Biocompatible injectable glycyrrhizic acid-based growth factor hydrogel for synergistic endometrial regeneration.

Regenerative therapies for endometrial repair are crucial for treating intrauterine adhesions (IUA) and restoring fertility. In this study, we present a biocompatible injectable GHD hydrogel based on glycyrrhizic acid (GA) and dopamine-modified hyaluronic acid (HA-DA) for synergistic endometrial regeneration. The hydrogel demonstrated shear-thinning behavior and rapid gelation, making it suitable for minimally invasive delivery. The BB/OA/GHD with the dual incorporation of Oroxylin A (OA) and platelet-derived growth factor-BB (PDGF-BB), exhibited sustained release of OA and PDGF-BB, and favorable degradation over 8 days. In an IUA rat model, the BB/OA/GHD significantly restored endometrial thickness, gland density, and stromal organization. Mechanistically, the BB/OA/GHD reduced pro-inflammatory cytokines, oxidative stress, and collagen deposition, while enhancing VEGFA-mediated angiogenesis. The BB/OA/GHD group demonstrated superior fertility restoration, with increased embryo and fetus numbers and improved live birth rates compared to other treatments. These results highlight the potential of the BB/OA/GHD as a therapeutic platform for endometrial regeneration and fertility restoration, offering a novel and effective strategy for the treatment of endometrial dysfunction and infertility.