Decellularized Human Dermis Matrix for Burn Reconstruction

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Solution Overview

Problem

Current methods for reconstructing full-thickness cutaneous substance losses, such as severe burns, require a dermal substrate that is immunogenically safe, easy to store, and promotes quick anatomical and functional tissue regeneration without causing immune responses or scar tissue formation.

Innovation Solution

A process involving the deepidermization, decellularization, freeze-drying, and sterilization of human dermis using a combination of zwitterionic detergents and sonication, followed by gamma irradiation, to create a histocompatible dermal matrix that retains the extracellular protein matrix and eliminates cellular components responsible for immune reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If deepidermized dermis allografts are used as substrate for skin reconstruction, then engraftment quality and wound repair are improved, but immune response and rejection reactions occur

Engineering Contradiction:
Improveengraftment qualityVSAvoidimmune response
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent removes cellular components from the dermal matrix through decellularization processes involving enzymatic treatment and detergent washing, extracting only the extracellular matrix while eliminating immunogenic cells. This resolves the contradiction by maintaining the structural scaffold needed for engraftment while removing the source of immune rejection.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies gamma irradiation at controlled doses (15-25 kGy) to modify the biological properties of the dermal matrix, transforming it from an immunogenic state to a histocompatible state. This parameter change in radiation dose achieves sterilization and further reduces immunogenicity while preserving mechanical properties.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If traditional dermal substitutes are sterilized and stored, then sterility is ensured, but storage conditions require special refrigeration and product stability deteriorates

Engineering Contradiction:
ImprovesterilityVSAvoidstorage conditions
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent employs freeze-drying (lyophilization) to transform the dermal matrix from a fresh, refrigerated state to a dried, stable state. This phase transition removes water through sublimation, enabling long-term storage at room temperature while maintaining sterility and structural integrity, thus resolving the storage condition contradiction.

Inventive Principle:
Principle #36Phase transitions

3Reliability

If decellularization is performed to eliminate immune reactions, then histocompatibility is improved, but cellular components necessary for tissue function are lost

Engineering Contradiction:
ImprovehistocompatibilityVSAvoidcellular components
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The patent selectively extracts cellular components through controlled decellularization while preserving the extracellular matrix structure. The enzymatic and detergent treatments remove nuclei and cytoplasmic elements that cause immune rejection, while the collagen and elastin framework remain intact to provide mechanical support and biological signaling functions.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies different treatment intensities to different aspects of the tissue: aggressive decellularization to remove immunogenic elements, followed by gentler washing and sterilization to preserve structural integrity. This localized quality control ensures histocompatibility without complete loss of functional components.

Inventive Principle:
Principle #3Local quality

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 resulting decellularized, freeze-dried, and sterilized dermis provides a safe, effective scaffold for tissue regeneration, minimizing immune responses and ensuring long-term sterility, allowing for quick engraftment and revascularization, and can be stored at room temperature for extended periods.

Implementation Method 1

A process involving the deepidermization, decellularization, freeze-drying, and sterilization of human dermis using a combination of zwitterionic detergents and sonication

Methodology Applied
Scientific EffectSonication: Ultrasonic Vibration

Implementation Method 2

A process involving the deepidermization, decellularization, freeze-drying, and sterilization of human dermis using a combination of zwitterionic detergents and sonication

Methodology Applied
Scientific EffectDetergent action: Surfactant

Implementation Method 3

followed by gamma irradiation, to create a histocompatible dermal matrix

Methodology Applied
Scientific EffectGamma irradiation: Radiation

Implementation Method 4

The dermis thus obtained retains the extracellular protein matrix, while eliminating the cellular component thereof

Methodology Applied
Scientific EffectFreeze-drying: Freeze Drying

Data Source

PatentEP3188596B1Human dermis, preparation and use thereof
Publication Date: 2020.10.28 TISSUELAB S R L CON UNICO SOCIO

AI summary

A process for treating human dermis is described, where a human dermis collected from a cadaver and deprived of the epidermal component is: decellularized, freeze-dried and sterilized by means of freeze drying and sterilization in the presence of a cryoprotective and radioprotective solution so as to preserve the tissue structure from freezing damage and gamma radiation.