GRANT RECIPIENTS

Dr. Shyam Prasad Aravindaksha – University of Detroit Mercy School of Dentistry

Abstract:
The aim of this study was to evaluate by histology and CBCT scans during a 6-month period, the efficacy of a Equimatrix®/Mucograft® placed in human extraction sockets in the maintenance of alveolar ridge.

A case controlled study design is adopted. Patients who will be having extraction of any tooth including surgical extraction but not due to any periodontal reasons are selected. Informed Consent of the patient will be taken for the procedure and all the effects and possibilities will be explained to the patients. Extraction will be done and scaffold material (Equimatrix®) will be placed inside the socket with a barrier material (Mucograft®). Sockets with the scaffold will be the variable studied and the sockets without scaffold placed inside the sockets will be the control group. An preoperative CBCT will be taken. A second CBCT will be taken following the same technique after six months.

This study will determine firstly whether the scaffold allows for bone regeneration in human alveolar sockets in the normal time and secondly whether it would help to preserve alveolar bone height as compared to cases without scaffold. Consent of the selected patient will be taken for the procedure. Extraction will be done and scaffold material will be placed inside the socket. Socket with the scaffold will be our cases and the socket without scaffold will be the control group in multiple extraction cases. Radiographic assessment will be done to assess bone regeneration
at the prescribed pre-extraction stage and at the 6-month (from initial extraction) implant planning stage as in usual clinical practice. Assessment of the bony architecture is made with from the CBCT taken and comparison will be made with the control cases. Core biopsies are taken from the grafted and non-grafted site. The following are the criteria for selecting the patients.

Sharon Aronovich, DMD – University of Michigan

Abstract:
Recently, several investigations revealed the potential for fluorapatite (FA) crystals to act as a bioactive implant coating material. In vitro, FA coating of etched metal surfaces stimulates the osteoinduction of stem cells to differentiate, express osteocalcin, and mineralize. When allowed to interact with cultured human dental pulp stem cells (DPSCs), the FA-coated polycaprolactone nanofiber scaffold (PCL) shows a unique ability to upregulate the expression of osteogenic molecules, increased alkaline phosphatase activity and osteocalcin expression that is not present when DPSCs are grown on PCL alone. In this study, an FA-coated PCL scaffold will be tested in vivo.

The goal of this study is to assess the osteoinductive capabilities of an FA-coated PCL membrane in a critical size calvarial defect in rats.

Eric J. Granquist, D.M.D., M.D. – University of Pennsylvania

Abstract:
My collaborator, Dr. Winkelstein, and I have developed a preclinical model in the rat that mechanically induces histologic evidence of temporomandibular joint degeneration, along with protocols to evaluate microCT imaging of the mandibular condyle and fossa. We are currently using our model of TMJ arthritis to study more precisely the ability of biologic imaging modalities to detect active disease through noninvasive imaging techniques. Specifically, we are interested in the ability of the biomarker 18F-Flouride to detect active degenerative disease in the TMJ along with its utility as a prognostic indicator of continued disease progression. This radioisotope localizes to areas of bone with increased metabolic activity and bone turnover. Utilizing positron emission tomography (PET) and co-registering with a microCT scan (PET/CT) allows for precise anatomic imaging of active metabolic processes. This imaging modality has the potential to function as a marker of disease progression. Current structural imaging modalities are only able to image evidence of prior tissue injury and cannot reliably detect active inflammation in the temporomandibular joint. The goals of tissue regenerative techniques are to allow for the reconstitution of lost anatomy and the reestablishment of function. Regenerative grafts placed in the area of active disease, particularly active inflammation, are likely to undergo similar tissue loss and degeneration as the native tissue. Methods: Via an IACUC approved injury model, female Holtzman rats undergo sustained mechanical loading of the TMJ via a pulley device. The mechanical pulley allows for varied newton loads enabling tunable degrees of joint injury under general anesthesia. Animals are loaded for 1 hour per day for 7 days. Imaging is performed under general anesthesia. An IV is placed in the dorsal tail vain and the radioisotope is administered. The mandible is placed in a fixed position and a microCT and positron emission tomography images are obtained. These images are then co-registered, allowing for anatomic localization of the PET uptake. The region of interest is identified and a standard uptake value (SUV) is calculated.

Umadevi Kandalam, Ph. D – Nova Southeaster University

Abstract:
Bone loss in craniofacial region due to traumatic events and congenital abnormalities and diseases have been conventionally repaired using autografts and allografts. While autografts have risk of donor site morbidity, use of allografts have potential threat of infections. Tissue engineering techniques emerged as a viable option to treat the bony defects. In bone tissue engineering techniques, growth factors have significantly role in inducing bone formation. Bone morphogenetic proteins (BMPs) are a family of osteoinductive proteins that promote differentiation of mesenchymal stem cells into osteoblasts. While BMP2 is known as potent osteoinductive growth factor, its short biological half- life and localized actions and rapid clearance during clinical administration warrants the use of optimal dose with sustained release. The goal of this study is to establish an optimal dose of BMP2and explore suitable method for its sustained release system. RGD peptide alginates are new class of alginates that can promote cell survival and release growth factor. The mild gelation of alginates under appropriate conditions enables entrap cells and growth factors. Our hypothesis is BMP2 entrapped in RGD alginates can enhance the ostegenic differentiation of mesenchymal stem cells. We intend to use gingival derived stem cells that are simple to isolate by minimally invasive methods and are equipotent in their ability to differentiate into osteogenic cells as those derived from bone marrow. The project has two specific aims 1) to establish optimal dose of BMP2. Various doses (50-200 ng/mL) of BMP2 will be added to alginate solution and ionically crosslinked with calcium chloride to form the beads and they will be exposed to the monolayer cell cultures for one week. The ostegenic potential of HGMSCS will be measured for various osteogenic markers using quantitative PCR method. 2) the established conditions will be used and further differentiation will be monitored and measured at 2 and 3 weeks’ time intervals. The outcome of the project will provide insight for the optimal use of BMP2.

Chan Park, DDS, MD – UOP/Alameda Health – Highland Hospital

Abstract:
Defects of hard tissue in maxillofacial region are still difficult reconstruct without creating morbidity to the patient.

Our goal is to design and validate an innovative tissue engineering technique yielding functionally and cosmetically satisfactory results.

The basic form of an implant is a thin-walled cylinder (tube) that can be fixed to proximal and distal bone fragments. It will be prepared:

1. Cone beam computed tomography (CBCT) image data of the defect are transformed and used to guide a 3D printer that will print a 3D polylactate resorbable correctly shaped cylindrical implant with porous walls (pore size at least 200 μm) and empty core.
2. The pores of the wall are infiltrated with autologous mesenchymal stem cells (MSC) suspended in fibrin with or without platelets. The MSC will be isolated from dental pulp, gingival submucosa or bone marrow aspirate and expanded in culture before the implantation.
3. The space inside the cylinder will be filled with fibrin mixed with platelets, PBMC or SDF1 that will attract MSC and angiogenic cells migrating from the scaffold’s walls and surrounding tissues into the core of the implant. Angiogenic cells will differentiate into capillaries and continued blood supply will support also homing of stromal cells released from bone marrow.

Initially, biological mechanisms of vascularization of the implant will be tested in a flat scaffold placed into a rat calvaria defect. If successful with a rat model, a rabbit large mandibular defect will be repaired with a cylindrical implant and conditions needed for osteogenesis in the implant will be analyzed. Histological, immunocytochemical and migration assay techniques will be utilized to follow dynamics of angiogenesis during the first year and dynamics of bone regeneration, vascularization and mineralization during the second year. The test implants will be compared with appropriate controls. Migration tests of the same MSC will be performed in vitro.