Visible-Light PEG Hydrogel Cross-Linking for Cell-Safe Polymerization

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Solution Overview

Problem

Existing methods for cross-linking polyethylene glycol (PEG) hydrogels are limited by the need for specialized UV equipment and can be toxic to cells during polymerization, making them unsuitable for certain biomedical applications.

Innovation Solution

A visible light photopolymerization system using a ruthenium complex, photoinitiator, and co-initiator, along with a di-thiol-terminated cross-linker and cysteine-containing peptides, allows for the formation of PEG hydrogels without the need for UV lamps, reducing toxicity and improving control over the process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If UV photopolymerization is used to cross-link PEG hydrogels, then cross-linking efficiency is improved, but cell toxicity increases and specialized UV equipment is required

Engineering Contradiction:
Improvecross-linking efficiencyVSAvoidcell toxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the wavelength parameter of light from UV to visible light range, and adjusts the photoinitiator system from conventional UV initiators to a ruthenium complex-based visible light system. This parameter change enables cross-linking at longer wavelengths that are less harmful to cells while maintaining cross-linking efficiency through optimized photoinitiator concentrations and visible light irradiation conditions.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces a ruthenium complex (Ru(bpy)3)2+ as an intermediary photoinitiator that absorbs visible light and transfers energy to activate the cross-linking reaction. This intermediary system allows the use of visible light instead of direct UV light, reducing cell toxicity while maintaining cross-linking efficiency through the mediating role of the ruthenium complex in energy transfer.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If UV equipment is used for photopolymerization, then hydrogel formation is achieved, but capital investment and device complexity increase

Engineering Contradiction:
Improvehydrogel formationVSAvoidspecialized equipment requirement
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent makes the photopolymerization system universal by using visible light which can be provided by common light sources already present in most laboratories, eliminating the need for specialized UV equipment. The ruthenium complex photoinitiator system can be activated by various visible light sources including LEDs, fluorescent lamps, and even ambient light, making the process widely applicable without requiring specialized device infrastructure.

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

Solution Approach 2:

The patent employs a chemical system (ruthenium complex photoinitiator) that is inexpensive and can be used in small quantities, replacing the need for expensive UV equipment infrastructure. The photoinitiator can be easily added to the hydrogel precursor solution and activated by simple visible light exposure, eliminating capital investment in specialized equipment while achieving reliable hydrogel formation.

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

3Object-affected harmful factors

If visible light photopolymerization is used, then cell toxicity is reduced and equipment investment is minimized, but cross-linking control precision must be optimized

Engineering Contradiction:
Improvecell toxicityVSAvoidcross-linking control
Core Design Contradiction:
Object-affected harmful factorsVSManufacturing precision

Solution Approach 1:

The patent implements control over the cross-linking process by adjusting visible light irradiation parameters (intensity, duration, wavelength) and photoinitiator concentration to achieve desired cross-linking degrees. The ruthenium complex system allows for tunable cross-linking kinetics that can be controlled by varying light exposure conditions, providing feedback control mechanisms to optimize cross-linking precision while maintaining low cell toxicity.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent enables dynamic control of the cross-linking process by adjusting visible light irradiation conditions and photoinitiator concentrations during hydrogel formation. The ruthenium complex system provides dynamic kinetics where cross-linking rate can be modulated by light intensity and exposure time, allowing precise control over gelation timing and cross-linking density to achieve manufacturing precision without requiring specialized equipment.

Inventive Principle:
Principle #15Dynamics

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 visible light photopolymerization system enables flexible and controlled hydrogel formation, suitable for cell encapsulation and tissue assembly, without the capital investment in specialized equipment and reduces cell toxicity.

Implementation Method 1

Visible light photopolymerization system using a ruthenium complex, photoinitiator, and co-initiator

Methodology Applied
Scientific EffectPhotopolymerisation: Photopolymerisation

Implementation Method 2

The visible light harvesting complex is RuBPY3. The photoinitiator is sodium persulfate (SPS)

Methodology Applied
Scientific EffectLight absorption and energy transfer: Absorption (EM radiation)

Data Source

PatentEP3630151B1Visible light polymerization of polyethylene glycol (PEG) hydrogels
Publication Date: 2025.12.17 STEM PHARM INC
  • EP3630151B1 patent drawingFigure 1
  • EP3630151B1 patent drawingFigure 2
  • EP3630151B1 patent drawingFigure 3

AI summary

Provided herein are compositions and methods for generating visible light photopolymerized hydrogels to support cell viability, expansion, and encapsulation. The present disclosure provides a composition, comprising a visible light harvesting complex, a photoinitiator, a co-initiator, a di-thiol-terminated crosslinker, and at least one cysteine-containing peptide. The present disclosure provides a method of generating a visible light photopolymerized hydrogel. In further embodiments that method comprises generating a 3-dimensional endothelial network comprising the visible light phtopolymerized hydrogel. In additional embodiments the method comprises generating a hydrogel network comprising the visible light photopolymerized hydrogel comprising at least one cell.