Programmable Macrophage Mimics for Inflammatory Meniscus Regeneration via Nanotherapy.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Meniscal injuries are common in the knee joint. Minor meniscal injuries usually respond well to conservative treatment, while severe cases often require complete meniscal replacement. Meniscal injuries cause inflammatory responses that importantly hinder meniscal tissue regeneration. Despite ongoing advances in research, considerable breakthroughs in meniscal regeneration remain out of reach. This study introduces programmable macrophage mimics (PMMs), which enable sequential regulation from anti-inflammatory responses to meniscal fibrocartilage regeneration. PMMs were prepared by encapsulating the transforming growth factor-β3 and insulin-like growth factor-1 growth factors within mesoporous silica nanoparticles modified with branched polyethyleneimine via disulfide bonding. This design allows the initial adsorption of proinflammatory cytokines followed by the controlled release of growth factors that promote adipose-derived stem cell (ADSC) differentiation into fibrochondrocytes. The PMMs were integrated into meniscus-specific acellular matrix hydrogels (mGC), which provided suitable mechanical properties critical for effective regeneration. In rabbit osteoarthritis models, ADSC-loaded PMMs@mGC hydrogels showed marked fibrocartilage regeneration. Additionally, the team developed an advanced biofabrication approach that combines a 3-dimensionally printed polycaprolactone frame

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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