Bioactive Hydrogel Heparin PEG Crosslinking

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Solution Overview

Problem

Existing bioactive hydrogels lack versatility in physical and biochemical properties, are restricted in mechanical properties, and fail to adequately support complex regenerative processes, including cell adhesion, signal molecule binding, and modular functionality.

Innovation Solution

A bioactive hydrogel composed of heparin and star-branched polyethylene glycol with functionalized end groups, where heparin is bound covalently via amide bonds or enzyme-cleavable peptide sequences, allowing for controlled gel formation and modification to achieve varied physical and biochemical properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If hydrogels with synthetic or biological main components are used to provide structural support and protection for regenerating cells, then the carrying and supporting function is improved, but the control over cell adhesion and the binding/release of signal molecules is insufficient

Engineering Contradiction:
Improvestructural supportVSAvoidcontrol over cell adhesion and signal molecule binding
Core Design Contradiction:
StrengthVSAdaptability or versatility

Solution Approach 1:

The hydrogel is segmented into distinct functional domains: star-branched PEG provides structural support through its branched architecture, while heparin segments provide signal molecule binding capability. This segmentation allows each component to independently fulfill its specific function without compromising the other.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention combines synthetic star-branched PEG and biological heparin into a composite hydrogel material. This composite structure integrates the mechanical stability of synthetic polymers with the bioactivity of natural ECM components, achieving both structural support and controlled signal molecule binding/release functions.

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If crosslinking chemistry is used to provide mechanical stability to hydrogels, then the structural integrity is improved, but the range of mechanical properties such as stiffness and swelling is restricted

Engineering Contradiction:
Improvestructural integrityVSAvoidrange of mechanical properties
Core Design Contradiction:
Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The invention enables parameter changes by varying the heparin-to-PEG ratio, crosslinking density, and molecular weight of components. These parameter adjustments allow continuous tuning of mechanical properties including stiffness, swelling ratio, and degradation rate, while maintaining structural integrity through the stable amide bond crosslinking.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If natural ECM components are used to provide bioactivity and cell interaction, then the biocompatibility is improved, but the mechanical properties and structural stability are limited

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidmechanical properties
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The hydrogel combines natural heparin for biocompatibility and signal molecule binding with synthetic star-branched PEG for mechanical stability. This composite approach allows the natural component to provide bioactivity while the synthetic component compensates for mechanical limitations.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The star-branched PEG backbone serves multiple functions: providing structural framework, enabling crosslinking for mechanical stability, and offering adjustable architecture through its branched structure. This multi-functionality allows a single synthetic component to support multiple requirements of the hydrogel system.

Inventive Principle:
Principle #6Universality (Multi-functionality)

4Reliability

If highly hydrated materials are used to support regenerative processes, then the biocompatibility and cell-friendly environment are improved, but the mechanical strength and structural stability decrease

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidmechanical strength
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The hydrogel exhibits local quality differentiation where the highly hydrated regions provide biocompatibility and nutrient diffusion, while the star-branched PEG crosslinked network provides localized mechanical strength. This spatial differentiation of properties allows simultaneous achievement of soft, cell-friendly environments and structural integrity.

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

The hydrogel provides a biocompatible, degradable scaffold with adjustable stiffness and swelling, enabling controlled cell adhesion, reversible signal molecule binding, and modular restructuring, suitable for regenerative therapies and tissue replacement.

Implementation Method 1

the heparin is bound directly by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimides/N-hydroxysulfosuccinimide (EDC/s-NHS) activated carboxyl groups of heparin to the terminal amino groups of the polyethylene glycol covalently by amide bonds

Methodology Applied
Scientific EffectChemical Bonding: Chemical Bonding

Implementation Method 2

combinations of synthetic and polysaccharide-based components of the natural ECM have also been developed, which exploit the special affinity of these molecules for important signal molecules, for example growth factors

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Data Source

PatentUS8859706B2Bioactive hydrogel
Publication Date: 2014.10.14 ZETASCI
  • US8859706B2 patent drawing

AI summary

The invention relates to a bioactive hydrogel as a hybrid material of heparin and star-branched polyethylene glycol with functionalized end groups, wherein the heparin is bound directly by reaction of the carboxyl groups activated with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimides/N-hydroxysulfosuccinimide (EDC/s-NHS) with the terminal amino groups of the polyethylene glycol covalently by amide bonds.