Irreversible Electroporation Tissue Scaffolds

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Solution Overview

Problem

Current tissue engineering techniques face limitations in creating scaffolds that promote cell growth and function, particularly in achieving microcirculation and preserving native mechanical and biologic properties, due to harsh decellularization methods that destroy vasculature and neural structures.

Innovation Solution

The use of non-thermal irreversible electroporation (IRE) to decellularize tissues, which applies electrical pulses to kill cells while preserving the extracellular matrix, blood vessels, and nerves, enabling the creation of scaffolds with integrated microcirculation and neural infiltration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If harsh decellularization methods (chemical, enzymatic, physical) are used to remove cells from tissue, then complete cell removal is achieved, but the extracellular matrix, blood vessels, and neural structures are degraded or destroyed

Engineering Contradiction:
Improvecell removal completenessVSAvoidstructural integrity of ECM, vessels, and nerves
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent replaces harsh chemical, enzymatic, and physical decellularization methods with irreversible electroporation (IRE), an electrical field-based technique. IRE applies controlled electrical pulses to create pores in cell membranes, selectively killing cells while leaving the extracellular matrix, blood vessels, and neural structures intact. This substitution of the decellularization mechanism resolves the contradiction by achieving complete cell removal without degrading the structural components needed for scaffold functionality.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent utilizes controlled changes in electrical field parameters (voltage, pulse duration, frequency) to achieve selective cell death. By adjusting these parameters, IRE can penetrate cell membranes irreversibly while maintaining the integrity of the surrounding extracellular matrix and structural elements. This parameter control allows complete decellularization while preserving the scaffold's mechanical and biological properties.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If traditional scaffold manufacturing methods (solvent-casting, particulate-leaching, electrospinning) are used, then scaffold formation is achieved, but the ability to create functional microcirculation and preserve native tissue architecture is limited

Engineering Contradiction:
Improvescaffold fabrication capabilityVSAvoidfunctional microcirculation and native architecture
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent applies irreversible electroporation to tissue before scaffold manufacturing to pre-decellularize the tissue while preserving its native architecture, blood vessels, and neural structures. This preliminary treatment creates a decellularized tissue matrix that maintains the original organ's microcirculation pathways, which then serves as the foundation for scaffold fabrication. This approach enables the creation of scaffolds with functional microcirculation that traditional manufacturing methods cannot achieve.

Inventive Principle:
Principle #10Preliminary action

3Volume of moving object

If scaffold size and thickness are increased for larger tissue engineering applications, then more complex tissues can be engineered, but passive diffusion of gases and nutrients becomes insufficient

Engineering Contradiction:
Improvetissue construct sizeVSAvoidgas and nutrient exchange efficiency
Core Design Contradiction:
Volume of moving objectVSReliability

Solution Approach 1:

The patent utilizes the preserved blood vessels and microcirculation structures within the decellularized tissue scaffold to provide self-service gas and nutrient exchange. Instead of relying on passive diffusion, the intact vascular network actively transports oxygen and nutrients throughout the tissue construct, enabling larger and thicker tissue engineering applications. This self-service microcirculation system resolves the limitation of diffusion-based exchange in large-scale tissue constructs.

Inventive Principle:
Principle #25Self-service

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

IRE allows for the production of scaffolds that support thicker tissue constructs with functional vascularization and neural structures, enhancing the potential for larger and more complex tissue engineering applications with reduced immunogenicity and improved tissue regeneration.

Implementation Method 1

treating a tissue with an electrical field to kill cells of the tissue and create pores in the cell membranes of the tissue

Methodology Applied
Scientific EffectIrreversible electroporation: Electrical Impedance Tomography

Data Source

PatentUS10286108B2Irreversible electroporation to create tissue scaffolds
Publication Date: 2019.05.14 VIRGINIA TECH INTELLECTUAL PROPERTIES INC
  • US10286108B2 patent drawing
  • US10286108B2 patent drawing
  • US10286108B2 patent drawing

AI summary

The present invention provides engineered tissue scaffolds, engineered tissues, and methods of using them. The scaffolds and tissues are derived from natural tissues and are created using non-thermal irreversible electroporation (IRE). Use of IRE allows for ablation of cells of the tissue to be treated, but allows vascular and neural structures to remain essentially unharmed. Use of IRE thus permits preparation of thick tissue scaffolds and tissues due to the presence of vasculature within the scaffolds. The engineered tissues can be used in methods of treating subjects, such as those in need of tissue replacement or augmentation.