Human-Derived Bioink for 3D Tumor Model Fabrication

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Solution Overview

Problem

Current in vitro tumor models and bioinks fail to accurately mimic the native tumor environment, particularly the three-dimensional extra-cellular matrix (ECM) of pancreatic ductal adenocarcinoma (PDAC) tumors, limiting their effectiveness in simulating tumor progression and response to therapies.

Innovation Solution

Development of bioink compositions primarily derived from human tissues, including collagens like collagen I, III, and IV, and embedded with cells such as tumor cells, immune cells, and fibroblasts, to create three-dimensional artificial tissues that closely resemble the tumor microenvironment, using extrusion bioprinting for tissue formation and a housing unit with a nutrient source for maintenance.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional in vitro tumor models and bioinks are used, then the models can be manufactured with existing technologies, but they fail to accurately mimic the native tumor environment and three-dimensional ECM composition

Engineering Contradiction:

Improveaccuracy of tumor environment mimicryVSAvoidcomplexity of bioink composition

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent employs composite bioink materials comprising multiple collagen types (I, III, and IV) combined in specific ratios to replicate the complex native tumor ECM composition. This composite approach enables accurate mimicry of the tumor microenvironment while maintaining manufacturability through established bioprinting technologies.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The bioink formulation uses different collagen types in specific spatial distributions and proportions to create localized regions that mimic different aspects of the native tumor ECM. This local quality variation allows precise replication of tumor heterogeneity without requiring overly complex manufacturing processes.

Inventive Principle:

Principle #3Local quality

2Reliability

If bioinks include multiple human-derived materials and cells to mimic native tumor environment, then the biological fidelity is improved, but the ease of manufacture decreases

Engineering Contradiction:

Improvebiological fidelity of tumor modelVSAvoidease of bioink preparation

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent optimizes specific parameters including collagen concentration ratios (I:III:IV), crosslinking conditions, and cell density to achieve high biological fidelity. By systematically tuning these parameters within defined ranges, the patent maintains reliable tumor model replication while keeping the manufacturing process manageable through standardized protocols.

Inventive Principle:

Principle #35Parameter changes

3Manufacturing precision

If three-dimensional artificial tissues are created with multiple cell types and collagen composition, then the tumor microenvironment accuracy is improved, but the manufacturing precision requirements increase

Engineering Contradiction:

Improveaccuracy of tissue structure formationVSAvoidvariety of materials and cells required

Core Design Contradiction:

Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The patent segments the tumor microenvironment into distinct functional components represented by different cell types (cancer cells, fibroblasts, immune cells) and collagen types. Each segment is independently formulated and then integrated through bioprinting, allowing precise control of tissue structure formation while managing material complexity through modular design.

Inventive Principle:

Principle #1Segmentation

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 bioink-based artificial tissues effectively mimic the in vivo tumor environment, enhancing the accuracy of drug screening, radiotherapy assessment, and immunotherapy analysis, with improved cell viability and proliferation, and providing a reliable platform for testing anti-cancer therapies.

Implementation Method 1

the bioinks of the present disclosure include collagens, such as collagen I, collagen III, and collagen IV at optimal weight ratios for artificial tissue formation

Methodology Applied

Scientific EffectCollagen structure:

Implementation Method 2

using extrusion bioprinting for tissue formation

Methodology Applied

Scientific EffectExtrusion: Extrusion

Implementation Method 3

a nutrient source in fluid communication with the housing unit

Methodology Applied

Scientific EffectFluid communication:

Data Source

PatentUS20230302202A1Vitro bioprinted tumor models and bioinks for solid tumor bioprinting

Publication Date: 2023.09.28 TEXAS TECH UNIV SYST

AI summary

Embodiments of the present disclosure pertain to bioink compositions that are operational to form an artificial tissue. The bioink may include materials that are completely or primarily derived from humans, such as human tissues. Additional embodiments of the present disclosure pertain to artificial tissues that include a plurality of cells and a bioink of the present disclosure, where the bioink is embedded with the cells, and the artificial tissue is in the form of a three-dimensional structure. Further embodiments of the present disclosure pertain to methods of making the artificial tissues of the present disclosure by applying a plurality of cells and a bioink onto a surface.