Thermally Reversible Support Medium for 3D Tissue Bioprinting
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Solution Overview
Problem
Conventional tissue bioprinting techniques are limited by the inability to use soft protein hydrogels effectively due to their reliance on two-dimensional support matrices, which restrict the addition of new tissues or components during the printing process and hinder tissue maturation.
Innovation Solution
A thermally reversible support medium, composed of betaine-modified methylcellulose and agarose microparticles, allows for the bioprinting of soft protein hydrogels within a bioreactor, enabling the gelation of the medium to form a solid structure around the hydrogel, facilitating the delivery of nutrients and allowing for the maturation of tissues over time, with the option to alter between gel and solid states for repeated structure formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If soft protein hydrogels are used as support matrix in conventional bioprinting, then the native extracellular matrix structure is preserved, but the hydrogels cannot be effectively used due to limitations of two-dimensional support matrices
Solution Approach 1:
The patent employs thermally reversible gelation of methylcellulose, which transitions from a liquid state at printing temperature to a gel state at physiological temperature. This phase transition enables the support matrix to provide structural stability after printing while maintaining printability during the bioprinting process, effectively resolving the contradiction between preserving native ECM structure and achieving versatile support matrix functionality.
2Strength
If tissues are secured to hydrogel support material after printing, then structural integrity is maintained, but new tissues or components cannot be added during the printing process
Solution Approach 1:
The patent creates a dynamic support matrix system where methylcellulose transitions between liquid and gel states based on temperature. During printing, the liquid state allows easy manipulation and addition of multiple tissue components. After printing, thermal gelation provides structural integrity. This dynamic property enables both structural strength and the versatility to add new tissues during the printing process.
3Ease of manufacture
If two-dimensional support matrices are used, then printing is simplified, but tissue maturation is hindered
Solution Approach 1:
The patent transitions from two-dimensional planar support matrices to three-dimensional volumetric gel structures through thermal gelation of methylcellulose. This dimensional change provides adequate space and structural environment for tissue maturation while maintaining the simplicity of the printing process. The 3D gel structure allows tissues to mature properly unlike constrained 2D matrices.
4Strength
If the support medium is in gel state during printing, then structural support is provided, but media delivery for nutrient transport is restricted
Solution Approach 1:
The patent utilizes thermal phase transitions of methylcellulose to resolve the contradiction between structural support and media delivery. During printing, the liquid state allows free media flow for nutrient transport. After printing, thermal gelation provides structural support while the gel structure remains permeable to media diffusion, enabling continued nutrient delivery to embedded tissues.
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 creation of complex, matured tissue structures by allowing for the growth and maturation of biologic populations within the bioprinted tissues before additional layers are added, increasing the viability of the final printed structures and providing a supportive environment for cellular growth and structural integrity.
Implementation Method 1
The support medium can act as a fluid (e.g., a viscosity between 1-10,000 centipoise) below a gelation temperature and a solid (e.g., a gel, e.g., a viscosity above 50,000 centipoise) above the gelation temperature
Implementation Method 2
The bioreactor and contents of the inner volume can be heated to raise the temperature of the support medium above the gelation temperature which causes the support medium to gel
Implementation Method 3
When introducing additional or supplementary structures or live biologic populations to an initial structure, the support medium can be cooled below a gelation temperature thereby acting a viscous fluid
Implementation Method 4
A solution (e.g., a media) can be delivered, such as via a peristaltic pump, to an entrance port in the base of the bioreactor
Data Source
AI summary
A method of forming a tissue or an organ, including: disposing, in a support medium in a gel state, a composition comprising a live biologic; changing a state of the support medium from the gel state to a solid state; and supporting, in the support medium at the solid state, the live biologic in the composition.