Application of Stem Cell-Derived Extracellular Vesicles in Craniomaxillofacial Bone Regeneration

The repair of craniofacial bone defects remains a significant challenge in regenerative medicine due to their unique embryonic origin (cranial neural crest cell-derived) and complex anatomical functions. To address the scarcity of autologous bone sources and the tumorigenic risks associated with traditional stem cell therapies, stem cell-derived extracellular vesicles (SC-EVs) offer a highly promising cell-free therapeutic strategy. However, a systematic summary of how to develop efficient EV-based treatments tailored to the specific osteogenic microenvironment of the craniofacial region is still lacking. This review systematically summarizes the current applications of SC-EVs in craniofacial bone tissue engineering. The article first focuses on mechanistic analysis, elucidating how EVs promote the repair of calvarial, alveolar, and jaw bones by delivering bioactive molecules (such as miRNAs and proteins) to activate osteogenic/angiogenic signaling pathways and modulate the inflammatory microenvironment. Finally, this paper reviews engineering modification strategies for SC-EVs, including donor cell pretreatment (hypoxia and inflammatory cytokine stimulation) and SC-EV drug loading/surface modification techniques, and explores the challenges and future prospects of SC-EVs in clinical applications.