Injectable Microspheres With Cartilage‐Like Structure Facilitate Inflammation Inhibition and Tissue Regeneration

Abstract The unique structure of cartilage tissue, characterized by a robust collagen fiber framework and a dynamic proteoglycan hydrogel filling, is crucial for maintaining biomechanical and biochemical homeostasis. Herein, a cartilage‐inspired microsphere with sponge framework and hydrogel filling (SponGel MS) is successfully prepared to restore cartilage homeostasis. Specifically, epigallocatechin gallate nanoparticles coated with MnO 2 (MnO 2 @EGCG) are first synthesized, which can scavenge H 2 O 2 and hydroxyl radicals. The formation of SponGel MS involves sequential fabrication of the sponge phase through cryogenic radical reaction and hydrogel phase via Schiff base reaction. The hydrogel phase can dynamically release MnO 2 @EGCG to inhibit inflammation and SDF‐1 to recruit stem cells. Porous sponge phase with favorable compressive performance and His‐Ala‐Val (HAV) peptide provides stable stem cell niches to regulate stem cell condensation, co‐assembly and chondrogenic differentiation. Animal experiments demonstrate that SponGel MS suppresses the expression of IL‐1β and collagen I, ultimately achieving cartilage regeneration. This study represents a novel strategy for constructing cartilage repair materials.