Regional-Specific Decellularized Meniscus Extracellular Matrix Elastic Nanofiber Aerogels Regulate Meniscal Regeneration and Vascularization

The meniscus is a heterogeneous structure with spatial distribution of cells and vessels. Promoting meniscus healing remains challenging, especially in its avascular inner region. The ideal repair mode shall promote meniscus repair while maintaining local avascularity to prevent pathological changes from vascular invasion. Given the natural biochemical components of native meniscus, decellularized meniscus extracellular matrix (dmECM) shows promise for meniscus repair. Compared to homogeneous dmECM, regional-specific dmECM (RS-dmECM) appears to offer greater potential for constructing heterogeneous meniscus structures. Furthermore, there is currently no study on the effects of RS-dmECM on vascularization. Thus, RS-dmECM is prepared and found dmECM-Outer induced stem cells fibrochondrogenic differentiation, while dmECM-Inner induced the chondrogenic differentiation and inhibited angiogenesis through suppressing the peroxisome proliferators-activated receptors signaling pathway. Subsequently, regional-specific poly(lactic acid)/gelatin/dmECM elastic 3D nanofiber aerogels (PG-dmECM) are fabricated to repair meniscal avascular area defects in a rabbit model. The PG-Outer promotes meniscal fibrocartilage regeneration without a significant effect on vascular invasion. In contrast, the PG-Inner achieves meniscal cartilage regeneration and inhibits vascular invasion. Moreover, the compressive stress can reach 117 kPa, comparable to that of the avascular area. This PG-Inner may have the potential to promote meniscal cartilage regeneration and prevent pathological changes within the avascular area.