Bioactive Bone Repair Granules with Sustained BMP-2 Release

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current bone repair materials, including synthetic and allografts, face limitations such as limited osteoconductive and osteoinductive properties, foreign body reactions, and inefficient delivery of bioactive growth factors, which hinder effective bone regeneration and are not suitable for all patient groups, especially the elderly or those with impaired bone metabolism.

Innovation Solution

A method for preparing bioactive bone repair substrates comprising granules with a homogeneous distribution of bioactive materials within a calcium phosphate matrix, allowing for sustained and controlled release of osteoconductive and osteoinductive factors, thereby enhancing bone repair and regeneration by mimicking natural growth factor signaling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If synthetic bone repair materials are used, then the supply limitation and donor site morbidity of autografts are avoided, but the osteoconductive and osteoinductive properties are reduced

Engineering Contradiction:
Improveavailability for bone repairVSAvoidosteoconductive and osteoinductive properties
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The invention uses a composite material system combining calcium phosphate (providing osteoconductive scaffold) with BMP-2 growth factor (providing osteoinductive signal). This composite approach allows synthetic materials to achieve both availability and biological effectiveness by integrating multiple functional components that work synergistically to overcome the limitations of pure synthetic materials.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The invention applies local quality by incorporating BMP-2 growth factor specifically at the bone defect site within the calcium phosphate matrix. The growth factor is localized within the granules and released at the target location, providing concentrated osteoinductive activity exactly where needed, thereby enhancing local bone regeneration while maintaining the advantages of synthetic materials.

Inventive Principle:
Principle #3Local quality

2Ease of manufacture

If growth factor is adsorbed superficially onto scaffold, then the process is simple, but the release is short-term and causes burst release with side effects

Engineering Contradiction:
Improvesimplicity of processVSAvoidduration of growth factor release
Core Design Contradiction:
Ease of manufactureVSDuration of action of moving object

Solution Approach 1:

The invention applies the nested doll principle by incorporating BMP-2 growth factor inside the calcium phosphate granule matrix structure. The growth factor is nested within the porous granules, allowing sustained release over extended periods. This nested configuration prevents burst release while maintaining manufacturing simplicity, as the growth factor is incorporated during granule formation rather than requiring separate coating steps.

Inventive Principle:
Principle #7Nested doll (Nesting)

Solution Approach 2:

The invention uses porous calcium phosphate granules as the delivery vehicle for BMP-2. The porous structure provides internal volume for growth factor incorporation and enables controlled release through the pore network. This porous material approach extends the duration of growth factor release from days to weeks, eliminating burst release while keeping the manufacturing process relatively simple.

Inventive Principle:
Principle #31Porous materials

3Reliability

If co-precipitation coating process is used, then osteoinductivity is enhanced, but the process is labour-intensive, expensive and causes significant loss of bioactive material

Engineering Contradiction:
Improveosteoinductive capacityVSAvoidcomplexity of coating process
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention merges the scaffold formation and growth factor incorporation steps into a single granulation process. Instead of separately creating the calcium phosphate scaffold and then coating it with BMP-2, the growth factor is incorporated during the granule formation itself. This combined approach maintains osteoinductive capacity while dramatically simplifying the manufacturing process and reducing bioactive material loss.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention applies preliminary action by incorporating the BMP-2 growth factor into the calcium phosphate granules during their formation, before the granules are applied to the bone defect. This preliminary incorporation ensures uniform distribution and prevents material loss that would occur during subsequent coating operations, while maintaining the osteoinductive effectiveness of the growth factor.

Inventive Principle:
Principle #10Preliminary action

4Reliability

If autologous bone is used, then immunocompatibility and osteoconductive properties are excellent, but additional surgery and donor site morbidity are required

Engineering Contradiction:
Improveimmunocompatibility and osteoconductive propertiesVSAvoidsurgical complexity and patient morbidity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The invention applies the copying principle by creating a synthetic calcium phosphate scaffold that replicates the osteoconductive properties of natural bone. The scaffold mimics the structural and biological functions of autologous bone, providing the same osteoconductive pathway for bone regeneration without requiring harvest from the patient's own body, thereby eliminating donor site morbidity and additional surgery.

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

The method provides a sustained release of bioactive materials over extended periods, improving bone repair and regeneration, increasing treatment potential, and reducing material loss and complexity in the manufacturing process, while being suitable for a wider range of patients, including those with impaired bone metabolism.

Implementation Method 1

The foreign body reactions of graft material may significantly hinder the regeneration of bone and the osseointegration of material used for filling bone defects though. Therefore the therapeutic effects of alternative graft materials for filling bone defects for bone repair are far from satisfactory.

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP3863691B1Bioactive bone repair particles
Publication Date: 2023.12.20 ACCESS2BONE IP BV
  • EP3863691B1 patent drawingFigure 1

AI summary

The invention relates to a bioactive bone repair substrate comprising granules obtainable by or obtained from a set solid state mixture of a calcium phosphate based bone repair matrix and a bioactive material, preferably granules having an average diameter between 25 and 10,000 µm.