A microneedle platform Co-encapsulating chondral organoids and PpIX for spatiotemporally orchestrated tumor ablation and osteochondral regeneration.

Tumor-derived osteochondral defects (OCDs) pose significant clinical challenges, necessitating integrated strategies for local tumor ablation while preserving the regenerative niche and enabling coordinated cartilage and subchondral bone repair. Herein, we introduce a spatiotemporal microneedle (MN) platform that synergistically combines protoporphyrin IX (PpIX)-mediated sonodynamic therapy (SDT) for precise tumor eradication with chondral organoid (CO)-driven regeneration, leveraging differential mechanical cues for lineage-specific guidance. COs were engineered from bone marrow stem cells (BMSCs) via agarose microwells, yielding uniform aggregates that matured into hyaline-like phenotypes over 30 days and demonstrated superior resilience to oxidative stress compared to monolayer BMSCs, as evidenced by reduced ROS accumulation, preserved proliferation, and modulated inflammatory/antioxidant pathways. MN was fabricated from gelatin methacryloyl (GelMA) in a bilayer architecture: stiff, discrete 10 %GelMA tips to facilitate penetration and promote osteogenesis, and a softer, monolithic 5 %GelMA base to enhance chondrogenesis. PpIX and COs were co-encapsulated for targeted delivery.