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. Author manuscript; available in PMC: 2021 Apr 1.
Published in final edited form as: Adv Healthc Mater. 2020 Mar 17;9(8):e1901682. doi: 10.1002/adhm.201901682

Figure 6. Emerging technologies to study fibrosis.

Figure 6.

(a) Sequential tethering and release of signaling factors (e.g., ECM ligands or fibrogenic factors such as TGF-ß1) can be achieved using allyl sulfide-modified PEG hydrogels, and could be used to understand spatial heterogeneity in ECM factors/properties and their contribution to fibrosis development. (b) Multicellular organoids have been developed from iPSCs, which enable stromal cell-epithelial cell interactions using personalized cell cultures. These methods could be expanded to use in biomaterial systems where the influence of ECM properties on fibrosis outcomes could be studied. (c) Heterogeneity in ECM topography and mechanical properties can be recapitulated with composite hydrogel systems composed of Dextran-vinyl sulfone (VS) electrospun fibers embedded in tunable bulk photocrosslinked hydrogels (gelatin-methacrylate hydrogel shown here). Fibroblasts display increased spreading and protrusions in 3D in response to local fiber density. Scale bar is 10 μm. (d) Hypoxia-inducible hydrogels can be fabricated with ferulic acid-modified polymers, where oxygen is consumed in a laccase-mediated reaction that crosslinks ferulic acid groups and simultaneously creates a hypoxic environment. Hypoxia-inducible gels promote multi-cellular vascular network formation with endothelial-colony-forming cells (ECFCs, bottom), while non-hypoxic gels show low levels of single cell network formation (top). Scale bar is 100 μm. Hypoxia-inducible gels have tunable mechanical properties, and thus could be explored to probe the impact of hypoxia and mechanics on fibrosis outcomes. Part (a) is adapted with permission from ref.[117] https://pubs.acs.org/doi/full/10.1021/acscentsci.8b00325 2019 American Chemical Society, part (b) is adapted with permission from ref.[121] 2019 Elsevier, part (c) is adapted with permission from ref.[86] 2019 American Chemical Society, part (d) is adapted with permission from ref.[131] CC BY-NC 4.0 https://creativecommons.org/licenses/by-nc/4.0/legalcode 2019 AAAS.