Collagen Nanofiber Coating for Controlled Antibiotic Release

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Solution Overview

Problem

Current orthopaedic and dental implants face challenges with bioinert metal surfaces that lack osteointegration and require additional surgeries for antibiotic delivery, as existing bioactive coatings suffer from non-controlled antibiotic release and cytotoxicity issues.

Innovation Solution

A bioactive nanocomposite layer composed of collagen type I nanofibers and hydroxyapatite nanoparticles, created through electrospinning and electroblowing, is developed for efficient antibiotic impregnation, ensuring controlled release and biocompatibility by minimizing poly(ethylene oxide content and using crosslinking agents like EDC and NHS.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibiotics are delivered through additional surgeries, then antibiotic delivery is achieved, but patient comfort deteriorates and costs increase

Engineering Contradiction:
Improveantibiotic deliveryVSAvoidpatient comfort
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

Antibiotics are pre-loaded into the collagen nanofiber matrix during the coating process, so that the implant is ready for controlled antibiotic release immediately upon implantation, eliminating the need for additional surgical interventions for antibiotic delivery

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The implant coating system autonomously provides antibiotic delivery through controlled release from the collagen nanofiber matrix, without requiring external surgical intervention or additional medical procedures

Inventive Principle:
Principle #25Self-service

2Reliability

If hydroxyapatite content is increased to enhance bioactivity, then osteointegration improves, but mechanical resistance decreases

Engineering Contradiction:
ImproveosteointegrationVSAvoidmechanical resistance
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The coating combines collagen type I nanofibers with hydroxyapatite nanoparticles to create a composite material that leverages the mechanical strength and structural integrity of collagen while incorporating the bioactive osteointegration properties of hydroxyapatite, achieving both high mechanical resistance and excellent osteointegration

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

Hydroxyapatite nanoparticles are distributed within the collagen nanofiber matrix at optimized local concentrations, providing sufficient bioactivity and osteointegration enhancement while maintaining the overall mechanical integrity of the coating structure

Inventive Principle:
Principle #3Local quality

3Ease of manufacture

If poly(ethylene oxide) is used to facilitate electrospinning, then nanofiber formation improves, but cytotoxicity increases

Engineering Contradiction:
Improvenanofiber formationVSAvoidcytotoxicity
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

Poly(ethylene oxide) is used only as a temporary processing aid during electrospinning and is completely removed through extensive washing with water and ethanol, leaving no detectable residues in the final coating, thus eliminating cytotoxicity while maintaining nanofiber formation capabilities

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Poly(ethylene oxide) serves as a disposable sacrificial component that facilitates the electrospinning process but is intentionally designed to be completely removed after processing, similar to a temporary mold or support structure that is discarded after serving its purpose

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Reliability

If antibiotics are released at high concentrations, then antimicrobial efficacy improves, but systemic toxicity increases

Engineering Contradiction:
Improveantimicrobial efficacyVSAvoidsystemic toxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The coating provides localized high-concentration antibiotic release at the implant surface where it is most needed for preventing infections, while the controlled release mechanism ensures that systemic exposure remains minimal, achieving high local efficacy without proportional systemic toxicity

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

Antibiotics are pre-loaded into the coating at high concentrations ready for immediate local release upon implantation, creating a high local concentration gradient that drives effective antimicrobial action at the implant site while limiting systemic absorption

Inventive Principle:
Principle #10Preliminary action

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 solution provides a biocompatible, biodegradable coating that achieves sustained antibiotic release exceeding minimum inhibition concentrations without systemic toxicity, enhancing osteoinductive properties and reducing the need for secondary surgeries.

Implementation Method 1

The layer is prepared by the combination of electrospinning and electroblowing of the collagen solution comprising hydroxyapatite nanoparticles

Methodology Applied
Scientific EffectElectrospinning: Electrohydrodynamics

Implementation Method 2

The layer is prepared by the combination of electrospinning and electroblowing of the collagen solution comprising hydroxyapatite nanoparticles

Methodology Applied
Scientific EffectElectroblowing: Electrostatic Deposition

Implementation Method 3

using crosslinking agents like EDC and NHS

Methodology Applied
Scientific EffectCrosslinking: Chemical Bonding

Data Source

PatentEP3311854B1A nanocomposite layer on the basis of collagen nanofibers, and a method of preparation thereof
Publication Date: 2020.08.05 PROSPON SPOL
  • EP3311854B1 patent drawingFigure 1a~1b
  • EP3311854B1 patent drawingFigure 1c~2
  • EP3311854B1 patent drawingFigure 3~4

AI summary

The subject of the invention is a bioactive nanocomposite layer prepared by the combination of electrospinning and electroblowing of a collagen solution comprising hydroxyapatite nanoparticles and poly(ethylene oxide), where, after the preparation and the crosslinking, the layer consists of 75 to 100 wt. % of collagen type I fibres, 5 - 15 wt. % of hydroxyapatite, and 0 - 1 wt. % of poly(ethylene oxide). The subject of this invention is also a method of production of said layer and a method of depositing antibiotics for a more effective releasing thereof without increasing the cytotoxicity. Said method comprises the impregnation of crosslinked sterilized collagen/hydroxyapatite layers with antibiotics in the form of a solution. The subject of the invention also comprises orthopaedic and dental implants based on metal or metal alloys, electrostatically coated with said composite layer based on collagen nanofibers with integrated hydroxyapatite nanoparticles and an antibiotic or a combination of antibiotics.