# Tissue Engineered Total Disc Replacement in a Large Animal Model

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

## Abstract

Low back pain, which is commonly caused by intervertebral disc (IVD) 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 parent Merit Award will evaluate how these engineered
discs function in a degenerative model, as well as their maturation over longer implantation times and with
remobilization of the spinal motion segment. Despite the promise of these engineered implants, the
inflammatory responses within the eDAPs and their potential for modulating inflammatory biological processes
within the intervertebral disc have yet to be evaluated. Thus, the overarching goal of this supplemental Award
is to evaluate the inflammatory milieu of the degenerating IVD in a large animal model, and to determine the
potential for an eDAPS implant to reset this milieu to enhance regeneration with remobilization. We will achieve
this goal via the following Specific Aims:
Specific Aim 1: Evaluate the inflammatory responses during intervertebral disc degeneration in a large animal
model. In this Aim we will induce degeneration in the goat cervical intervertebral disc via a previously validated
chondroitinase ABC injection degeneration model. Following induced degeneration, at 3 months, we will then
perform an in-depth analysis of the inflammatory responses involved in degenerative pathology by utilizing next
generation sequencing at the single cell level.
Specific Aim 2: Determine the immunomodulatory effect of an engineered disc replacement either following
injury or following remobilization of the disc replacement. To evaluate the immunomodulatory effect of
engineered disc replacements following degeneration (Aim 2a) we will again induce degeneration in the goat
cervical intervertebral disc. After the induced degeneration, at 3 months, a second surgery will be performed to
implant the eDAPS. Animals will be euthanized after 1 year of eDAPs implantation, and compared to animals
which underwent chondroitinase ABC injection but did not have eDAPs implantation. At the 1 year study
endpoints, immunophenotyping and inflammatory assessment will be carried out via single cell sequencing
followed by validation of specific cellular markers by immunohistochemical analysis. To evaluate whether the
mechanical loading environment influences the immunomodulatory effect of eDAPs (Aim 2b), we will utilize
remobilization surgeries following implantation. eDAPs will be implanted in the goat cervical spine and
immobilize...

## Key facts

- **NIH application ID:** 10670562
- **Project number:** 3I01RX002274-06S1
- **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:** 3
- **Project period:** 2017-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10670562

## Citation

> US National Institutes of Health, RePORTER application 10670562, Tissue Engineered Total Disc Replacement in a Large Animal Model (3I01RX002274-06S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10670562. Licensed CC0.

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