Fig. 4: Hydrogels evoke fibrotic responses at the material–tissue interface that can involve stromal or astroglial cells.

a, b Detail images of stromal-associated markers, collagen-1a1 (Col1a1), fibronectin, laminin, and galectin-3 (Gal-3) and their relationship to non-neural CD13-positive cells at the tissue interface of DCHMO a and DCHK b at 1 week after injection (hydrogels, G). Colocalization of markers with CD13-positive cells is seen as white staining. c Quantification of total Col1a1 and Gal-3 staining at 1 week after hydrogel injection. ***P = 0.0003 and =0.0002 for DCHMO versus DCHK for Col1a1 and Gal-3 stromal markers, respectively, two-way ANOVA with Bonferroni. Graphs show mean ± s.e.m with individual data points showing n = 5 and 7 mice for DCHMO and DCHK, respectively. d Detail image showing that adjacent to DCHMO, Gal-3 colocalizes with a narrow band of GFAP-positive astrocytes that border the gel at 1 week. Gal-3 and GFAP colocalization is seen as white staining. e, f Detail images showing the temporal evolution of Gal-3 expression at the interface of DCHMO e and DCHK f at acute (48 h, 48 h), subacute (1 week, 1wk) and chronic (6 weeks, 6wk) timepoints after injection. Gal-3 and GFAP colocalization is seen as yellow staining. Gal-3 and CD13 colocalization is seen as white staining.