Patient-Derived 3D Brain Tumor Models on Solid Scaffolds
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Solution Overview
Problem
Current in vitro brain tumor models, particularly those for pediatric brain tumors, lack genetic characterization and fail to accurately replicate the in vivo microenvironment, making it difficult to assess clinical relevance and develop targeted therapies.
Innovation Solution
Development of patient-derived 3D brain tumor models using a three-dimensional scaffold made of silk protein, extracellular matrix components, and endothelial cells, which mimic the in vivo microenvironment, allowing for the assessment of drug responses and tumor progression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional 2D cell culture models are used, then the models are simple to manufacture and maintain, but they fail to replicate the in vivo microenvironment and lack genetic characterization
Solution Approach 1:
The patent transitions from traditional two-dimensional cell culture models to three-dimensional scaffold-based models. The 3D scaffold provides spatial structure that enables cells to interact with each other and the extracellular matrix in ways that replicate the in vivo microenvironment, thereby improving reliability while accepting increased complexity
Solution Approach 2:
The patent employs composite materials including silk protein scaffold, extracellular matrix components (collagen, matrigel), and various cell types (tumor cells, endothelial cells, glial cells). This composite approach creates a physiologically relevant microenvironment that accurately represents pediatric brain tumors while maintaining manufacturability through standardized material combinations
2Reliability
If patient-derived 3D models are created, then clinical relevance is improved, but the quantity of available models is limited
Solution Approach 1:
The patent establishes a systematic protocol for creating patient-derived 3D models from fresh pediatric brain tumor tissue at the time of diagnosis. By performing preliminary actions such as tissue dissociation, cell sorting, and scaffold preparation during the initial workup, the models can be generated efficiently and scaled to serve multiple patients
Solution Approach 2:
The patent creates in vitro copies of patient tumors using 3D scaffold models that replicate the genetic and phenotypic characteristics of the original tumors. These models serve as reproducible copies that can be studied multiple times without depleting the original tissue, thereby increasing the quantity of available models while maintaining clinical relevance
3Quantity of substance
If existing cell lines are used, then the quantity of cell sources is abundant, but genetic characterization is lacking and clinical relevance is difficult to assess
Solution Approach 1:
The patent extracts and preserves genetic information from fresh pediatric brain tumor tissue at the time of diagnosis, before the tissue is processed into 3D models. By taking out and storing genetic data (DNA, RNA, proteomics) alongside the cellular models, the patent maintains comprehensive genetic characterization while preserving the functional properties of the tumor cells in 3D configuration
Data Source
AI summary
Provided herein is a personalized in vitro brain tumor model including a culture medium and patient tumor cells, wherein a brain tumor tissue sample is extracted directly from the patient. dissociated, and the patient tumor cells from the brain tumor tissue sample seeded directly onto a three-dimensional solid scaffold in the absence of extracellular matrix or endothelial cells to provide tumor growth on the scaffold. The three-dimensional solid scaffold includes a biocompatible and/or biodegradable material, wherein the three-dimensional solid scaffold and directly seeded patient tumor cells are optionally coated with extracellular matrix and/or endothelial cells.