# Tissue Engineering of Immuno-Universal Cartilage Implants for Temporomandibular Joint Disc Regeneration

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $159,583

## Abstract

PROJECT SUMMARY
Temporomandibular joint (TMJ) disc degeneration and perforation are the leading causes of debilitating TMJ
disorders in people, while current treatments remain palliative at best. Novel tissue-engineering methods using
allogeneic chondrocytes can produce tissue akin to native in terms of biological and mechanical properties.
Little attention, however, has been given to the immunological aspects of the engineered tissue-recipient
interface. Understanding and defining key parameters that affect this interface are critical in the rapidly
developing field of tissue-engineering and TMJ disc regeneration.
 MHC class I compatibility is one of the major parameters defining acceptance of the tissue implant.
Chondrocytes constitutively express MHC I and thus can be identified as non-self and subsequently destroyed
by CD8 cytotoxic T cells. The latter premise challenges the conventional concept of immunoprivileged status of
cartilage tissue. Because MHC compatibility in tissue transplantation has not been explored in the context of
TMJ or its disc, our first aim will determine the relevance of MHC class I matching in TMJ disc repair using
allogenic cell-sourced tissue-engineered cartilage. We postulate that tissue-engineered constructs sourced
from MHC I-matched chondrocytes will have better long-term outcomes in the restoration of TMJ disc defects
as compared to constructs sourced from mismatched chondrocytes. Further, by dissecting the type of host
inflammatory response towards TE cartilage constructs in MHC I matched versus mismatched minipig
recipients, we will determine if the type of immune response can predict long-term outcomes of implantation in
the TMJ disc.
 MHC I silencing or knockout has not been attempted in primary chondrocytes but was achieved
successfully in other types of primary cells. Our specific aim two will generate MHC I-null primary chondrocytes
by knocking out the beta 2 macroglobulin gene using CRISPR/Cas9. We hypothesize that allogeneic
lymphocyte proliferation will be decreased in coculture with MHC I-null chondrocytes as opposed to WT
chondrocytes and that mechanically robust and biologically functional implants can be manufactured from
MHC I-null chondrocytes. If successful, this strategy will provide a novel platform for the manufacturing of
immunouniversal TMJ cartilage implants.
 We propose to carry out the proposed experiments in the minipig animal model, which is a well-
established large animal model for translational studies of human TMJ. Our team has ample experience and
expertise in working with this model. In summary, this project will deliver essential information on the
immunology of the TMJ compartment and will boost the clinical translation of regenerative modalities of the
TMJ disc.

## Key facts

- **NIH application ID:** 10590543
- **Project number:** 1R03DE030900-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Natalia Vapniarsky Arzi
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $159,583
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10590543

## Citation

> US National Institutes of Health, RePORTER application 10590543, Tissue Engineering of Immuno-Universal Cartilage Implants for Temporomandibular Joint Disc Regeneration (1R03DE030900-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10590543. Licensed CC0.

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