The dysregulation of the neutrophil death pathway constitutes a key obstacle to tissue regeneration in diabetes, where reactive oxygen species (ROS) can perpetuate chronic inflammation, while apoptosis promotes tissue homeostasis. However, achieving reliable control over the neutrophil death pattern to regulate the inflammatory and repair processes remains a significant challenge. We have developed a multifunctional aerogel scaffold based on piezoelectric ceramic nanofibers, which collaboratively guides the fate of neutrophils. Specifically, (K, Na)NbO3 piezoelectric ceramics are incorporated into a gelatin/polylactic acid nanofiber membrane, which is homogenized by high-speed fragmentation and freeze-dried to form a porous aerogel scaffold. After combining with the retinol derivative piperidine, the final product is the piezoelectric ceramic nanofiber aerogel (KAP). The calcium peptides released by KAP inhibit the cleavage of gasdermin E (GSDME) mediated by caspase-3, shifting neutrophil death from a heat-induced transition to apoptosis. Simultaneously, when activated by ultrasound, KAP generates surface potential, enhancing the phagocytic ability of macrophages through calcium influx and lysosomal acidification. This mechanical-chemical dual approach promotes the phagocytic activity of neutrophils and reprograms macrophages to a phenotype promoting regeneration, thereby breaking the cycle of chronic inflammation in the diabetic microenvironment. In diabetic rodent models, KAP significantly accelerates the healing of soft and hard tissues. This study demonstrates a piezoelectric ceramic nanofiber aerogel, providing a potential therapeutic approach for diabetic tissue regeneration. This research was published under the title "Piezoelectric Ceramic Nanofiber Aerogels Directly Regulate Neutrophil Fate for Diabetic Tissue Regeneration" in Advanced Materials.
Reference News: DOI: 10.1002/adma.202520475