolayers, and AW-dECM favored confluent monolayers. Gene expression varied by substrate; stiffer matrices promoted greater secretory differentiation and AW-dECM increased expression of MMP9, MMP7, and TJP1. Inhibition of actomyosin contractility enhanced cell adhesion/spreading on softer matrices, further supporting the influence of matrix properties on airway epithelial cell behavior.
AW-dECM and Matrigel™ exhibit distinct mechanical and biochemical properties that differentially influence airway epithelial cell growth, organization, and differentiation. This work establishes a detailed characterization of human airway-derived ECM hydrogels and provides a framework linking matrix properties with airway epithelial responses, thereby informing the development of more physiological airway models.
Created in BioRender. Wanczyk, H. (2025) https://BioRender.com/z5mzufy. [Display omitted]
Details
- Title: Subtitle
- Characterization of human airway-derived decellularized extracellulr matrix hydrogels and their effects on airway epithelial cell growth, organization and differentiation
- Creators
- Heather Wanczyk - UConn HealthLaura Porritt - University of VermontJulia Linke - Boston UniversityJoanne Walker - UConn HealthBéla Suki - Boston UniversityAmy Ryan - University of IowaDaniel J. Weiss - University of VermontChristine Finck - Connecticut Children's Medical Center
- Resource Type
- Journal article
- Publication Details
- Biomaterials, Vol.336, 124420
- DOI
- 10.1016/j.biomaterials.2026.124420
- PMID
- 42419184
- ISSN
- 0142-9612
- eISSN
- 1878-5905
- Publisher
- Elsevier Ltd
- Grant note
- NIH/NHLBI: N01: 75N92020C00005 National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: T32AR079114 NSF Recode 3 Award: 2225554, P20GM103449 NIH from the INBRE Program of the National Institute of General Medical Sciences: P20GM103449
Human iPSCs (or their derivatives) were received from the Center for Regenerative Medicine of Boston University and Boston Medical Center, supported by NIH/NHLBI resource sharing grant N01: 75N92020C00005.Primary human airway epithelial cells (2023-80 and 2023-83) were graciously donated by Dr. Amy Ryan, Department of Anatomy and Cell Biology at Carver College of Medicine.Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number T32AR079114. Also, R21 HD104069, NSF Recode 3 Award 2225554 and The Vermont Biomedical Research Network Proteomics Facility (RRID: SCR_018667) supported through NIH grant P20GM103449 from the INBRE Program of the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily repre-sent the official views of the National Institutes of Health.
- Language
- English
- Electronic publication date
- 07/04/2026
- Date published
- 01/01/2027
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9985183136202771
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