3D Bioprinted Tumor Models With Perfusable Vasculature
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Solution Overview
Problem
Current two-dimensional cell cultures fail to replicate tissue-specific and differentiated functions of multiple cell types in disease progression and do not accurately predict in-vivo drug effects, while existing three-dimensional models lack multiscale architecture and tissue-tissue interfaces crucial for organ function.
Innovation Solution
A three-dimensional tumor model is created using additive manufacturing, comprising a synthetic material and a plurality of cell types with full HLA match, embedded in an extracellular matrix, which mimics the tumor's structure and includes a perfusable vasculature, formed through bioprinting methods using materials like fibrin and anionic polymers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If two-dimensional cell cultures are used, then ease of manufacture and operation are improved, but the ability to replicate tissue-specific functions and predict in-vivo drug effects deteriorates
Solution Approach 1:
The invention transitions from two-dimensional cell culture to three-dimensional bioprinted tumor models, adding spatial dimensionality to replicate in-vivo tissue architecture. This dimensional change enables cells to interact in three-dimensional space, forming realistic tissue structures with proper cell-cell and cell-matrix interactions, thereby improving predictive accuracy while maintaining manufacturing feasibility through automated bioprinting processes
2Shape
If three-dimensional cell cultures are used, then the representation of tissue structure is improved, but the presence of multiscale architecture and tissue-tissue interfaces deteriorates
Solution Approach 1:
The invention segments the tumor model into distinct functional zones (necrotic core, proliferating rim, invasive front) and prints each zone with appropriate cell types and ECM compositions. This segmentation enables the creation of realistic multiscale architecture from micro-level cell arrangements to macro-level tissue organization, including vascular interfaces and stromal compartments
Solution Approach 2:
The invention uses composite bio-ink formulations combining multiple cell types (cancer cells, stromal cells, immune cells), extracellular matrix components (collagen, fibrin, hyaluronic acid), and functional materials (vascular channels, drug reservoirs). These composite materials enable simultaneous representation of multiple tissue types and scales within a single bioprinted construct
3Manufacturing precision
If additive manufacturing is used to create 3D tumor models, then the structural match to actual tumors is improved, but the complexity of the manufacturing process increases
Solution Approach 1:
The invention performs preliminary actions by preparing cell suspensions, ECM formulations, and vascular channel templates before bioprinting. Digital 3D models of target tumors are pre-processed into printable formats with optimized layer configurations. This preliminary preparation enables the bioprinting process to focus on precise material deposition, achieving high structural fidelity without overwhelming process complexity
Solution Approach 2:
The invention creates accurate copies of actual tumor structures by using imaging data (MRI, CT, or histology) to generate digital 3D models that are then bioprinted with matching architecture. This copying approach replicates tumor geometry, cellular distribution, and structural features without requiring de novo design, simplifying the manufacturing process while maintaining high precision
4Reliability
If multiple cell types with full HLA match are used, then the accuracy of personalized therapy simulation is improved, but the complexity of cell preparation and matching increases
Solution Approach 1:
The invention uses patient-derived cells that automatically provide full HLA matching without requiring external cell sourcing or complex immunological compatibility testing. The patient's own cells serve their own therapeutic simulation needs, eliminating the need for donor matching and reducing preparation complexity while maintaining high personalized therapy accuracy
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The model exhibits viability for at least 30 days and gene expression patterns similar to in-vivo tumors, allowing for accurate drug responsiveness testing and personalized therapy simulations.
Implementation Method 1
Exposure to the UV laser light cures and solidifies the pattern traced on the building material and joins it to the layer below
Implementation Method 2
comprising fibrinogen and thrombin, which form a fibrin gel
Data Source
AI summary
A three dimensional (3D) model of a tumor made of a synthetic material and a plurality of cell types, including malignant cells and non-malignant cells of the tumor, having a full HLA match, such that the synthetic material and the plurality of cell types are arranged in high matchability to a 3D image of the tumor, is provided. Methods of forming the 3D tumor model by bioprinting are also provided, as well as systems in which the 3D tumor model can be perfused and fluidly connected to a medium containing immune cells and/or other cells and factors present in the tumor's microenvironment. Methods utilizing the 3D tumor model or the system in, for example, personalized therapy, are also provided.