Related Experiment Video
Updated: Jul 6, 2025
Three-Dimensional In Vitro Biomimetic Model of Neuroblastoma Using Collagen-Based Scaffolds
Published on: July 9, 2021
Three-dimensional in vitro model of bone metastases of neuroblastoma as a tool for pharmacological evaluations
Sanja Aveic1,2, Max Seidelmann1, Roswitha Davtalab1
1Department of Dental Materials and Biomaterials Research, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany.
Abstract:
In vitro metastatic models are foreseen to introduce a breakthrough in the field of preclinical screening of more functional small-molecule pharmaceuticals and biologics. To achieve this goal, the complexity of current in vitro systems requests an appropriate upgrade to approach the three-dimensional (3D) in vivo metastatic disease. Here, we explored the potential of our 3D β-tricalcium phosphate (β-TCP) model of neuroblastoma bone metastasis for drug toxicity assessment. Tailor-made scaffolds with interconnected channels were produced by combining 3D printing and slip casting method. The organization of neuroblastoma cells into a mesenchymal stromal cell (MSC) network, cultured under bioactive conditions provided by β-TCP, was monitored by two-photon microscopy. Deposition of extracellular matrix protein Collagen I by MSCs and persistent growth of tumor cells confirmed the cell-supportive performance of our 3D model. When different neuroblastoma cells were treated with conventional chemotherapeutics, the β-TCP model provided the necessary reproducibility and accuracy of experimental readouts. Drug efficacy evaluation was done for 3D and 2D cell cultures, highlighting the need for a higher dose of chemotherapeutics under 3D conditions to achieve the expected cytotoxicity in tumor cells. Our results confirm the importance of 3D geometry in driving native connectivity between nonmalignant and tumor cells and sustain β-TCP scaffolds as a reliable and affordable drug screening platform for use in the early stages of drug discovery.
Insights
This study presents a novel 3D beta-tricalcium phosphate (β-TCP) model for neuroblastoma bone metastasis, improving preclinical drug screening. The 3D model requires higher drug doses than 2D cultures for effective cancer cell killing.
Area of Science:
- Biomaterials Science
- Oncology
- Drug Discovery
Background:
- Current in vitro models lack the complexity to accurately mimic in vivo metastatic disease.
- Three-dimensional (3D) models are crucial for advancing preclinical drug screening of pharmaceuticals and biologics.
- Neuroblastoma bone metastasis requires sophisticated models for effective drug toxicity assessment.
Purpose of the Study:
- To explore the potential of a 3D beta-tricalcium phosphate (β-TCP) scaffold for modeling neuroblastoma bone metastasis.
- To evaluate the β-TCP model's utility in preclinical drug toxicity and efficacy assessment.
- To compare drug efficacy in 3D versus 2D cell cultures.
Main Methods:
- Fabrication of tailor-made β-TCP scaffolds with interconnected channels using 3D printing and slip casting.
- Culturing neuroblastoma cells and mesenchymal stromal cells (MSCs) within the 3D β-TCP scaffold.
- Monitoring cell organization and extracellular matrix deposition using two-photon microscopy.
- Assessing drug efficacy and cytotoxicity of chemotherapeutics in both 3D and 2D cultures.
Main Results:
- The 3D β-TCP model successfully supported neuroblastoma cell growth and MSC network formation, confirmed by Collagen I deposition.
- The model demonstrated reproducibility and accuracy in experimental readouts for drug treatment.
- Higher chemotherapeutic doses were required in the 3D model compared to 2D cultures to achieve similar cytotoxicity.
- 3D geometry was shown to drive native connectivity between nonmalignant and tumor cells.
Conclusions:
- The developed 3D β-TCP scaffold is a reliable and affordable platform for preclinical drug screening in early drug discovery.
- The model effectively mimics key aspects of neuroblastoma bone metastasis, including cell-matrix interactions.
- Findings highlight the critical role of 3D architecture in drug response and the need for adjusted dosing strategies in 3D models.
