Thermoresponsive Injectable Microsphere Glycopeptide Hydrogels for Remodeling Dynamic Cell Microenvironments

Hydrogel microspheres have attracted extensive attention as the key carriers for drug delivery and cell culture. The traditional microspheres are limited in their application in the regenerative medicine fields due to their closed surface structure and biological inertness. To this end, this study used polylactic acid and selenocysteine modified hyaluronic acid through microfluidic technology and a microsphere surface modification strategy to prepare a hydrogel porous microsphere with reactive oxygen species (ROS) responsive properties and achieved effective removal of ROS through Se–Se rupture. It was then incorporated into a glycopeptide hydrogel, cross-linked by polyglutamic acid and hyaluronic acid, incorporating poloxamer. The glycopeptide hydrogels/microspheres with temperature response characteristics were prepared to reconstruct the dynamic microenvironment required for the repair and regeneration of damaged tissues. The interaction between dynamic and static bonds in the hydrogel system gives the microsphere composite hydrogel excellent injectability, mechanical strength, structural stability, organizational adaptability, and biocompatibility. It can be used as a tissue implant material in the field of tissue regeneration and cell microenvironment reconstruction with a broad application potential.