Abstract
Oral and craniofacial diseases represent a significant global public health concern, profoundly impacting patient quality of life and imposing a substantial socioeconomic burden. While cell-based, particularly stem cell-based, regenerative strategies have shown promise in addressing the limitations of conventional therapies, they are also constrained by inherent challenges associated with cell therapy. Instead of relying on whole cells, cell-derived nanovesicles (CDNs), which inherit diverse biological functions from their parent cells, have emerged as a promising frontier in regenerative medicine. CDNs play a pivotal role in restoring microenvironmental homeostasis and modulating inflammation, thereby promoting angiogenesis and osteogenesis to support effective tissue regeneration. Furthermore, the therapeutic efficacy of CDNs can be enhanced through cell pretreatment and bioengineering strategies, such as cargo loading and surface modification. Owing to their ability to penetrate biological barriers, exhibit prolonged circulation, and achieve tissue-specific targeting, CDNs represent an advantageous drug delivery platform. Indeed, the development of engineered CDNs and hybrid composite systems has yielded excellent therapeutic outcomes by enhancing the precision and efficiency of drug delivery. This review systematically categorizes four major classes of CDNs, including exosomes (Exos), exosome mimetics (EMs), cell membrane nanovesicles (mNVs), and apoptotic extracellular vesicles (ApoEVs), evaluating their roles in treating craniofacial bone defects, osteoporosis, periodontitis, and dentin-pulp complex regeneration. Finally, we highlight the clinical potential of CDN-based therapies and outline future research directions for their application in oral and craniofacial tissue regeneration.