Application of DPSC-Extracellular Vesicles in Bone Regeneration in Critical Mandibular Defects
Dr. James Choi is a resident in the Department of Oral and Maxillofacial Surgery at the Hospitals of University of Pennsylvania, Philadelphia, PA. He earned his DMD from University of Pennsylvania School of Dental Medicine and his MD from Perelman School of Medicine, University of Pennsylvania. His research interests include regenerative medicine, benign tumors and temporomandibular joint disorders.
Reconstruction of large craniofacial bone defects remains one of the major challenges in oral and maxillofacial surgery. The current craniofacial bone reconstructive modalities have significant limitations due to the limited availability of bone autografts, the donor site morbidity, cosmetic deformities, psychological effects, some degree of compromised oral functions, and decline in the quality of life of patients, thus representing an unmet clinical need. Therefore, novel approaches are imperatively needed to fabricate TE/RM products to meet the increasing clinical demand for reconstruction of large craniofacial bone defects. MSCs are multipotent and possess potent immunomodulatory and anti-inflammatory functions. DPSCs have been shown to possess osteogenic propensity and promote bone regeneration in various preclinical animal models. Accumulating evidence has shown that MSC-derived extracellular vesicles (EVs) possess regenerative potentials that are comparable to that conferred by MSCs per se. MSC-derived EVs may represent a novel cell-free platform for regeneration of both soft and hard tissues. In the present project, we propose two specific aims to test our hypothesis that DPSC-derived EVs have potent pro-osteogenic effects on jaw bone-derived mesenchymal stem cells (JB-MSCs) in vitro and osteo-inductive effects on jaw bone regeneration in a critical-sized mandibular bone defect model in rats. In Aim 1, we will explore the pro-osteogenic effect of DPSC-derived EVs on JB-MSCs in vitro. In Aim 2, we will determine the effect of DPSC-derived EVs on bone regeneration in a critical-sized mandibular defect model in rats, whereby DPSC-derived EVs will be mixed with collagen hydrogel which allows EVs to be slowly released. Accomplishment of the proposed study will provide substantial evidence that DPSC-derived EVs have significant potentials for fabricating cell-free TE/RM products for clinical application in reconstruction of large craniofacial bone defects.