Core Insights - The study highlights the role of M2 macrophage-derived migrasomes in enhancing fracture healing through the coordination of CXCL12/CXCR4 signaling and neutrophil-MMP-9/MSC-EphB2 pathways, providing a promising strategy for tissue engineering in fracture repair [3][7]. Group 1: Mechanisms of Action - M2 macrophage-derived migrasomes are found to be rich in CXCL12, which activates the CXCL12/CXCR4 signaling axis to promote the migration of mesenchymal stem cells (MSCs) [6]. - The study reveals that M2-migra regulates the expression of neutrophil-derived MMP-9, enhancing the expression of EphB2 receptors on MSCs, thereby promoting osteogenic differentiation and fracture healing [6][9]. - Compared to M2-exosomes, M2-migra exhibits superior MSC homing capabilities through a dual mechanism involving CXCL12/CXCR4 recruitment and neutrophil-MMP-9/MSC-EphB2 induced osteogenic differentiation [7][9]. Group 2: Experimental Findings - The research team isolated migrasomes and exosomes from polarized M2 and M1 macrophages and co-cultured them with MSCs to assess their effects on MSC migration [5]. - An injectable thermosensitive hydrogel was developed to first release migrasomes to recruit MSCs, followed by the delivery of BMP-2 to enhance osteogenic activity, resulting in accelerated bone healing in mouse models [9][10]. - The study suggests a new paradigm of using immune cell-derived vesicles as programmable delivery vehicles for recruiting and guiding endogenous repair cells, applicable not only for fracture healing but potentially for other tissue regeneration [9].