Hydrogels in the Management of Peripheral Venous Disease: Bridging Material Design and Clinical Evidence

Peripheral venous disease represents one of the most prevalent and most persistently undertreated chronic conditions in adult populations, with venous leg ulceration standing at the severe end of a spectrum that also includes symptomatic chronic venous insufficiency and superficial venous thrombosis. The venous wound microenvironment is shaped by mechanisms that are largely specific to this etiology, including ambulatory venous hypertension, erythrocyte extravasation with cutaneous iron deposition, sustained oxidative stress, proteolytic imbalance and fibroblast senescence. Hydrogels, as three-dimensional hydrophilic polymer networks with high water content, tunable mechanics and versatile payload capacity, offer an appealing platform for addressing several of these mechanisms simultaneously. The preclinical literature is correspondingly abundant. The clinical evidence base, however, remains thin and inconclusive, and the most rigorous synthesis available has been unable to establish whether hydrogel dressings outperform simpler alternatives in venous ulcer healing. This review examines that discrepancy rather than setting it aside. We summarize the physicochemical properties that determine hydrogel performance specifically under compression and in a heavily exudating wound, map hydrogel mechanisms of action onto venous pathobiology, survey therapeutic applications across the venous spectrum, including topical formulations for superficial venous thrombosis, and appraise the preclinical and clinical evidence with attention to why translation has stalled. We conclude by proposing design criteria for venous-specific hydrogel systems and methodological priorities for the trials needed to test them.