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.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
Project #
Application #
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wan, Jason
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Irvine
Biomedical Engineering
Biomed Engr/Col Engr/Engr Sta
United States
Zip Code
Huwe, Le W; Brown, Wendy E; Hu, Jerry C et al. (2018) Characterization of costal cartilage and its suitability as a cell source for articular cartilage tissue engineering. J Tissue Eng Regen Med 12:1163-1176
Vapniarsky, Natalia; Huwe, Le W; Arzi, Boaz et al. (2018) Tissue engineering toward temporomandibular joint disc regeneration. Sci Transl Med 10:
Cissell, Derek D; Link, Jarrett M; Hu, Jerry C et al. (2017) A Modified Hydroxyproline Assay Based on Hydrochloric Acid in Ehrlich's Solution Accurately Measures Tissue Collagen Content. Tissue Eng Part C Methods 23:243-250
Lee, Jennifer K; Huwe, Le W; Paschos, Nikolaos et al. (2017) Tension stimulation drives tissue formation in scaffold-free systems. Nat Mater 16:864-873
Vapniarsky, Natalia; Aryaei, Ashkan; Arzi, Boaz et al. (2017) The Yucatan Minipig Temporomandibular Joint Disc Structure-Function Relationships Support Its Suitability for Human Comparative Studies. Tissue Eng Part C Methods 23:700-709
DuRaine, Grayson D; Brown, Wendy E; Hu, Jerry C et al. (2015) Emergence of scaffold-free approaches for tissue engineering musculoskeletal cartilages. Ann Biomed Eng 43:543-54
Makris, Eleftherios A; Gomoll, Andreas H; Malizos, Konstantinos N et al. (2015) Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol 11:21-34
Murphy, Meghan K; Masters, Taylor E; Hu, Jerry C et al. (2015) Engineering a fibrocartilage spectrum through modulation of aggregate redifferentiation. Cell Transplant 24:235-45
Lee, Jennifer K; Responte, Donald J; Cissell, Derek D et al. (2014) Clinical translation of stem cells: insight for cartilage therapies. Crit Rev Biotechnol 34:89-100
Murphy, M K; Arzi, B; Hu, J C et al. (2013) Tensile characterization of porcine temporomandibular joint disc attachments. J Dent Res 92:753-8

Showing the most recent 10 out of 41 publications