# Tissue Engineered Total Disc Replacement in a Large Animal Model

> **NIH VA I01** · PHILADELPHIA VA MEDICAL CENTER · 2024 · —

## Abstract

Low back pain, which is most commonly caused by intervertebral disc degeneration, is the most common source
of chronic pain in veterans. Current clinical treatments for disc degeneration, including spinal fusion, are limited
in that they do not restore healthy disc structure or function. To overcome this limitation, our group has developed
a whole, tissue engineered endplate-modified disc-like angle ply structure (eDAPS) composed of engineered
annulus fibrosus, nucleus pulposus and endplate regions. To date, we have completed the long-term evaluation
of the eDAPS in a small animal model, in addition to short-term evaluation in a large animal, goat cervical disc
replacement model. The overarching goal of the current proposal is to generate in vitro and in vivo data to
motivate the first in man trials of this technology. We will achieve this translational goal via the following specific
aims: Specific Aim 1: Evaluate the long-term function of a tissue-engineered intervertebral disc replacement that
is subjected to physiologic loading in our large animal model. In this Aim, we will first establish the duration of
immobilization necessary for optimal long-term performance of the tissue engineered disc in vivo. We will then
develop and test a resorbable provisional fixation system to be utilized in conjunction with the engineered disc
implant, which will eliminate the need for a second surgery and increase the clinical translatability of our
technology. Specific Aim 2: Determine the ability of a tissue-engineered disc replacement to restore healthy
motion segment structure and function when implanted in a degenerative environment. In this Aim, we will induce
degeneration of the goat cervical intervertebral disc using our established model of chondroitinase ABC injection.
After degeneration has progressed for 12 weeks, a second surgery will be performed to implant the eDAPS with
the resorbable fixation system developed in Aim 1. Animals will be euthanized after 1 year of eDAPS
implantation. During this time, implant status will be tracked with serial radiographs and in vivo MRI. A custom
EMG and kinematic tracking system will be implemented to assess cervical spine muscle activation and range
of motion as objective measures of pain and function. At the 1 year study endpoint, eDAPS implants will be
compared to untreated, degenerative controls by analyzing the structural and function properties across the
whole motion segment (disc/implant, facet joints, neural structures) using a multiscale and multimodal approach.
Aim 3: Fabricate anatomical tissue-engineered discs from human cell sources. In Aim 3, we will evaluate the use
of different human mesenchymal cell sources for the seeding of the eDAPS constructs. Human bone marrow
derived stem cells will be utilized, in addition to AF-like and NP-like cells derived from human induced pluripotent
stem cells and compared to native disc tissue cells. The cell source yielding constructs with structure-function
p...

## Key facts

- **NIH application ID:** 10793585
- **Project number:** 5I01RX002274-08
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Robert L Mauck
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10793585

## Citation

> US National Institutes of Health, RePORTER application 10793585, Tissue Engineered Total Disc Replacement in a Large Animal Model (5I01RX002274-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10793585. Licensed CC0.

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