3D Bioprinted Intestinal Tissue for Predictive Drug Toxicity Testing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current in vitro systems and preclinical models fail to adequately recapitulate the complexities of human intestinal tissue, leading to low safety and efficacy predictability in drug development due to limitations in modeling intestinal function, absorption, metabolism, and toxicity, and genetic disparities in animal models.
Innovation Solution
Development of a three-dimensional, engineered, bioprinted, biological intestinal tissue model that includes a layer of intestinal interstitial tissue comprising myofibroblasts and a layer of intestinal epithelial cells, which supports cell-cell and cell-matrix interactions, expressing key metabolic enzymes and transporters, and is compatible with standard assay approaches.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If 2D cell monolayer models are used, then ease of manufacture and operation are improved, but physiological relevance and predictive accuracy deteriorate
Solution Approach 1:
The patent transitions from 2D cell monolayer models to 3D bioprinted tissue models that replicate the three-dimensional architecture of native intestinal tissue. This dimensional change enables cells to form realistic cell-cell and cell-matrix interactions, tight junctions, and tissue polarity, thereby improving physiological relevance and predictive accuracy while maintaining operational feasibility through automated bioprinting systems
2Reliability
If 3D bioprinted intestinal tissue models are developed, then physiological relevance and predictive accuracy are improved, but device complexity and manufacturing difficulty increase
Solution Approach 1:
The intestinal tissue model is segmented into distinct functional layers including epithelial cells, lamina propria with immune cells, and muscularis layers. Each layer is bioprinted separately with appropriate cell types and then assembled into a complete tissue model, reducing manufacturing complexity while maintaining physiological accuracy
Solution Approach 2:
The patent utilizes bioprinting parameters such as cell density, layer thickness, and printing resolution to control tissue architecture and function. By optimizing these parameters, the system achieves physiologically relevant tissue models with improved predictive accuracy while managing manufacturing complexity through parameter standardization
3Ease of operation
If standard 2D systems are used, then ease of operation is improved, but ability to model intestinal function and metabolism deteriorates
Solution Approach 1:
The tissue model incorporates composite structures with multiple cell types (epithelial cells, immune cells, fibroblasts) and extracellular matrix components arranged in physiologically relevant configurations. This composite approach enables the model to perform multiple intestinal functions including absorption, metabolism, and immune response while maintaining operational simplicity through integrated tissue construction
Data Source
AI summary
Disclosed are methods of assessing the ability of a candidate therapeutic agent to reverse, reduce or prevent intestinal injury by a potential toxic agent using a three-dimensional, engineered, bioprinted, biological intestinal tissue model. Also disclosed are methods of assessing the effect of an agent on intestinal function, the method comprising contacting the agent with a three-dimensional, engineered, bioprinted, biological intestinal tissue model.