# Bioactive injectable implants for functional intervertebral disc regeneration

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

## Abstract

Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Over a 10 year
period, more than 130,000 active service members received diagnoses of disc degeneration, with annual
incidence rates more than doubling during this time. Current treatment approaches are mostly conservative,
and in severe cases, patients may undergo surgical procedures such as spinal fusion, which do not maintain or
restore native tissue structure or mechanical function. Mesenchymal stem cells (MSCs) are attractive options
for cell-based therapies due to their potential for autologous harvest, expansion, and re-implantation making
them highly translational. A key challenge to successful application of MSCs for disc regeneration is the unique
biochemical and physical microenvironment cells are exposed to upon implantation. To overcome this
challenge, one strategy is preconditioning of MSCs by exposure to hypoxia, soft physical substrates and
developmentally-relevant stimuli during monolayer expansion in order to enhance their in vivo performance in
applications for disc regeneration. It has also been shown that MSCs isolated from bone marrow are highly
heterogeneous, both within and between donors, exhibiting distinct phenotypic characteristics, including
sensitivity to microenvironmental stress in culture. Aim 1 will therefore establish the in vitro preconditioning and
donor characteristics that maximize the survival and extracellular matrix production of MSCs in the oxygen and
nutrient-poor disc microenvironment. Preclinical demonstration of the long term efficacy of disc therapies with
respective to structural and functional regeneration, and alleviation of symptoms, using rigorously validated,
clinically-relevant outcome measures is critical to their successful future clinical translation. Our team recently
established a preclinical goat model of disc degeneration that recapitulates key characteristics of human disc
degeneration. Therefore, in Aim 2 we will establish the long term efficacy of a combined hydrogel and
optimized stem cell therapy to potentiate structural and functional disc regeneration, and alleviate symptoms, in
an established preclinical goat model of disc degeneration. To maximize the clinical impact of our findings we
will further refine our goat model to include progressive and clinically relevant functional, imaging, and
molecular biomarkers of pain and disability. Finally, in Aim 3 we will take an additional important step towards
clinical application of this therapy by establishing that adult human MSCs respond to preconditioning, and
undertake transcriptome-wide screening studies to identify unique molecular signatures that predispose MSCs
from certain human donors to enhanced performance and response to preconditioning.

## Key facts

- **NIH application ID:** 10025604
- **Project number:** 5I01RX001321-07
- **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:** 2014-08-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025604

## Citation

> US National Institutes of Health, RePORTER application 10025604, Bioactive injectable implants for functional intervertebral disc regeneration (5I01RX001321-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10025604. Licensed CC0.

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