Chen Yaoqi, Cao Xu, Yao Jie, Hu Zeming, Luo Yang, Li Gonghui, Zhang Hua, Wu Kerong
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.
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.
Int J Biol Macromol. 2024 Dec;283(Pt 4):137487. doi: 10.1016/j.ijbiomac.2024.137487. Epub 2024 Nov 22.
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.
出血性膀胱炎（HC）由于膀胱内动态的液体环境和周期性机械应力，呈现出重大的治疗挑战。组织粘附水凝胶在治疗HC方面已显示出前景；然而，在这些波动条件下维持强粘附力和机械完整性仍然是一个关键障碍。在此，我们利用茶多酚（TP）对受损组织的亲和力及其通过丰富的氢键迅速增强光交联甲基丙烯酰化丝素蛋白（SFMA）稳定性的能力，设计了一种坚固的膀胱粘附水凝胶。所得的SFMA/TP水凝胶能够承受高压缩和拉伸负荷，同时在尿液环境下保持高效粘附，达到高达15.1 kPa以适应膀胱的动态机械环境。此外，尿素解离破坏了氢键，使SFMA/TP水凝胶在膀胱内体外和体内均表现出尿素响应性和有效的生物降解性。在环磷酰胺诱导的HC大鼠模型中，这种尿液环境下的水凝胶粘合剂表现出卓越的止血效果，并通过调节炎症、增强新血管形成和促进平滑肌形成来促进愈合。总体而言，这种膀胱适应性水凝胶粘合剂通过在膀胱环境中提供靶向和持续治疗，代表了一种用于HC的微创治疗选择。
