Bioactive ECM Gel Manufacturing via Alkaline Solubilization

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Solution Overview

Problem

Current methods for manufacturing bioactive gels from extracellular matrix material are time-consuming and require aggressive purification steps, leading to bioactivity depletion and increased regulatory barriers.

Innovation Solution

The method involves solubilizing ECM in a basic environment, followed by neutralization, to create bioactive gels that retain bioactivity, avoiding cumbersome purification and reducing regulatory burdens, using alkaline compounds like NaOH and controlling solubilization and neutralization conditions to maintain bioactive molecule content.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If aggressive purification steps are used to manufacture bioactive gels from ECM, then purity of the gel is improved, but bioactivity is depleted and manufacturing time increases

Engineering Contradiction:
ImprovepurityVSAvoidbioactivity
Core Design Contradiction:
Manufacturing precisionVSReliability

Solution Approach 1:

The patent changes the chemical parameters of the manufacturing process by using mild solubilization conditions (pH 2.0-3.0, specific salt concentrations) instead of aggressive purification steps. This parameter change allows the gel to maintain bioactivity while achieving sufficient purity for tissue repair applications.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a simplified, single-use manufacturing approach where the ECM is directly solubilized and formed into gels without complex multi-step purification. This disposable-style process reduces manufacturing complexity and time while preserving bioactive components.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Manufacturing precision

If aggressive purification steps are used to manufacture bioactive gels from ECM, then purity of the gel is improved, but manufacturing time increases

Engineering Contradiction:
ImprovepurityVSAvoidmanufacturing time
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent modifies the process parameters by using controlled solubilization at specific pH and temperature conditions, replacing time-consuming aggressive purification steps. This achieves adequate purity in a fraction of the time, significantly improving manufacturing productivity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent skips the traditional multi-step aggressive purification sequence and rushes through the manufacturing process using direct solubilization and gel formation. This streamlined approach maintains essential purity while dramatically reducing manufacturing time.

Inventive Principle:
Principle #21Skipping (Rushing through)

3Manufacturing precision

If aggressive purification steps are used to manufacture bioactive gels from ECM, then purity of the gel is improved, but regulatory burden increases

Engineering Contradiction:
ImprovepurityVSAvoidregulatory burden
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent changes the manufacturing parameters to use mild, well-characterized solubilization conditions rather than complex purification protocols. This simplifies the process documentation and validation requirements, reducing regulatory burden while maintaining adequate purity for medical use.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent adopts a simplified manufacturing paradigm analogous to disposable products, where a single-step solubilization and gel formation process replaces complex multi-step purification. This reduces the regulatory complexity associated with validating multiple process steps and purification stages.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 approach results in bioactive gels that effectively assist tissue repair with reduced scar tissue formation and improved restoration of tissue structure and function, while minimizing time and regulatory hurdles.

Implementation Method 1

solubilizing a particularized ECM in a basic (greater than pH 7) environment, which when neutralized with acid provides bioactive gels

Methodology Applied
Scientific EffectSolubilization in basic environment: Solvation

Implementation Method 2

solubilizing a particularized ECM in a basic (greater than pH 7) environment, which when neutralized with acid provides bioactive gels

Methodology Applied
Scientific EffectNeutralization reaction: Chemical Bonding

Data Source

PatentEP2953659B1Methods of manufacturing bioactive gels from extracellular matrix material
Publication Date: 2019.10.16 ACELL INC
  • EP2953659B1 patent drawingFigure 1
  • EP2953659B1 patent drawingFigure 2

AI summary

The present invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels which retain bioactivity, and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment and neutralizing to provide bioactive gels.