Scaffold-Free 3D Tissue Constructs Using Shear-Thinning Hydrogel Support

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Solution Overview

Problem

Current scaffold-based tissue engineering approaches face challenges such as interference with cell-cell interactions, immunogenicity, unsynchronized degradation rates, and inhomogeneity, while 3D printing with biodegradable thermoplastics limits simultaneous cell printing due to the use of organic solvents or high temperatures.

Innovation Solution

The use of a self-healing, shear-thinning, crosslinkable, biocompatible hydrogel support medium allows for the precise formation and maintenance of scaffold-free 3D tissue constructs by printing living cells without external biomaterial carriers, enabling controlled spatial placement and long-term culture with defined geometries.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If scaffold-based approaches are used to create functional tissues, then structural support is provided, but cell-cell interactions are interfered with and immunogenicity occurs

Engineering Contradiction:
Improvestructural supportVSAvoidinterference with cell-cell interactions and immunogenicity
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and removes the scaffold component from the tissue engineering system, transitioning from scaffold-based to scaffold-free approaches. By eliminating the external scaffold structure, cells are allowed to self-assemble and form tissue constructs without interference, thereby resolving the contradiction between structural support and cell-cell interaction interference.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces a temporary support medium that acts as an intermediary during the printing and initial formation stage. This medium provides necessary structural support during fabrication but is designed to be removable or degradable, allowing cells to eventually form their own structural framework without permanent external scaffolding.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If biodegradable thermoplastics are used for printing, then stable constructs with delicate structural control are formed, but cells cannot be printed simultaneously due to organic solvents or high temperature

Engineering Contradiction:
Improvestructural controlVSAvoidincompatibility with living cells
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The invention changes the material parameters from traditional thermoplastics to hydrogel-based bioinks that can be processed at lower temperatures and without harmful organic solvents. This parameter change enables simultaneous printing of both structural material and living cells, resolving the contradiction between structural control and cell compatibility.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention uses composite bioink formulations that combine hydrogel matrices with living cells, creating a material that provides both structural integrity and biological functionality. This composite approach allows the printed construct to maintain structural control while being compatible with and supportive of living cell viability.

Inventive Principle:
Principle #40Composite materials

3Object-affected harmful factors

If scaffold-free tissue engineering is used with multicellular building blocks, then cell-cell interactions are improved, but precise control of architecture and organization is difficult

Engineering Contradiction:
Improvecell-cell interactionsVSAvoidarchitecture and organization control
Core Design Contradiction:
Object-affected harmful factorsVSManufacturing precision

Solution Approach 1:

The invention applies preliminary action by pre-programming the spatial arrangement and organization of multicellular building blocks before they self-assemble. Through controlled printing sequences and positioning strategies, the initial architecture is established in a way that guides subsequent self-organization while maintaining precise overall control over the final tissue structure.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention embraces dynamics by allowing the tissue construct to evolve and reorganize over time through controlled cell self-assembly processes. The system transitions from a statically controlled printing phase to a dynamically self-organizing culture phase, where cells can interact and reorganize while maintaining the overall architectural framework established during printing.

Inventive Principle:
Principle #15Dynamics

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 generation of biomimetic cellular condensation-based engineered tissues with precise architecture and controlled spatial placement, overcoming the limitations of traditional scaffold-based approaches and allowing for the removal of the hydrogel support medium without damaging the constructs.

Implementation Method 1

a self-healing, sheer thinning, crosslinkable, biocompatible hydrogel support medium

Methodology Applied
Scientific EffectShear thinning: Shear Thinning

Implementation Method 2

a self-healing, sheer thinning, crosslinkable, biocompatible hydrogel support medium

Methodology Applied
Scientific EffectSelf-healing: Elastic Recovery

Implementation Method 3

a self-healing, sheer thinning, crosslinkable, biocompatible hydrogel support medium

Methodology Applied
Scientific EffectCrosslinking: Chemical Bonding

Data Source

PatentUS20210154368A1Bioink and crosslinkable support medium for printing
Publication Date: 2021.05.27 CASE WESTERN RESERVE UNIV
  • US20210154368A1 patent drawing
  • US20210154368A1 patent drawing
  • US20210154368A1 patent drawing

AI summary

A system for forming a scaffold-free 3D tissue construct includes a three dimensional (3D) printer; a self-healing, shear thinning, crosslinkable, biocompatible hydrogel support medium; and a first bioink that includes a plurality of cells. The first bioink is capable of being printed with the 3D printer into the hydrogel support medium in a defined shape.