Enhanced Ear Cartilage Regeneration with Dual-Network LT-GelMA/F127DA Hydrogel Featuring Nanomicelle Integration

Tissue-engineered cartilage, supported by advancements in photo-cross-linkable hydrogels, offers a promising solution for the repair and regeneration of damaged cartilage in anatomically complex and mechanically demanding sites. Low-temperature soluble GelMA (LT-GelMA) remains in a liquid state at room temperature, allowing for easier handling; however, it has limitations in mechanical strength and structural stability. To address these limitations, we developed a novel dual-network hydrogel combining LT-GelMA with Pluronic F127-diacrylate (F127DA). The resulting hydrogel uniquely integrates the low-temperature solubility of LT-GelMA with the enhanced mechanical strength provided by photo-cross-linkable F127DA nanomicelles. Additionally, the hydrogel exhibits controlled swelling and biodegradation rates. In vitro studies revealed a significant increase in chondrocyte viability by day 7 in formulations with higher F127DA concentrations. In vivo, the hydrogel demonstrated superior neo-cartilage formation in a subcutaneous nude mouse model, as indicated by increased deposition of cartilage-specific extracellular matrix components at 4 and 8 weeks. In summary, we developed a hydrogel with fluidity at room temperature and enhanced mechanical performance. These results indicate that the LT-GelMA/F127DA hydrogel effectively addresses the current gaps in cartilage tissue engineering. The hydrogel's superior performance, especially in promoting cartilage regeneration, positions it as a promising alternative for reconstructive surgery, representing a significant improvement over existing cartilage repair strategies.