Injectable Liposome-Anchored Hydrogel Microspheres Promote Spinal Cord Injury Repair by Modulating the Inflammatory Microenvironment and Recruiting Endogenous Stem Cells

Early local inflammatory response following spinal cord injury (SCI) hinders achievement of satisfactory clinical outcomes because of surrounding bone marrow-derived mesenchymal stem cells (BMSCs) dysfunction and endogenous repair mechanisms inhibition. In this study, we develop a liposome-anchored hydrogel microsphere composite with dual functionality: modulating inflammation and promoting neural repair. Cationic liposomes modified with aldehyde groups (R-L), encapsulating traditional Chinese medicine monomer Rg1, are fabricated using thin-film dispersion method. These liposomes are subsequently combined with gelatin methacrylate (GelMA) microspheres loaded with stem cell chemoattractant SDF1α via a spontaneous Schiff base reaction and electrostatic adsorption, forming the composite R-L@S-GMs. Release assays reveal that Rg1 reaches a cumulative release of 74.8% by day 7, while SDF1α releases more gradually, reaching a comparable level by day 28. In vitro, R-L@S-GMs effectively induce macrophage polarization toward M2 phenotype, significantly enhance anti-inflammatory cytokine IL-10 secretion, and promote neuronal differentiation of recruited BMSCs. In vivo, local injection of R-L@S-GMs effectively suppresses local and systemic acute inflammatory responses, reduces scar formation, promotes angiogenesis and neuronal regeneration, and consequently improve hindlimb motor function. In conclusion, R-L@S-GMs developed in this study successfully reconcile early-phase inflammation control with late-stage neural repair, offering promising potential for minimally invasive therapies in SCI.