# Nanoengineered bone repair scaffolds generated from stem cells and their secreted products for improved spinal fusion

> **NIH NIH R21** · TEXAS A&M UNIVERSITY · 2020 · $189,906

## Abstract

Degenerative disc disease is an epidemic, ultimately resulting in untenable pain and immobility. In advanced
cases, spinal fusion is performed where vertebrae are surgically fixed with a mechanical device and an
osteogenic material (bone substitute) is bridged between them in an attempt to induce fusion. Of the 600,000
yearly procedures performed in the US, the most common is posterolateral lumbar arthrodesis but the failure
rate can reach 25-40% with standard commercial bone substitutes. The reason for failure rests in part with limited
biocompatibility of synthetic bone substitutes, inconsistencies with processed cadaveric bone substitutes and in
some cases, health complications caused by supraphysiologic doses of bone morphogenic protein. Autologous
bone grafts are much more effective, but the approach is associated with donor site morbidity and the volume of
available graft is limited. Compromising strategies that employ bone substitutes and bone marrow aspirate (BMA)
are becoming common, but efficacy continues to be limited by the bone substitute. The fact that spine related
disability is a growing global problem and standard of care interventions have an unacceptable failure rate clearly
demonstrates the need for implants that safely and effectively promote bone fusion. The successes and failures
of past spinal fusion strategies indicate that a bone substitute that mimics autograft will meet this need.
Therefore, the goal of this proposal is to develop a 3D printed biomimetic bone graft substitute (the scaffold) by
an innovative combination of stem cell biology, matrix biology, and biomedical engineering.
The scaffold will consist of a tough, porous and flexible nanoengineered hydrogel consisting of gelatin
methacrylate (gel-MA) coated with extracellular matrix (ECM) purified from osteogenically enhanced human
mesenchymal stem cells derived from induced pluripotent stem cells (OEihMSCs). By mimicking the composition
of bone matrix, OEihMSC-derived ECM is highly osteogenic. The gel-MA will be further enhanced by addition of
novel silicate nanoparticles that impart stiffness and further stimulate osteogenesis. The scaffold will be designed
to drive fusion with efficacy equivalent to autograft, but it will be manufactured from a standardized and
sustainable source of materials.
To achieve this goal, we will: optimize methodology for the generation of various forms of scaffold with a range
of gel-MA, nanosilicate and ECM formulations with variations in macroporosity and stiffness (Aim1), optimize
attachment, distribution, viability and osteogenesis of cells on the scaffold using in vitro 3D cell culture assays
based on rotating wall bioreactor technology (Aim2) and finally, test the optimized scaffold with human BMA in
a rodent posterolateral fusion model, incorporating imaging and biomechanical testing approaches (Aim 3).
The rationale for this approach is that it has the capacity to satisfy a need for safe and effective autologous bone
repair...

## Key facts

- **NIH application ID:** 9989785
- **Project number:** 5R21AR072292-02
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** CARL A. GREGORY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $189,906
- **Award type:** 5
- **Project period:** 2019-08-06 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989785

## Citation

> US National Institutes of Health, RePORTER application 9989785, Nanoengineered bone repair scaffolds generated from stem cells and their secreted products for improved spinal fusion (5R21AR072292-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9989785. Licensed CC0.

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