Demineralized Bone Matrix Protein Control via Acid-EDTA Segmentation

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Solution Overview

Problem

Current methods for protein extraction and demineralization of mineralized biocomposites, such as bone and teeth, often result in demineralized biocomposites with higher protein content than desired, limiting their manufacturing efficiency.

Innovation Solution

A multi-step process involving demineralization and salt extraction steps, where pulverized bone is first treated with an acidic solution to remove minerals and some proteins, followed by a salt solution to extract collagen-bound proteins, optimizing the extraction of proteins from the biocomposite matrix.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If a single-step demineralization process is used, then the process is simple and fast, but the protein content in the demineralized biocomposite remains high

Engineering Contradiction:
Improveprotein content controlVSAvoidprocess steps
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The demineralization process is divided into multiple sequential steps: initial demineralization in acidic solution followed by secondary demineralization in EDTA solution. This segmentation allows progressive removal of minerals and proteins, achieving lower residual protein content (below 5% dry weight) that cannot be achieved in a single step, while maintaining reasonable process complexity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

EDTA solution is introduced as an intermediary demineralizing agent after the initial acid treatment. The EDTA chelates calcium ions differently than strong acids, enabling selective extraction of remaining mineral components bound to proteins without excessive protein denaturation, thus achieving better protein control

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If strong acidic solution is used for demineralization, then mineral removal is efficient, but protein extraction is excessive

Engineering Contradiction:
Improvemineral removal efficiencyVSAvoidprotein loss
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The process uses periodic alternation between strong acid demineralization and milder EDTA demineralization. The strong acid provides rapid initial mineral removal, then the EDTA phase continues mineral extraction with gentler action on proteins, achieving cumulative mineral removal efficiency while limiting excessive protein extraction through the alternating treatment regimes

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The demineralization approach changes chemical parameters between steps: using strong acid (low pH) for initial rapid demineralization, then switching to EDTA solution (higher pH, chelating mechanism) for secondary demineralization. This parameter change allows efficient mineral removal in both phases while the milder second phase prevents excessive protein loss

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

This process effectively reduces the protein content in demineralized bone matrix, achieving a higher yield of extracted proteins and resulting in demineralized biocomposites with lower residual protein levels compared to existing methods.

Implementation Method 1

The demineralizing process typically involves placing the bone or other mineralized biocomposite into an acidic solution to dissolve the mineral component

Methodology Applied
Scientific EffectChemical dissolution:

Implementation Method 2

followed by a salt solution to extract collagen-bound proteins, optimizing the extraction of proteins from the biocomposite matrix

Methodology Applied
Scientific EffectSolvation: Solvation

Data Source

PatentUS11976107B2Method for manufacture of demineralized biocomposite materials
Publication Date: 2024.05.07 ORTHOGRAFT PTE LTD
  • US11976107B2 patent drawing
  • US11976107B2 patent drawing
  • US11976107B2 patent drawing

AI summary

The invention comprises several embodiments of a multi-step method for processing hard tissues, including bone, teeth, tooth enamel and dentin, mollusk shells, crustacean shells, deep sea sponge, coral, radiolarians, diatoms, antler bone, and other naturally occurring mineralized biocomposites, and soft tissues, including connective tissue, cartilage, tendon, ligament, vertebral discs, pathological mineralized soft tissues and other soft tissues, including at least processing a portion of tissue by one or more of contacting, immersing, adding and mixing a portion of tissue with a first solution, obtaining a first material, derived from processing the portion of tissue with the first solution, processing the first material using one or more alkali metal and ammonium salts of citrate, acetate, phosphate, sulfate, tartarate and chloride, and obtaining a resulting material, derived from processing the first material with the one or more salts.