Decellularized Organ Matrix Recellularization

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Solution Overview

Problem

Current biologically derived matrices for tissue engineering and regeneration often have compromised matrix structures and lack a functional vascular bed, hindering effective reconstitution of organs and tissues.

Innovation Solution

The method involves decellularizing organs, such as hearts, to preserve the extracellular matrix while removing cells, and then recellularizing them with regenerative cells like pluripotent or stem cells, which can engraft, multiply, and differentiate within the decellularized matrix.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If biologically derived matrices are used for tissue engineering, then tissue regeneration is enabled, but the matrix structure is compromised and vascular bed is insufficient

Engineering Contradiction:
Improvematrix structure integrityVSAvoidmatrix quality
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by decellularizing the organ matrix before recellularization. This removes cellular debris and creates a clean scaffold in advance, ensuring structural integrity is maintained while preparing the matrix for subsequent cell seeding. The decellularization step preserves the extracellular matrix architecture while eliminating components that would compromise matrix quality.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent employs local quality by selectively treating different regions of the organ matrix with specific decellularization agents and conditions. This allows preservation of critical structural regions while removing cellular components, and creates localized zones optimized for different recellularization needs, thereby maintaining overall matrix integrity while improving manufacturability.

Inventive Principle:
Principle #3Local quality

2Shape

If decellularization is performed to preserve extracellular matrix morphology, then matrix architecture is maintained, but cells are removed

Engineering Contradiction:
Improveextracellular matrix morphologyVSAvoidcell population
Core Design Contradiction:
ShapeVSQuantity of substance

Solution Approach 1:

The patent applies the extraction principle by removing cells from the organ matrix through decellularization while leaving the extracellular matrix intact. This separation allows the matrix morphology to be preserved and studied or used as a scaffold, while the extracted cells can be processed separately for recellularization, thus resolving the contradiction between maintaining shape and managing cell quantity.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent implements discarding and recovering by removing (discarding) cellular components during decellularization that compromise matrix quality, while simultaneously recovering and preserving the extracellular matrix structure. The discarded cells can be processed for therapeutic use, and the recovered matrix serves as a functional scaffold for regenerative applications.

Inventive Principle:
Principle #34Discarding and recovering

3Reliability

If regenerative cells are seeded onto decellularized matrix, then functional tissue can be generated, but the process complexity increases

Engineering Contradiction:
Improvefunctional organ generationVSAvoidrecellularization process
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the tissue engineering process into distinct stages: decellularization, matrix preparation, cell seeding, and maturation. This segmentation allows each step to be optimized independently, reducing overall process complexity while ensuring reliable functional organ generation. The decellularized matrix serves as a pre-prepared scaffold that simplifies subsequent recellularization.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses preliminary action by completing decellularization and matrix preparation before recellularization. This advance preparation creates an optimized scaffold with proper porosity, surface area, and structural integrity, which simplifies the cell seeding process and improves functional outcomes without requiring complex real-time adjustments during recellularization.

Inventive Principle:
Principle #10Preliminary action

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

This approach maintains the morphology and architecture of the extracellular matrix, allowing for the generation of functional organs that can be transplanted and exhibit contractile function, with potential for long-term functionality.

Implementation Method 1

the cellular disruption medium comprises at least one detergent such as SDS, PEG, or Triton X

Methodology Applied
Scientific EffectDetergent solubilization: Solvation

Data Source

PatentUS20200222456A1Decellularization and recellularization of organs and tissues
Publication Date: 2020.07.16 MIROMATRIX MEDICAL INC
  • US20200222456A1 patent drawing
  • US20200222456A1 patent drawing

AI summary

The invention provides for methods and materials to decellularize a solid organ and to recellularize such a decellularized organ to thereby generate a solid organ.