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Development of Drug Delivery Technology for Stem Cell Based TMJ Regeneration

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R42DE028215-02A1
Agency Tracking Number: R42DE028215
Amount: $1,494,885.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: NIDCR
Solicitation Number: PA19-270
Timeline
Solicitation Year: 2019
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-08-01
Award End Date (Contract End Date): 2022-07-31
Small Business Information
156 RALEIGH ST
Rochester, NY 14620-4148
United States
DUNS: 080949312
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 MO CHEN
 (585) 880-8768
 chenmo999@gmail.com
Business Contact
 MO CHEN
Phone: (585) 880-8768
Email: wntscientific@yahoo.com
Research Institution
 COLUMBIA UNIVERSITY
 
1700 BROADWAY
NEW YORK, NY 10019-5905
United States

 Nonprofit College or University
Abstract

1 ABSTRACT2 The temporomandibular joint (TMJ) is a complex joint system critical for dental occlusion, mastication,
3 respiration and speech. The TMJ is comprised of a network of muscles, ligaments, and a4 fibrocartilaginous disc and condyle. Temporomandibular disorders (TMDs) afflict over 10 million5 Americans at an annual cost of ~$4 billion, per the NIDCR. Degenerative types of TMDs, including6 TMJ osteoarthritis (OA), are debilitating, compromise quality of life, and causes permanent tissue7 loss. Current TMJ OA treatments are typically two-fold, involving either pain management or invasive8 surgeries, such as total joint replacements with high failure rates. There is a paucity of minimally9 invasive TMJ therapies that promote tissue regeneration.
10 Regenerative medicine promises the recreation functional tissue that is loss from disease. Thus
11 exploiting the regenerative capabilities of resident stem cells to repair TMJ may represent a minimally
12 invasive stem cell-based treatment for TMJ OA. We have identified fibrocartilage stem cells
13 (FCSCs) that reside in the TMJ condyle superficial zone. Transplanted FCSCs self-organize and
14 regenerate cartilage. Wnt/Catenin signaling promotes proliferation and inhibits chondrogenic
15 differentiation of FCSCs. However, over-active Wnt/Catenin deplete FCSCs and cause TMJ OA
16 in mice, rabbits and humans. These data suggest that inhibiting Wnt/Catenin in FCSCs may serve
17 as a stem cell-based therapeutic strategy for the treatment of TMJ OA. In fact, we showed that
18 blocking Wnt via weekly TMJ intra-articular injections of the Wnt inhibitor sclerostin ameliorated TMJ
19 OA in a rabbit TMJ injury model. However, a pharmacological drug delivery system for chairside,
20 sustained release sclerostin administration to human TMJ OA patients has not been defined.
21 Based on our preliminary data, we hypothesize that delivery of an injectable, sustained release
22 hyaluronic acid-sclerostin hydrogel will target resident TMJ fibrocartilage stem cells to regenerate
23 TMJ.PROJECT NARRATIVE
An innovative targeting treatment for TMJ osteoarthritis is being developed by collective effort
between Wnt Scientific LLC and TMJ Biology and Regenerative Medicine Laboratory at
Columbia University. The innovative treatment is to deliver recombinant sclerostin, a potent Wnt
signal inhibitor, in hyaluronic acid.

* Information listed above is at the time of submission. *

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