A Janus-inspired sodium alginate/polyacrylamide/guar gum hydrogel-backed bilayer microneedle patch for combating wound biofilms via synergistic photodynamic and nitric oxide gas therapy.

Chronic wounds are frequently complicated by bacterial biofilms, in which the extracellular polymeric substance (EPS) significantly impedes drug penetration and diminishes therapeutic efficacy. To overcome this limitation, we designed an innovative "asymmetric" Janus-structured bilayer microneedle (MN) system, termed SPG-PH MNs, which integrates a sodium alginate/polyacrylamide/guar gum (SPG) hydrogel backing with a polyvinyl alcohol/hyaluronic acid (PH) bilayer MN layer. Upon penetration into the biofilm, the polyvinyl alcohol (PVA) tip layer enables sustained release of α-amylase (α-Amy) for enzymatic EPS degradation and tannic acid (TA) for anti-inflammatory activity. Simultaneously, the rapidly dissolving hyaluronic acid (HA) base layer delivers 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra(p-toluenesulfonate) (TMPyP) and L-arginine (L-Arg) directly to bacterial colonies within the EPS. This co-delivery facilitates synergistic antibacterial therapy via combined photodynamic therapy (PDT) and nitric oxide (NO) gas generation under near-infrared (NIR) irradiation. Following treatment, the sodium alginate/polyacrylamide/guar gum backing hydrogel forms a flexible and adhesive physical barrier that helps prevent secondary infection. Both in vitro and in vivo studies validated the feasibility and efficacy of this integrated strategy, achieving a wound closure ratio of 99.26 % within 11 days in a biofilm-infected mouse model. The proposed multifunctional platform thus demonstrates strong potential for effective eradication of wound-infecting biofilms and promotion of tissue regeneration.