Figure 1.

(a) Modifications of hyaluronic acid (HA) can affect its activity. Thiol-modified HA (HA-S) is not biologically active compared to native HA [64]. Bar graph shows extent of binding of fluorescently labeled HA (Fl-HA) to human MSCs, which is significantly reduced by adding HA as a competing partner, but not upon adding HA-S with its chemical modification. (b) Fibronectin (FN) streaks seen on soft HA substrates. Myocytes were cultured on (1000 μm²) square FN micro-patterned 300 Pa HA and 30 kPa PAA substrates for a period of 72 hours. Myocytes were unable to migrate out of the micropatterns even after attachment to HA substrates for a 3 day period. Arrowheads indicate formation of integrin α5 clusters. FN streaks seen on soft HA substrates are due to micro-contact printing on soft substrates and existed before cell plating [49]. (c) Mesenchymal stem cells (MSCs) are perivascular cells in nearly all tissues and have a major role in fibrosis. Ablation of Gli1+ MSCs by diphtheria toxin, DTX, reduced severity of kidney fibrosis as demonstrated by trichrome staining and immunostaining for α-SMA and quantification of interstitial fibrosis. Scale bars, left two panels, 500 μm; others, 50 μm [58]. (d) Scar in a dish reveals key role of matrix rigidity, even if heterogeneous. Scar-like islands of collagen-I are heterogeneously entrapped at the subsurface of the soft hydrogel. The heterogeneity of the MMMS was confirmed by both immunofluorescence and staining with the histochemical dye, Sirius Red. Human MSCs cultured on conventional homogeneous gels and separately on MMMS [57].