Engineering Mesenchymal Stem Cells with Antioxidant Catalase‐Loaded Metal–Organic Frameworks for Targeted Spinal Cord Injury Therapy

Abstract Spinal cord injury (SCI) therapy is challenging because of the associated irreversible neurological deficits. These deficits are caused by primary damage and secondary pathological processes such as oxidative stress and inflammation. Although mesenchymal stem cells (MSC) demonstrate potential in SCI treatment by promoting tissue repair and neuroprotection, the high reactive oxygen species (ROS) levels in the SCI microenvironment compromise their therapeutic efficacy. In this study, an MSC‐based cell–drug conjugate (CDC) system is developed by conjugating catalase (CAT)‐loaded metal–organic frameworks (MOF) to MSC, generating a C@M‐MSC platform. The C@M‐MSC system maintains MSC viability, preserves stemness, and mitigates ROS‐induced cellular damage. Furthermore, C@M‐MSC substantially modulates the inflammatory microenvironment by reducing inflammatory cytokine production and shifting microglial polarization toward the anti‐inflammatory M2 phenotype. In vivo studies confirm the targeted accumulation of C@M‐MSC in SCI lesions. This accumulation improves motor functioning, bladder control, and neuronal recovery. Thus, the C@M‐MSC system is a versatile therapeutic strategy that mitigates oxidative stress and enhances tissue repair, offering potential applications beyond SCI. It offers a foundation for broader clinical applications in regenerative medicine and can be integrated with other therapeutic strategies.