Vinyl-Lactam Hydrogel Coatings for Non-Destructive Cell Sheet Detachment

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Solution Overview

Problem

Current methods for detaching cell monolayers or sheets from thermosensitive substrates often cause damage due to the disruption of cell membranes and extracellular matrices, necessitating the development of more moderate and effective alternatives for cellular manipulation.

Innovation Solution

A polymeric substrate coated with a hydrogel based on vinyl-lactam type monomers, forming a semi-interpenetrated network interface, which allows for controlled detachment of cell sheets without damaging the cells, using a combination of vinylcaprolactam, ionic methacrylates, and crosslinkers like ethylene glycol dimethacrylate and 3,3'-(propyl)-di-1-vinyl-2-pyrrolidone, enabling stable coating and rehydration for cell culture and tissue engineering applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If conventional thermosensitive substrates (pNIPAm) are used for cell detachment, then cell sheets can be detached by thermal stimulus, but cell membranes and extracellular matrices are damaged

Engineering Contradiction:
Improvecell detachmentVSAvoidcell membrane disruption
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent changes the detachment mechanism from thermal stimulus (pNIPAm) to pH-responsive swelling (polyacrylic acid). By adjusting pH parameters, the hydrogel swells and detaches cells gently without thermal damage, resolving the contradiction between ease of operation and harmful effects

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes pH-induced phase transition in polyacrylic acid hydrogel. At low pH, the hydrogel is collapsed and adherent; at high pH, it swells and detaches. This phase transition enables gentle, controlled detachment without thermal damage to cells

Inventive Principle:
Principle #36Phase transitions

2Ease of operation

If pVCL-based supports are used for cell collection, then partial cell detachment is achieved, but the method lacks robustness and controlled detachment capability

Engineering Contradiction:
Improvecell detachmentVSAvoiddetachment control
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent introduces pH as a controllable parameter for detachment. By varying pH levels, complete control over detachment timing and extent is achieved, unlike pVCL which provides only partial detachment. This resolves the reliability issue while maintaining ease of operation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite structure with polyacrylic acid hydrogel coating on a porous substrate. This composite provides both the robustness of the substrate and the controlled detachment capability of the pH-responsive hydrogel, overcoming the limitations of standalone pVCL

Inventive Principle:
Principle #40Composite materials

3Adaptability or versatility

If hydrogel coatings are applied to polymeric substrates, then cell culture support is provided, but the interface stability and coating robustness are compromised

Engineering Contradiction:
Improvecell culture supportVSAvoidinterface stability
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent uses porous polymeric substrates that allow hydrogel precursor diffusion into the substrate structure. This creates an interpenetrated network interface where the hydrogel and substrate are mechanically intertwined, greatly enhancing interface stability while maintaining cell culture functionality

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent creates a composite system where the hydrogel coating and porous substrate form an integrated interpenetrated network. This composite structure provides both the versatility for cell culture and the stability needed for robust coating, resolving the contradiction

Inventive Principle:
Principle #40Composite 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

The solution provides a non-destructive method for cell detachment, maintaining cell viability and proliferation, and allows for the creation of complex constructs with improved handling and storage properties, enhancing cell sheet engineering and tissue regeneration processes.

Implementation Method 1

a hybrid interface has been formed between the substrate and the hydrogel as a result of the diffusion of hydrogel precursor molecules in the outer layers of the polymeric substrate

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

a hydrogel coating based on vinyl-lactams, with or without methacrylates... formed on the substrate

Methodology Applied
Scientific EffectPhotopolymerization: Photopolymerisation

Data Source

PatentEP3569623B1Vinyl-lactam-based hydrogel coatings
Publication Date: 2023.08.09 CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (CSIC)
  • EP3569623B1 patent drawingFigure 1
  • EP3569623B1 patent drawingFigure 2
  • EP3569623B1 patent drawingFigure 3(a)~3(c)

AI summary

The invention relates to a material formed by a polymer substrate and a hydrogel based on vinyl-lactams and ionic methacrylates. The invention also relates to a method for producing this material and to the use thereof for cell culture and cell monolayer engineering, for preparing 3D scaffolds and manufacturing thermosensitive mechanical actuators.