Neutralized Glucomannan Scaffold for 3D Tissue Culture

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Solution Overview

Problem

Current biomaterial scaffolds for tissue engineering, particularly for bone regeneration, face challenges with inconsistent mechanical properties and limited porosity, which hinder cell growth and vascularization, necessitating the development of scaffolds with larger pores for efficient ion/gas exchange and protein adsorption.

Innovation Solution

A neutralized glucomannan scaffold with a pH of 6.0 to 8.0 is created by contacting a basic glucomannan scaffold with an aqueous solution under controlled pressure, providing a porous structure suitable for cell growth and tissue engineering, and is amenable to surface modification for enhanced cell adhesion and proliferation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If natural biomaterials such as collagen, alginate and chitosan are used as substrates for 3D tissue culture, then biocompatibility is improved, but mechanical properties consistency deteriorates

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidmechanical properties consistency
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent employs composite material strategy by combining glucomannan with other biomaterials such as hyaluronic acid, chitosan, or collagen to create hybrid scaffolds. This composite approach allows the system to maintain the biocompatibility of natural materials while achieving more consistent and tunable mechanical properties through the synergistic effects of multiple materials with complementary characteristics.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent applies parameter changes by systematically varying the molecular weight, degree of substitution, crosslinking density, and compositional ratios of glucomannan-based materials. These parameter adjustments enable precise control over mechanical properties such as stiffness, elasticity, and strength while maintaining biocompatibility, thereby resolving the inconsistency issue.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If scaffold porosity is increased to promote ion/gas exchange and protein adsorption, then bone regeneration capability is improved, but structural integrity deteriorates

Engineering Contradiction:
Improvebone regeneration capabilityVSAvoidstructural integrity
Core Design Contradiction:
ProductivityVSStrength

Solution Approach 1:

The patent utilizes porous material design with specifically engineered pore sizes (200-300 μm) and interconnected pore structures in glucomannan-based scaffolds. The porous architecture is optimized to provide adequate surface area for ion/gas exchange and protein adsorption while maintaining structural integrity through controlled pore distribution and wall thickness, enabling both high bone regeneration capability and sufficient mechanical strength.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent employs composite materials strategy by combining glucomannan with reinforcing materials such as hydroxyapatite, beta-tricalcium phosphate, or other ceramics to create composite scaffolds. These composite structures enhance both the mechanical strength and the osteoconductivity of the scaffold, allowing simultaneous improvement of structural integrity and bone regeneration capability through the synergistic effects of organic and inorganic components.

Inventive Principle:
Principle #40Composite materials

3Ease of manufacture

If basic glucomannan scaffold is used for cell culture, then scaffold formation is simplified, but cell growth efficiency deteriorates due to unsuitable pH

Engineering Contradiction:
Improvescaffold formationVSAvoidcell growth efficiency
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The patent applies preliminary action by pre-neutralizing the glucomannan scaffold with weak acids such as citric acid, acetic acid, or lactic acid during the scaffold fabrication process. This preliminary neutralization ensures that the scaffold achieves an appropriate pH range (6.5-7.5) before cell seeding, eliminating the need for complex post-fabrication pH adjustment procedures and creating an immediately cell-friendly environment that enhances cell growth efficiency.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses intermediary substances such as buffer solutions containing phosphate buffers or HEPES buffers as mediators to adjust and stabilize the pH of glucomannan scaffolds. These intermediary buffers facilitate gentle pH adjustment without causing material degradation, bridging the gap between the inherently basic glucomannan and the neutral pH required for optimal cell growth, thereby maintaining both ease of manufacture and cell growth efficiency.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 neutralized glucomannan scaffold supports efficient cell growth, diffusion of nutrients and waste, and promotes osteogenic differentiation, offering a thermally stable, non-toxic, and biodegradable solution for 3D cell culture and tissue regeneration, including bone regeneration.

Implementation Method 1

contacting a basic glucomannan scaffold having a pH of greater than 8 with an aqueous solution to form a neutralized glucomannan scaffold having a pH of 6.0 to 8.0

Methodology Applied
Scientific EffectAcid-base reaction: Redox Reactions

Implementation Method 2

a porous structure that can permit diffusion of oxygen, nutrients, expressed products and cellular waste

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 3

Hydrolysis of the acetyl group in the presence of alkali decreases the solubility of glucomannan and results in aggregation followed by gel formation

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 4

Glucomannan has a backbone of approximately 5-10% substituted acetyl groups that participate in hydrogen bonding and hydrophobic interactions that confers solubility

Methodology Applied
Scientific EffectHydrogen bonding: Chemical Bonding

Data Source

PatentEP2785830B1Glucomannan scaffolding for three-dimensional tissue culture and engineering
Publication Date: 2018.06.20 RGT UNIV OF CALIFORNIA
  • EP2785830B1 patent drawingFigure 1A~1D
  • EP2785830B1 patent drawingFigure 2
  • EP2785830B1 patent drawingFigure 3A~3B

AI summary

The present invention provides a neutralized glucomannan scaffold capable of promoting cell growth and suitable for three-dimensional tissue culture and engineering. The present invention also provides methods for making and degrading the neutralized glucomannan scaffold. The present invention further provides a method of growing cells on a neutralized glucomannan scaffold.