Lactobacillus-Loaded Easily Injectable Hydrogel Promotes Endometrial Repair via Long-Term Retention and Microenvironment Modulation

Abstract

Regeneration of the injured endometrium, particularly the functional layer, is crucial for the prevention of uterine infertility. At present, clinical treatment using sodium hyaluronate hydrogel injection is limited by its relatively low fluidity, short-term retention, and insufficient bioactive ingredients, so it is necessary to develop an advanced healing-promoting hydrogel. The modulation of the microenvironment by Lactobacillus presents a bioactive component that can facilitate the regeneration of the functional layer. Our study introduces a multifunctional Lactobacillus-loaded poly(N-isopropylacrylamide)-grafted bacterial cellulose (BC-g-PN@L) hydrogel designed with superior injectability and in situ stability. At 25 °C (room temperature), a uniform distribution is achieved with a low injection pressure of only 7.90 kPa. At 37 °C (body temperature), the BC-g-PN@L hydrogel forms a robust three-dimensional nanonetwork, providing space and substance exchange channels for Lactobacillus to maintain its viability and bioactivity. Enhanced by the hydrophobic isopropyl groups in poly(N-isopropylacrylamide) side chains and the rigid bacterial cellulose substrates, the BC-g-PN@L hydrogel exhibits prolonged retention properties in the uterine cavity, persisting for over 21 days. These attributes endow the BC-g-PN@L hydrogel with versatile pro-healing capacity and microenvironment modulation in a rat model of endometrial injury. Our BC-g-PN@L hydrogel promotes the development of advanced injectable hydrogels to facilitate both histological and functional repair of the injured endometrium.