Ultrasound-Excited Injectable Piezoelectric Composite Hydrogels for Enhancing Diabetic Flap Survival via Synergistic...

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 (H₂O₂), 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 (Fe₃O₄) 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 Fe₃O₄ nanozymes through the piezoelectric effect, significantly enhancing their efficiency in scavenging H₂O₂ 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.