A double network composite hydrogel with enhanced transdermal delivery by ultrasound for endometrial injury repair and fertility recovery

Endometrial injury and resulting female infertility pose significant clinical challenges due to the notable shortcomings of traditional treatments. Herein, we proposed a double network composite hydrogel, CSMA-RC-Zn-PNS, which forms a physical barrier on damaged tissue through photo-crosslinking while enabling sustained release of the active ingredient PNS. Based on this, we developed a combined strategy to enhance transdermal delivery efficiency using ultrasound cavitation. <i>In vitro</i> experiments demonstrated that CSMA-RC-Zn-PNS exhibits excellent biosafety, biodegradability, and promotes cell proliferation, migration, and tube formation, along with antioxidant and antibacterial properties. In a rat endometrial injury model, the ultrasound cavitation effect was demonstrated to enhance transdermal delivery efficiency, and the ability of CSMA-RC-Zn-PNS to promote endometrial regeneration, anti-fibrosis and fertility restoration was verified. Overall, this strategy combining CSMA-RC-Zn-PNS hydrogel and ultrasound treatment shows promising applications in endometrial regeneration and female reproductive health.