Immune Cell Activation via Polysaccharide-TLR2 Composition

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Solution Overview

Problem

Conventional methods for processing bone marrow aspirates often separate out erythrocytes, which are considered valueless and potentially detrimental, and fail to effectively activate immune cells for regenerative medicine applications.

Innovation Solution

A composition comprising non-ionic hydrophilic branched polysaccharides, such as poly(sucrose-co-epichlorhydrin), combined with a Toll-like Receptor 2 (TLR2) ligand, is used to activate bone marrow-derived myeloid cells, allowing for the activation of immune cells without separating erythrocytes, using a bone marrow container and separation system.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional separation methods are used to remove erythrocytes, then the mononuclear cell fraction is enriched, but the erythrocytes are lost along with potentially valuable immune cells

Engineering Contradiction:
Improvecell separation purityVSAvoiderythrocyte loss
Core Design Contradiction:
Manufacturing precisionVSLoss of substance

Solution Approach 1:

The invention extracts and removes only the unwanted components (erythrocytes and debris) from the bone marrow aspirate while retaining the valuable immune cells. This is achieved through a filtration system that selectively removes cells based on size and morphology, extracting harmful elements without sacrificing beneficial ones.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention applies different processing qualities to different cell types within the same sample. Rather than uniform separation, the system allows immune cells to pass through while blocking erythrocytes and debris, creating localized quality differences in the filtration process based on cell-specific properties.

Inventive Principle:
Principle #3Local quality

2Object-generated harmful factors

If conventional separation methods are used, then erythrocytes are removed, but the process complexity increases and therapeutic effectiveness decreases

Engineering Contradiction:
Improveerythrocyte detrimental effectsVSAvoidseparation process complexity
Core Design Contradiction:
Object-generated harmful factorsVSDevice complexity

Solution Approach 1:

The invention combines filtration and activation functions into a single integrated system. The bone marrow aspirate is filtered and immune cells are activated simultaneously in one container, eliminating the need for separate separation and activation steps, thereby reducing device complexity while maintaining effectiveness.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The filtration system serves multiple functions: it removes erythrocytes, eliminates debris, concentrates immune cells, and prepares the sample for activation. This multi-functional approach replaces multiple specialized devices with a single universal system, reducing overall process complexity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Manufacturing precision

If erythrocytes are separated out, then the mononuclear cell fraction is enriched, but the volume of usable cells decreases

Engineering Contradiction:
Improvecell fraction enrichmentVSAvoidusable cell volume
Core Design Contradiction:
Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The invention converts the harmful presence of erythrocytes into a beneficial concentration effect. By filtering out erythrocytes and debris, the system naturally concentrates the immune cells in the remaining volume, transforming what was previously considered waste removal into a valuable concentration process that increases both purity and usable cell quantity.

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 solution effectively activates immune cells, including myeloid lineage cells, without separating erythrocytes, enhancing their therapeutic effectiveness and concentration for regenerative medicine applications.

Implementation Method 1

a non-ionic hydrophilic branched polysaccharide at a density, in which, if the composition is contacted with whole blood and centrifuged, the density is sufficient to permit fluid movement of whole blood through the non-ionic hydrophilic branched polysaccharide without separation of erythrocytes

Methodology Applied
Scientific EffectDensity gradient: Density Gradient

Implementation Method 2

a Toll-like Receptor 2 (TLR2) ligand, wherein the composition is contained within the container

Methodology Applied
Scientific EffectToll-like receptor ligand binding:

Data Source

PatentUS11781111B2Activation of immune cells
Publication Date: 2023.10.10 BREAKTHROUGH TECHNOLOGIES LLC
  • US11781111B2 patent drawing
  • US11781111B2 patent drawing
  • US11781111B2 patent drawing

AI summary

Bone marrow containers are described herein. Separation systems for separating activated immune cells from other components are described herein. Methods of activating an immune cell are described herein.