Ionic Acid Demineralization for Bone Protein Release

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Solution Overview

Problem

The existing methods for producing osteoinductive compositions from demineralized bone matrix (DBM) are limited in their ability to effectively release native bone proteins, which are essential for bone formation and healing, due to the trapping of these proteins within the mineral component of bone tissue.

Innovation Solution

A method involving demineralization of bone tissue using an acid solution containing salt, specifically with concentrations between 0.5M to 10M, to expose native bone proteins, followed by optional processing into shaped materials like putty, gel, or blocks, to enhance the osteoinductive potential by increasing the concentration of bone proteins available for release.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If deionized water acid solution is used for demineralization, then the demineralization process is simple, but the bone protein concentration in the resulting composition is lower

Engineering Contradiction:
Improvebone protein concentrationVSAvoiddemineralization process complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent changes the ionic parameters of the demineralization solution by adding salts (NaCl, KCl, CaCl2, etc.) to achieve optimal protein release. The salt concentration is optimized at 0.5M to 10M, which significantly increases bone protein concentration in the resulting composition compared to deionized water-based solutions.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If salt concentration is increased in the acid solution, then bone protein release is enhanced, but protein stability may be affected by ionic interactions

Engineering Contradiction:
Improvebone protein releaseVSAvoidprotein stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent optimizes salt concentration parameters to balance protein release and stability. The specific concentration range of 0.5M to 10M was determined to provide optimal conditions where ionic strength enhances protein extraction while maintaining protein conformational stability through controlled ionic interactions.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replicates physiological ionic conditions found in natural bone environments by using salt solutions that mimic body fluid composition, thereby maintaining protein stability while enhancing release. This approach copies the natural conditions under which bone proteins function optimally.

Inventive Principle:
Principle #26Copying

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 method results in an osteoinductive composition with a higher concentration of native bone proteins, thereby accelerating bone formation and healing by optimizing the demineralization process, leading to improved bone grafting and repair applications.

Implementation Method 1

demineralizing the bone tissue to expose one or more native bone proteins, wherein demineralizing in step (c) comprises: (i) combining the bone tissue with an acid solution containing salt

Methodology Applied
Scientific EffectDemineralization:

Implementation Method 2

This demineralization leaves behind a collagen matrix and the various growth factors that may now be readily released in vivo

Methodology Applied
Scientific EffectAcid washing:

Implementation Method 3

Ionic content and concentration have complex effects on protein stability by modifying conformational stability and solubility. Ions binding to proteins may crosslink charged protein surfaces and lead to stabilization of the protein's native state

Methodology Applied
Scientific EffectIonic interactions:

Implementation Method 4

The net effect of salt on protein stability is a balance of multiple mechanisms by which ions interact with protein molecules individually and protein-protein interactions

Methodology Applied
Scientific EffectSalt effect on protein stability:

Data Source

PatentUS20230040249A1Method of Demineralizing Bone with an Ionic Solution
Publication Date: 2023.02.09 SEASPINE
  • US20230040249A1 patent drawing

AI summary

A method of producing an osteoinductive composition for in vivo use, in which the method includes obtaining bone tissue; cleaning the bone tissue with a plurality of washes; milling, grinding, and/or cutting the cleaned bone tissue into a plurality of bone pieces or fibers of a desired size; and demineralizing the plurality of bone pieces or fibers of a desired size to expose one or more native bone proteins, with demineralizing including combining the plurality of bone pieces or fibers in a reaction vessel with an ionic acid solution, soaking the plurality of bone pieces or fibers in the ionic acid solution, and exposing the one or more native proteins in the bone pieces or fibers.