Critical limb ischemia (CLI) is characterized by the impairment of microcirculation,
necrosis and
inflammation of the muscular tissue. Although the role of
glycans in mediating
inflammation has been reported, changes in the glycosylation following muscle
ischemia remains poorly understood. Here, a murine CLI model was used to show the increase of high
mannose, α-(2, 6)-sialic
acid and the decrease of hybrid and bisected N-
glycans as glycosylation associated with the ischemic environment. Using this model, the efficacy of an
elastin-like recombinamers (ELR)
hydrogel was assessed. The
hydrogel modulates key angiogenic signaling pathways, resulting in capillary formation, and ECM remodeling. Arterioles formation, reduction of
fibrosis and anti-inflammatory macrophage polarization wa also induced by the
hydrogel administration. Modulation of glycosylation was observed, suggesting, in particular, a role for mannosylation and sialylation in the mediation of tissue repair. Our study elucidates the angiogenic potential of the ELR
hydrogel for CLI applications and identifies glycosylation alterations as potential new therapeutic targets.