Dehydrated Granular Bone Substitute Composition

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Solution Overview

Problem

Existing bone substitute compositions for vertebroplasty and mini-invasive surgeries face stability issues due to high solubility and inflammatory responses, with injectable mixtures hardening prematurely and experiencing volumetric contraction and viscosity drops after sterilization, leading to inadequate bone resorption and substitution processes.

Innovation Solution

A dry or quasi-dry granular composition comprising 0.1-5% cellulose-derived polymer, 75-99.9% hydroxyapatite and/or β tricalcium phosphate, and up to 10% water, which can be hydrated extemporaneously to form an injectable gel using various aqueous solutions, including radio-opaque agents for enhanced visibility during surgical procedures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If a cement for hard tissues comprising alpha tricalcium phosphate and carboxymethylcellulose is used, then the composition can be injected initially, but it hardens prematurely after a few minutes and is incapable of injection after sterilization

Engineering Contradiction:
ImproveinjectabilityVSAvoidcompositional stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical composition parameters by replacing alpha tricalcium phosphate with beta tricalcium phosphate and hydroxyapatite, and uses a mixture of cellulose derivatives (hydroxyethyl cellulose and carboxymethyl cellulose) with specific viscosity ranges. These parameter changes ensure the composition remains injectable after sterilization and maintains stability without premature hardening.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses a composite material system combining beta tricalcium phosphate and hydroxyapatite in specific ratios (40-70% and 30-60% respectively) with a dual cellulose derivative system. This composite approach provides both injectability and long-term stability, resolving the contradiction between ease of operation and compositional stability.

Inventive Principle:
Principle #40Composite materials

2Ease of manufacture

If alpha tricalcium phosphate is used in the cement composition, then the material can be formed initially, but it generates detrimental inflammatory processes and is insufficiently stable for bone resorption/substitution

Engineering Contradiction:
Improvematerial formationVSAvoidinflammatory response
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent changes the mineral phase composition by eliminating alpha tricalcium phosphate and using only beta tricalcium phosphate (40-70%) and hydroxyapatite (30-60%). This parameter change removes the harmful inflammatory effects while maintaining the ability to form the cement material and support bone resorption/substitution processes.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent converts the potentially harmful high solubility of calcium phosphate materials into a benefit by carefully controlling the composition of beta tricalcium phosphate and hydroxyapatite, achieving optimal degradation rates that match bone formation rates, thus converting potential harm into beneficial bone regeneration.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If the injectable composition is sterilized in an autoclave, then the material becomes sterile, but the viscosity drops and the composition becomes unsuitable for injection

Engineering Contradiction:
ImprovesterilityVSAvoidinjectability
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent selects cellulose derivatives with specific viscosity parameters (hydroxyethyl cellulose: 5-20 Pa.s; carboxymethyl cellulose: 2-10 Pa.s) that maintain adequate viscosity after autoclave sterilization. This parameter selection ensures the composition remains injectable even after sterilization, resolving the contradiction between achieving sterility and maintaining ease of operation.

Inventive Principle:
Principle #35Parameter changes

4Ease of operation

If a ready-for-use injectable composition is prepared, then the material can be used immediately, but it experiences demixing after one to two weeks of storage

Engineering Contradiction:
Improveimmediate usabilityVSAvoidstorage stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent optimizes the concentration parameters of cellulose derivatives (0.5-5% hydroxyethyl cellulose, 0.1-2% carboxymethyl cellulose) and mineral phase (85-95% beta tricalcium phosphate and hydroxyapatite) to achieve a balance between immediate usability and long-term storage stability, preventing demixing during storage while maintaining injectability.

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 composition forms a stable, radio-opaque hydrogel with exceptional rheological properties, allowing for effective bone reconstruction and visualization during surgeries, with no adverse reactions or foreign body rejection, ensuring prolonged visibility and effectiveness of bone substitutes.

Implementation Method 1

hydrated extemporaneously in order to form an injectable gel

Methodology Applied
Scientific EffectHydrogel formation: Hydrogel

Implementation Method 2

mixing the granular composition according to the invention, with a liquid selected from the group comprising water, saline, plasma or biological fluids

Methodology Applied
Scientific EffectHydration: Hydrates

Implementation Method 3

radio-opaque agents for enhanced visibility during surgical procedures

Methodology Applied
Scientific EffectRadio-opacity: Absorption (EM radiation)

Data Source

PatentUS8663676B2Dehydrated granular composition and biomedical applications thereof
Publication Date: 2014.03.04 BIOMATLANTE

AI summary

The invention relates to a granular composition for a biomaterial, that comprises from 0.1 to 5 wt % of at least one polymer derived from cellulose, 75 to 99.9 wt % of a mineral phase containing hydroxyapatite and/or β tricalcic phosphate, and 0 to 10 wt % of water, preferably 0 to 7 wt % of water, more preferably 0 to 5 wt % of water, and even more preferably approximately 5 wt % of water.