Thermo-responsive Scaffold for Perfusion Channels in 3D Tissue Constructs
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Solution Overview
Problem
Current methods for fabricating artificial 3D tissues face challenges in creating perfusable constructs due to size limitations, nutrient supply issues, and difficulties in forming precise microchannels, leading to cell death and leakage problems in existing hydrogel-based systems.
Innovation Solution
A device with a perfusion chamber using a thermo-responsive polymer sacrificial scaffold that dissolves at temperatures below human body temperature, creating a liquid channel network within a hydrogel matrix without clogging, allowing for leakage-free fluid connections and nutrient supply.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If conventional hydrogel-based systems are used for fabricating artificial 3D tissues, then the tissue construct can be formed with cells, but the size is limited to approximately 1 mm due to insufficient nutrient supply in the interior
Solution Approach 1:
The patent applies preliminary action by pre-forming a sacrificial scaffold structure within the hydrogel matrix before cell encapsulation. This scaffold creates predefined channels that will later serve as nutrient pathways. The scaffold is positioned and fixed in advance, allowing the hydrogel to be cast around it, ensuring that when the scaffold is removed, functional channels already exist to support larger tissue constructs.
Solution Approach 2:
The sacrificial scaffold acts as an intermediary object that temporarily occupies space within the hydrogel matrix. It serves as a placeholder that defines the future channel geometry and facilitates subsequent channel formation. The scaffold material is specifically chosen to be removable after hydrogel setting, leaving behind clean channels for nutrient transport.
2Volume of moving object
If microchannels are fabricated in hydrogels to enable nutrient supply, then larger tissue constructs can be supported, but channel formation is difficult and prone to leakage
Solution Approach 1:
The sacrificial scaffold is pre-formed with precise channel geometries using manufacturing techniques suitable for the scaffold material. This preliminary structuring ensures high precision channels are created before hydrogel encapsulation, avoiding the need to create channels through the already-set hydrogel matrix.
Solution Approach 2:
The sacrificial scaffold serves as an intermediary that defines channel geometry with high precision. By forming channels in the scaffold rather than directly in the hydrogel, the method achieves better manufacturing precision. The scaffold material allows for controlled fabrication of intricate channel networks that would be difficult to create directly in the hydrogel matrix.
3Manufacturing precision
If sacrificial scaffolds are used to create channels in hydrogels, then microchannels can be formed, but the scaffolds clog the fluid connections at inlet and outlet
Solution Approach 1:
The sacrificial scaffold is designed with local quality variations: it has a lower density or different composition at the inlet and outlet regions compared to the bulk scaffold structure. This localized modification allows the scaffold to be easily removed or creates open pathways at connection points, preventing clogging while maintaining channel integrity in other regions.
Solution Approach 2:
The scaffold is pre-designed with features that facilitate fluid connection, such as pre-formed openings or lower-density zones at inlet and outlet positions. This preliminary preparation ensures that when the scaffold is removed or dissolves, fluid connections are already established and ready for medium perfusion.
4Ease of operation
If channels are created in hydrogels by manual methods, then fluid connections can be established, but the process is time-consuming and requires further modification of the cultivation matrix
Solution Approach 1:
All channel formation and fluid connection preparation is performed preliminarily during scaffold fabrication, before hydrogel encapsulation. The scaffold is pre-configured with complete channel networks and inlet/outlet access points, eliminating the need for post-encapsulation channel creation or matrix modification.
Solution Approach 2:
The sacrificial scaffold acts as an intermediary that carries the complete channel network design from the fabrication stage through to the functional stage. It eliminates the need for secondary operations by encoding the full channel architecture in its structure, which is then transferred to the hydrogel matrix upon scaffold removal.
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
Enables the creation of larger, perfusable 3D tissue constructs with improved nutrient supply and reduced cell death, allowing for more realistic tissue models and potential tissue replacement applications.
Implementation Method 1
The sacrificial scaffold comprises a thermo-responsive polymer, which is not dissolvable in water at human body temperature and becomes dissolvable in water at a temperature below 30° C.
Data Source
AI summary
A device for fabricating a perfusable three-dimensional tissue construct includes a chamber in which the tissue construct may be cultivated, the chamber including an inlet and an outlet for perfusing the tissue construct, and a sacrificial scaffold fixed in the chamber. The sacrificial scaffold includes a thermo-responsive polymer, the thermo-responsive polymer being not dissolvable in water at human body temperature and becoming dissolvable in water at a temperature below 30° C. The sacrificial scaffold includes at least one filament extending from the inlet to the outlet such that dissolution of the sacrificial scaffold provides for a liquid channel from the inlet to the outlet. The sacrificial scaffold seals the inlet and/or the outlet such that dissolution of the sacrificial scaffold after receiving a cultivation matrix in the chamber provides for a liquid channel from the inlet to the outlet through the cultivation matrix. Methods of use and manufacture are also disclosed.