# Tissue Engineered Total Disc Replacement in a Large Animal Model

> **NIH VA I01** · PHILADELPHIA VA MEDICAL CENTER · 2020 · —

## Abstract

Title: Tissue Engineered Total Disc Replacement in a Large Animal Model
The objective of this project is to develop a tissue-engineered construct including an engineered
nucleus pulposus and annulus fibrosus to treat degenerative changes of the intervertebral disc
(IVD). In Specific Aim 1, we will build on our preliminary small animal studies to construct cell-
seeded DAPS whose geometric dimensions are comparable to human and goat IVDs. A novel
compression-torsion bioreactor and simulated ex vivo disc-like microenvironment will be utilized
to promote growth; we will also establish an endplate region to promote boney integration. In
Specific Aim 2, we will investigate the impact of physiological loading on DAPS in vivo
maturation and integration in a large animal (goat) cervical spine disc replacement model. Pre-
matured DAPS constructs will be implanted into the goat cervical spine following a single-level
cervical discectomy. Constructs will be implanted either with or without an integrated PCL foam
endplate. Immediately after implantation, a cohort of animals will have their implanted motion
segment stabilized using an anterior cervical plate. An additional cohort will undergo
implantation without instrumentation. In vivo DAPS maturation will be assessed via MRI, based
on our prior in vivo DAPS work. Motion of the goat cervical spine and head will be monitored
using a custom large animal motion-tracking device that our group has developed. Terminal
assays will assess motion segment mechanics and DAPS biochemical content and ECM
distribution at 12 weeks post-implantation. In Specific Aim 3, we will investigate remobilization
of the tissue-engineered motion segment and analysis of longer-term viability/segmental
stability. The DAPS construct with best biomechanical performance in Aim 2 will be implanted
after discectomy; at 12 weeks post-implantation, instrumentation will be removed, restoring
unconstrained motion. Animals will continue free-range activity for 12 additional weeks, with
regular acquisition of cervical motion and fluoroscopy data. At 24 weeks post-implantation,
animals will be sacrificed and DAPS-implanted motion segments will be assessed via MRI
analysis, biomechanical testing, histological analysis of matrix content and distribution, and
biochemical analysis. The goal of this project is to develop tissue-engineered constructs and to
assess their therapeutic potential in the treatment of degenerative disc disease. It is anticipated
that the proposed study will offer an increased understanding of degenerative disc disease and
demonstrate the potential of a novel therapeutic treatment.

## Key facts

- **NIH application ID:** 9889811
- **Project number:** 5I01RX002274-04
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Robert L Mauck
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889811

## Citation

> US National Institutes of Health, RePORTER application 9889811, Tissue Engineered Total Disc Replacement in a Large Animal Model (5I01RX002274-04). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/9889811. Licensed CC0.

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