Biomimetic Interface Device for Vascular Tissue Modeling
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Solution Overview
Problem
Current methods for modeling diseases and evaluating therapeutics in vitro are inadequate due to the inability to mimic in vivo physiological conditions, particularly in vascular systems, as they fail to replicate essential hemodynamic stresses and layered tissue architecture, leading to high failure rates of therapeutics in human trials.
Innovation Solution
A biomimetic apparatus featuring a spun elastomer scaffold within a cassette system with connected chambers and tubing, allowing for controlled fluid flow, pressure, and shear simulation, seeded with human cells to mimic vascular conditions and evaluate pharmacokinetics of therapeutics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional static culture dishes are used for cell culture, then the device complexity is low and ease of manufacture is high, but the physiological relevance is insufficient because they cannot replicate hemodynamic stresses and layered tissue architecture
Solution Approach 1:
The device is divided into multiple cassettes, each containing a spun elastomer scaffold with seeded cells. This segmentation allows independent configuration of different tissue layers and hemodynamic conditions in each cassette, enabling physiological relevance while maintaining modular simplicity that doesn't excessively increase overall device complexity
Solution Approach 2:
A spun elastomer scaffold acts as an intermediary structure between the culture medium and the cells. This scaffold provides the necessary mechanical support and architectural framework to replicate layered tissue structure, while allowing cells to be seeded and exposed to controlled hemodynamic stresses, thereby achieving physiological relevance without requiring complex synthetic systems
2Reliability
If animal models are used for therapeutic evaluation, then the physiological conditions are more realistic, but ethical concerns arise and approximately 90% of therapeutics fail in subsequent human trials
Solution Approach 1:
The device creates an in vitro copy of the in vivo human physiological environment using human cells cultured on spun elastomer scaffolds under controlled hemodynamic conditions. This copying approach provides a more ethically acceptable alternative to animal models while maintaining high predictive accuracy for human therapeutic responses, as the system directly replicates human tissue architecture and physiological stresses
Solution Approach 2:
The system enables precise control and adjustment of physiological parameters such as shear stress, pressure, and flow rate to match in vivo human conditions. By dynamically adjusting these parameters, the device achieves high predictive accuracy for human therapeutic responses without requiring animal subjects, thereby eliminating ethical concerns while maintaining reliability
3Adaptability or versatility
If current proposed solutions are used, then some specific functions are addressed, but they fail to provide comprehensive interfacial function configurability for perfusion and cannot mimic layered tissue architecture
Solution Approach 1:
The spun elastomer scaffold system serves multiple functions simultaneously: it provides structural support for layered tissue architecture, enables cell seeding and attachment, allows configurable perfusion through its porous structure, and facilitates exposure to hemodynamic stresses. This multi-functionality achieves comprehensive interfacial function configurability while maintaining high physiological suitability for therapeutic evaluation
Solution Approach 2:
The spun elastomer scaffold utilizes a porous structure that naturally allows fluid perfusion while providing mechanical support and cell attachment sites. This porous architecture enables configurable flow patterns and interfacial functions without requiring complex additional components, thereby achieving both adaptability and physiological suitability through the inherent properties of the porous material
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 apparatus effectively simulates in vivo conditions, enabling more accurate evaluation of therapeutics and disease modeling, reducing the risk of therapeutic failures in human trials by replicating essential physiological stresses and tissue architecture.
Implementation Method 1
vascular cells cultured in the absence of appropriate hemodynamic stresses, such as shear, pressure, and stretch
Implementation Method 2
appropriate hemodynamic stresses, such as shear, pressure, and stretch
Implementation Method 3
the pump is configured to flow fluid in a circuit through the tubing and each cassette
Data Source
AI summary
The present disclosure generally pertains to a biomimetic apparatus configured to simulate physiological conditions by, in part, providing for both barrier and transport interfaces. The presently disclosed apparatus may be used to: test therapeutics for different diseases; to study transport; form a substrate for any organ tissue with a barrier and/or transport function; provide a closed loop assembly for fluid flow; mimic underlying and enveloped tissue; and model external environmental conditions.