Microcapsule Cell Composition for Immune-Isolated Islet Engraftment

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Solution Overview

Problem

The challenges of immune rejection and poor engraftment of heterologous pancreatic islets in transplantation therapies for diabetes, particularly when using immunoisolation capsules, lead to unsustainable function and low engraftment rates, respectively.

Innovation Solution

A composition comprising microcapsules made of a polymer hydrogel with biodegradable biocompatible polymer blocks, encapsulating insulin-secreting cells or pancreatic islets, including mesenchymal stem cells, to facilitate immune isolation and enhance engraftment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If a grafting reaction is performed in a bulk solvent to ensure complete reaction, then reaction completeness is improved, but solvent residue in the microcapsule interior increases and causes safety issues

Engineering Contradiction:
Improvereaction completenessVSAvoidsolvent residue
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The reaction system is segmented into two distinct environments: a bulk aqueous phase for grafting polymerization and an internal microcapsule phase for drug loading. This segmentation allows the grafting reaction to occur completely in the bulk phase while preventing solvent residue in the microcapsule interior, thereby resolving the contradiction between reaction completeness and solvent residue.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The microcapsule shell acts as an intermediary barrier that separates the bulk solvent environment from the internal drug-containing space. This intermediary structure enables complete grafting reaction in the bulk phase while preventing solvent penetration into the microcapsule interior, thus eliminating solvent residue-related safety issues.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of manufacture

If conventional microencapsulation methods are used, then microcapsule formation is achieved, but the microcapsule shell is heterogeneous and contains unreacted monomers and initiators

Engineering Contradiction:
Improvemicrocapsule formationVSAvoidshell homogeneity
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The grafting polymerization is performed preliminarily in the bulk aqueous phase before microencapsulation, ensuring complete reaction and formation of homogeneous polymer shells. This preliminary action eliminates unreacted monomers and initiators that would otherwise remain in the shell structure, thereby improving shell homogeneity and reliability.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The reaction parameters are optimized by conducting grafting polymerization in an aqueous bulk phase rather than within the microcapsule interior. This parameter change (reaction location and medium) enables complete polymerization while maintaining microcapsule formation, resulting in homogeneous shells free of unreacted monomers and initiators.

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If organic solvents are used for grafting polymerization to ensure complete reaction, then reaction completeness is improved, but toxicological issues arise from solvent residue

Engineering Contradiction:
Improvereaction completenessVSAvoidtoxicological effects
Core Design Contradiction:
Manufacturing precisionVSObject-generated harmful factors

Solution Approach 1:

An aqueous bulk phase environment is used for grafting polymerization, replacing organic solvents with water as the reaction medium. This inert, non-toxic environment enables complete polymerization reactions while eliminating toxicological issues associated with organic solvent residue in the microcapsule interior.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Solution Approach 2:

The potential harm of requiring complete reaction in organic solvents is converted into a benefit by using an aqueous bulk phase system. This approach maintains reaction completeness while eliminating toxicological effects, as water is non-toxic and can be easily removed or degraded, thereby converting a harmful constraint into a beneficial feature.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 composition achieves high treatment efficacy by preventing immune rejection and improving engraftment rates, allowing for effective insulin secretion and glucose control in vivo.

Implementation Method 1

a microcapsule shell having a first wall thickness and comprising a polymer

Methodology Applied
Scientific EffectPhysical containment: Physical Containment

Implementation Method 2

a microcapsule shell having a first wall thickness and comprising a polymer

Methodology Applied
Scientific EffectPolymer structural support:

Implementation Method 3

The microcapsule shell may have a porous structure

Methodology Applied
Scientific EffectPermeation: Permeation

Data Source

PatentEP4019025B1Composition comprising microcapsule and cell structure
Publication Date: 2026.05.06 FUJIFILM CORP
  • EP4019025B1 patent drawingFigure 1
  • EP4019025B1 patent drawingFigure 2
  • EP4019025B1 patent drawingFigure 3~4

AI summary

An object of the present invention is to provide a composition containing at least microcapsules and cell structures, where the composition can exhibit a high treatment effect in a case of being transplanted into a living body. There is provided a composition including at least (a) a microcapsule containing a polymer hydrogel; and (b) a cell structure containing a biocompatible polymer block and a cell, in which a plurality of biocompatible polymer blocks are arranged in gaps between a plurality of cells, where at least a part of the cell structures are encapsulated in the microcapsules.