Dental Pulp Stem Cell-Derived Extracellular Vesicles Promote Rat Maxillofacial Bone Regeneration

Alisa E. Lee

Qunzhou Zhang

Anh D Le

Lee, Alisa E., Choi, James
Faculty / Advisor: Zhang, Qunzhou, Le, Anh, D
University of Pennsylvania School of Dental Medicine,Department of Oral & Maxillofacial Surgery/Pharmacology


There has been increasing enthusiasm for the potential application of dental pulp stem cells (DPSCs) in bone regeneration. Extracellular vesicles (EVs) produced by mesenchymal stem cells (MSCs) contribute to their therapeutic potency by facilitating angiogenesis, immune regulation, and tissue regeneration. Although the use of DPSCs holds a great promise, less is known about the effects of DPSC-derived EVs on bone regeneration in maxilla or mandible defects. Thus, we aim to study whether DPSC-derived EVs have osteo-inductive effects on bone regeneration in a critical-sized mandibular bone defect model in vivo.


A total of 24 Sprague Dawley rats (8-weeks-old, female) were randomly divided into four groups: (1) defect alone; (2) DPSC-EVs 100µg/rat; (3) Collagen membrane; (4) Collagen membrane + DPSC-EVs 100µg/rat. A stainless steel tissue punch was used to create a 3mm diameter circular defect with approximate depth of 2mm. Mandibles were harvested 6 weeks post-surgery and fixed in 10% formalin. Mandibles were scanned and three-dimensionally reconstructed using high resolution micro-CT. Area of residual defect, volume of regenerated bone, and bone density were measured using ImageJ and AnalyzePro Software. The preliminary data were evaluated with one-way ANOVA and two-tailed t test with GraphPad Software. P-value <0.05 was considered statistically significant.


DPSC-EV treated groups displayed increased signs of bone regenerative morphology compared to the control groups. Application of both collagen membrane and DPSC-EVs appears to promote bone regeneration. In the current experimental condition, we did not observe statistically significant effects of DPSC-EVs on jaw bone regeneration.


Our data suggest that DPSC-derived EVs possess potent osteo-inductive effects on jaw-bone regeneration in rats. As a good candidate source of MSCs due to their abundant availability, accessibility, rapid proliferation, and osteogenic propensity, the use of DPSC-derived EV products may provide a safe and effective approach for craniofacial bone regeneration.