In vitro and in vivo Hydrogel Model Systems Core Unit

The investigation of functional and structural properties of the hydrogels covering the epithelial surfaces of the lung and the intestine, and the elucidation of their contribution to mucosal function in health and disease, requires access to consistent and appropriately processed samples of these native hydrogels, as well as model systems of these delicate biointerfaces.

In the first funding period, we developed reliable protocols for the procurement, processing, and long-term storage of native airway and intestinal mucus of healthy individuals and patients with cystic fibrosis (CF) as a genetic model of muco-obstructive lung disease and patients with inflammatory bowel disease (IBD), as well as disease-relevant cell and mouse models and respective controls, with minimal alteration of its native properties. Furthermore, the microbiota analysis in mucus was established jointly with B05|Fulde/Forslund/Schaupp and will be expanded in the second funding period. We also established and provided validated in vitro (2D and 3D cell/tissue culture) and in vivo (mouse) models for studies of hydrogel (dys)function on airway and intestinal surfaces in health and disease, which has been frequently used by almost all projects of the CRC. Especially the projects A01|Mall/Gradzielski, A04|Seitz/Block, A05|Hedtrich/Bartfeld, C03|Pagel/Mertins and C04|Haag/Mall were supported with airway-related model systems, while intestinal mucus-related models were provided to A04|Seitz/Block and B05|Fulde/Forslund/Schaupp. Furthermore, protocols for the processing, solubilization, and chemical functionalization of thermosensitive pregels made of decellularized small intestinal submucosa have been established for the biofabrication of mucus-producing intestinal models (B04|Siegmund/Weinhart and A05|Hedtrich/Bartfeld). Both intestinal gel matrix and established human healthy and diseased small intestinal organoid lines are available to the consortium.