Enhancing under-urine adhesion and bladder adaptation of silk fibroin hydrogels with tea polyphenols for hemorrhagic cystitis

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.