# TMJ Disc Regeneration

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $550,201

## Abstract

Project Summary / Abstract
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.

## Key facts

- **NIH application ID:** 10165686
- **Project number:** 5R01DE015038-15
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Kyriacos A Athanasiou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $550,201
- **Award type:** 5
- **Project period:** 2004-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165686

## Citation

> US National Institutes of Health, RePORTER application 10165686, TMJ Disc Regeneration (5R01DE015038-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10165686. Licensed CC0.

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