Ultrasound‐Excited Injectable Piezoelectric Composite Hydrogels for Enhancing Diabetic Flap Survival via Synergistic Redox Homeostasis and Angiogenesis

ABSTRACT The low survival of skin flap transplantation in diabetic patients is a serious challenge for clinical plastic surgery. The root cause lies in the vicious cycle formed by metabolic disorders caused by persistent hyperglycemia, leading to excessive accumulation of Hydrogen peroxide (H ₂ O ₂ ), oxidative stress‐mediated inflammation, and impaired angiogenesis. This study develops an ultrasound (US)‐excited injectable piezoelectric composite hydrogel (iPCH) composed of piezoelectric poly‐L‐lactic acid (PLLA) short fibers, ferroferric oxide (Fe ₃ O ₄ ) nanozymes, and a crosslinked gelatin matrix. The PLLA short fibers in the US‐excited iPCH can generate piezoelectric stimulation under US‐excited conditions, enhancing endothelial cell proliferation, migration, and pro‐angiogenic potential. Furthermore, the generated piezoelectric charge accelerates electron transfer on the surface of Fe ₃ O ₄ nanozymes through the piezoelectric effect, significantly enhancing their efficiency in scavenging H ₂ O ₂ and alleviating the local inflammatory response. This improves the long‐standing inflammatory microenvironment of diabetic wounds, increasing the survival of endothelial cells under oxidative stress. In vivo studies show that the US‐excited iPCH can reduce oxidative stress‐mediated inflammatory responses, accelerate flap angiogenesis, and ultimately improve flap survival. This study utilizes the synergistic effect of physical stimulation and microenvironment regulation to provide a simple and efficient clinical intervention strategy for the survival of complex flaps.