Injectable DBM Bone Graft with Alginate Carrier

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Solution Overview

Problem

Current bone graft materials face limitations such as availability, immunogenic reactions, and reduced osteoinductivity, particularly with allograft bone and collagen-derived products, and sterilization methods can compromise bone formation capabilities.

Innovation Solution

An injectable and moldable implant comprising lyophilized demineralized bone matrix (DBM) in fiber and particle forms, combined with alginate and a liquid carrier, is developed to enhance osteoinductivity and osteoconductivity, avoiding collagen and requiring aseptic processing to prevent property stripping.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If sterilization is applied to bone graft materials, then infectious agents are eliminated, but natural properties such as osteoinductivity and osteoconductivity are compromised

Engineering Contradiction:
Improvesterilization efficacyVSAvoidosteoinductivity and osteoconductivity
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent extracts and removes collagen from the bone graft material through enzymatic digestion, eliminating the immunogenic component while preserving the osteoinductive and osteoconductive properties of the demineralized bone matrix. This extraction approach resolves the contradiction by removing the harmful immunogenic factor without compromising the beneficial bone formation properties.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs aseptic processing techniques that maintain different parameter conditions compared to traditional sterilization. By controlling processing parameters to prevent protein denaturation and growth factor degradation, the method preserves osteoinductivity and osteoconductivity while achieving sterilization through alternative means that do not compromise these critical properties.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If allograft bone is used to avoid donor site morbidity, then availability and convenience are improved, but osteogenic capacity and immunogenic response are worsened

Engineering Contradiction:
Improveavailability and convenienceVSAvoidosteoogenic capacity and immunogenic response
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent removes collagen from allograft bone material through enzymatic digestion, eliminating the source of immunogenic reactions while preserving the osteoinductive growth factors and osteoconductive mineral matrix. This extraction process resolves the contradiction by removing the harmful immunogenic component while maintaining the beneficial bone regeneration properties of allograft material.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent creates a composite bone graft material consisting of demineralized bone matrix with removed collagen, combining the osteoinductive properties of growth factors with the osteoconductive properties of the mineral framework. This composite approach eliminates immunogenicity while preserving and enhancing bone formation capabilities.

Inventive Principle:
Principle #40Composite materials

3Manufacturing precision

If collagen is included in bone graft materials to assist osteoconduction, then bone formation is improved, but immunogenic reactions are increased

Engineering Contradiction:
ImproveosteoconductionVSAvoidimmunogenic reactions
Core Design Contradiction:
Manufacturing precisionVSObject-generated harmful factors

Solution Approach 1:

The patent applies enzymatic digestion to extract and remove collagen from the bone graft material, eliminating the immunogenic component while preserving the osteoconductive mineral matrix and osteoinductive growth factors. This selective extraction resolves the contradiction by removing the harmful immunogenic factor while maintaining the beneficial bone conduction properties.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies different treatments to different components of the bone material: enzymatic digestion specifically targets collagen for removal while leaving the mineral matrix and growth factors intact. This localized treatment approach resolves the contradiction by selectively eliminating immunogenicity from collagen while preserving the osteoconductive and osteoinductive qualities of other bone components.

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 implant demonstrates high performance in promoting bone growth, with aseptically processed DBM implants showing 100% fusion in rat studies compared to irradiated controls, and improved osteoinductivity and osteoconductivity, facilitating faster bone healing and reduced immunogenic reactions.

Implementation Method 1

DBM is osteoinductive due to the presence of active bone growth factors including bone morphogenetic proteins (BMP). Osteoinductivity depends not only on the concentration of growth factors in DBM, but also on their availability to cells after implantation.

Methodology Applied
Scientific EffectOsteoinduction:

Implementation Method 2

DBM is osteoinductive due to the presence of active bone growth factors including bone morphogenetic proteins (BMP). Moreover, DBM is fully resorbable, and bone graft materials containing organic DBM are highly biocompatible because it contains many of the components of natural bone.

Methodology Applied
Scientific EffectOsteoconduction:

Implementation Method 3

An injectable and moldable implant comprising lyophilized demineralized bone matrix (DBM) in fiber and particle forms, combined with alginate and a liquid carrier

Methodology Applied
Scientific EffectGel formation: Gel

Implementation Method 4

requiring aseptic processing to prevent property stripping

Methodology Applied
Scientific EffectPrevention of protein denaturation:

Data Source

PatentEP3530295B1Demineralized bone matrix having improved handling characteristics
Publication Date: 2024.07.31 WARSAW ORTHOPEDIC INC
  • EP3530295B1 patent drawingFigure 1
  • EP3530295B1 patent drawingFigure 2
  • EP3530295B1 patent drawingFigure 3

AI summary

Provided is an injectable implant configured to fit at or near a bone defect to promote bone growth, the injectable implant comprising lyophilized demineralized bone matrix (DBM) being in fiber and particle forms; alginate; and a liquid carrier, wherein the DBM is in an amount of about 20 wt. % to about 40 wt. % of a total weight of the injectable implant, the alginate is in an amount of from about 3 wt. % to about 10 wt. % of the total weight of the injectable implant, and the liquid carrier is in an amount from about 50 wt. % to about 70 wt. % of the total weight of the injectable implant. A moldable implant and methods of making the implants are further provided.