# Model of Human Disc Regeneration in the spectrum of Degenerative Disc Disease

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $562,869

## Abstract

PROJECT SUMMARY
Low back pain is the second most common cause of doctor visits and intervertebral disc (IVD) herniation is a
direct cause of pain. Lumbar discectomy is the standard of care for herniation, yet this very common procedure
has 5-25% complication rates including re-herniation and recurrent back pain at the same level. Discectomy
complications cannot be further reduced by optimizing the amount of tissue removed during procedures, but
instead discectomies require a reparative component to greatly reduce complications. This project develops,
optimizes and validates biomaterials that seal the annulus fibrosus and restore nucleus pulposus swelling
following discectomy procedures.
The first funding period of this grant resulted in 34 papers that developed human and bovine organ culture
models of IVD degeneration and determined that methods to repair large IVD defects are lacking and a critical
scientific barrier that must be addressed to limit degeneration following IVD herniation and injury. We also
developed novel hydrogels with promise to seal the annulus fibrosus, restore nucleus pulposus swelling, and
return IVD biomechanical behaviors to the healthy state. Additional acellular biomaterial optimization,
modification of biomaterials for use as cell carriers, and pre-clinical evaluations are required before clinical
translation. Aim 1 optimizes in situ performance of acellular biomaterials for IVD repair with biomaterial
refinements and TGFβ3 dose studies using bovine organ culture discectomy models. Aim 2 optimizes in situ
performance of biomaterials for mesenchymal stem cell delivery using these same models. Aim 3 validates
these IVD repair strategies in pre-clinical human organ culture and sheep in vivo studies. We apply a genipin-
crosslinked fibrin hydrogel capable of sealing annulus fibrosus defects without risk of herniation under rigorous
biomechanical loading. We also apply a novel carboxymethylcellulose/methylcellulose hydrogel formulation
capable of restoring nucleus pulposus swelling and returning IVD biomechanical behaviors to intact conditions.
The investigative team closely collaborates with extensive biomaterials, biomechanics, tissue engineering, and
spine surgery expertise. All methods are well-established in the labs of this team.
This project is highly significant because of the tremendous health burden of IVD herniation and injury,
because discectomy procedures are among the most common spine surgery procedures, and because this
project has a clear translational trajectory. This project is innovative because it uses novel biomaterial
formulations and approaches for discectomy repair that are capable of transforming current surgical
interventions and thinking since no IVD repair strategies exist. The approach is robust because it addresses
fundamental questions for IVD repair in a systematic manner that allows iterative optimization with evaluation
tests that increasingly challenge the repair strategies.

## Key facts

- **NIH application ID:** 9872109
- **Project number:** 5R01AR057397-09
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** James C. Iatridis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $562,869
- **Award type:** 5
- **Project period:** 2011-07-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872109

## Citation

> US National Institutes of Health, RePORTER application 9872109, Model of Human Disc Regeneration in the spectrum of Degenerative Disc Disease (5R01AR057397-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9872109. Licensed CC0.

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