2013 AAO Annual Session Milo Hellman Research Award, Harry Sicher Research Award, Thomas
M. Graber Awards of Special Merit
The Milo Hellman Research Award, Harry Sicher Research Award and Thomas M. Graber Awards of
Special Merit lectures will be held on Monday, May 6 in Pennsylvania Convention Center Room 103 from
1:00pm-3:00pm. Continuing education credit is available for attending these lectures.
Milo Hellman Research Award
1:00pm-1:20pm
Skeletal Regeneration by Human Very Small Embryonic-Like (VSEL) Cells, A Potential Autogenous
Treatment for Craniofacial Maladies
Aaron M. Havens, DMD, MS
University of Michigan
Introduction: Craniofacial defects such as cleft palate pose a great challenge in bone regeneration. A
large unmet need exists to identify donor cells within the recipient that regenerate tissue without the
increased morbidity of a secondary harvest site. We need to develop effective therapies for the
regeneration of craniofacial region following trauma, infection, resection of neoplasms and repair of
congenital maladies. Human very small embryonic-like (hVSEL) cells are a rare cellular population found
in marrow and blood which express pluripotency markers and may be able to differentiate into cells from
all three germ lineages. Thus they are prime candidates for cells with the capacity to regenerate
craniofacial structures. The purpose of this study is to evaluate the ability of human VSEL cells to repair
a craniofacial wound within an animal. Methods: For this study, human VSELs were isolated from blood
by apheresis following granulocyte–colony-stimulating factor mobilization. The human cells were
implanted into cranial skeletal defects generated in SCID mice and allowed to heal for 3 months. Results:
At 3 months, analysis by µCT showed that a cell population containing human VSEL cells produced
significant mineralized tissue within the cranial defects compared to controls. Further confirmation that the
donor tissues had participated in tissue regeneration was obtained by identifying human specific
osteocalcin present in the peripheral blood of hVSEL cell recipient animals. Moreover, histologic studies
show significant bone formation of human origin along with well-organized human vascular, nerve and
collagenous structures able to support the newly formed bone. Conclusions: This study demonstrates
that hVSEL cells can generate human tissue within an animal; the first step toward advancing this
technology into clinical use with human patients. . Moreover, these studies lay the foundation for future
cell-based regenerative therapies for osseous and connective tissue disorders within humans such as
repairing craniofacial clefts and malformations.
Harry Sicher Research Award
1:20pm-1:40pm
Bony Adaptation after Expansion with Light-to-Moderate Continuous Forces
Collin D. Kraus, DDS, MS
Baylor College of Dentistry
Purpose: To evaluate the biological response of dentoalveolar bone to archwire expansion with light-tomoderate, continuous forces. Methods: Using a split-mouth experimental design, the right maxillary 2nd
premolars of seven adult male dogs were expanded for 9 weeks using passive, self-ligating brackets
(Damon Q) and two sequential arch wires (.016x.022" CuNiTi, followed by .019x.025" CuNiTi). Intraoral
and radiographic measurements were made to evaluate tooth movements and tipping associated with
expansion; archwire forces were measured using a Correx force gauge. Micro-computed tomography
was used to compare buccal bone height (BBH), total tooth height (TTH), total root height (TRH), and
buccal bone thickness (BBT). Bone formation was evaluated histologically using tetracycline and calcein
fluorescent labels and H&E stains. Results: Buccal expansion was produced by forces ranging between
73 and 178 grams. Compared to the control side, which showed no tooth movements, the experimental
2nd premolars were expanded 3.5 ±0.9 mm and tipped 15.8°. BBT was significantly thinner (0.2 mm) in
the coronal aspects and significantly thicker ( 0.9 mm) in the apical aspects over the mesial roots. The
tipping and expansion significantly (p<.05) reduced BBH (i.e. caused dehiscences) at the mesial (2.9
mm) and distal ( 1.2 mm) roots. Bony apposition occurred on the trailing edges of tooth movement, as
well as on leading edge of the 2nd premolar apices. Most important, the axial µ-CT slices and bone
histomorphometry demonstrated newly laid-down bone on the periosteal side of buccal cortical surface.
Ordered osteoblast aggregation was also evident on the periosteal surface of buccal bone, just cervical to
the apparent center of rotation of the tooth. Tooth and root heights showed no significant differences
between the experimental and control 2nd premolars. Conclusions: Buccal expansion using light-tomoderate continuous forces produced 3.5 mm of toot movement, uncontrolled tipping and bone
dehiscence, but no root resorption. Bone formation that occurred on the periosteal surfaces of cortical
bone indicates that apposition is possible on the leading edge of tooth movements.
Thomas M. Graber Awards of Special Merit
1:40pm-2:00pm
A Single Injection of Low Dose Recombinant Osteoprotegerin Protein Prevents Orthodontic Relapse after
Tooth Movement
Dylan A. Schneider, DDS, MS
University of Michigan
Introduction: Previous studies have shown that local injections of recombinant osteoprotegerin protein
(OPG-Fc) inhibit orthodontic tooth movement and relapse after tooth movement, but these studies
involved multiple injections at high dose levels and resulted in significant systemic exposure to the
protein. The goal of this study was to determine minimal dose levels required and the longevity of a
single dose of OPG-Fc on orthodontic relapse post-tooth movement, while also determining effects of
injected OPG-Fc on alveolar and long bone tissues. Materials and Methods: Rat maxillary molars were
moved with nickel-titanium springs and then allowed to relapse. Upon appliance removal, animals were
locally injected with a single dose of 0.1 mg/kg OPG-Fc, 1.0 mg/kg OPG-Fc, or phosphate buffered saline
(vehicle). Tooth movement and relapse measurements were made from stone casts. Alveolar tissues
were examined by histology. Micro-computed tomography was used to quantify changes in alveolar and
femur bone. Results: Injection of a single dose of 1.0 mg/kg OPG-Fc significantly inhibited molar relapse
for at least 24 days, when compared to vehicle injected animals. Incisor relapse was not inhibited by
injection with OPG-Fc. No significant differences in alveolar bone were seen between the OPG-Fc and
vehicle injected animals. Minimal differences in femur bone were seen between the OPG-Fc and vehicle
injected animals. Conclusions: A single, local injection of 1.0 mg/kg OPG-Fc substantially decreased
relapse when delivered immediately following orthodontic tooth movement. This dose level had minimal
effects on alveolar bone and on bones distant from the injection site. Together, these results indicate that
low doses of OPG-Fc can be injected locally to prevent orthodontic relapse with minimal systemic effects
on the skeleton.
2:00pm-2:20pm
Enhanced Longitudinal Miniscrew Implant Stability with the Local Application of Zoledronate
Cecilia Cuairan, DDS, MS
Baylor College of Dentistry
Purpose: The primary purposes of this study were to evaluate how locally delivered zoledronate affects
the 1) longitudinal stability of miniscrew implants (MSIs) and 2) healing of bone around MSIs. Methods:
Using a randomized split-mouth design, 60 unloaded MSIs (5 mm X 1.6 mm) were placed in skeletally
mature male foxhound-mixed-breed dogs. The MSIs were randomly assigned to bilateral pairs of pilot
holes (1.1 mm) that had been injected with either the bisphosphonate zoledronate (N=30 experimental) or
buffered saline (N=30 control). MSI stability was evaluated weekly for 8 weeks using resonance
frequency analyses (Osstell Mentor™). Micro-computed tomography (6 µm voxel size) was used to
determine the bone volume fractions of three layers of bone (6-to-24, 24-to-42, and 42-to-60 µm)
surrounding the MSIs. Results: Resonance frequency analysis showed that the control MSIs were
significantly (p<.05) less stable than the experimental MSIs. While there was little or no change in stability
over time for the zoledronate treated MSIs, the stability of the controls MSIs decreased over the first 4
weeks, increased through week 6 and then decreased again. The layer of bone closest to the MSI (6-to-
24 µm) showed significantly less (p<.05) bone than the 24-to-42 µm and 42-to-60 µm layers. After eight
weeks, there was significantly more cortical bone surrounding the control than experimental MSIs. In
contrast, there was significantly more trabecular bone surrounding the experimental than control MSIs.
Conclusion: A single, small, locally delivered dose of zoledronate maintained the stability of miniscrew
implants over time, due primarily to greater amounts of trabecular bone surrounding the MSIs, suggesting
that a pharmacological approach to MSI stability is feasible and that trabecular bone formation plays a
greater role in secondary stability than previously thought.
2:20pm-2:40pm
Real-Time Monitoring of the Growth of the Nasal Septal Cartilage and Nasofrontal Suture
Ayman Al Dayeh, BDS, MSD, PhD
University of Washington
Introduction: The nasal septum is thought to be a primary growth cartilage for the midface, and as such,
has been implicated in syndromes involving midfacial hypoplasia. However, this internal structure is very
difficult to study directly. Objectives: The aim of this study was to provide direct, continuous
measurements of the growth of the nasal septal cartilage and to compare these to similar measurements
of the nasofrontal suture in order to test (1) whether the growth of the cartilage leads to growth of the
suture, and (2) whether the growth of the septal cartilage is constant or episodic. Methods: Ten Hanford
minipigs were used. Linear displacement transducers were implanted surgically in the septal cartilage and
across the nasofrontal suture. Length measurements of the cartilage and suture were recorded
telemetrically each minute for a period of several days. Results: The growth rate of the nasal septal
cartilage (0.07 ± 0.03% length/hour) was significantly higher than that of the suture (0.03 ± 0.02%
length/hour) (p=0.004, 2 sample t-test). The growth of both structures was episodic with alternating
periods of growth (5-6/day) and periods of stasis or shrinkage. No diurnal variation in growth of the
cartilage was detected. Conclusions: These results are consistent with the notion that growth of the
septal cartilage might lead to growth of the nasofrontal suture. Growth of the midface is episodic rather
than constant.
2:40pm-3:00pm
Naturally Missing Teeth are Associated with rs10088218, an Ovarian Cancer Susceptibility Marker on
8q24: Link between Hypodontia and Ovarian Cancer?
Anna N. Vu, DMD, MS
University of Kentucky
Introduction: The aim of this nested case-control study was to determine the association between
naturally missing teeth (NMT) and SNP rs10088218 within an ovarian cancer susceptibility locus on
chromosome 8q24. Methods: DNA from 30 orthodontic patients with NMT and 80 controls was
examined for variation at rs10088218 using Taqman genotyping. Hardy-Weinberg Equilibrium testing
assessed genotyping quality, and logistic regression examined association. Results: More females had
NMT than males. Maxillary-lateral-incisors were most commonly affected by agenesis, followed by
mandibular-2nd-premolars and maxillary-2nd-premolars. With gender-adjustment, rs10088218 was
significantly associated with hypodontia (p=0.019) and generalized-NMT (p=0.021). Conclusions: After
adjusting for gender differences, each copy of the G-allele at rs10088218 conferred a 11.51-times higher
odds of having hypodontia and an 4.37-times higher odds of having generalized-NMT. Clinical
Implications: Future studies will need to examine the dual association of rs10088218 with both NMT and
EOC within a single population. If rs10088218 and/or other markers along with NMT status prove to be
better indicators of EOC risk than NMT status alone or a marker alone, then together they may
revolutionize dental referrals for EOC early detection, and provide a link between a developmental dental
finding and cancer susceptibility in other parts of the body.