# Novel Bioprinted Neural Stem Cell-Embedded Hydrogel Matrices for Enhanced Treatment of Glioblastoma

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $40,492

## Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumor affecting adults, with a median survival
time of 12-15 months. The standard of care for treating GBMs is maximum tumor resection followed by
concomitant radiation and temozolomide therapy. However, tumor cells remain in the brain after resection,
posing the threat of disease recurrence. Systemically administered treatments like radiation and chemotherapies
are not targeted to the microscopic tumor lesions present in the brain post-surgery and are thus ineffective at
preventing recurrence for 90% of GBM patients. Our group and others have demonstrated the promise of
therapeutic neural stem cells (tNSCs) as a drug delivery platform for treating post-operative GBM due to an
innate property known as tumor tropism. tNSCs interact with cytokines secreted by GBM cells, initiating a
signaling cascade which results in tNSC migration in the direction of the tumor. This directional migration can be
leveraged as a targeting mechanism for the delivery of drugs secreted by genetically engineered tNSCs.
However, the platform's durability is limited by rapid clearance of tNSCs implanted directly into the GBM resection
cavity. Encapsulation of tNSCs in biomaterials when delivered into the cavity could prevent this rapid clearance
and lengthen the duration of therapeutic efficacy. Our group has demonstrated that biocompatible materials such
as commercially available hemostats are able to support long-term in vivo tNSC viability. However, these
matrices can pose a barrier to tNSC migration, resulting in insignificant tumor killing compared to tNSCs injected
in PBS alone. Thus, we discovered that a balance between enhanced tNSC viability and unimpaired cell
migration must be reached to optimize tNSCs for long-term GBM therapy. To do so, we will develop a novel
adaptation of the 3D printing technology, continuous liquid interface production (CLIP), in which tNSCs are 3D
printed into hydrogels in a process known as bioprinting. This results in cell-embedded 3D hydrogels which could
be implanted into the GBM resection cavity without any intermediate cell seeding steps. We have shown that
bioprinted cell-laden hydrogels exhibit higher seeding consistency than cells seeded externally onto hydrogel
surfaces. However, cell behavior and function has not been characterized or optimized inside bioprinted
hydrogels. Moreover, the most biocompatible hydrogels which support the longest cell viability exhibit the lowest
printing resolution. Thus, we propose to optimize this novel bioprinting strategy by developing a biocompatible
and printable resin that can support cell viability for at least one month. Furthermore, we will characterize cell
health and functionality pre- and post-bioprinting to ensure that toxic resin monomers and UV light have not
compromised the efficacy or safety of the embedded cells. Finally, we will characterize the efficacy of cell-laden
bioprinted hydrogels in a post-resection GBM mouse ...

## Key facts

- **NIH application ID:** 10936514
- **Project number:** 5F31NS134198-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Lauren Kass
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,492
- **Award type:** 5
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936514

## Citation

> US National Institutes of Health, RePORTER application 10936514, Novel Bioprinted Neural Stem Cell-Embedded Hydrogel Matrices for Enhanced Treatment of Glioblastoma (5F31NS134198-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10936514. Licensed CC0.

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