Bioactive Materials (Aug 2025)

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

  • Xin Zhang,
  • Shufang Wang,
  • Siyu Wang,
  • Zeyi Long,
  • Cong Lu,
  • Jianlin Wang,
  • Lijun Yang,
  • Cancan Yao,
  • Bin He,
  • Xihua Chen,
  • Taifeng Zhuang,
  • Xiangbo Xu,
  • Yufeng Zheng

Journal volume & issue
Vol. 50
pp. 273 – 286

Abstract

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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. In vitro 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.

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