Enhanced immunoregulation in traumatic urethral stricture repair utilizing a glycyrrhizic acid-infused antiswelling biogel scaffold

Abstract

As a prevalent complication following urinary system trauma, urethral stricture is characterized by progressive fibrosis and luminal narrowing often leading to recurrent dysuria and impaired renal function. Current treatments including surgical interventions face challenges such as high recurrence rates and secondary stenosis. Hydrogel-based drug delivery systems offer therapeutic potential but are limited by material swelling under urinary flow and insufficient modulation of inflammatory microenvironments. This study introduces an innovative anti-swelling carrageenan biogel scaffold (Car/Ga) functionalized with glycyrrhizic acid (Ga), a dual anti-inflammatory and immunoregulatory phytochemical. The Car matrix ensures structural stability in biological fluids by resisting swelling-induced obstruction while Ga targets trauma-induced inflammatory cascades through M1 macrophage polarization mitigation to reduce fibrotic progression. In vitro and in vivo evaluations demonstrate that the Car/Ga system synergistically combines urine stability with immunomodulatory bioactivity, significantly reducing pro-inflammatory cytokine levels (iNOS) and promoting M2 macrophage polarization (Arg1). Histological analyses reveal attenuated collagen deposition and enhanced epithelial regeneration in urethral stricture models, highlighting its capacity to disrupt the inflammation–fibrosis cycle. By addressing both urine stability and immunological dysregulation, this dual-functional biogel represents a transformative strategy for precise urethral repair, demonstrating potential for clinical translation in urethral repair applications.