Hydrophobically Modified Gelatin Tissue Adhesive

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Solution Overview

Problem

Current tissue adhesives face challenges in achieving high bonding strength, stable bonding properties, and good spreadability, with existing biopolymers like gelatin often resulting in inadequate bonding strength or gelation issues that hinder uniform application.

Innovation Solution

A tissue adhesive composed of an aqueous solution of hydrophobically modified fish-derived gelatin and a water-soluble crosslinking reagent, specifically pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-PEG), is used, which allows for uniform dispersion and application in a liquid state, enhancing bonding strength and biocompatibility.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If gelatin is used as a non-blood preparation to avoid medicinal product approval requirements, then biocompatibility is improved and approval efforts are reduced, but bonding strength becomes insufficient

Engineering Contradiction:
Improveapproval effortsVSAvoidbonding strength
Core Design Contradiction:
Ease of manufactureVSStrength

Solution Approach 1:

The patent introduces hydrophobic groups (such as cholesteryl groups) onto the gelatin side chains, fundamentally changing the chemical parameters of gelatin. This modification enables gelatin to achieve high bonding strength comparable to blood-based products while maintaining the regulatory advantages of non-blood preparations. The hydrophobic modification allows gelatin to effectively crosslink with tissues through both hydrophilic and hydrophobic interactions.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite structure by combining hydrophilic gelatin backbone with hydrophobic side groups. This composite material approach allows the adhesive to exhibit dual characteristics: the biocompatibility and ease of manufacture of gelatin combined with the high bonding strength typically associated with blood-based products containing hydrophobic components.

Inventive Principle:
Principle #40Composite materials

2Strength

If the molecular weight of gelatin is increased to improve bonding properties, then bonding strength is improved, but the adhesive may gel at normal temperatures and lose spreadability

Engineering Contradiction:
Improvebonding strengthVSAvoidspreadability
Core Design Contradiction:
StrengthVSEase of operation

Solution Approach 1:

The patent modifies the chemical structure of gelatin by introducing hydrophobic groups, which changes the gelation temperature parameter. This allows the use of higher molecular weight gelatin (which provides better bonding strength) without the adverse effect of premature gelation at normal temperatures. The hydrophobic modification stabilizes the liquid state of the adhesive during application.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention applies hydrophobic modification locally to the side chains of gelatin molecules rather than changing the entire molecular structure. This localized modification allows the backbone structure to maintain high molecular weight for bonding strength while the modified side chains prevent unwanted gelation, thus maintaining spreadability.

Inventive Principle:
Principle #3Local quality

3Strength

If water-insoluble molecules like tartaric acid are added to water solvent to achieve crosslinking, then bonding strength is improved, but uniform dispersion becomes impossible and bonding properties vary

Engineering Contradiction:
Improvebonding strengthVSAvoiduniform dispersion
Core Design Contradiction:
StrengthVSStability of the object's composition

Solution Approach 1:

The patent transforms the crosslinking agent from water-insoluble (tartaric acid) to water-soluble form by incorporating it into the gelatin structure during synthesis. The hydrophobic groups are introduced onto gelatin side chains in an aqueous environment, ensuring uniform dispersion throughout the water-based adhesive formulation while maintaining effective crosslinking capability for high bonding strength.

Inventive Principle:
Principle #35Parameter changes

4Strength

If blood-based products like HSA are used to achieve high bonding strength, then bonding strength is improved, but considerable efforts are required for approval and continuous usage record keeping

Engineering Contradiction:
Improvebonding strengthVSAvoidapproval efforts
Core Design Contradiction:
StrengthVSEase of manufacture

Solution Approach 1:

The patent replaces expensive, regulated blood-based products (HSA) with a more accessible, non-blood alternative (modified gelatin). While the adhesive itself has a limited functional lifespan, the modification approach creates a product that doesn't require the extensive regulatory oversight and long-term tracking associated with blood-derived products, effectively making the approval process more accessible.

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

Solution Approach 2:

The hydrophobic groups act as intermediaries between the gelatin and tissue, mediating the bonding interaction. This intermediary mechanism allows gelatin to achieve bonding strength comparable to blood-based products without requiring the use of actual blood components, thus avoiding the regulatory burdens associated with blood product usage.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 tissue adhesive with high bonding strength, stable properties, and excellent spreadability, as well as enhanced biocompatibility by anchoring hydrophobic groups into tissues, forming physically firm bonds and allowing for easy decomposition during wound healing.

Implementation Method 1

enhanced biocompatibility by anchoring hydrophobic groups into tissues, forming physically firm bonds

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 2

a tissue adhesive including human serum albumin (henceforth referred to as HSA) and a crosslinking agent has high bonding strength

Methodology Applied
Scientific EffectCrosslinking: Chemical Bonding

Data Source

PatentEP2946795B1Tissue adhesive and process for producing same
Publication Date: 2019.04.17 NAT INST FOR MATERIALS SCI
  • EP2946795B1 patent drawingFigure 1
  • EP2946795B1 patent drawingFigure 2
  • EP2946795B1 patent drawingFigure 3

AI summary

There is provided a tissue adhesive to be applied to a tissue by mixing an adhesive component including an aqueous solution of a fish-derived gelatin with a curable component including an aqueous solution of a water-soluble crosslinking reagent, wherein the water-soluble crosslinking reagent has an amide linkage or an ethylene glycol unit or a sugar chain in the molecular main chain thereof and has two or more of an active ester group or an acid anhydride or an aldehyde group.