# A Metabolic Strategy Utilizing a Zein Scaffold for Bone Repair

> **NIH NIH R21** · NEW JERSEY INSTITUTE OF TECHNOLOGY · 2021 · $213,424

## Abstract

Project Summary
More than one million operations are performed annually in the United States for reconstructive surgery, trauma,
or abnormal skeletal defects. To achieve reconstructive goals, large amounts of autologous bone graft or
alternative large bulk allograft are needed in the surgical procedure. Autologous bone is limited in supply and
allograft bone material and alternatives such as synthetic grafts often result in delayed osseous integration.
Allograft bone and synthetic substitutes may provide an osteoconductive environment but they do not provide
the necessary cellular and/or other biological activity for bony union and healing to occur. A novel approach to
overcome these limitations is the use of a metabolic strategy to promote healing. Recent studies by our group
have identified the amino acid glutamine as a critical regulator of osteoblast specification and differentiation in
mesenchymal stem cells (MSCs). MSCs are critical for bone healing and regeneration by providing a reservoir
of osteoblasts in response to injury. The proposed studies will utilize a glutamine enriched scaffold that can
stimulate endogenous MSCs to proliferate and differentiate into osteoblasts and be osteoconductive to promote
bone repair of skeletal defects. Zein, which is a protein derived from corn, is high in glutamine thus providing a
source of glutamine to cells upon enzymatic degradation. It can be readily processed, is biocompatible and
biodegradable and recent studies have demonstrated that cell attachment is enhanced on zein via interaction
with tissue transglutaminase. We have demonstrated, for the first time, that we can form hydrolytically stable,
fibrous zein scaffolds. Fibers are a beneficial structural feature for cell adhesion and growth due to the large
surface-to-volume and high aspect ratio and the fibrous structure mimics the collagen fiber structure of the native
extracellular matrix (ECM). Zein is also classified by the U.S. Food and Drug Administration as a generally
recognized as safe substance (GRAS) and is being sought for a variety of biomedical applications. This proposal
will develop fibrous zein scaffolds for use in bone regeneration with the goal of providing a source of glutamine
to cells to promote repair. The following specific aims will be addressed. Aim 1 will determine zein scaffolds that
promote MSC osteogenesis. The studies will examine zein scaffolds that vary with degree of crosslinking, which
can affect glutamine availability, and its effect on MSC growth and osteogenesis. We also will examine glutamine
uptake and metabolism via glutaminase (GLS) activity, which is the primary enzyme responsible for glutamine
catabolism. We will inhibit GLS activity to determine the contribution of zein’s glutamine content on differentiation.
Aim 2 will investigate the efficacy of zein scaffolds in a bone defect model. Bone healing will be evaluated over
time. We will also knockout GLS specifically in MSCs using LeprCre and determine ...

## Key facts

- **NIH application ID:** 10109396
- **Project number:** 1R21AR078399-01
- **Recipient organization:** NEW JERSEY INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Treena Lynne Arinzeh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $213,424
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109396

## Citation

> US National Institutes of Health, RePORTER application 10109396, A Metabolic Strategy Utilizing a Zein Scaffold for Bone Repair (1R21AR078399-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10109396. Licensed CC0.

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