Biomimetic Composite Hydrogel Laden with Ginsenoside Rh1 Facilitates Perianal Ulcer Healing by Regulating Anti-Inflammatory and Antioxidant Responses

Perianal ulcers are a challenging proctological condition characterized by persistent inflammation and delayed healing. Herein, a biomimetic composite hydrogel (H-Rh1) was developed by embedding ginsenoside Rh1-loaded silk fibroin microspheres into a dopamine/chitosan/polyvinyl alcohol/starch matrix, inspired by mussel wet adhesion. The H-Rh1 hydrogel exhibited shear-thinning behavior, strong tissue adhesion (12.45 kPa), sustained drug release, favorable preliminary cytocompatibility, and enhanced antibacterial activity (80% against E. coli and 60% against S. aureus). In a rat perianal ulcer model, H-Rh1 treatment achieved nearly complete wound closure by day 13, with markedly reduced inflammation and improved tissue regeneration. Mechanistically, H-Rh1 treatment was associated with suppressed MAPK/NF-κB signaling while activating the Nrf2/HO-1 antioxidant axis, significantly decreasing serum IL-1β (86.46 pg/mL), IL-6 (70.83 pg/mL), and TNF-α (113.33 pg/mL). These results demonstrate that the H-Rh1 composite hydrogel offers a promising therapeutic strategy for perianal ulcer healing through synergistic anti-inflammatory and antioxidant mechanisms.