Topical nitric oxide (NO) delivery has been shown to accelerate wound healing. However, delivering NOto wounds at appropriate rates and doses requires new biomaterial-based strategies. Here, we describethe development of supramolecular interpolymer complex hydrogels comprising PEO-PPO-PEO (F127)micelles embedded in a poly(acrylic acid) (PAA) matrix, with S-nitrosoglutathione (GSNO) molecules dis-solved in the hydrophilic domain. We show that PAA:F127/GSNO hydrogels start releasing NO uponhydration at rates controlled by their rates of water absorption. SAXS measurements indicate that thesupramolecular structure of the hydrogels retains long-range order domains of F127 micelles. ThePAA/F1227 hydrogels displayed dense morphologies and reduced rates of hydration. The NO release ratesremain constant over the first 200 min, are directly correlated with the hydration rates of the PAA:F127/GSNO hydrogels, and can be modulated in the range of 40 nmol/g h to 1.5lmol/g h by changing the PAA:F127 mass ratio. Long-term NO-release profiles over 5 days are governed by the first-order exponentialdecay of GSNO, with half-lives in the range of 0.5–3.4 days. A preliminaryin vivostudy on full-thickness excisional wounds in mice showed that topical NO release from the PAA:F127/GSNO hydrogelsis triggered by exudate absorption and leads to increased angiogenesis and collagen fiber organization, aswell as TGF-b, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue. In summary, these resultssuggest that hydration-controlled NO release from topical PAA:F127/GSNO hydrogels is a potential strat-egy for enhancing wound healing Ver menos