PEG Crosslinked Hydrogel Bioink for 3D Bioprinting

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Solution Overview

Problem

Current hydrogel 3D printing technologies face challenges in forming self-supporting structures due to low viscosity of hydrogel precursor solutions, which result in poor structural definition and incompatibility with multi-layer printing, and existing strategies like high polymer concentrations or co-printing with support inks have limitations such as inhibiting cell spreading and proliferation or causing nozzle clogging.

Innovation Solution

Development of crosslinked hydrogel compositions comprising a biocompatible polymer, functionalized polyethylene glycol as a crosslinker, and optionally cells or bioactive factors, which transition from a low-viscosity solution to a self-supporting gel phase during extrusion, allowing for the formation of 3D structures that retain shape and integrity without requiring a supporting structure.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If hydrogel precursor solutions are used for 3D printing, then cell encapsulation and biological compatibility are improved, but structural definition and self-supporting capability deteriorate due to low viscosity

Engineering Contradiction:
Improvecell encapsulation and biological compatibilityVSAvoidstructural definition
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent applies preliminary action by pre-crosslinking the hydrogel precursor solution to form a gel phase bioink before the printing process. This pre-gelation provides the necessary structural support and shape fidelity while maintaining cell encapsulation, resolving the contradiction between biological compatibility and structural definition.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the physical state parameter of the bioink from liquid solution to gel phase through controlled crosslinking. This parameter change increases viscosity and provides self-supporting capability while preserving the biocompatible nature of the hydrogel matrix for cell encapsulation.

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If polymer concentration is increased to improve structural definition, then shape fidelity is improved, but cell spreading, migration, and proliferation are inhibited

Engineering Contradiction:
Improveshape fidelityVSAvoidcell spreading, migration, and proliferation
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The patent changes the physical state parameter of the bioink from liquid solution to gel phase through controlled crosslinking. This parameter change increases viscosity and provides self-supporting capability while preserving the biocompatible nature of the hydrogel matrix for cell encapsulation.

Inventive Principle:
Principle #35Parameter changes

3Strength

If post-printing cross-linking is performed to improve gel strength, then structural integrity is improved, but layer definition deteriorates due to rapid solution diffusion

Engineering Contradiction:
Improvegel strengthVSAvoidlayer definition
Core Design Contradiction:
StrengthVSManufacturing precision

Solution Approach 1:

The patent applies preliminary action by pre-crosslinking the hydrogel precursor solution to form a gel phase bioink before the printing process. This pre-gelation provides the necessary structural support and shape fidelity while maintaining cell encapsulation, resolving the contradiction between biological compatibility and structural definition.

Inventive Principle:
Principle #10Preliminary action

4Manufacturing precision

If rapid cross-linking is performed to improve layer definition, then strand definition is improved, but nozzle clogging and poor inter-layer adhesion occur

Engineering Contradiction:
Improvestrand definitionVSAvoidnozzle clogging and inter-layer adhesion
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by pre-crosslinking the hydrogel precursor solution to form a gel phase bioink before the printing process. This pre-gelation provides the necessary structural support and shape fidelity while maintaining cell encapsulation, resolving the contradiction between biological compatibility and structural definition.

Inventive Principle:
Principle #10Preliminary action

5Ease of operation

If conventional solution phase bioinks are used, then ease of extrusion is improved, but multi-layer printing compatibility deteriorates

Engineering Contradiction:
Improveease of extrusionVSAvoidmulti-layer printing compatibility
Core Design Contradiction:
Ease of operationVSAdaptability or versatility

Solution Approach 1:

The patent changes the physical state parameter of the bioink from liquid solution to gel phase through controlled crosslinking. This parameter change increases viscosity and provides self-supporting capability while preserving the biocompatible nature of the hydrogel matrix for cell encapsulation.

Inventive Principle:
Principle #35Parameter changes

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

The method enables the creation of well-defined, self-supporting 3D structures with controlled mechanical properties, suitable for cell growth scaffolds, that maintain cell viability and allow for intricate, porous structures with fine features, overcoming the limitations of existing hydrogel printing techniques.

Implementation Method 1

the crosslinks between the biocompatible polymer chains comprise repeating units having the following structure

Methodology Applied
Scientific EffectChemical crosslinking: Chemical Bonding

Implementation Method 2

transition from a low-viscosity solution to a self-supporting gel phase during extrusion

Methodology Applied
Scientific EffectGelation: Gel

Data Source

PatentUS10173357B2Poly(ethylene glycol) cross-linking of soft materials to tailor viscoelastic properties for bioprinting
Publication Date: 2019.01.08 NORTHWESTERN UNIV
  • US10173357B2 patent drawing
  • US10173357B2 patent drawing
  • US10173357B2 patent drawing

AI summary

Extrudable hydrogel compositions for printing 3D objects, such as cell growth scaffolds, are provided. Also provided are methods for making the crosslinked hydrogel compositions and the printed objects and methods for culturing cells using the cell growth scaffolds. The hydrogel precursor solutions are aqueous solutions comprising a biocompatible polymer, functionalized polyethylene glycol as a crosslinker and, optionally, cells and/or bioactive factors.