Perfusable Hydrogel Microchannel Shell for Tissue Models

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Solution Overview

Problem

Current in vitro tissue models fail to fully recapitulate the biological complexity of in vivo microvascular systems, particularly in terms of spatial and temporal cues such as pulsatile flow, modifiable wall compliance, and induced wall shear stress, limiting the size and complexity of tissue constructs and the accuracy of disease models.

Innovation Solution

The development of core-shell hydrogel constructs with addressable microfluidic cores that enable perfusion with specific flow profiles, mimicking the topology of microvasculature and allowing for the delivery of temporal cues to cells, using microfluidic imprint lithography to pattern high-resolution lumens within a PDMS superstructure, which can recreate physiological flow conditions and mechanical factors like cyclical stretch and shear stress.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If current in vitro tissue models are used, then simplicity and ease of manufacture are maintained, but the ability to recapitulate biological complexity and deliver physiological cues is insufficient

Engineering Contradiction:

Improveability to recapitulate biological complexityVSAvoidmodel complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The tissue model is segmented into distinct functional zones including a perfusable lumen region, a transition zone, and a tissue region, each capable of supporting different cell types and physiological functions. This segmentation allows the model to recapitulate the spatial organization of microvasculature while maintaining manufacturing feasibility through modular fabrication approaches

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The design employs a nested structure where the perfusable lumen is embedded within the tissue construct, creating a core-shell configuration. The lumen region contains endothelial cells, which are nested within the broader tissue matrix containing other cell types, mimicking the hierarchical organization of native microvascular systems

Inventive Principle:

Principle #7Nested doll (Nesting)

2Manufacturing precision

If microfluidic imprint lithography is used to pattern high-resolution lumens, then manufacturing precision and flow profile control are improved, but device complexity increases

Engineering Contradiction:

Improvelumen patterning precisionVSAvoidfabrication process complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The lumen pattern is pre-formed using microfluidic imprint lithography to create a precise mold, which then serves as a template for subsequent hydrogel casting. This preliminary patterning action enables high-resolution lumen formation without requiring complex real-time fabrication processes, as the pattern is established in advance and replicated

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The microfluidic imprint process creates a physical copy or replica of the desired lumen geometry, which is then used to cast the hydrogel tissue construct. This copying approach allows precise reproduction of complex lumen patterns while simplifying the overall fabrication by separating pattern generation from material formation

Inventive Principle:

Principle #26Copying

3Adaptability or versatility

If core-shell hydrogel constructs with perfusable lumens are created, then the ability to deliver temporal cues and mechanical factors is improved, but the ease of operation and cell seeding becomes more difficult

Engineering Contradiction:

Improvedelivery of temporal cuesVSAvoidcell seeding ease

Core Design Contradiction:

Adaptability or versatilityVSEase of operation

Solution Approach 1:

The construct features local quality variations with distinct regions optimized for different functions: the perfusable lumen region is designed with specific porosity and surface properties to facilitate endothelial cell seeding and perfusion, while the surrounding tissue region contains different biochemical cues for other cell types, allowing targeted cell delivery to specific zones

Inventive Principle:

Principle #3Local quality

4Adaptability or versatility

If the hydrogel structure is made more compliant to mimic tissue, then biological fidelity is improved, but structural strength and perfusion reliability may be compromised

Engineering Contradiction:

Improvewall complianceVSAvoidperfusion reliability

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The construct uses composite material strategies where the hydrogel tissue regions provide biological fidelity and compliance, while the perfusable lumen structure incorporates reinforcing elements or geometric designs that enhance mechanical strength. This composite approach allows the tissue to remain soft and compliant while the perfusion channels maintain structural integrity under flow pressures

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20220118446A1Perfusable hydrogel microchannel shell and methods thereof

Publication Date: 2022.04.21 UNIV OF VIRGINIA PATENT FOUND

AI summary

A microfluidic device can include a superstructure defining a microfluidic channel therein and a first hydrogel bonded to the microfluidic channel to define a perfusable channel therein, the first hydrogel including cells embedded therein or thereon. The microfluidic device can optionally include a second hydrogel bonded to the microfluidic channel or to the hydrogel.