Vinyl Caprolactam Hydrogels for Cell Detachment

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Solution Overview

Problem

Current methods for cell detachment in tissue engineering, such as those using Poly N-isopropylacrylamide (pNIPAm) coatings, are expensive, complex, and require specific thickness, limiting their application and efficiency in cell harvesting and transplantation.

Innovation Solution

Development of hydrogels composed of vinyl caprolactam and at least two crosslinkers, which are robust, easy to handle, and can be used without a substrate, allowing for controlled cell detachment using thermal stimuli, and can be functionalized with additional monomers for enhanced cell growth and detachment efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If pNIPAm based coatings are used for cell detachment, then cell detachment is achieved, but the method becomes expensive and complex

Engineering Contradiction:

Improvecell detachment efficiencyVSAvoidmethod complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the chemical composition parameters by using vinyl caprolactam as the base polymer instead of pNIPAm, and employs a mixture of two specific crosslinkers (ethylene glycol dimethacrylate and 3,3'-di-1-vinyl-2-pyrrolidone) in controlled molar ratios. This parameter optimization achieves reliable cell detachment while simplifying the overall method by eliminating the need for ultra-thin graft requirements.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite hydrogel system combining vinyl caprolactam polymer chains with a dual-crosslinker network. This composite structure integrates the thermoresponsive properties of VCL with the mechanical stability provided by the crosslinking agents, achieving both effective cell detachment and structural robustness without the complexity of pNIPAm-based systems.

Inventive Principle:

Principle #40Composite materials

2Reliability

If pNIPAm based coatings are used for cell detachment, then cell detachment is achieved, but the application is limited by specific thickness requirements

Engineering Contradiction:

Improvecell detachment efficiencyVSAvoidapplication flexibility

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent modifies the physical parameters of the hydrogel system by controlling the molecular weight of vinyl caprolactam (10,000-1,000,000 g/mol) and optimizing crosslinker concentrations (0.1-10% molar ratio). These parameter adjustments enable the hydrogel to maintain mechanical integrity and thermoresponsive detachment functionality across a wide range of thicknesses, from thin films to thick blocks, greatly enhancing application versatility.

Inventive Principle:

Principle #35Parameter changes

3Productivity

If traditional cell harvesting methods are used, then cell detachment is achieved, but cell damage occurs

Engineering Contradiction:

Improvecell harvesting efficiencyVSAvoidcell damage

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces mechanical harvesting methods (scraping, enzymatic digestion) with a thermal field-based mechanism. The hydrogel undergoes a temperature-induced volume phase transition that mechanically detaches cells through bulk material contraction rather than direct mechanical or chemical action on cells, thereby maintaining high harvesting efficiency while minimizing cell damage.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention exploits the lower critical solution temperature (LCST) phase transition of vinyl caprolactam hydrogel. Upon cooling below the LCST point, the hydrogel undergoes a sharp volume contraction that detaches adhered cells from the substrate. This phase transition mechanism enables gentle, non-destructive cell harvesting while maintaining high productivity.

Inventive Principle:

Principle #36Phase transitions

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 hydrogels provide a cost-effective and efficient method for cell harvesting and transplantation, enabling complete detachment of cell layers with maintained cell-to-cell and cell-to-extracellular matrix junctions, promoting cell growth and metabolic activity, and are suitable for both 2D and 3D biomedical applications.

Implementation Method 1

capable of holding cells to confluence and providing a detachment of cells and cell layers induced by a decrease in temperature

Methodology Applied

Scientific EffectVolume phase transition: Phase Change

Implementation Method 2

Hydrogels based on vinyl-caprolactam

Methodology Applied

Scientific EffectHydrogel swelling: Absorption (physical)

Data Source

PatentUS11572429B2Hydrogels based on vinyl-caprolactam

Publication Date: 2023.02.07 CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (CSIC)

AI summary

The invention relates to a hydrogel based on vinyl caprolactam, with or without additional monomers, and at least two crosslinkers. The invention also relates to a method for obtaining said material and to the use thereof to culture cells/engineer cell monolayers, as well as supports for cell culture and transplant.