An Integrated Whole-Process Repair System with Programmed Regulation of Healing Performance Facilitates Urethral Wound Restoration and Scarless Reconstruction

The harsh microenvironment of the urethral injury often carries high risks of early undesirable healing as well as late scar tissue formation. Indeed, the infection and inflammatory response in the early stages as well as blood vessel formation and tissue regeneration in the later stages fundamentally impact the outcomes of urethral wound healing. Innovatively, an integrated whole-process repair hydrogel (APF/C/L@dECM) is designed. After rigorous testing, it is found that hydrogels formed by hydrophobic association and double cross-linking of amide bonds can procedurally regulate wound healing in all phases to match the repair process. In rabbit models of urethral wound, APF/C/L@dECM hydrogel can achieve scarless reconstruction with significantly better results than other hydrogels. Noteworthily, multi-stage mechanistic explorations reveal the expression profiles of inflammation, vascularization, and extracellular matrix secretion-related genes in wound tissue at different times. In summary, this study develops an overall treatment for urethral injury through a whole-process repair system that promotes healthy healing of urethral wounds and prevents the formation of scar tissue.