Injectable Hydrogel Loaded with Plasma-Rich Platelets Repairing Endometrial Injury and Remodeling Reproductive Function by Regulating PI3K/AKT Pathway

Abstract

Infertility resulting from uterine damage has emerged as a significant challenge confronting the development of modern society. Existing therapeutic approaches frequently encounter limitations due to the intricate physical and physiological environment of uterus. Platelet-rich plasma (PRP), a concentrate of platelets enriched with various growth factors, has been used in uterine injury repair. However, the rapid release of activating factors from PRP limits its timeliness in therapeutic applications. This work involves the synthesis of a biodegradable hydrogel based on natural polysaccharides through dynamic Schiff base. The hydrogel demonstrates tissue adhesion, self-healing, and injectability. Furthermore, its internal porous architecture facilitates the loading and sustained release of PRP. In vitro experiments, the hydrogel loaded with RPR (HOHP) exhibits a significant enhancement in cell proliferation and migration and promotes vascular regeneration by upregulating the expression of VEGFA and further activating the intracellular phosphatidylinositol kinase (PI3K)/protein kinase B (AKT) pathway. In vivo experiments on uterine endometrial injury model, HOHP restores endometrial thickness and gland number, reduces collagen deposition, promotes angiogenesis to repair uterine damage and restore fertility, which provides reinforced endorsement for the clinical management of uterine injury and enhances fertility.