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Updated: Sep 15, 2025
Hydrogel Arrays Enable Increased Throughput for Screening Effects of Matrix Components and Therapeutics in 3D Tumor Models
Published on: June 16, 2022
Hydrogel microdroplet based glioblastoma drug screening platform
Brittany A Payan1, Annika Carrillo Diaz De Leon1, Tejasvi Anand2
1Dept of Bioengineering, University of Illinois at Urbana-Champaign Urbana, IL 61801.
Abstract:
Glioblastoma is the most common primary malignant brain tumor with a five-year survival rate less than 5%. The standard of care involves surgical resection followed by treatment with the alkylating agent temozolomide (TMZ). GBM cells that evade surgery eventually become resistant to TMZ and lead to recurrence of tumors in patients. With only four drugs currently FDA-approved for GBM treatment, there is a need for a clinically relevant model capable of accelerating the identification of new therapies. Microgels are microscale (~10-1,000 μm) hydrogel particles that can be used to encapsulate cells in a tailorable 3D matrix. Microdroplets offer short diffusion lengths relative to conventional hydrogel constructs (>1 mm) to limit spatial distributions of hypoxia and potentially screen therapeutics in a controlled and physiologically relevant environment. Here, we establish a method to encapsulate GBM cells in gelatin and polyethylene glycol (PEG) microgels. We show that microgel composition can affect cell morphology and further, that collections of GBM-laden hydrogels can be used to quantify the effect of single vs. metronomic doses of TMZ. GBM metabolic activity is maintained in microgel culture and GBM cells display drug response kinetics similar to previously established literature using macro-scale hydrogel constructs. Finally, we show microgels can be integrated with a liquid handler to enable high-throughput screening using cell-laden microgels.
Insights
This study introduces microgels for culturing glioblastoma cells, enabling faster drug screening. These 3D microgels mimic tumor environments, aiding the development of new glioblastoma treatments.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Drug Discovery
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with poor prognosis.
- Current treatments like temozolomide (TMZ) face drug resistance and tumor recurrence.
- There is a critical need for advanced models to develop novel GBM therapies.
Purpose of the Study:
- To develop a microgel-based platform for encapsulating glioblastoma cells.
- To assess the utility of this platform for drug screening and studying treatment responses.
- To enable high-throughput screening of potential glioblastoma therapeutics.
Main Methods:
- Encapsulation of glioblastoma cells within gelatin and polyethylene glycol (PEG) microgels.
- Characterization of cell morphology and metabolic activity within the microgels.
- Quantification of drug response to temozolomide (TMZ) using single and metronomic dosing.
- Integration of microgel cultures with liquid handling systems for high-throughput screening.
Main Results:
- Microgel composition influences glioblastoma cell morphology.
- GBM cells maintain metabolic activity and show predictable drug response kinetics in microgels.
- The microgel system accurately reflects drug response compared to macro-scale models.
- Successful integration with liquid handlers demonstrates potential for high-throughput drug screening.
Conclusions:
- Microgels provide a viable and physiologically relevant 3D culture system for glioblastoma.
- This microgel platform facilitates efficient drug response assessment and accelerates therapeutic development.
- The developed method supports high-throughput screening, crucial for identifying new glioblastoma treatments.
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