Oriented hydrogel biomimicking muscle fibers to treat pelvic organ prolapse via integrated immunomodulation and electrical stimulation.

Pelvic organ prolapse is a displacement disorder caused by the weakening of pelvic support tissues, leading to severe urinary incontinence, compromised organ support, and a high recurrence risk. Although clinically used polypropylene meshes provide mechanical reinforcement, their inherent stiffness often causes persistent mechanical overstimulation and chronic inflammation, ultimately resulting in implantation failure. Here, inspired by the parallel-aligned architecture of muscle fibers, we fabricate an oriented and hydrophilic hydrogel via directional freezing, composed of poly(vinyl alcohol), glycyrrhizic acid, Zn2+, and an aniline tetramer-grafted oxidized alginate. The oriented microstructure not only delivers stable mechanical support but also facilitates directional cell proliferation and migration, thereby promoting reconstruction of the damaged pelvic floor architecture. Glycyrrhizic acid and Zn2+ synergistically scavenge reactive oxygen species and regulate macrophage-associated inflammatory responses, establishing a regeneration-favorable immune microenvironment. Simultaneously, the aniline tetramer-grafted oxidized alginate endows the hydrogel with electroactivity, and when in combination with electrical stimulation, promoting the migration and functional maturation of collagen-producing cells and myogenic cells at the prolapse site. In vivo, the oriented hydrogel exhibits good adaptation to pelvic tissues, effectively attenuating inflammation and inducing orientation-dependent tissue ingrowth. Overall, this muscle-inspired hydrogel with a parallel-aligned architecture, when integrated with electrical stimulation and immunomodulation, promotes connective tissue repair and offers a highly promising strategy for treating pelvic organ prolapse.