# Alginate–Gelatin Hydrogel Scaffold Model for Hypoxia Induction in Glioblastoma Embedded Spheroids

**Authors:** Janette del Rocío Aguilera-Marquez, Alejandro Manzanares-Guzmán, Lorena García-Uriostegui, Alejandro A. Canales-Aguirre, Tanya A. Camacho-Villegas, Pavel H. Lugo-Fabres

PMC · DOI: 10.3390/gels11040263 · 2025-04-02

## TL;DR

Researchers created a 3D model using a hydrogel scaffold to simulate hypoxia in glioblastoma, offering a new way to study tumor behavior and treatment resistance.

## Contribution

A novel alginate–gelatin hydrogel scaffold model was developed to simulate hypoxia in glioblastoma spheroids for improved study of tumor microenvironments.

## Key findings

- The scaffold model showed high reproducibility and enabled analysis of HIF-1α expression under hypoxic conditions.
- The model's cell viability and hydrogel water absorption were successfully evaluated, supporting its use for therapeutic studies.
- The 3D glioblastoma spheroid model is a promising platform for investigating hypoxia-driven tumor progression and resistance.

## Abstract

Glioblastoma (GBM) is a highly aggressive and malignant brain tumor, characterized by hypoxia in its microenvironment, which drives its growth and resistance to treatments. Hypoxia-inducible factor 1 (HIF-1) plays a central role in GBM progression by regulating cellular adaptation to low oxygen availability, promoting processes such as angiogenesis and cell invasion. However, studying and modeling GBM under hypoxic conditions is complex, especially due to the limitations of animal models. In this study, we developed a glioma spheroid model using an alginate–gelatin hydrogel scaffold, which enabled the simulation of hypoxic conditions within the tumor. The scaffold-based model demonstrated high reproducibility, facilitating the analysis of HIF-1α expression, a key protein in the hypoxic response of GBM. Furthermore, cell viability, the microstructural features of the encapsulated spheroids, and the water absorption rate of the hydrogel were assessed. Our findings validate the three-dimensional (3D) glioblastoma spheroids model as a valuable platform for studying hypoxia in GBM and evaluating new therapies. This approach could offer a more accessible and specific alternative for studying the tumor microenvironment and therapeutic resistance in GBM.

## Linked entities

- **Proteins:** HIF1A (hypoxia inducible factor 1 subunit alpha), HIF1A (hypoxia inducible factor 1 subunit alpha)
- **Chemicals:** alginate (PubChem CID 5102882)
- **Diseases:** Glioblastoma (MONDO:0018177), GBM (MONDO:0018177)

## Full-text entities

- **Genes:** HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}
- **Diseases:** Hypoxia (MESH:D000860), glioma (MESH:D005910), GBM (MESH:D005909), brain tumor (MESH:D001932), hypoxic (MESH:D002534), tumor (MESH:D009369)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12026674/full.md

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Source: https://tomesphere.com/paper/PMC12026674