NDGA-Polymerized Collagen Fibers for Tendon-Strength Bioprostheses

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Solution Overview

Problem

Current methods for producing nordihydroguaiaretic acid (NDGA) polymerized collagen fibers fail to achieve tensile strengths comparable to natural tendons, limiting their effectiveness in medical constructs and implants.

Innovation Solution

A method involving treating collagen with NDGA, drying it under tension, washing to remove unreacted intermediates, and repeating the process to produce fibers with an average tensile strength of 150-350 MPa, matching or exceeding the strength of natural ligaments and tendons.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If conventional NDGA polymerized collagen fiber methods are used, then the fibers are biocompatible, but the tensile strength is insufficient (only 30-91 MPa compared to 150-350 MPa needed)

Engineering Contradiction:
Improvetensile strengthVSAvoidbiocompatibility
Core Design Contradiction:
StrengthVSReliability

Solution Approach 1:

The patent applies parameter changes by modifying the polymerization process parameters including using specific NDGA concentrations (0.01-10% w/v), controlling pH levels (6.0-8.0), adjusting temperature ranges (4-37°C), and optimizing treatment times (1 hour to 1 week). These parameter adjustments enable achieving tensile strengths of 150-350 MPa while preserving biocompatibility through controlled cross-linking density and complete removal of unreacted NDGA intermediates

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material system combining collagen fibers with NDGA cross-linking agents. The composite structure integrates the biocompatibility of collagen with the strength-enhancing properties of NDGA polymerization, resulting in fibers that achieve both high tensile strength (150-350 MPa) and biocompatibility through the synergistic combination of natural collagen matrix and chemical cross-linking network

Inventive Principle:
Principle #40Composite materials

2Strength

If the collagen is dried under tension to improve fiber alignment and strength, then the tensile strength increases, but the process time and complexity increase

Engineering Contradiction:
Improvetensile strengthVSAvoidprocess complexity
Core Design Contradiction:
StrengthVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by performing tensioning during the drying phase before complete polymerization occurs. The collagen-NDGA complex is stretched and held under tension while moisture is removed, establishing the desired fiber alignment and structural configuration before the cross-linking network fully develops. This preliminary structural preparation simplifies subsequent processing while achieving the target tensile strength of 150-350 MPa

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent maintains continuous useful action by combining the drying process with the polymerization process in a continuous operation. The collagen is treated with NDGA, then dried under tension without interruption, allowing the cross-linking to proceed continuously as moisture is removed. This continuous process eliminates separate steps for alignment and strengthening, reducing overall process complexity while achieving high tensile strength

Inventive Principle:
Principle #20Continuity of useful action

3Strength

If multiple cycles of treatment, drying, and washing are performed, then the tensile strength reaches 150-350 MPa, but the manufacturing time increases

Engineering Contradiction:
Improvetensile strengthVSAvoidmanufacturing speed
Core Design Contradiction:
StrengthVSProductivity

Solution Approach 1:

The patent applies periodic action through multiple cyclic treatments where the collagen-NDGA complex undergoes repeated cycles of drying under tension, washing to remove intermediates, and re-treatment. Each cycle incrementally increases the cross-linking density and fiber strength. By optimizing the number of cycles (typically 2-5 cycles) and the duration of each cycle, the process achieves tensile strengths of 150-350 MPa while managing manufacturing time through efficient cycle optimization

Inventive Principle:
Principle #19Periodic action

4Strength

If NDGA concentration is increased to enhance cross-linking and strength, then the tensile strength improves, but the risk of cytotoxicity from unreacted intermediates increases

Engineering Contradiction:
Improvetensile strengthVSAvoidcytotoxicity
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent converts the potentially harmful unreacted NDGA intermediates into a benefit by implementing thorough washing protocols that remove these intermediates. The process uses multiple washing steps with buffer solutions to completely eliminate cytotoxic residues after polymerization. This approach allows the use of higher NDGA concentrations (up to 10% w/v) to achieve strong cross-linking and high tensile strength (150-350 MPa) while ensuring the final product is biocompatible and free of harmful substances

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 high-strength NDGA polymerized collagen fibers suitable for bioprostheses and implants with tensile strengths between 180-300 MPa, matching the mechanical properties of natural tissues, enhancing their suitability for tendon and ligament repair, augmentation, or replacement.

Implementation Method 1

treating collagen with a solution comprising NDGA

Methodology Applied
Scientific EffectChemical bonding: Chemical Bonding

Implementation Method 2

drying the NDGA-treated collagen while holding the treated collagen in tension

Methodology Applied
Scientific EffectEvaporation: Evaporation

Data Source

PatentEP2111240B1Methods of making high-strength NDGA polymerized collagen fibers and related medical devices and constructs
Publication Date: 2012.08.08 SHRINERS HOSPITALS FOR CRIPPLED CHILDREN
  • EP2111240B1 patent drawingFigure 1
  • EP2111240B1 patent drawingFigure 2
  • EP2111240B1 patent drawingFigure 3

AI summary

The disclosure describes methods of making high-strength NDGA collagen and associated methods of preparing collagen preparatory material and medical bioprostheses.