Osteo Science Foundation is proud to award research grants supporting residents and fellows in their effort to bring about new developments and treatment concepts more quickly at the clinical level. We are proud to be their partners and to help lead the way by funding initiatives that are making a true difference.
Grant submission periods for the Resident Research Award are April 1 – June, and October 1 – December 1. To start your application, click here.
The following are grant recipients of the Resident Research Award.
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.
Matthew T. Dailey is currently a PGY-2 resident in the 6 year M.D. Oral and Maxillofacial Surgery program at the University of Pittsburgh, Pittsburgh, PA. He obtained his DDS from the University of California, Los Angeles in 2013. Following graduation, Dr. Dailey entered the U.S. Air Force, completed a 1 year Advanced Education in General Dentistry residency and served an additional three years as a general dentist. Dr. Dailey’s research interests pertain to the use of dental pulp cells for craniofacial tissue engineering.
The goal of this study is to improve care for treating facial nerve injuries. Facial nerve defects may result from trauma, tumor ablation, and iatrogenic surgical injury. The current gold standard for peripheral nerve repair is to replace damaged tissue with an autograft, however cable grafting comes with slow or incomplete recovery of volitional movement. One factor contributing to these results is diminished Schwann cell support. Schwann cells provide neurotrophic factors (NTFs), which are known to promote neuron survival and axon extension. The dental pulp contains a population of stem/progenitor cells that are being investigated for several clinical applications. These dental pulp cells (DPCs) have been shown to endogenously express high levels of NTFs, a characteristic likely due to their neural crest origins. Cell sheets are a form of scaffold- free tissue engineering where cells proliferate to confluence and produce endogenous extracellular matrix (ECM) to form a layer of tissue that can be separated from the substrate. The ECM within these cell sheets would provide a substrate to enable axon growth and extension. We hypothesize that scaffold-free DPC sheets will 1- provide continuous delivery of NTFs to promote axon regeneration and 2- provide an ECM substrate that will support axon growth. In this study we are evaluating the functional effect of DPC sheets on neurons in vitro. Then we will be assembling our DPC sheets into solid, cylindrical constructs and using them to bridge segmental defects in the rat facial nerve. We will be determining the ability of these scaffold-free DPC constructs to restore motor nerve function in vivo. This project will provide foundational information on engineering a biological nerve conduit that provides both the trophic cues needed to promote axon regeneration and also and ECM that will support axon extension. The success of these studies will lead to a novel and feasible method for facial nerve regeneration.
Axially Vascularized 3D Printed Bone Flaps
Dr. Aslan Baradaran has over four years of experience as a researcher and editor in clinical journals. He received his Doctor of Medicine from Mashhad University of Medical Sciences and performed a period of fellowship in Plastic Surgery at The University of Milan.
He is a peer-reviewer for surgical journals and has more than 10 reviewed articles in the literature. He is currently doing a Master of Science in Experimental Surgery (Surgical Innovation) parallel to his residency program at the Oral and Maxillofacial Surgery Department at McGill University.
The current gold standard for repair of large facial and long bone defects is the use of bone and blood vessels harvested from another part of the body and transplanted to the area of the missing tissue. This creates significant donor site injury and is an inadequate anatomical match. Although there are great advances in 3D printing and tissue engineering, the ability to reliably grow a custom bone transplant with intact blood vessels is lacking. The work of our multi-disciplinary team has made great strides in being able to reproducibly generate a proof of principle of the first transplantable synthetically grown bone graft containing blood vessels created with a 3D printer.
The creation of a blood vessel network from a single vessel that is large enough (>1mm) to be transplanted as a ‘synthetic’ pedicle is not yet exploited clinically. This has been a fundamental impediment to regeneration of many tissues and could open several new reconstructive approaches. We hypothesize that nutrition and oxygenation from 3D printed transplantable blood vessel networks is sufficient to support new bone growth and to sustain it after transplant to a damaged jawbone.
Making 3D printed materials free of potentially dangerous and expensive growth factors, inducing new blood vessels and tissue engineering custom bones that are identical to the bones that are missing due to trauma or tumor surgery can revolutionize reconstructive surgery and provide significant improvements in patients’ lives.
This novel approach could open a new route in reconstructive surgery by redefining the limits of reconstruction that currently devastate the lives of many Head & Neck cancer and other trauma survivors. Although this is a preclinical project, it is designed to generate the information required for a clinical study of this new technique. The materials we use are FDA approved, less invasive than current techniques and readily translatable clinically.
Immediate Reconstruction of Mandibular Osteomyelitis Defects with rhBMP-2
Dr. Rodney Nishimoto is a Resident in the Department of Oral and Maxillofacial Surgery at the University of Washington, Seattle, WA. He earned his dental degree, valedictorian/summa cum laude, from Tufts University School of Dental Medicine, and medical degree from the University of Washington School of Medicine. His research interests pertain to dentoalveolar and maxillofacial reconstruction, dental implants and anesthesia. Dr. Nishimoto has received awards for his research including the American Association of Oral and Maxillofacial Surgeons (AAOMS) Resident Scientific Research Award and American Dental Society of Anesthesiology (ADSA) Scientific Essay Award.
Reconstruction of mandibular defects secondary to osteomyelitis presents a common, severe, and challenging problem for oral and maxillofacial surgeons. The off-label use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for mandibular bone regeneration has become an accepted and reliable method of reconstruction, however, active infection at the operative site is a contraindication to its use. As such, the clinical utility of rhBMP-2 for mandibular reconstruction in settings of active infection is unknown. Immediate reconstruction of mandibular osteomyelitis defects with rhBMP-2 may allow for improved patient outcomes and a faster return to function by obviating the need for a secondary reconstruction procedure and the morbidity associated with an autologous bone donor site. The purpose of this study will be to answer the following clinical question: Among patients with mandibular osteomyelitis treated with surgical debridement and immediate reconstruction with rhBMP-2, are there any significant histologic, histomorphometric or immunohistochemical differences between native and reconstructed bone after complete bone healing? The investigators hypothesize that after complete bone healing, defined as > 6-months post-reconstruction, there are no significant histologic, histomorphometric or immunohistochemical differences between native and reconstructed bone. The specific aims of this study will be to: 1) evaluate the histologic, histomorphometric and immunohistochemical features of mandibular bone regenerated with rhBMP-2 placed immediately into an area of active infection; and 2) compare the histologic, histomorphometric and immunohistochemical characteristics of regenerated bone with native bone. If mandibular bone reconstructed with rhBMP-2 in a site of active infection is found to be comparable to native bone, this could lead to expanded clinical indications for its use and a paradigm shift in the reconstruction of mandibular osteomyelitis defects.
CD90+ adipose-derived mesenchymal stem cells in an alveolar extraction socket model
Seth R. Brooks obtained his DDS from the University of Oklahoma College of Dentistry in 2014. Following graduation he completed a 1 year fellowship in Dental Anesthesia at the Indiana University School of Medicine prior to starting his residency in Oral and Maxillofacial Surgery at the University of Tennessee Medical Center in Knoxville.
The proposed study aims to evaluate the use of adult adipose-derived mesenchymal stem cells in bony tissue regeneration of extraction sockets in rats. Due to time, economical and restorative concerns associated with implant placement after dental extractions, bone regenerative therapies have garnered much attention in recent years. Current treatments, based on autologous and allogenic bone grafts, suffer from inherent challenges and hence, the ideal bone replacement therapy is yet to be found. In this proposal, a team of clinicians and researchers at UTMCK along with colleagues at UTCVM will test, in vitro, three scaffolds and determine which is the most biocompatible with adult mesenchymal stem cells. Subsequently we will test the in vivo efficiency of these scaffolds seeded with adult mesenchymal stem cells in a rat model of extraction socket defect. The long term goal is to translate this rat model to a large animal and ultimately make this strategy available to human medicine.
Third Molar Autotransplantation in the Pediatric Patient: Pilot Study
Alex Musser is a Chief Oral and Maxillofacial Surgery resident at the University of Cincinnati. He obtained his dental degree at the University of Louisville.
Lon Hinckley is currently a 3rd year oral and maxillofacial surgery resident at the University of Cincinnati Medical Center. He received his DDS degree from the University of Nebraska Medical Center College of Dentistry in 2016. His current research involves 3rd molar autotransplantation in pediatric patients.
Abstract: It is well documented in the literature that the autotransplantation of teeth is a clinically successful procedure given the right indications. Currently, the literature is lacking in studies specifically addressing immature third molar to first molar autotransplantation. Without transplant, the patient would need mechanical space maintenance after loss of the first molar. Although mechanical space maintenance is an option, these prosthetics are not esthetic, they do not preserve hard and soft tissue, they do not provide proprioception, and orthodontic treatment is most assuredly needed in the future. By providing esthetics, bone and soft tissue preservation, proprioception and reducing the need for possible future orthodontic treatment, autotransplantation is clearly advantageous to the patient long term. The goals of this study are to evaluate if this surgery is a successful option for replacement of a first molar, occlusal space and alveolar bone maintenance and to provide the background for future studies. Our central hypothesis is that autotransplantation of an immature third molar to a first molar recipient site (using a specifically defined pre-operative, surgical, and post-operative protocol with a multidisciplinary approach) will be a successful alternative to extraction with or without other forms of space maintenance.
Application of Dental Pulp Stem Cells (DPSCs) in Facial Nerve Regeneration
Dr. Pasha Shakoori is a PGY-3 resident in Oral and Maxillofacial Surgery at the Hospital of the University of Pennsylvania and the Children’s Hospital of Philadelphia. He completed dental school and a master’s degree at Columbia University in the City of New York with a focus on stem cell research and biomaterials. His research is in regeneration and applications of regenerative medicine in reconstructive surgery. He will be continuing his research while pursuing a Doctor of Science degree in biomaterials at the University of Pennsylvania while in residency. He is also active in professional organizations where he serves as an executive board member of the Resident Organization of the American Association of Oral and Maxillofacial Surgeons (ROAAOMS).
Dental pulp-derived stem cells (DPSCs) are capable of differentiating into different lineages of neural cells, thus rendering them a promising candidate seed cells for peripheral nerve regeneration. Tissue-engineered nerve conduits with DPSCs have been shown to promote facial nerve regeneration in rats. Our preliminary data showed that DPSCs can be differentiated into both Schwann and neuron-like cells when cultured under 2D- and small-intestine submucosa (SIS) membranes. Based on these findings, we hypothesize that DPSCs seeded on SIS-scaffolds could represent a promising alternative stem cell-based nerve wrap for facial nerve repair/regeneration. Our project aims to optimize the conditions to differentiate DPSCs into both Schwann and neuronal cells under 2D- and SIS 3D-culture conditions. Human DPSCs can be an excellent candidate for peripheral nerve regeneration due to its neural crest origin, sufficient availability, ready accessibility, non-invasive harvesting procedures, rapid proliferation, multipotent differentiation, and successful integration into host tissues with immunologic tolerance. In addition, in combination with tissue engineering technologies, these DPSCs can also serve as a superior seed cell source for the development of engineered nerve products that hold great promises for clinical application for peripheral nerve repair/regeneration.