156S Proceedings of the NASS 22nd Annual Meeting / The Spine Journal 7 (2007) 1S–163S

CONCLUSIONS: While the rate of device-related complications for both

groups of anterior cervical patients was low, ACDF had more second

surgical procedures requiring supplemental fixation than the BRYAN Cer-

vical Disc, which by its design could not have a non-union or pending

non-union. In regard to all other complications, the two types of anterior

cervical surgery devices used in this study were found comparable and

not statistically different.

FDA DEVICE/DRUG STATUS: Bryan cervical disc: Investigational/ Not

approved; Cervical plate: Approved for this indication.

doi: 10.1016/j.spinee.2007.07.368

P159. Nell-1 Enhances Bone Formation in Rat and Sheep Spinal

Fusion Models

Steven Lu, MD1, Julie Whang, DDS1, Chia Soo, MD1, Xinli Zhang,

MD,PhD1, Tara Aghaloo1, Ahmet Alanay, MD2, Antonia Napoli2,

Benjamin Wu3, Shelby Hiles, BS1, Simon Turner, BVSC4, Kang Ting, DMD,

DMSC1, Jeffrey Wang, MD5; 1UCLA Dept of Craniofacial Research, Los

Angeles, CA, USA; 2UCLA Dept of Orthopedics, Los Angeles, CA, USA;3UCLA Dept of Bioengineering, Los Angeles, CA, USA; 4Colorado State

University - Dept of Veterinary Sciences, CO, USA; 5UCLA Dept of

Orthopedics, Santa Monica, CA, USA

BACKGROUND CONTEXT: Osteogenic growth factors such as bone

morphogenic proteins (BMPs) are increasingly being used as bone graft ex-

tenders to enhance the success rate of spinal fusion. However, many of them

have extended roles in cell line growth outside of bone formation. BMP2 and

BMP7, approved for use in humans, have been associated with adverse reac-

tions such as local inflammation, ectopic bone formation, and nerve compres-

sion. Researchers have been searching for alternative growth factors which

act specifically in the pathway of bone formation. Nell-1 [Nel-like mole-

cule-1; Nel (a protein strongly expressed in neural tissue encoding epidermal

growth factor like domain)] is a novel secretory molecule originally discov-

ered in the prematureyl fused sutures of patient with craniosynostosis. Nell-1

is directly regulated by Runx2, the master regulatory gene controlling bone

formation, and targets those cells committed to an osteochondrocytic lineage.

PURPOSE: The purpose of this experiment was to study the ability of

Nell-1 protein to successfully promote spinal fusion in a rat and sheep

model.

STUDY DESIGN/SETTING: In vivo study of Nell-1 protein in rats and

sheep.

METHODS: Two well understood spinal fusion models were used to

study the osteogenic properties of Nell-1. First, twelve athymic rats were

divided into three groups and implanted with sheep DBM alone, sheep

DBM with 5ug Nell-1 and sheep DBM with 10ug Nell-1. These rats were

sacrificed at 4 weeks. Manual palpation was used to determine spinal fu-

sion. Adjunctive radiographic and histological evidence was obtained to

study detailed bone formation. Secondly, due to the biomechanical similar-

ities of sheep and human spines, a pilot study was conducted consisting of

eight sheep. They were divided into four groups: sheep DBX alone, 0.3

mg/ml of Nell-1, 0.6 mg/ml of Nell-1, and 1.5 mg/ml of Nell-1. The ani-

mals were sacrificed at 3 months and computerized tomography in addition

to plain radiography was obtained to assess for bone formation.

RESULTS: Compared to rat spines containing sheep DBM alone which

had no fusion at 4 weeks, rats implanted with 5ug and 10ug of Nell-1 dis-

played fusion in 50% and 75% of the spines, respectively, as determined by

manual palpation. This difference was evident on radiographic studies by

microCT and Faxitron as well as histologically. MicroCT images verified

enhanced compact bone formation especially at sites adjacent to the trans-

verse processes. Stained histological sections demonstrated early integra-

tion of sheep DBM into bone remodeling and active bridging between

bone fragments. Our pilot sheep studies also confirmed accelerated bone

formation within sheep spines implanted with sheep DBM and Nell-1.

Two month CT images showed callus formation and intervertebral spacer

filling over control with sheep DBM alone, particularly at the dosage of

0.6mg/ml Nell-1.

CONCLUSIONS: Our experiments in rat and sheep spinal fusion demon-

strate enhancement of bone formation when Nell-1 protein is incorporated

into sheep DBM. Most importantly, Nell-1 acted specifically at the site of

implantation and did not exhibit ectopic bone production or swelling. This

is likely due to the inherent nature of Nell-1 as a downstream growth factor

of those cells already committed toward the osteochondrocytic pathway.

Therefore, Nell-1 may serve as an effective growth factor in spinal fusion

with less potential less adverse effects.

FDA DEVICE/DRUG STATUS: This abstract does not discuss or include

any applicable devices or drugs.

doi: 10.1016/j.spinee.2007.07.369

P160. An Investigational Study of Nucleus Pulposus Replacement

Using an In-situ Curable Polyurethane: An In Vivo Non-human

Primate Model

Bryan W. Cunningham, MSc1, Nianbin Hu, MD1, Helen J. Beatson, BSc2,

Paul C. McAfee, MD3, Hansen Yuan, MD4; 1St. Joseph Medical Center,

Towson, MD, USA; 2Baltimore, MD, USA; 3St. Joseph Hospital, Towson,

MD, USA; 4SUNY - Upstate Medical University, Syracuse, NY, USA

BACKGROUND CONTEXT: N/A.

PURPOSE: The current study was designed to evaluate the biodurability

and elicited histopathological response of an in situ curable polyurethane

nucleus pulposus replacement following long-term implantation in a pri-

mate model.

STUDY DESIGN/SETTING: N/A.

PATIENT SAMPLE: N/A.

OUTCOME MEASURES: MRI, Biomechanics and Histology.

METHODS: A total of 14 mature male baboons were randomized into

a six-month (n57) and twelve-month (n57) postoperative time periods.

Each animal underwent a lateral transperitoneal surgical approach fol-

lowed by nucleotomy at the L3/4 and L5/6 levels. The L5/6 level was im-

planted with the DASCOR� device having an elastic modulus similar to

that of the natural disc. The L3/4 served as a surgical (nucleotomy) control

in each case. Post-mortem analysis included MRI assessment of implant

position and Modic Type endplate changes (0–III), multi-directional flex-

ibility testing, systemic histopathology and undecalcified histology.

RESULTS: All animals survived the procedure and postoperative interval

without significant peri-operative complication. Post-mortem MRI analysis

revealed Modic Type I changes in 5/7 nucleus replacement levels versus 0/7

in control levels, which were identified as Modic Type 0. For the twelve-

month group, Modic Type I changes were identified in 3/7 nucleus replace-

ment levels versus 0/7 in the respective control levels. Intervertebral hydra-

tion signals at the operative and control levels were markedly reduced at both

time intervals. Multidirectional flexibility testing indicated no difference in

axial rotation (pO0.05) for the six and twelve-month groups, when compar-

ing the two surgical motion segment groups and intact spine. Flexion-exten-

sion and lateral bending exhibited reduced segmental motion for the nucleus

replacement and operative control levels at six-months versus the non-oper-

ative intact spine (p!0.05). By twelve months, flexion-extension motion at

the nucleus replacement level was restored to intact condition (pO0.05).

Histopathologic analysis of the nucleus replacement treatments exhibited

increased densification of trabeculae along the endplate periphery, corrobo-

rating the Modic Type I changes observed radiographically. No change in

densification or endplate sclerosis was observed at the L3-L4 surgical control

levels. Histopathology of all local and systemic tissues demonstrated no

evidence of significant pathological changes.

CONCLUSIONS: Using a non-human primate model, the current study

investigated the in-vivo response to nucleus pulposus replacement follow-

ing nucleotomy. Modic Type I changes were observed to a greater extent at

the operative versus control levels, and these changes appeared to reduce

from the six-month to twelve-month intervals. The Modic changes

observed at the implanted sites are considered normal and have been docu-

mented in a number of in vivo non-human primate studies. Multidirec-

tional flexibility testing indicated restoration of segmental motion for the