Enhancing under-urine adhesion and bladder adaptation of silk fibroin hydrogels with tea polyphenols for hemorrhagic cystitis
Yaoqi Chen, Xu Cao, Jie Yao, Zeming Hu, Yang Luo, Gonghui Li, Hua Zhang, Kerong Wu
Abstract
Hemorrhagic Cystitis (HC) presents a significant therapeutic challenge due to the dynamic fluid environment and cyclical mechanical stress within the bladder. Tissue-adhesive hydrogels have shown promise in treating HC; however, maintaining strong adhesion and mechanical integrity under these fluctuating conditions remains a critical obstacle. Herein, we designed a robust bladder-adhesive hydrogel by leveraging the affinity of tea polyphenols (TP) for damaged tissues and their ability to rapidly enhance the stability of photo-crosslinked silk fibroin methylacryloyl (SFMA) through abundant hydrogen bonding. The resulting SFMA/TP hydrogel could withstand high compressive and tensile loads while maintaining efficient under-urine adhesion, achieving up to 15.1 kPa to adapt to the dynamic mechanical environment of the bladder. Furthermore, urea dissociation disrupted hydrogen bonding, enabling the SFMA/TP hydrogels to exhibit urea-responsiveness and effective biodegradation both in vitro and in vivo within the bladder. In a rat model of cyclophosphamide-induced HC, this under-urine hydrogel adhesive demonstrated superior hemostatic effects and promoted healing by modulating inflammation, enhancing neovascularization, and facilitating smooth muscle formation. Overall, this bladder-adaptive hydrogel adhesive represents a minimally invasive therapeutic option for HC by offering targeted and sustained treatment within the bladder environment.