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

doi:10.1016/j.ijbiomac.2024.137487

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

Int J Biol Macromol. 2024 Nov 21:137487. doi: 10.1016/j.ijbiomac.2024.137487. Online ahead of print.

Authors

Yaoqi Chen¹, Xu Cao², Jie Yao³, Zeming Hu⁴, Yang Luo⁴, Gonghui Li⁵, Hua Zhang⁶, Kerong Wu⁷

Affiliations

¹ Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Research Institute of Smart Medicine and Biological Engineering, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China; Department of Urology, Translational Research Laboratory for Urology, Ningbo Clinical Research Center for Urological Disease, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China.
² Research Institute of Smart Medicine and Biological Engineering, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China; Department of Urology, Translational Research Laboratory for Urology, Ningbo Clinical Research Center for Urological Disease, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China.
³ Department of Urology, Translational Research Laboratory for Urology, Ningbo Clinical Research Center for Urological Disease, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China.
⁴ Research Institute of Smart Medicine and Biological Engineering, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China.
⁵ Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China. Electronic address: 3193119@zju.edu.cn.
⁶ Research Institute of Smart Medicine and Biological Engineering, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China; Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China. Electronic address: zhanghua@nbu.edu.cn.
⁷ Department of Urology, Translational Research Laboratory for Urology, Ningbo Clinical Research Center for Urological Disease, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China; Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China. Electronic address: fyywukerong@nbu.edu.cn.

PMID: 39579834
DOI: 10.1016/j.ijbiomac.2024.137487

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.

Keywords: Hemorrhagic cystitis; Intravesical instillation; Tissue-adhesive hydrogel.