Cold-Cleaning Bone Grafts for Pathogen Removal and Collagen Integrity

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Solution Overview

Problem

Existing bone graft cleaning processes fail to effectively remove bone marrow, prions, bacteria, and viruses while maintaining the polycrystalline mineral structure and collagen integrity, leading to potential health risks and mechanical instability.

Innovation Solution

A low-temperature cleaning process combining mechanical and chemical treatments, including soaking in distilled water, slightly alkaline solutions, organic solvents, alkaline solutions, and oxidizing agents, with centrifugation and sonication, to decellularize bone and osteochondral tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If high temperature sintering (650-1200 °C) is used to eliminate pathogens, then pathogen removal is effective, but the collagen structure is destroyed and mineral structure becomes overly crystalline

Engineering Contradiction:
Improvepathogen eliminationVSAvoidcollagen structure integrity
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent changes the temperature parameter from high (650-1200 °C) to low (below 60 °C) and uses chemical agents (enzymes, detergents, oxidizing agents) instead of thermal energy to achieve pathogen elimination while preserving the organic matrix structure

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent replaces the thermal-mechanical sintering process with a chemical cleaning process using enzymes, detergents, and oxidizing agents to remove pathogens without destroying the collagen-mineral composite structure

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Object-affected harmful factors

If strong chemical agents (sodium hydroxide, hydrogen peroxide) are used for pathogen inactivation, then pathogen removal is effective, but the mineral and collagen structure is damaged

Engineering Contradiction:
Improvepathogen inactivationVSAvoidmineral and collagen structure
Core Design Contradiction:
Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent changes the concentration and type of chemical agents used, employing milder enzymes and controlled amounts of detergents and oxidizing agents at low temperatures to reduce structural damage while maintaining pathogen elimination efficacy

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses controlled, partial exposure to chemical agents with multiple washing steps to remove pathogens while minimizing damage to the organic-inorganic composite structure through limited contact time and sequential treatment

Inventive Principle:
Principle #16Partial or excessive action

3Object-affected harmful factors

If extensive cleaning treatments are applied to remove all organic material, then pathogen removal is maximized, but mechanical strength and osteoconductivity are reduced

Engineering Contradiction:
Improvebone marrow and lipid removalVSAvoidmechanical integrity
Core Design Contradiction:
Object-affected harmful factorsVSStrength

Solution Approach 1:

The patent selectively extracts only the harmful components (bone marrow, lipids, cellular material) using targeted enzymes and detergents while leaving the structural collagen and mineral phases intact to maintain mechanical strength

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies different cleaning agents to different aspects of the tissue structure - using proteases for cellular material, detergents for lipids, and mild oxidizing agents for surface decontamination, thereby achieving thorough cleaning without uniform destruction of the matrix

Inventive Principle:
Principle #3Local quality

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 process effectively removes bone marrow, prions, and pathogens while preserving the mineral and collagen structure, resulting in a biocompatible graft with maintained mechanical properties for bone regeneration.

Implementation Method 1

sonication of said biological material sample as a mechanical cleaning treatments

Methodology Applied
Scientific EffectUltrasonic vibration: Ultrasonic Vibration

Implementation Method 2

sonication of said biological material sample as a mechanical cleaning treatments

Methodology Applied
Scientific EffectAcoustic cavitation: Acoustic Cavitation

Implementation Method 3

centrifugation and sonication of said biological material sample as a mechanical cleaning treatments

Methodology Applied
Scientific EffectCentrifugal force: Centrifugal Force

Implementation Method 4

Reacting biological material sample/s treated/obtained according to step bii) into Alkaline solution (pH=10.0-14.0) as a chemical cleaning treatment in combination with centrifugation and sonication of said biological material sample as a mechanical cleaning treatments. v. Reacting biological material sample/s treated/obtained according to step biv) with Oxidating agent as a chemical cleaning treatment

Methodology Applied
Scientific EffectOxidation: Oxidation

Data Source

PatentEP4643893A1A cold-cleaning process for deriving a decellularized graft tissue to be used as a medical device, or as a raw material
Publication Date: 2025.11.05 IND BIOMEDICHE INSUBRI
  • EP4643893A1 patent drawingFigure 1A~1C
  • EP4643893A1 patent drawingFigure 2A~3
  • EP4643893A1 patent drawingFigure 4~5

AI summary

The present invention deals with a cold-cleaning process for deriving a decellularized bone tissue sample or decellularized osteochondral tissue sample to be used as a medical device, or as a raw material.