Enzymatically Degradable PEG Hydrogels via Acetylation Tuning

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Solution Overview

Problem

Conventional hydrogels and medical implants based on synthetic biocompatible polymers, such as PEG, undergo passive degradation primarily due to hydrolysis, lacking controlled enzymatic degradation profiles suitable for in-vivo applications.

Innovation Solution

The development of enzymatically degradable compositions comprising synthetic biocompatible polymers with reactive electrophilic groups and glycosaminoglycans with varying degrees of acetylation, allowing for tunable enzymatic degradation profiles, forming biocompatible polymers and degradable hydrogels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional hydrogels based on synthetic biocompatible polymers like PEG are used, then biocompatibility is achieved, but degradation is passive and uncontrolled due to hydrolysis

Engineering Contradiction:
ImprovebiocompatibilityVSAvoiddegradation control
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent modifies the chemical structure of PEG by incorporating hydrolyzable linkages (esters, carbonates, anhydrides) and reactive electrophilic groups (NHS esters, epoxides, anhydrides) into the polymer backbone. This allows the material to transition from passive hydrolytic degradation to active enzymatic degradation while maintaining biocompatibility, enabling controlled degradation rates through parameter adjustment of the polymer structure

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite hydrogel systems by crosslinking functionalized PEG polymers with glycosaminoglycans (GAGs) such as hyaluronic acid, chondroitin sulfate, or heparin. This composite structure combines the biocompatibility and tunable degradation of PEG derivatives with the natural occurrence and enzymatic degradability of GAGs, achieving both reliability and controlled degradation

Inventive Principle:
Principle #40Composite materials

2Duration of action of moving object

If PEG derivatives with reactive electrophilic groups are used to enable enzymatic degradation, then degradation control is improved, but device complexity increases

Engineering Contradiction:
Improvedegradation controlVSAvoidpolymer structure complexity
Core Design Contradiction:
Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent divides the PEG polymer structure into distinct functional segments: hydrophilic PEG chains for biocompatibility, hydrolyzable linkage segments for controlled breakdown, and electrophilic functional group segments for enzymatic recognition. This segmentation allows each component to perform its specific function while maintaining overall system manageability and synthetic feasibility

Inventive Principle:
Principle #1Segmentation

3Object-affected harmful factors

If hydrogels are made non-adherent and non-thrombogenic for surgical use, then safety is improved, but affinity for binding to proteins and cell adsorption is reduced

Engineering Contradiction:
ImprovethrombogenicityVSAvoidprotein binding affinity
Core Design Contradiction:
Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality modification by incorporating specific functional groups (NHS esters, epoxides, anhydrides) at specific locations within the PEG polymer structure. These localized electrophilic sites provide controlled reactivity for crosslinking with GAGs and proteins, enabling targeted protein binding and cell adhesion in specific regions while maintaining overall non-thrombogenic properties of the bulk hydrogel material

Inventive Principle:
Principle #3Local quality

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

These compositions enable controlled and tunable in-vivo degradation, enhancing the persistence and functionality of hydrogels and polymers by varying the degree of acetylation, providing a more controllable and less passive degradation process.

Implementation Method 1

synthetic biocompatible polymer having reactive electrophilic groups which are capable of reacting with a combination of glycosaminoglycans

Methodology Applied
Scientific EffectChemical bonding: Chemical Bonding

Implementation Method 2

suitable for in-vivo enzymatic degradation

Methodology Applied
Scientific EffectEnzymatic degradation: Enzyme

Data Source

PatentEP2688940B1Enzymatically degradable compositions
Publication Date: 2017.07.12 SOFRADIM PRODUCTION SAS

AI summary

Enzymatically degradable compositions containing biocompatible polymers reactive with glycosaminoglycan compositions having a first glycosaminoglycan compound having a first degree of acetylation and a second glycosaminoglycan compound having a second degree acetylation different than the first degree of acetylation.