Cross-linkable Microgel Bath for Embedded Bioprinting
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Solution Overview
Problem
Current methods for fabricating engineered tissue constructs, such as perfusable tissue constructs, face challenges in achieving robust and versatile approaches for creating complex tissue structures with perfusable channels.
Innovation Solution
A cross-linkable microgel composite matrix bath is used for embedded bioprinting, where a sacrificial material is extruded into the bath, allowed to solidify, and then removed to create voids that form perfusable channels within the composite matrix.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional methods are used to fabricate engineered tissue constructs, then the process is simpler, but the ability to create complex tissue structures with perfusable channels is limited
Solution Approach 1:
The fabrication process is segmented into distinct functional modules: a support bath for shape control, an extrusion system for material deposition, and a cross-linking system for structure stabilization. This segmentation allows each component to be optimized independently while working together to create complex tissue structures with perfusable channels.
Solution Approach 2:
A sacrificial material is introduced as an intermediary element that is extruded into the hydrogel precursor to define channel pathways. This sacrificial material serves as a temporary placeholder that is later removed to create the desired perfusable channel network, enabling complex internal structures without requiring direct manipulation of the final tissue matrix.
2Adaptability or versatility
If sacrificial material is used to create perfusable channels, then channel formation is achieved, but the fabrication time increases due to solidification and removal steps
Solution Approach 1:
The sacrificial material undergoes a phase transition from liquid to solid state through cross-linking, allowing it to maintain defined channel shapes during the fabrication process. This phase change enables the material to be extruded in a controllable state and then stabilized to preserve the intended channel geometry before removal.
Solution Approach 2:
The sacrificial material is extruded and cross-linked in advance to define the complete channel network geometry before the actual tissue construct fabrication is finalized. This preliminary action allows the channel pathways to be pre-established, enabling faster subsequent steps and improving overall fabrication efficiency.
3Stability of the object's composition
If the composite matrix bath is kept solid-like for structure stability, then shape control is improved, but the extrusion tip cannot easily deposit sacrificial material
Solution Approach 1:
The composite matrix bath exhibits dynamic rheological properties, transitioning from a solid-like state during storage and handling to a more fluid state during extrusion. This dynamic behavior allows the matrix to maintain structural integrity when stationary while becoming sufficiently fluid to allow easy deposition of sacrificial material when subjected to extrusion forces.
Solution Approach 2:
The rheological parameters of the composite matrix bath are carefully controlled to enable easy material deposition. By adjusting parameters such as viscosity, yield stress, and cross-linking density, the matrix bath is optimized to flow readily during extrusion while maintaining stability during subsequent processing and channel formation.
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 method enables the rapid and reproducible production of customized cell-laden bulk hydrogel thick tissue analogues with integrated perfusable channels, enhancing cell proliferation and supporting complex tissue engineering applications.
Implementation Method 1
cross-linking the hydrogel precursor to change one or more rheological properties of the composite matrix bath
Implementation Method 2
a portion of the composite matrix bath adjacent to the traveling extrusion tip is liquified, allowing the sacrificial material to be disposed along the predefined course, and as the extrusion tip continues along the predefined course, the portion of the composite matrix bath adjacent the disposed sacrificial material reverts to being substantially solid-like
Data Source
AI summary
Described herein are apparatuses, systems, and methods for fabricating tissue constructs, such as by fabricating perfusable tissue constructs by embedding a sacrificial material into a composite matrix yield stress support bath. A composite matrix bath can include a microgel filler and a hydrogel precursor. An extrusion tip can be used for embedded printing of perfusable tissue constructs by disposing sacrificial material into the composite matrix bath while the extrusion tip travels along a predefined course through the composite matrix bath. This sacrificial material can be the printed tissue construct or can be removed to render the matrix bath a perfusable tissue construct. The composite matrix bath can include acellular or cell-laden hydrogels. The sacrificial material can include a salt and a physiological buffer or a non-cytotoxic porogen material. The hydrogel precursor can include at least one of gellan and gelatin. Cross-linking can be carried out chemically, thermally, enzymatically, or physically.