Aptamer-empowered hydrogel depot with ultrasound-stimulated drug activation and centripetal contraction for accelerated diabetic wound closure

While hydrogel dressings can accelerate healing of infected diabetic wounds, further therapeutic improvement requires hydrogels to display controllable drug activation and wound physical contraction. Herein, we develop an aptamer-empowered hydrogel depot through crosslinking of 4-arm polyethylene glycol methacrylate and acrydite-modified kanamycin aptamer (Apt Kan )/complementary DNA (cDNA) duplex in the presence of hyaluronic acid and growth factor, followed by loading and inactivating kanamycin via the aptamer’s binding capability, which simultaneously triggers DNA duplex dissociation. To achieve region-selective adhesion, we develop a low-frequency ultrasound for adhesion (LFUS A ) technique that anchors chitosan to the infected diabetic wound margin, enabling hyaluronic acid in the hydrogel disc to adhere to chitosan-anchored tissue through hydrogen bonding. The low-frequency ultrasound for release (LFUS R ) technique is subsequently applied to the hydrogel positioned above the wounds, and its shear forces re-activate the antibacterial activity of kanamycin by destabilizing the Apt Kan -kanamycin complex and simultaneously enhance the release of growth factor for augmented angiogenesis. Critically, this kanamycin release enables re-hybridization of Apt Kan /cDNA, inducing gel contraction, which drives centripetal wound contraction and ultimately accelerates wound closure. This aptamer-functionalized hydrogel depot, which integrates drug release with concurrent wound contraction, provides proof of concept for a materials platform designed to promote impaired wound healing.