Four-dimensional hydrogel dressing adaptable to the urethral microenvironment for scarless urethral reconstruction

• Published in: Nature communications Vol. 14; no. 1; p. 7632
• Main Authors: Hua, Yujie, Wang, Kai, Huo, Yingying, Zhuang, Yaping, Wang, Yuhui, Fang, Wenzhuo, Sun, Yuyan, Zhou, Guangdong, Fu, Qiang, Cui, Wenguo, Zhang, Kaile
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.11.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/107; 631/61/54/994; 639/301/923/1027; 692/4025/1862; Crosslinking; Extracellular matrix; Gelatin; Growth factors; Humanities and Social Sciences; Hydrogels; Microenvironments; Molecular modelling; multidisciplinary; Photopolymerization; Physiology; Science; Science (multidisciplinary); Signal transduction; Time dependence; Vascular endothelial growth factor; Viscoelasticity; Wound healing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43421-w

The harsh urethral microenvironment (UME) after trauma severely hinders the current hydrogel-based urethral repair. In fact, four-dimensional (4D) consideration to mimic time-dependent physiological processes is essential for scarless urethral reconstruction, which requires balancing extracellular matrix (ECM) deposition and remodeling at different healing stages. In this study, we develop a UME-adaptable 4D hydrogel dressing to sequentially provide an early-vascularized microenvironment and later-antifibrogenic microenvironment for scarless urethral reconstruction. With the combination of dynamic boronic ester crosslinking and covalent photopolymerization, the resultant gelatin methacryloyl phenylboronic acid/ cis -diol-crosslinked ( GMPD ) hydrogels exhibit mussel-mimetic viscoelasticity, satisfactory adhesion, and acid-reinforced stability, which can adapt to harsh UME. In addition, a temporally on-demand regulatory ( TOR ) technical platform is introduced into GMPD hydrogels to create a time-dependent 4D microenvironment. As a result, physiological urethral recovery is successfully mimicked by means of an early-vascularized microenvironment to promote wound healing by activating the vascular endothelial growth factor (VEGF) signaling pathway, as well as a later-antifibrogenic microenvironment to prevent hypertrophic scar formation by timing transforming growth factor-β (TGFβ) signaling pathway inhibition. Both in vitro molecular mechanisms of the physiological healing process and in vivo scarless urethral reconstruction in a rabbit model are effectively verified, providing a promising alternative for urethral injury treatment. Urethral repair can be carried out using hydrogels, but the harsh microenvironment hinders the repair. Here, the authors report the development of a 4D hydrogel dressing that can provide an early-vascularised and later-antifibrogenic microenvironment to assist in scarless reconstruction.