Polyurethane Foam Synthesis for Tissue Regeneration

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Solution Overview

Problem

The application of cross-linked polyurethane foams in tissue engineering is hindered by slow degradation, toxicity of degradation products, and poor wettability due to issues with miscibility, reaction kinetics, and hydrophilicity, particularly when using oily surfactants and polymer segments with low glass transition temperatures.

Innovation Solution

A method involving the use of two catalysts for cross-linking and foaming reactions, along with a polar aprotic high-boiling solvent, to produce aliphatic polyurethane foams with improved hydrophilicity, controlled porosity, and reduced toxicity, avoiding the need for oily surfactants and maintaining physical and chemical properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If oily surfactants are used to improve miscibility and reaction kinetics, then the hydrophilic nature of the foams is permanently reduced, compromising cellular colonization and degradation kinetics

Engineering Contradiction:
Improvemiscibility of reactive componentsVSAvoidreduced hydrophilicity
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes the harmful oily surfactants from the system by using a solvent extraction process with miscible solvents. The reactive components are allowed to react first, then the oily surfactants are extracted away, leaving a foam with restored hydrophilicity while maintaining the benefits of improved miscibility and reaction kinetics that occurred during the reaction phase.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the physical state parameters of the system by controlling temperature and solvent properties. By heating to activate terminal groups and then cooling to solidify, the patent transforms the system from liquid to solid state, enabling the use of solid or semi-solid monomers while controlling the hydrophilicity through solvent selection and extraction.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If polymer precursors with low glass transition temperatures are used to improve flexibility and reactivity, then the choice of soft or rigid segments is limited, reducing ability to manipulate physical and chemical properties

Engineering Contradiction:
Improvereactivity of polymer precursorsVSAvoidchoice of soft or rigid segments
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent applies preliminary action by heating the reaction mixture to a temperature above the glass transition temperature of the polymer precursors before adding the isocyanate. This preliminary heating activates the terminal groups and ensures proper reactivity, while allowing the use of a broader range of polymer precursors with different Tg values, thus restoring versatility in segment selection.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the temperature parameter dynamically during the process: heating during the reaction phase to activate precursors, then cooling to solidify the foam. This parameter change allows the use of diverse polymer precursors with different thermal properties while maintaining control over the final foam characteristics and segment flexibility.

Inventive Principle:
Principle #35Parameter changes

3Strength

If solid or semi-solid monomers are used to improve mechanical properties, then miscibility at ambient temperature is lost and activation of terminal groups becomes difficult in heterogeneous conditions

Engineering Contradiction:
Improvemechanical properties of foamVSAvoidmiscibility of components
Core Design Contradiction:
StrengthVSStability of the object's composition

Solution Approach 1:

The patent changes the temperature parameter to above the glass transition temperature of the solid or semi-solid monomers during the reaction phase, transforming them into a liquid state that ensures miscibility with other reactive components. After the reaction is complete, cooling solidifies the foam, providing the desired mechanical strength while maintaining homogeneous composition throughout the process.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies preliminary heating to dissolve and homogenize the solid or semi-solid monomers before initiating the cross-linking reaction. This preliminary action ensures complete miscibility and uniform distribution of reactive groups, enabling the subsequent reaction to proceed homogeneously and produce foams with consistent mechanical properties.

Inventive Principle:
Principle #10Preliminary action

4Ease of manufacture

If conventional synthesis methods are used to simplify production, then degradation products may be toxic and degradation rate is slow, compromising biocompatibility

Engineering Contradiction:
Improvesimplicity of synthesis methodVSAvoidtoxicity of degradation products
Core Design Contradiction:
Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical composition parameters by selecting specific aliphatic polyisocyanates and biocompatible polyol combinations, and controlling the reaction conditions to produce a cross-linked network structure that degrades into non-toxic products. The controlled cross-linking density and hydrophilicity parameters further optimize degradation rate while maintaining structural integrity during use.

Inventive Principle:
Principle #35Parameter changes

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 method enables the production of polyurethane foams with enhanced hydrophilicity, controlled porosity, and biocompatibility, promoting cellular colonization and tissue regeneration while minimizing environmental impact and production costs.

Implementation Method 1

providing a solution of a polyol or a mixture of polyols in a solvent or mixture of solvents; a polar aprotic high-boiling solvent

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 2

adding to the mixture in step e) simultaneously a cross-linking catalyst of polyols with poly-isocyanates

Methodology Applied
Scientific EffectCatalysis: Catalysis

Implementation Method 3

the foaming reaction before the solidification thereof due to cross-linking; a porogenic additive

Methodology Applied
Scientific EffectGas evolution:

Implementation Method 4

the heat produced by the exothermic polyaddition reaction between the polyols and the polyisocyanates

Methodology Applied
Scientific EffectExothermic reaction: Exothermic Reaction

Data Source

PatentEP3134447B9Foamed polyurethane polymers for the regeneration of connective tissue
Publication Date: 2022.01.19 TENSIVE SRL
  • EP3134447B9 patent drawingFigure 1A~1F
  • EP3134447B9 patent drawingFigure 2A~2F

AI summary

The present invention relates to a method of synthesis and the use of foamed, cross-linked polyurethane polymers, as a three-dimensional support called a "scaffold" for cell cultures in vitro and for in vivo implantation for the regeneration of connective tissues such as adipose tissue, osteochondral tissue and bone tissue. In particular, the invention relates to a method of preparing polymers or foamed polyurethane co polymers, having improved hydrophilia, which involves the use of two types of catalyst, one for the cross- linking reaction and one for the foaming reaction and the use of at least one polar aprotic high-boiling solvent. Said method comprises the following steps in sequence : a) providing a solution of a polyol or a mixture of polyols in a solvent or mixture of solvents; b) heating the solution in step a) to a temperature higher than the softening temperature of the polymer precursors; c) optionally adding an organic or inorganic filler material; d) adding to the mixture in step c) an aliphatic poly-isocyanate or a mixture of poly-aliphatic isocyanates; e) adding to the mixture in step (d) ) a porogenic additive; f) adding to the mixture in step e) simultaneously a cross-linking catalyst of polyols with poly-isocyanates and a foaming catalyst to form a foamed polyurethane polymer or co-polymer; g) isolating the foamed polyurethane polymer or co-polymer produced in step f ).