Injectable Hydroxyapatite Collagen Implant for Oral Tissue Regeneration

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Solution Overview

Problem

Current injectable implant formulations for periodontal tissue regeneration face challenges such as discomfort, pain, and inefficiency due to the need for incisions, and existing formulations often clog small cannulas or do not replicate the natural in vivo environment effectively, limiting their effectiveness and ease of use.

Innovation Solution

A dried implant composition of nanocrystalline hydroxyapatite particles derived from natural bone and naturally crosslinked fibrous collagen, with a specific size and ratio, is rehydrated and mixed to create an injectable aqueous formulation that can be extruded through a gauge 18 cannula with minimal force, providing a matrix close to the natural environment for regeneration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If hydroxyapatite particles derived from natural bone are used to provide a matrix close to the natural in vivo environment, then the regeneration effectiveness is improved, but the risk of clogging the cannula increases due to irregular and longitudinal particle shape

Engineering Contradiction:
Improveregeneration effectivenessVSAvoidextrusion through cannula
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent changes the particle size parameter of hydroxyapatite to nanocrystalline dimensions (30-50 nm length, 14-25 nm width) to maintain natural bone morphology while enabling extrusion through gauge 18 cannula. This parameter change resolves the contradiction by making particles small enough to pass through the cannula while retaining the nanocrystalline structure essential for regeneration effectiveness.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent copies the natural nanocrystalline structure and morphology of hydroxyapatite from human bone mineral, creating particles that replicate the hexagonal space group P63/m structure with specific dimensions. This copying approach ensures the material provides a matrix close to the natural in vivo environment while the reduced size enables successful extrusion through the cannula.

Inventive Principle:
Principle #26Copying

2Ease of operation

If the implant formulation is made injectable to avoid incisions and reduce patient discomfort, then the ease of operation and patient comfort are improved, but the formulation may clog small cannulas

Engineering Contradiction:
ImproveinjectabilityVSAvoidextrusion capability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent changes the particle size parameter to nanocrystalline dimensions and controls the collagen-hydroxyapatite ratio (1:4 to 4:1) to achieve optimal viscosity and flow properties. These parameter changes enable the formulation to be injectable through gauge 18 cannula while maintaining extrusion capability with force not exceeding 60 N.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material combining nanocrystalline hydroxyapatite particles with collagen in specific ratios. This composite structure provides both the injectability needed to avoid incisions and the structural integrity required for successful extrusion through small cannula, resolving the contradiction between ease of operation and reliability.

Inventive Principle:
Principle #40Composite materials

3Reliability

If nanocrystalline hydroxyapatite particles with natural bone morphology are used to replicate the natural environment, then the biological compatibility and regeneration quality are improved, but the particle irregularity increases clogging risk

Engineering Contradiction:
Improvebiological compatibilityVSAvoidflowability
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent changes the size parameter to nanocrystalline dimensions (30-50 nm × 14-25 nm) while maintaining the hexagonal morphology characteristic of natural bone. This parameter change enables particles with irregular natural morphology to flow readily and extrude through gauge 18 cannula, resolving the contradiction between biological compatibility and flowability.

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

The formulation allows for convenient and effective oral tissue regeneration with reduced patient discomfort, improved extrusion properties, and a matrix that closely mimics the natural environment, enhancing bone and periodontal ligament regeneration.

Implementation Method 1

it can be sterilized by gamma-ray or X-ray- irradiation while preserving its extrusion properties

Methodology Applied
Scientific EffectGamma-ray or X-ray irradiation: X-Ray

Implementation Method 2

Ascorbic acid is consumed for scavenging the radicals released during sterilization by gamma-ray or X-ray- irradiation

Methodology Applied
Scientific EffectRadical scavenging: Oxidation

Data Source

PatentEP3941542B1Injectable aqueous implant formulation containing ascorbic acid
Publication Date: 2022.12.28 GEISTLICH PHARMA
  • EP3941542B1 patent drawingFigure 1
  • EP3941542B1 patent drawingFigure 2
  • EP3941542B1 patent drawingFigure 3A~3B

AI summary

The invention relates to: An injectable aqueous implant formulation for use in oral tissue regeneration which has been sterilized by gamma-ray or X-ray- irradiation and can be extruded through a tapering system and an 18 gauge (0.838 mm inner diameter) 25.4 mm long cannula with a force not exceeding 60 N, which comprises 25-45 w/w % of a mixture of nanocrystalline hydroxyapatite particles derived from natural bone having a size of 50 to 200 pm as determined by sieving and fragments of naturally crosslinked fibrous collagen material that pass through a 0.5 mm sieve, whereby the w/w ratio of nanocrystalline hydroxyapatite to collagen is from 1.8 to 4.5, which contains at least 0.05 % (w/w) ascorbic acid, and a process for preparing the above injectable aqueous implant formulation