Immunoisolation Membrane with Porosity Gradient for Angiogenesis

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Solution Overview

Problem

Current cell transplant devices face challenges in inducing sufficient angiogenesis around the transplanted cells, leading to inadequate nutrient supply and secretion of physiologically active substances due to insufficient blood vessel formation, often triggered by inflammatory reactions.

Innovation Solution

A cell transplant device comprising a biocompatible polymer block structure with cells, where the polymer blocks are disposed in gaps between cells, enclosed by an immunoisolation membrane with a layered compact portion and increasing pore diameter, promoting vascular network formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If an immunoisolation membrane with uniform pore structure is used, then immune cells are prevented from permeating, but blood vessel induction is insufficient and nutrient delivery is inadequate

Engineering Contradiction:
Improveimmune cell barrier functionVSAvoidblood vessel induction efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The immunoisolation membrane is designed with non-uniform pore diameter distribution, where the inner side has smaller pores (0.01-1 μm) for effective immune cell barrier function, while the outer side has larger pores (1-10 μm) to promote blood vessel induction and nutrient delivery. This local quality variation allows the membrane to simultaneously achieve both protective and promotional functions.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The membrane is segmented into distinct functional zones: an inner compact layer with small pores for immune isolation and an outer porous layer with large pores for angiogenesis promotion. This segmentation allows each zone to optimize its specific function without compromising the other.

Inventive Principle:
Principle #1Segmentation

2Quantity of substance

If the cell structure thickness is increased to ensure sufficient cell presence, then nutrient delivery becomes insufficient, but reducing thickness compromises cell survival activity

Engineering Contradiction:
Improvecell density in structureVSAvoidnutrient delivery efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The immunoisolation membrane incorporates a porous structure with controlled pore diameter distribution, where the outer porous layer with larger pores (1-10 μm) facilitates efficient nutrient delivery and waste removal, enabling the maintenance of thicker cell structures with sufficient cell density while ensuring adequate nutrient supply.

Inventive Principle:
Principle #31Porous materials

3Productivity

If blood vessel induction is promoted through inflammatory reactions, then new blood vessels form, but the induction is insufficient and causes harmful inflammatory effects

Engineering Contradiction:
Improveblood vessel formation rateVSAvoidinflammatory reaction
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The outer porous layer of the immunoisolation membrane acts as an intermediary that promotes blood vessel induction through physical structure (larger pores) rather than chemical inflammatory stimuli. This mediator function achieves angiogenesis while avoiding the harmful inflammatory reactions associated with conventional induction methods.

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 device effectively induces angiogenesis around the transplanted cells, ensuring continuous nutrient supply and secretion of active substances while protecting cells from host immune responses, achieving a high efficiency in generating new blood vessels.

Implementation Method 1

An immunoisolation membrane is a selectively permeable membrane that performs immunoisolation by allowing water, oxygen, glucose, and the like to permeate therethrough while preventing permeation of immune cells and the like involved in an immune rejection

Methodology Applied
Scientific EffectPermeation: Permeation

Implementation Method 2

A cell transplant device comprising a cell structure and an immunoisolation membrane enclosing the cell structure

Methodology Applied
Scientific EffectSelective permeability: Semipermeable Membrane

Implementation Method 3

within an inner side of the porous membrane, a layered compact portion in which a pore diameter is minimized is present, and a pore diameter continuously increases in a thickness direction from the compact portion toward at least one surface of the porous membrane

Methodology Applied
Scientific EffectPorosity gradient: Porosity

Data Source

PatentEP3677287B1Cell transplantation device and method for manufacturing same
Publication Date: 2024.05.29 FUJIFILM CORP
  • EP3677287B1 patent drawingFigure 1
  • EP3677287B1 patent drawingFigure 2
  • EP3677287B1 patent drawingFigure 3

AI summary

An object of the present invention is to provide a cell transplant device having an ability to induce angiogenesis around the cell transplant device, and a method for manufacturing the same. According to the present invention, a cell transplant device including a cell structure (A) that includes a plurality of biocompatible polymer blocks and a plurality of cells of at least one type, and in which at least one of the biocompatible polymer blocks is disposed in gaps between the plurality of cells; and an immunoisolation membrane (B) that encloses the cell structure is provided.