Collagen Isolation via Enzymatic Treatment for Controlled Polymerization

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Solution Overview

Problem

Existing methods for isolating collagen from natural sources struggle to achieve controlled polymerization and enhanced microstructural and mechanical properties, leading to inefficient repair of damaged or diseased tissues.

Innovation Solution

A method involving the isolation of collagen from collagen-containing sources, such as placental or skin tissue, through comminution, extraction, and precipitation, followed by resuspension in an acidic solution, allowing for controlled polymerization and enhanced mechanical integrity of engineered ECMs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If existing methods for isolating collagen from natural sources are used, then collagen can be obtained, but controlled polymerization and enhanced microstructural and mechanical properties cannot be achieved

Engineering Contradiction:
Improvecontrolled polymerizationVSAvoidisolation process complexity
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by treating collagen with enzymes (collagenase, pepsin, or protease) during the isolation process to pre-process the collagen molecules before polymerization. This enzymatic treatment modifies the collagen structure in advance, enabling controlled polymerization and enhanced microstructural properties while maintaining a manageable isolation process

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs parameter changes by controlling specific conditions during collagen isolation and polymerization, including pH levels, temperature, ionic strength, and enzyme concentration. By systematically adjusting these parameters, the patent achieves controlled polymerization and enhanced mechanical properties without excessively complicating the manufacturing process

Inventive Principle:
Principle #35Parameter changes

2Productivity

If collagen is isolated using conventional methods, then collagen preparation is achieved, but enhanced rate of polymerization and improved mechanical properties are not obtained

Engineering Contradiction:
Improvepolymerization rateVSAvoidcollagen purity
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The patent applies the extraction principle by selectively removing impurities and non-collagenous proteins from the source material during the isolation process. Through differential extraction steps and enzymatic treatments, pure collagen is separated from the complex tissue matrix, achieving high collagen purity while maintaining the ability to enhance polymerization rate through controlled polymerization conditions

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses preliminary enzymatic action on isolated collagen to prepare it for enhanced polymerization. The enzymatic treatment modifies collagen molecules in advance, creating structures that polymerize faster and form more stable microstructures, thereby increasing productivity without sacrificing purity

Inventive Principle:
Principle #10Preliminary action

3Stability of the object's composition

If collagen polymerization is attempted without controlled conditions, then polymerization occurs, but unstructured aggregation of misfolded proteins results

Engineering Contradiction:
Improvemicrostructural organizationVSAvoidpolymerization control system
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent introduces intermediary substances and conditions to mediate the polymerization process. Buffer solutions with specific pH and ionic strength, along with enzymatic treatments, act as intermediaries that guide collagen molecules into proper conformations and facilitate organized assembly into stable microstructures, preventing unstructured aggregation

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent achieves stable microstructural organization by systematically controlling polymerization parameters including pH, temperature, ionic strength, and collagen concentration. These parameter changes create optimal conditions for controlled self-assembly of collagen into organized fibrillar structures rather than random aggregates

Inventive Principle:
Principle #35Parameter changes

4Strength

If existing collagen preparations are used, then tissue graft compositions can be formed, but enhanced mechanical integrity and controlled polymerization are not achieved

Engineering Contradiction:
Improvemechanical integrityVSAvoidpreparation method complexity
Core Design Contradiction:
StrengthVSEase of manufacture

Solution Approach 1:

The patent applies preliminary enzymatic treatment and controlled isolation steps to prepare collagen with enhanced properties before forming tissue graft compositions. This advance preparation ensures that the collagen will polymerize with improved mechanical integrity while keeping the overall manufacturing process manageable through standardized protocols

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent enhances mechanical integrity by optimizing preparation parameters including pH, temperature, ionic strength, and polymerization time. These controlled parameter changes produce collagen preparations with superior mechanical properties without excessively complicating the manufacturing process

Inventive Principle:
Principle #35Parameter changes

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 method results in collagen compositions with increased polymerization rates, reduced lag time, and improved mechanical properties, such as strength and stiffness, facilitating effective tissue repair and cell proliferation.

Implementation Method 1

resuspending the precipitate in an aqueous solution wherein the aqueous solution used to resuspend the collagen precipitate is an acidic solution

Methodology Applied
Scientific EffectAcidic solution solubility:

Implementation Method 2

The molecular forces that orchestrate the self assembly of soluble, monomeric collagen into higher ordered structures are weak so their assembly can easily turn into an unstructured aggregation of misfolded proteins

Methodology Applied
Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 3

mixing the comminuted source material with an extraction solution, extracting the comminuted source material to form a soluble fraction and an insoluble fraction

Methodology Applied
Scientific EffectExtraction:

Implementation Method 4

precipitating the collagen from the soluble collagen fraction

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Data Source

PatentUS8512756B2Collagen preparation and method of isolation
Publication Date: 2013.08.20 PURDUE RES FOUND
  • US8512756B2 patent drawing
  • US8512756B2 patent drawing
  • US8512756B2 patent drawing

AI summary

Collagen compositions, methods for preparing those collagen compositions, and graft compositions formed from those collagen compositions are provided. In particular, methods of isolating collagen that exhibits an enhanced rate of polymerization and enhanced microstructural and mechanical properties upon polymerization, such collagen compositions, and graft compositions formed from such collagen compositions are provided.