Locally applied lipid nanoparticle (LNP)-encapsulated hepatocyte growth factor (HGF) mRNA, delivered directly to uterine incisions in mice, significantly increased endometrial thickness, gland density, and smooth muscle regeneration while reducing pathological collagen deposition at both day 7 and day 30 post-surgery. Transcriptomic profiling confirmed upregulation of cell proliferation, migration, and survival pathways. In vitro, HGF enhanced endothelial tube formation and migration, supporting a pro-angiogenic mechanism. No adverse hematological or biochemical signals were detected, and favorable pregnancy outcome trends were observed.
Previous cesarean scar defect (PCSD) affects up to 76% of women after three cesarean deliveries and currently has no well-validated pharmacological treatment — making even early-stage mechanistic advances here clinically significant. The approach is conceptually aligned with the broader mRNA-LNP therapeutic wave catalyzed by COVID-19 vaccine success, now being extended into tissue repair applications. HGF is an established pleiotropic growth factor with known roles in angiogenesis and epithelial regeneration, so the biological rationale is sound. However, mouse uterine anatomy differs substantially from human, and local delivery logistics in an operative field remain a translational hurdle. This is confirmatory-to-incremental work rather than paradigm-shifting, but the demonstration that mRNA-LNP can be repurposed for site-specific reproductive tissue repair is a meaningful proof-of-concept warranting rigorous large-animal and eventual human safety trials.
