research registry and repository for the evaluation of

Research Registry and Repository for the Evaluation of Temporomandibular Joint Implants

Contractor: Dr. James Fricton, School of Dentistry University of Minnesota

Research Team:Lois J. Kehl, DDS, PhDPatrick M. Gaffney, M.D. Ching-Chang Ko, DDS, Ph.D Walter Bowles DDS, MS Sandra Myers, DDSJohn Look, DDS, Ph.DJames Swift, DDS, MS

The purpose of the contract is to support the establishment and maintenance of a registry and repository of TMJ retrieved implants and biological materials. It is envisioned that the information gained by the registries and the repository will provide quality specimens to researchers investigating the mechanisms of TMJ implant failure and the biological response to these implants, including factors that may contribute to the development of chronic pain.

Challenges

•Collection of human tissue requires multiple regulatory steps•Collection of samples from remote sites•TMJ tissues are comprised of multiple tissue types that may require different processing protocols prior to archival•Remote site clinicians unaware of how to acquire and handle dry ice, liquid nitrogen•Cost of shipping frozen samples with sufficient dry ice to guarantee constant temp

Fig I. Status of recruitment of new cases over time in NIDCR’s TIRR compared to targets in original work plan

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100

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total # of new subjects

# of clinicians recruiting

Target for new subjects

total # of newsubjects

1 21 74 104 122 148 170 177 192 201

# of cliniciansrecruiting

0 5 4 9 14 16 17 19 22 38

Target for newsubjects

60 160 220

Qtr1-03

Qtr2-03

Qtr3-03

Qtr4-03

Qtr1-04

Qtr2-04

Qtr3-04

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Qtr1-05

Qtr2-05

Distribution of Gender and Age in database

Age Histogram

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60

10 20 30 40 50 60 70 80 More

Age

Fre

qu

ency

Female 182 90.55%Male 19 9.45%Total 201 100.00%

Quality Control

•Anatomical gross characterization

•Pathology report

•Hemotoxylin & eosin histologic stains

•Documentation of time from tissue removal in O.R. to archival (i.e. fixation, snap freezing)

•Analysis of Genomic DNA from Peripheral Blood to define common HLA DR haplotypes

•Development of protocols to determine appropriate antibody concentrations to identify substance P positive nerve fibers in TMJ implant tissues .

•Measurement of IL-1β/ΙL-6 levels in the saliva of TMJD patients•Spot-testing of specimens using anatomical, biochemical, and molecular biological methods (i.e. PCR)

Salivary IL-1β/ΙL-6 Levels Increased in TMD patients

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IL-1

β (p

g/m

l)

Control TMD

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n=20; p=0.011

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4 0

IL-6

(pg/m

l)

C o n tr o l T M D

*

n=17; p=0.05

Estimated HLA Haplotypes

The leftmost column is the subject ID number. The next two columns are the 3 marker haplotypes (one haplotype for each haploid strand of DNA) determined by 3 marker PCR assay. The two columns on the right represent the HLA-DR type predicted by the assay.

Contain Substance P in Human Intervertebral Disc

PGP9.5 Substance P

Immunohistochemistry of a single nerve fiber for protein gene product 9.5 (PGP 9.5) and substance P. PGP 9.5 is a non-selective marker for nerve fibers that labels sensory, motor, and autonomic nerve fibers. In this study the PGP 9.5 was used to demonstrate the patterns of innervation in these tissues. Double-stained with substance P was used to identify the subset of PGP9.5 positive nerve fibers that are C polymodal nociceptors (these fibers only transmit pain) which are known to express substance P.

Patient Recruitment Plan

• Direct recruitment of TMJ Surgeons and TMJ Orofacial Pain Clinicians at national meetings

• Provide data collection support for TMJ Implant manufacturers as required by FDA

• Communicate with and support TMJ advocacy groups

• Recruitment and education through Web site• National publicity campaign• FDA Initiatives including a Patient Electronic

Record for Device Safety proposal