Local Recruitment of Autologous Stem Cells via a Targeting Microgel for Precise Cartilage Repair without Surgery

Abstract The treatment of advanced osteoarthritis (OA) remains clinically intractable due to the inability to regenerate multifocal cartilage defects, stemming from poor targeted recruitment of bone marrow‐derived mesenchymal stem cells (BMSCs) and the absence of a sustained chondrogenic microenvironment at the injury sites. In this work, an antibody‐mediated gelatin methacrylate‐based hydrogel microsphere modified by TGFβ‐affinity peptides (TRG microsphere) is developed, to precisely target and repair scattered cartilage injuries by only intraarticular injection without any surgical assistance. By leveraging the specific expression of type I collagen in OA cartilage lesions, the type I collagen antibodies anchoring on TRG's surface enable the specific and accurate targeting of the multiple injury areas that need regeneration. In the meantime, the TGFβ‐affinity peptides incorporated in the TRG microsphere can capture the endogenous TGFβ, a growth factor that can recruit BMSCs and promote their differentiation, to precisely induce the hyaline‐like cartilage regeneration locally. In a rat model of advanced OA, a single intra‐articular injection of TRG microspheres can repair scattered cartilage defects, restore glycosaminoglycan deposition, and alleviate joint dysfunction. This study proposes an injection‐based strategy that enables continuous recruitment of endogenous BMSCs for precise cartilage regeneration, eliminating complex invasive procedures and patient discomfort.