# Harnessing Continuous Liquid Interface 3D Printing to Improve Tumor-homing Stem Cell Therapy for Post-surgical Brain Cancer

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $409,786

## Abstract

Project Summary/Abstract
Glioblastoma is the most common primary brain tumor and one of the deadliest forms of cancer. Recently, we
found that biocompatible matrices significantly improve the transplant of tumor-homing neural stem cells into
the post-surgical GBM cavity allowing them to deliver anti-cancer gene products that suppress tumor
recurrence. Yet, the optimal scaffold figuration that maximizes tNSC transplant, migration, drug release, and
subsequent GBM kill remain unknown. Using clinically relevant human tNSCs, matrices, and mouse models of
GBM resection/recurrence, we have found that 3D architecture and scaffold composition markedly enhance
tNSC persistence in the surgical cavity. Here in, we hypothesize that optimizing features through unique 3D
printing of custom designed scaffolds will achieve superior suppression of post-surgical GBMs by tNSC
therapy. Leveraging Continuous Liquid Interface Printing (CLIP), a novel continuous fabrication method with
high spatial resolution, we propose to fabricate a panel of 3D matrices with different architectural, biophysical,
and mechanical response features design rationally selected to improve tNSC therapy. We will define the
impact of each design feature on tNSC persistence, homing and killing in vitro and in vivo, then test a final
optimized matrix incorporating the most beneficial features into a single matrix using surgical resection models
of patient-derived human xenografts in immune-depleted mice and syngeneic GBM allografts in immune-
competent animals. We propose to undertake the following Aims: 1) Utilize CLIP to fabricate a panel of 3D
printed matrices with varied design features; 2) Define the impact of 3D design features on tNSC efficacy for
post-operative GBM; 3) Investigate the efficacy and safety of 3D matrix/tNSC therapy in immune-competent
models of GBM resection/recurrence. The results of our study will generate a therapeutic tNSC/scaffold
transplant strategy capable of robust GBM killing that can be translated for human patient testing. It will also
uncover the scaffold features that regulate different aspects of tNSCs, allowing us to modulate tNSC cancer
therapy through matrix design.

## Key facts

- **NIH application ID:** 10769716
- **Project number:** 5R01CA269974-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Shawn Hingtgen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $409,786
- **Award type:** 5
- **Project period:** 2022-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769716

## Citation

> US National Institutes of Health, RePORTER application 10769716, Harnessing Continuous Liquid Interface 3D Printing to Improve Tumor-homing Stem Cell Therapy for Post-surgical Brain Cancer (5R01CA269974-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10769716. Licensed CC0.

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