In Vitro Vessel Fabrication via Gravitational Lumen Patterning

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Solution Overview

Problem

Conventional methods for fabricating in vitro vessels fail to create physiologically relevant models of in vivo human vessels due to limitations in replicating radial and circumferential stresses and strains, often resulting in asymmetrical lumen formation and lack of uniform muscle cell layers, which impede the vessels' ability to accurately model vascular disease progression.

Innovation Solution

The use of gravitational lumen patterning (GLP) technique to orient microfluidic channels vertically, allowing cells to form a uniformly distributed layer around the circumference, creating an elliptical lumen with both endothelial and muscle cells, which mimics the structure and functionality of in vivo vessels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional fabrication methods are used for in vitro vessels, then the manufacturing process is simple, but the vessels fail to form uniform muscle cell layers and asymmetrical lumens, reducing physiological relevance

Engineering Contradiction:

Improveuniformity of muscle cell layersVSAvoidcomplexity of fabrication process

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent introduces a vertical dimension to the microfluidic channel orientation, positioning the channel at an acute angle relative to the substrate surface. This dimensional change enables gravity to act along the channel length, creating hydrostatic pressure gradients that drive uniform cell distribution and lumen formation, thereby resolving the contradiction between manufacturing simplicity and structural uniformity

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent modifies the orientation parameter of the microfluidic channel, specifically setting it at an acute angle (e.g., 30 degrees) relative to the substrate. This parameter change transforms the gravitational force into a useful driving force for cell seeding and lumen formation, achieving uniform muscle cell layers without complex fabrication processes

Inventive Principle:

Principle #35Parameter changes

2Manufacturing precision

If microfluidic channels are oriented horizontally, then fabrication is straightforward, but cells fail to form uniform annular layers around the circumference

Engineering Contradiction:

Improveuniformity of cell distributionVSAvoidease of substrate orientation

Core Design Contradiction:

Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent transitions from horizontal to vertical/oriented channel configuration, introducing a dimensional change that allows gravity to act along the channel axis. This orientation enables uniform cell distribution through gravity-driven hydrostatic pressure, achieving precise cell layering while maintaining manufacturing simplicity through standard substrate processing

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

3Manufacturing precision

If the lumen is formed without gravitational patterning, then the fabrication process is simpler, but the lumen becomes asymmetrical and non-physiological

Engineering Contradiction:

Improvesymmetry of lumen cross-sectionVSAvoidcomplexity of cell culture process

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent changes the orientation parameter of the microfluidic channel to an acute angle relative to the substrate, which transforms gravitational force into a driving force for uniform cell distribution. This parameter change achieves symmetrical lumen formation and uniform muscle cell layers while maintaining relatively simple cell culture procedures

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces complex mechanical cell seeding and positioning systems with a gravity-based mechanical field. By orienting the channel vertically, gravity naturally drives cell sedimentation and distribution, eliminating the need for complex mechanical manipulation while achieving symmetrical lumen structure

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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

This approach enables the fabrication of in vitro vessels with a cylindrical lumen and uniform muscle cell layers, enhancing their physiological relevance and ability to model vascular functions, including lymphatic and blood vessel behaviors, thereby improving the accuracy of disease progression studies.

Implementation Method 1

positioning the substrate in a vertical orientation whereby an acute angle is formed between the longitudinal axis of the microfluidic passage and the direction of gravity

Methodology Applied

Scientific EffectGravity: Gravitation

Data Source

PatentUS20230264191A1Systems and methods for fabricating physiologically relevant in vitro vessels

Publication Date: 2023.08.24 TEXAS A&M UNIVERSITY

AI summary

A method for fabricating an in vitro vessel includes forming a substrate that defines a microfluidic passage therein extending along a longitudinal axis and defined by an inner surface, positioning the substrate in a vertical orientation whereby an acute angle is formed between the longitudinal axis of the microfluidic passage and the direction of gravity, and culturing a plurality of first cells in the microfluidic passage while the substrate is disposed in the vertical orientation whereby an annular layer of the plurality of first cells is formed in the microfluidic channel, wherein the layer of the plurality of first cells defines a lumen extending longitudinally through the microfluidic channel.