Faculty Bibliography

Postoperative reossification is a common clinical correlate following surgery. It has been suggested that an underexpression of transforming growth factor-beta3 (TGF-beta3) may be related to craniosynostosis and postoperative reossification. Adding TGF-beta3 may delay reossification and improve postoperative growth. The present study was designed to test this hypothesis. Thirty 10-day-old New Zealand white rabbits with hereditary coronal suture synostosis were divided into three groups: (1) suturectomy controls (n = 14), (2) suturectomy treated with bovine serum albumin (n = 8), and (3) suturectomy treated with TGF-beta3 protein (n = 8). At 10 days of age, a 3-mm x 15-mm coronal suturectomy was performed, and serial three-dimensional (3D) computed tomography (CT) scans and cephalographs were taken at 10, 25, 42, and 84 days of age. Calvaria were harvested at 84 days of age for histomorphometric analysis. Mean differences were analyzed using a group by age analysis of variance. Analysis of the 3D CT scan data revealed that sites treated with TGF-beta3 had significantly (P < .05) greater defect areas and significantly (P < .05) greater intracranial volumes through 84 days of age compared with controls. Histomorphometry showed that sites treated with TGF-beta3 had patent suturectomy sites and significantly (P < .001) less new bone in the suturectomy site compared with controls. Serial radiograph data revealed significant (P < .05) differences in craniofacial growth from 25 to 84 days in TGF-beta3-treated rabbits compared with controls. Data show that TGF-beta3 administration delayed reossification and improved craniofacial growth in this rabbit model. These findings also suggest that this molecular-based therapy may have potential clinical use.

Over the past seven years, the Department of Pediatric Dentistry at New York University College of Dentistry (NYUCD) and the Advanced Practice: Pediatrics and the Pediatric Nurse Practitioner (PNP) program at New York University College of Nursing (NYUCN) have engaged in a program of formal educational activities with the specific goals of advancing interprofessional education, evidence-based practice, and interprofessional strategies to improve the oral-systemic health of infants and young children. Mentoring interprofessional students in all health care professions to collaboratively assess, analyze, and care-manage patients demands that faculty reflect on current practices and determine ways to enhance the curriculum to include evidence-based scholarly activities, opportunities for interprofessional education and practice, and interprofessional socialization. Through the processes of interprofessional education and practice, the pediatric nursing and dental faculty identified interprofessional performance and affective oral health core competencies for all dental and pediatric primary care providers. Students demonstrated achievement of interprofessional core competencies, after completing the interprofessional educational clinical practice activities at Head Start programs that included interprofessional evidence-based collaborative practice, case analyses, and presentations with scholarly discussions that explored ways to improve the oral health of diverse pediatric populations. The goal of improving the oral health of all children begins with interprofessional education that lays the foundations for interprofessional practice.

A combination of modified HIV-1 Tat (mTat) peptide and cationic lipids, FuGENE HD (FH), dramatically enhanced transfection efficiency across a range of cell lines when compared to mTat or FH alone (Biomaterials 35:1705-1715 2014). The efficiency of this Tat peptide combination was significantly higher than many commercial non-viral vectors. In this present study, we tested the feasibility of this non-viral vector, mTat/FH, in vivo using plasmid DNA encoding a luciferase gene. The results of the in vivo studies showed that animals administered mTat/FH/DNA intramuscularly had significantly higher and longer luciferase expression ( approximately 7 months) than those with mTat/DNA, FH/DNA, or DNA alone. Histological evaluation showed little immune response in the muscles, livers, and kidneys of mice administered with the mTat/FH. The combination of mTat with FH could significantly improve transfection efficiency, expanding the potential use of non-viral gene vectors in vivo.

Regenerative procedures using barrier membrane technology are presently well established in periodontal/endodontic surgery. The objective of this study was to compare the subsequent effects of the released platelet-derived growth factor (PDGF) and growth/differentiation factor 5 (GDF-5) from collagen membranes (CMs) on bone regeneration in vitro and in vivo. In vitro studies were conducted using MC3T3-E1 mouse preosteoblasts cultured with or without factors. Cell viability, cell proliferation, alkaline phosphatase (ALP) activity and bone marker gene expression were then measured. In vivo studies were conducted by placing CMs with low or high dose PDGF or GDF-5 in rat mandibular defects. At 4 weeks after surgery new bone formation was measured using muCT and histological analysis. The results of in vitro studies showed that CM/GDF-5 significantly increased ALP and cell proliferation activities without cytotoxicity in MC3T3-E1 cells when compared to CM/PDGF or CM alone. Gene expression analysis revealed that Runx2 and Osteocalcin were significantly increased in CM/GDF-5 compared to CM/PDGF or control. Quantitative and qualitative muCT and histological analysis for new bone formation revealed that although CM/PDGF significantly enhanced bone regeneration compared to CM alone or control, CM/GDF-5 significantly accelerated bone regeneration to an even greater extent than CM/PDGF. The results also showed that GDF-5 induced new bone formation in a dose-dependent manner. These results suggest that this strategy, using a CM carrying GDF-5, might lead to an improvement in the current clinical treatment of bone defects for periodontal and implant therapy.

Polyethylenimine (PEI), a cationic polymer, has been widely studied and shown great promise as an efficient gene delivery vehicle. Likewise, the HIV-1 Tat peptide, a cell-permeable peptide, has been successfully used for intracellular gene delivery. To improve the favorable properties of these two vectors, we combine PEI with the modified Tat peptide sequence bearing histidine and cysteine residues (mTat). In vitro mTat/PEI-mediated transfection was evaluated by luciferase expression plasmid in two cell types. mTat/PEI produced significant improvement ( approximately 5-fold) in transfection efficiency of both cell lines with little cytotoxicity when compared to mTat alone, PEI alone, or four commercial reagents. The particle size of mTat/PEI/DNA complex was significantly smaller than mTat or PEI alone, and it was correlated with higher transfection efficiency. Filipin III, an inhibitor of caveolae-mediated endocytosis, significantly inhibited mTat/PEI transfection. In contrast, chlorpromazine, an inhibitor of clathrin-mediated endocytosis, did not. This suggested caveolae-mediated endocytosis as the transfection mechanism. Furthermore, the results of in vivo studies showed that animals administered mTat/PEI/DNA intramuscularly had significantly higher and longer luciferase expression ( approximately 7 months) than those with mTat/DNA, PEI/DNA, or DNA alone, without any associated toxicity. The combination of mTat with PEI could significantly improve transfection efficiency, expanding the potential use as a non-viral gene vector both in vitro and in vivo.

Objectives: We evaluated the relationship between child dental anxiety and selected child and parental characteristics. Study design: Children and their parents were interviewed at the New York University, College of Dentistry, Pediatric Dentistry Clinic. The Children's Fear Survey Schedule - Dental Subscale (CFSS-DS) evaluated child self-reported anxiety; the Modified Dental Anxiety Scale (MDAS) measured self-reported parental anxiety when the parent received dental treatment. Results: Ninety-three children and their parents completed the questionnaires. Mean CFSS-DS scores were higher for girls than boys (32.5 vs. 26.3, p=0.003) and for children whose accompanying parents had MDAS scores of 11+ vs. <11 (32.8 vs. 26.6, p=0.001). There was little difference in mean CFSS-DS scores among those aged 6-10 yrs. vs. 11-14 yrs. (30.1 vs. 29.3). Significant correlations were found between CFSS-DS and both gender (Spearman's rho, rs=0.31) and MDAS scores (rs=0.33), but not between CFSS-DS and child age (rs=-0.05). Controlling simultaneously for gender, MDAS score and child age, a high CFSS-DS score (38+ vs. <38) was positively associated with girls (ORadj=3.76, 95% CI: 1.13-12.54) and an MDAS score of </=15 vs. <11 (ORadj=2.50, 0.73-8.54), but weakly and inversely associated with age (ORadj=0.80, 0.25-2.52). Conclusion: Child gender and parental anxiety are indicators of child dental anxiety.

Objective : Studies described in this paper were designed to test the hypothesis that an increase in nonviral, plasmid-encoded Tgf-beta3 production, localized to the rat posterior frontal suture, prevents programmed suture fusion. Design : We developed a gene delivery system based on a dense collagen gel to deliver nonviral plasmids that encode for Tgf-beta3. Studies were performed to test the ability of this system to rescue rat cranial suture fusion in vitro and in vivo. Immunohistochemical studies were conducted to characterize the possible mechanisms by which increased production and presence of Tgf-beta3 protein interferes with suture fusion. Results : Posterior frontal sutures in the Tgf-beta3 plasmid-treated group exhibited 77% to 85% less bony bridging than the collagen control and untreated groups after 15 days in culture. In animals treated with Tgf-beta3 plasmid or Tgf-beta3 protein, there was a significant reduction in suture fusion in the middle region of the posterior frontal sutures when compared with control groups. In this region the Tgf-beta3 plasmid-treated group revealed 70% to 75% less bony bridging than control groups in vivo. Conclusions : Collagen gel can be formulated to provide release of nonviral plasmid DNA that results in cell transfection and elevated Tgf-beta3 protein production. Tgf-beta3 is an important regulator of suture fusion, and an increase in plasmid-encoded Tgf-beta3 protein is effective in inhibiting programmed suture fusion in rats.

Abstract Objectives: Craniosynostosis affects 1 in 2,000-3,000 live births and may result in craniofacial and neural growth disturbances. Histological data have shown that thick collagenous bundles are present in the sutural ligament, which may tether the osteogenic fronts, resulting in premature fusion. The hormone relaxin has been shown to disrupt collagen fiber organization, possibly preventing craniosynostosis by relaxing the sutural ligament and allowing osteogenic fronts to separate normally and stay patent. This study tested this hypothesis in a rabbit model of delayed onset coronal suture synostosis. Methods: 18 New Zealand White rabbits with craniosynostosis were randomly assigned to three groups: Sham control, protein control (BSA), relaxin treatment. After initial diagnosis, sham surgery, BSA, or relaxin were delivered to the fusing coronal suture in a slow release (56 day) collagen vehicle. Longitudinal radiographs and body weights were collected at 10, 25, 42, and 84 days of age and sutures were harvested for histology. Results: Relaxin treated animals had more disorganized intra-suture content than control groups. These specimens also appeared to have relatively wider sutures ectocranially. There were no significant differences in relaxin treated animals for all craniofacial growth measures, or suture separation compared to controls. Conclusions: These data do not support our initial hypothesis that the use of relaxin may rescue sutures destined to undergo premature suture fusion. These findings suggest that collagen fiber arrangement may not be important for suture fusion. This protein therapy would not be clinically useful for craniosynostosis. Key Words: Relaxin, Craniosynostosis, Extracellular Matrix, Collagen Fibers, Cephalometrics

PURPOSE: The purpose of this study was to determine the quantity and quality of DNA extracted from a dental bite impression wafer immediately after impression and after 12 months of home storage. The authors' hypothesis was that the wafer would retain sufficient DNA with appropriate genetic markers to make an identification match. METHODS: Two impression wafers (Toothprints((R)) brand) were administered to 100 3- to 26-year-olds. A cotton swab was used as a control. DNA from wafers stored for 12 months at home were compared to DNA collected at time 0 and compared to swabs at specific sites to determine quality and accuracy. The amount of DNA captured and recovered was analyzed using MagAttract technology and a quantitative real-time polymerase chain reaction. Capillary gel electrophoresis was performed to determine the quality of the DNA profiles obtained from the wafers vs those generated from the swabs of each subject. RESULTS: Average DNA concentration was: 480 pg/muL (wafer at time 0); 392 pg/muL (wafer after 12 months kept by subjects); and 1,041 pg/muL (buccal swab). Sufficient DNA for human identification was recovered from all sets of wafers, producing clear DNA profiles and accurate matches to buccal swabs. No inhibitors were found that could interfere with DNA profiling. CONCLUSIONS: Toothprints(R) impression wafers can be useful for DNA collection and child identification. After 12 months, the wafer was still usable for DNA capture and identification match.