Data from: Matrix stiffness governs fibroblasts' regulation of gingival immune homeostasis

Periodontal disease is characterized by inflamed gingival tissues and
degradation of the gingival extracellular matrix (ECM), yet the role of
mechanical cues remains poorly understood. Gingival ECM in periodontal
disease showed reduced fibrillar collagen compared to healthy samples. We
hypothesized that ECM softening in periodontal disease contributes to
inflammation by dysregulating gingival fibroblasts (GFs). A mechanically
tunable hydrogel model of the gingival ECM was developed to investigate
the mechano-immune crosstalk. Stiff and soft collagen-alginate hydrogels
matched the rheological properties of healthy and diseased gingival
biopsies, respectively. Human donor GFs encapsulated in these stiff
hydrogels showed significantly suppressed toll-like receptor-mediated
inflammatory responses compared to those in soft hydrogels. The
non-canonical NFκB pathway and epigenetic nuclear organization directed
stiffness-dependent inflammatory responses of GFs. The direct impact of
mechanical cues on immune responses was investigated ex vivo by co-culture
of donor-derived human GFs with myeloid cells and in human gingival
explants. Myeloid progenitors co-cultured with GFs in stiff hydrogels
differentiated into immunomodulatory dendritic cells. Ex vivo crosslinking
of human gingival tissue increased stiffness and reduced the production of
inflammatory cytokines. Gingival mechano-immune regulation offers a novel
approach to biomaterial-based treatments for periodontitis.