High-resolution spatial transcriptomics of irradiated submandibular glands treated with fortified fibrin hydrogels.

Previous studies showed that fortified fibrin hydrogel (Ep-FH), generated by conjugating laminin-1 peptides (A99 and YIGSR) and growth factors (FGF7 and FGF10) to fibrin hydrogels, improves epithelial organization and secretory function in irradiated mouse submandibular glands (SMG). To define the cell type-specific mechanisms underlying these effects, we generated high-resolution spatial transcriptomic profiles using the Xenium Prime Mouse Pan Tissue and Pathways Panel (5,000 genes). Treatment with Ep-FH partially reactivated secretory- and polarity-related genes, shifted stromal and immune transcriptional programs toward the non-irradiated state, and reduced profibrotic signaling. Integrative clustering further showed increased similarity of acinar, stromal, immune, and myoepithelial populations to non-irradiated controls, whereas ductal, endothelial, and glial cells showed limited responses. These findings indicate that Ep-FH partially restores transcriptional programs in selected cell populations, suggesting that further optimization may improve regeneration throughout the irradiated SMG.