Crosslinked Polyelectrolyte Multilayer Films for Sustained Protein Release

Solution Overview

Problem

Current methods for coating surfaces with polyelectrolyte multilayers struggle to achieve high protein incorporation rates and maintain protein bioactivity, especially in biomedical applications where controlled release and biocompatibility are crucial, often resulting in protein degradation and burst release effects.

Innovation Solution

A process involving sequential deposition of alternate polyelectrolytes with complementary reactive groups, followed by cross-linking with a coupling agent like 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and subsequent treatment with a protein solution, particularly growth factor proteins, to form stable and bioactive cross-linked polyelectrolyte multilayer films.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If proteins are incorporated into polyelectrolyte multilayer films using conventional methods, then protein incorporation is achieved, but protein bioactivity is lost due to degradation and burst release

Engineering Contradiction:

Improveprotein bioactivityVSAvoidprotein stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The polyelectrolyte multilayer film is cross-linked before protein incorporation using EDC coupling agent. This preliminary cross-linking creates a stable network structure that prevents protein degradation and burst release, while still allowing controlled protein incorporation and sustained bioactivity

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention creates a composite structure combining cross-linked polyelectrolyte multilayers with incorporated proteins. The cross-linked polyelectrolyte matrix provides structural stability and protection, while the incorporated proteins maintain bioactivity through controlled release mechanisms

Inventive Principle:

Principle #40Composite materials

2Reliability

If polyelectrolyte multilayer films are made from biopolymers or polyaminoacids to achieve biocompatibility, then biocompatibility is improved, but structural integrity is compromised due to sensitivity to solvents, pH and ionic strength

Engineering Contradiction:

ImprovebiocompatibilityVSAvoidstructural integrity

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The polyelectrolyte multilayer film is cross-linked before protein incorporation using EDC coupling agent. This preliminary cross-linking creates a stable network structure that prevents protein degradation and burst release, while still allowing controlled protein incorporation and sustained bioactivity

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention changes the chemical parameters of the polyelectrolyte system by introducing cross-links through EDC coupling. This transforms the physical and chemical properties of the film, enhancing stability against solvents, pH changes, and ionic strength variations while preserving biocompatibility

Inventive Principle:

Principle #35Parameter changes

3Stability of the object's composition

If cross-linking is performed to stabilize polyelectrolyte multilayer films against aggressive media, then stability is improved, but protein incorporation rate decreases

Engineering Contradiction:

Improvefilm stabilityVSAvoidprotein incorporation rate

Core Design Contradiction:

Stability of the object's compositionVSProductivity

Solution Approach 1:

The polyelectrolyte multilayer film is cross-linked before protein incorporation using EDC coupling agent. This preliminary cross-linking creates a stable network structure that prevents protein degradation and burst release, while still allowing controlled protein incorporation and sustained bioactivity

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The cross-linked polyelectrolyte multilayer film maintains a porous or network structure that allows protein diffusion and incorporation. The cross-links provide stability while the network architecture preserves pathways for protein penetration and binding

Inventive Principle:

Principle #31Porous materials

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

This method enables high protein incorporation with sustained bioactivity, preventing burst release and ensuring efficient slow release, as demonstrated by persistent bioactivity of rhBMP-2 for at least 10 days, while maintaining biocompatibility and stability under various conditions.

Implementation Method 1

reacting said complementary reactive groups of the coated surface in the presence of a coupling agent, as to form amide bonds between said complementary reactive groups giving rise to a cross-linked polyelectrolyte multilayers film

Methodology Applied

Scientific EffectCondensation reaction:

Implementation Method 2

treating said cross-linked polyelectrolyte multilayers film with a protein containing solution, preferably with a growth factor type protein containing solution, as to incorporate said protein on and inside said cross-linked polyelectrolyte multilayers film

Methodology Applied

Scientific EffectAdsorption: Adsorption

Data Source

PatentEP2387423B8Process for preparing a surface coated by crosslinked polyelectrolyte multilayer films as a biomimetic reservoir for proteins

Publication Date: 2016.04.06 UNIVERSITY OF MONTPELLIER

AI summary

The invention relates to processes for coating a surface with a crosslinked polyelectrolytes multilayer film incorporating a protein, preferably a growth factor type protein. The invention also relates to crosslinked polyelectrolytes multilayer films obtained by this process, and a coated surface obtained therefrom.