Hierarchical Scaffold for Uniform Cell Distribution and High Loading

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Solution Overview

Problem

Current large-scale cell culture systems face challenges in achieving uniform cell distribution, sufficient nutrient and mass transfer, mechanical stability, and non-destructive cell collection while maintaining cell phenotype and function.

Innovation Solution

A scaffold with a hierarchical structure is developed, featuring high porosity, permeability, and mechanical properties, made from biocompatible materials like alginate and gelatin, with adjustable pore sizes and customizable shapes, allowing for high cell loading and non-destructive cell recovery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If 3D scaffolds are used for large-scale cell culture, then cell amplification capacity is improved, but uniform cell distribution and sufficient nutrient mass transfer become difficult to achieve

Engineering Contradiction:
Improvecell amplification capacityVSAvoiduniform cell distribution
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The scaffold is divided into multiple modules that can be independently configured. Each module contains a porous structure with controlled pore sizes (10-500 μm) and porosity (10%-95%), creating segmented pathways for nutrient distribution and cell penetration throughout the large-scale culture system.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The scaffold incorporates hollow channels (0.1-5 cm diameter) positioned at specific locations to provide localized fluid flow pathways. The macro structure (columnar, blocky, lamellar, cystic or tubular) is optimized for specific regions to enhance nutrient mass transfer and maintain uniform cell distribution throughout the entire scaffold volume.

Inventive Principle:
Principle #3Local quality

2Quantity of substance

If scaffold porosity is increased to improve cell loading, then mechanical stability deteriorates

Engineering Contradiction:
Improvecell loadingVSAvoidmechanical stability
Core Design Contradiction:
Quantity of substanceVSStrength

Solution Approach 1:

The scaffold utilizes composite material structures combining natural and/or synthetic biomaterials with controlled cross-linking. The material composition is engineered to achieve high porosity (10%-95%) for cell loading while maintaining adequate mechanical strength through the cross-linked network structure and hollow channel reinforcement.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The scaffold employs porous material structures with controlled pore sizes (10-500 μm) and porosity (10%-95%) that balance cell loading capacity with mechanical integrity. The porous architecture provides pathways for cell infiltration and nutrient transport while the material matrix maintains structural stability.

Inventive Principle:
Principle #31Porous materials

3Object-affected harmful factors

If cross-linking conditions are made milder for biocompatibility, then scaffold mechanical strength deteriorates

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidmechanical strength
Core Design Contradiction:
Object-affected harmful factorsVSStrength

Solution Approach 1:

The cross-linking process parameters are optimized to achieve mild conditions compatible with cell biology while sufficient to generate mechanical strength. Cross-linking agents and conditions are adjusted to create a stable scaffold structure that does not harm cell phenotype or function, balancing biocompatibility with mechanical integrity.

Inventive Principle:
Principle #35Parameter changes

4Ease of manufacture

If scaffold structure is simplified for ease of manufacture, then cell culture performance deteriorates

Engineering Contradiction:
Improvescaffold fabricationVSAvoidcell culture performance
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The scaffold design incorporates adjustable and customizable parameters including porosity (10%-95%), pore size (10-500 μm), hollow channel dimensions (0.1-5 cm), and macro structure type (columnar, blocky, lamellar, cystic or tubular). These dynamic design elements allow optimization for specific cell culture applications while maintaining manufacturability through standardized fabrication processes.

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

The scaffold enables efficient cell proliferation, aggregation, and function maintenance, with high cell loading rates and mechanical stability, facilitating in vitro cell culture and potential applications in tissue repair and regeneration.

Implementation Method 1

a porosity of the scaffold body is 10% to 95%

Methodology Applied
Scientific EffectPorosity: Porosity

Implementation Method 2

a Young's modulus of the scaffold body is 0.1 kPa to 10 MPa

Methodology Applied
Scientific EffectMechanical properties: Elasticity

Implementation Method 3

a scaffold with hierarchical structure having a high porosity and permeability

Methodology Applied
Scientific EffectPermeability: Permeation

Implementation Method 4

Among matrix materials, alginate and gelatin are widely used due to good biocompatibility, biodegradability and mild cross-linking conditions

Methodology Applied
Scientific EffectBiocompatibility:

Implementation Method 5

the hydration characteristic of alginate and reversible cross-linking of gelatin at a cell culture temperature

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Implementation Method 6

the cells in the scaffold can be recovered nondestructively... efficient cell proliferation, aggregation, and function maintenance

Methodology Applied
Scientific EffectCell aggregation:

Data Source

PatentUS20230048690A1Scaffold with hierarchical structure, preparation method therefor and application thereof
Publication Date: 2023.02.16 TSINGHUA UNIVERSITY
  • US20230048690A1 patent drawing
  • US20230048690A1 patent drawing

AI summary

A scaffold with hierarchical structure, a preparation method therefor and an application thereof. The scaffold with hierarchical structure has a structure ranging from centimeters to micrometers, and is used in the fields of three-dimensional cell culture, in vitro large-scale amplification, in vitro tissue-like construction, tissue engineering and regenerative medicine, pathological model research, new drug research and development, drug toxicology research and the like.