Recipient Organization
TUFTS UNIVERSITY
200 WESTBORO ROAD
N. GRAFTON,MA 01536
Performing Department
CLINICAL SCIENCES
Non Technical Summary
7 million Americans suffer pain in the temporomandibular joint (i.e., the jaw joint) each year. The only long term non-invasive therapy for TMJ pain is non-steroidal anti-inflammatories, and they are less than 50 percent effective. The overall objective of this project is to develop a biologically absorbable polymer gel that may serve as a long-term minimally invasive therapy for treating pain in the temporomandibular joint associated with internal derangement and/or osteoarthritis (ID/OA).
Animal Health Component
50%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Goals / Objectives
Currently the NIH recommends that minimally invasive procedures be used to treat TMJ disorders (TMD). Despite this, there are few minimally invasive therapies available to TMD patients or the doctors who treat them. Biologically absorbable polymer gels are currently used to treat osteoarthritis of the knee. There has been some work performed that suggests these gels would provide a benefit to TMD patients, but the work is limited. If a product of this type were available, it would be one of the only long-term minimally invasive therapies available to TMD sufferers. The primary objective of this Phase I study is to determine the feasibility of using proprietary Crescent Innovations polymer gels to treat ID/OA TMD. This will lead to a Phase II study, which will determine the long-term efficacy and safety impact of the polymer gel treatment. Therefore, the Specific Aim is to: Determine if Crescent Innovations enhanced formulations, specifically catering to the unique
characteristics of the TM joint, provide superior clinical benefits in an animal model compared to a product used to treat OA of the knee.
Project Methods
Yorkshire pigs will have internal derangement / osteoarthritis (OA) surgically induced via a proven and used method. Group 1 will be an untreated control group. Group 2 will be treated with commercial products approved for treating OA of the knee. Group 3 will be treated using Crescent Innovations polymer gels. Injections will be made in the superior space of the treated joint, with saline injected in the contralateral joint. No injections will be made in Group 1. Differences in the tissues will be evaluated histologically and reported. Inter-group comparisons will then be made and multi-point ANOVA analysis will be performed. Success will be determined by a statistically significant P value. Six female Yorkshire pigs will be used in this study. Pigs in the groups undergoing surgery will be anesthetized, have gentle removal of the condylar surface, and a disk perforation done in the temporomandibular joint (TMJ) bilaterally to induce ID/OA. The groups will be as
follows: Group 1: Two pigs with surgery left untreated and used as a control. Group 2: Two pigs with surgery treated with commercial products approved for treating OA . Group 3: Two pigs with surgery treated with Crescent Innovations polymer gels. After an initial five day minimum acclimation and evaluation period, TMJ OA will be surgically induced bilaterally in six mature miniature pigs. HA will be intra-articularly injected into the left TMJs of all six pigs at 5, 10, 15, 20, and 25 days post-surgery. An equal volume of 0.9% sterile saline will be identically injected into the contralateral TMJs at the same time points. Three of the six pigs will be sacrificed at post-operative day (POD) 30 and 3 at POD 60. At that time the TMJs will be resected en bloc, radiographed and then stored in 10% formalin for subsequent decalcified histologic scoring. The physiological response to treatment will be assessed by means of daily physical evaluations, sequential radiographs and post-sacrifice
gross pathology and histology. Group 1 will be done first to assure the surgical procedure is successful at inducing OA.