Temporomandibular joint (TMJ) disorders (TMD) represent the second most common musculoskeletal condition, resulting in pain and disability, costing the US economy $4 billion per year. TMD represent a spectrum of TMJ disc conditions, beginning with small (focal), partial-thickness (disc-thinning) lesions that eventually grow into large, full-thickness (perforation) defects. The overall objective of this competitive renewal is to treat TMJ lesions that span the spectrum of TMJ disc defect conditions via the use of scaffold-free tissue- engineering. Building on the successful healing of focal disc-thinning defects, demonstrated in the parent grant, we will expand the clinical indications that can be addressed by tissue-engineered TMJ disc implants. In the parent grant, we engineered and implanted TMJ-specific biomimetic tissues with 42% of native disc properties into disc-thinning defects 3mm in diameter in the minipig. Compared to empty controls, treatment with the scaffold-free implants healed TMJ focal disc-thinning defects by 1) inducing 4.4-times more complete defect closure and 2) forming 3.4-fold stiffer repair tissue. The osteoarthritis score of the untreated group was 3.0-fold of the implant-treated group. For this competitive renewal, using the minipig, indications will be broadened 1) from disc-thinning to perforation defects and 2) from focal defects to large defects, to culminate in 3) the healing of large perforation defects. The proposed study comprises three aims, each containing an in vitro phase to engineer tissues appropriate for the aim's indication, followed by a large animal study using the porcine model. The goal of Aim 1 is to heal focal (3mm dia.) perforation defects of the TMJ disc using tissue- engineered TMJ implants with improved functionality. The objective of Aim 2 is to heal large (6mm dia.) disc- thinning defects in the porcine model by tissue-engineering large implants formed with highly passaged costochondral cells. Knowhow developed from these aims will be translated to Aim 3 to tissue-engineer large, robust implants for the treatment of large perforation defects. With an estimated 9 million patients having perforations in the TMJ disc and many more with disc-thinning defects, successful completion of the proposed work will further the translation of tissue-engineering therapies for an important medical problem that is currently without satisfactory long-term solutions.

Public Health Relevance

Epidemiologically, over 80 million people in the U.S. have symptoms of temporomandibular joint (TMJ) disorders, with roughly 60 million people exhibiting defects in the TMJ disc. Disc defects begin as focal thinning that eventually grows into large perforations, with the number of people suffering from disc perforation estimated at 9 million. This proposal's public health relevance is in its potential to use tissue-engineered implants to address morbidity caused by disc-thinning and perforation defects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE015038-12
Application #
9595735
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wan, Jason
Project Start
2004-08-01
Project End
2023-05-31
Budget Start
2018-08-01
Budget End
2019-05-31
Support Year
12
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92617
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