# Bioactive Scaffold for TMJ Disc Regeneration by Endogenous Stem/Progenitor Cells

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $689,540

## Abstract

Project summary
Temporomandibular joint disorders (TMJDs) are estimated to affect over 10 million Americans as per NIDCR.
Total 80 - 90% of symptomatic TMJDs patients have internal derangement (ID), also referred to as disc
displacement, which is highly associated with osteoarthritis (OA) that may necessitate surgical treatment.
Previous attempts to replace the TMJ disc with alloplastic and/or synthetic grafts have failed, resulting in further
joint degradation. Thus, regeneration of TMJ disc has recently emerged as an alternative approach to overcome
limitations of current treatments for TMJ disorders. In our preceding studies, we developed anatomically correct
3D-printed polycaprolactone (PCL) scaffolds with native-like anisotropic microfiber orientation. To engineer the
native-like heterogeneous fibrocartilage, connective tissue growth factor (CTGF; profibrogenic cue) and
transforming growth factor beta 3 (TGFβ3; chondrogenic cue) were spatially embedded in the scaffolds as
encapsulated in poly(lactic-co-glycolic acids) (PLGA) microspheres (μS). The spatiotemporal release of CTGF
and TGFβ3 guided recruitment of TMJ syMSCs, followed by spatially controlled fibrocartilaginous differentiation
toward regeneration of TMJ in rabbits and mini-pigs. Despite the promising in vivo outcome, our CTGF/TGFβ3
μS-embedded scaffolds encountered few outstanding translational challenges for TMJ discs regeneration,
including PLGA degradation-derived acidic environment, a notable interspecies variance in the in vivo
degradation rate of scaffolds, and potential side effect of over-physiological dose of growth factor. To address
these issues, here we propose to develop and validate a novel combination of pharmaceutical small molecules
to replace CTGF and TGFβ3 as incorporated in bioactive scaffolds, to refine the in vivo degradation rate as
balanced with de novo tissue formation through our advanced imaging modality, and then to promote
regeneration of TMJ discs in a pre-clinical large animal model. Our preliminary study identified novel small
molecules that are safe and highly efficient and specific for promoting fibrocartilaginous differentiation of TMJ-
derived syMSCs. We also achieved a precisely controlled delivery of the small molecules in 3D-printed TMJ disc
scaffolds by adopting a self-assembling multi-domain peptide (MDP) hydrogel as a delivery vehicle. We also
devised a highly efficient and reliable imaging modality that will enable to track in vivo scaffold degradation and
new tissue formation. We will perform a comprehensive comparative study between small molecules and
CTGF/TGFβ3 as control-delivered in our scaffolds regarding local/tissue pH change, cytotoxicity, degradation
and tissue formation in our TMJ disc engineering model in vitro. We will conduct a comprehensive in vivo study
to balance scaffold degradation with tissue regeneration. The degradation rate will be controlled by applying
surface micro-porosity, and in vivo tracking of scaffold degr...

## Key facts

- **NIH application ID:** 10450853
- **Project number:** 5R01DE029321-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Chang Hun Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $689,540
- **Award type:** 5
- **Project period:** 2020-08-11 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450853

## Citation

> US National Institutes of Health, RePORTER application 10450853, Bioactive Scaffold for TMJ Disc Regeneration by Endogenous Stem/Progenitor Cells (5R01DE029321-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10450853. Licensed CC0.

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