Exosomes derived from mucoperiosteum Krt14+Ctsk+ cells promote bone regeneration by coupling enhanced osteogenesis and angiogenesis†

Repair of large bone defects is a sophisticated physiological process involving the meticulous orchestration of cell activation, proliferation, and differentiation. Cellular interactions between different cell types are paramount for successful bone regeneration, making it a challenging yet fascinating area of research and clinical practice. With increasing evidence underscoring the essential role of exosomes in facilitating intercellular and cell–microenvironment communication, they have emerged as an encouraging therapeutic strategy to promote bone repair due to their non-immunogenicity, diverse sources, and potent bioactivity. In this study, we characterized a distinctive population of Krt14⁺Ctsk⁺ cells from the orbital mucoperiosteum. In vitro experiments confirmed that exosomes from Krt14⁺Ctsk⁺ cells dramatically boosted the capacities of human umbilical vein endothelial cells (HUVECs) to proliferate, migrate, and induce angiogenesis. Additionally, the exosomes notably elevated the expression of osteogenic markers, thereby indicating their potential to augment osteogenic capabilities. Furthermore, in vivo experiments utilizing a rat calvarial defect model verified that exosome-loaded sodium alginate (SA) hydrogels accelerated local vascularized bone regeneration within the defective regions. Collectively, these findings suggest that exosomes secreted by Krt14⁺Ctsk⁺ cells offer an innovative method to accelerate bone repair via coupling enhanced osteogenesis and angiogenesis, highlighting the therapeutic potential in bone repair.