A pH/glucose dual-responsive Janus dressing with optimized gradient modulus/tissue adhesion promotes diabetic wound healing by dynamic drug-payload release

A dynamic drug-payload release dressing (H@GmJ-P) was logically engineered for promoting diabetic wound healing using two purpose-specific units: a pH/glucose dual-responsive hydrogel and a Janus membrane with centrally graded-thickness. ‌The underlying hydrogels were created by a sequential functionalization strategy with recipes of dopamine-grafted oxidized sodium alginate, methacrylate-phenylboronic acid functionalized carboxymethyl chitosan, tannic acid and borax, which functionalized the H@GmJ-P with excellent bio-adhesive (∼74.5 kPa), antibacterial (>98 %), antioxidant, hemostatic, and self-healing properties. The upper Janus membranes composed of polycaprolactone (PCL) hydrophobic layer and PCL/F127 hydrophilic layer were engineered by thickness-varied design, functionalizing the H@GmJ-P with gradient decreasing modulus from ∼1.5 MPa (middle) to ∼0.6 MPa (periphery) for superior wound tear-resistance (∼197 kPa). Functional collaboration between the two units established unidirectional drug delivery platform following drug-sustained release behavior by pathophysiological wound pH/glucose stimuli. In vivo chronic diabetes skin wound model confirmed that H@GmJ-P promoted wound closure with only 8.2 ± 2.2 % unhealed area by day 21. This work proposes rational design of soft hydrogel dressing with stiff membrane can create matched modulus/tissue adhesion against wound tear. In addition, an innovative regenerative strategy emphasizing precise drug-sustained release offers a novel paradigm for managing challenging wounds.