HGF mRNA LNP therapy promotes uterine repair after cesarean section in a mouse model

Previous cesarean scar defect (PCSD) is the most common complication following cesarean delivery, characterized by myometrial thinning or disruption. Its incidence rises with increasing number of cesarean sections, reaching 76% after three procedures, yet effective clinical interventions remain lacking. Inadequate blood supply and weak regeneration of the lower uterine segment are key pathogenic contributors, suggesting that improving local perfusion could facilitate wound healing. In this study, we developed lipid nanoparticle (LNP)-encapsulated hepatocyte growth factor (HGF) mRNA and applied it locally to uterine incisions in a mouse model. HGF mRNA LNP treatment significantly increased endometrial thickness and gland density, reduced collagen deposition, and promoted smooth muscle regeneration and angiogenesis at days 7 and 30 postoperatively. Favorable trends in pregnancy outcomes were observed. Hematological and serum biochemical parameters remained comparable between groups at all time points examined. Transcriptomic profiling revealed that upregulated genes in the HGF mRNA LNP group were involved in cell proliferation, migration, and survival. In vitro, HGF enhanced endothelial cell migration and tube formation. Collectively, these findings indicate that HGF mRNA LNP delivery at the site of uterine incision injury can promote structural and functional uterine repair in a small‑animal model, and provide a rationale for further preclinical evaluation.