Collagen Bio-ink Fabrication via Segmented Mixing

Solution Overview

Problem

Conventional bio-inks for 3D printing face challenges in achieving rapid formation, mild reaction conditions, biocompatibility, and structural stability, which are essential for printing artificial structures with specific functions and high structural stability.

Innovation Solution

A method for fabricating a collagen bio-ink using a collagen powder mixed with a neutral or acid solution, forming a hydrogel, and incorporating a cross-linking agent like genipin, which is then used in a 3D printing process with an extrusion-based bio-printer to create stable and biocompatible structures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional bio-ink is used for 3D printing, then the printing process can be performed, but the structural stability and biocompatibility of the printed structure are insufficient

Engineering Contradiction:
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The bio-ink preparation process is divided into two separate components: Component A (collagen solution with crosslinking agent) and Component B (basic solution). These components are prepared separately and then mixed immediately before printing, allowing each component to be optimized independently for stability and ease of use.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The collagen solution is pre-prepared with the crosslinking agent (genipin) already dissolved in it. This preliminary preparation ensures that the crosslinking agent is uniformly distributed and ready to react, improving the reliability of the final structure without adding complexity to the printing process itself.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If rapid formation is achieved in bio-ink, then printing efficiency improves, but reaction conditions become harsher

Engineering Contradiction:
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The reaction is designed to proceed rapidly at physiological temperature (37°C) by adjusting the pH trigger. When Component A and Component B mix, the pH change initiates rapid crosslinking without requiring high temperature or extreme conditions, thus maintaining productivity while avoiding harsh reaction conditions that would harm cells.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The crosslinking reaction is self-triggered by the pH change that occurs when Component A and Component B mix. No external catalyst, high temperature, or additional energy input is required - the mixing itself provides the trigger for rapid gelation, achieving both speed and mild conditions.

Inventive Principle:
Principle #25Self-service

3Reliability

If biocompatibility is improved in bio-ink, then cell viability increases, but structural stability decreases

Engineering Contradiction:
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

Genipin serves as a natural crosslinking agent that acts as an intermediary between collagen molecules. It forms crosslinks that provide structural stability while being biocompatible and non-toxic to cells, thus reconciling the contradiction between strength and biocompatibility.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The bio-ink combines collagen (for biocompatibility and biological functionality) with genipin (for crosslinking and structural integrity). This composite approach allows the system to exhibit both the biocompatibility of natural collagen and the mechanical strength provided by the crosslinked network.

Inventive Principle:
Principle #40Composite materials

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 collagen bio-ink demonstrates improved rheological properties, mechanical strength, and biocompatibility, enabling successful 3D printing with high structural stability and cell viability, suitable for tissue engineering applications.

Implementation Method 1

pushing back and forth to mix the first component and the second component to form a hydrogel and become a collagen bio-ink

Methodology Applied
Scientific EffectGelation: Gel

Implementation Method 2

incorporating a cross-linking agent like genipin

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Data Source

PatentUS11945958B2Method for fabricating collagen bio-ink, collagen bio-ink and 3D bio-printing method
Publication Date: 2024.04.02
  • US11945958B2 patent drawing
  • US11945958B2 patent drawing
  • US11945958B2 patent drawing

AI summary

A method for fabricating a collagen bio-ink includes steps as follows. A first component is provided, wherein the first component is to fill a collagen powder to a first syringe. A second component is provided, wherein the second component is to fill a neutral solution or an acid solution to a second syringe. A mixing step is performed, wherein the first syringe is connected to the second syringe with a Lure lock connector and pushing back and forth to mix the first component and the second component to form a hydrogel and become a collagen bio-ink.