Decellularized Matrix Preparation for Low-Immunogenic Tissue Scaffolds

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Solution Overview

Problem

Existing decellularization methods for animal-derived biomaterials face challenges in effectively removing immunogenic ingredients while minimizing damage to the extracellular matrix (ECM) structure and retaining bioactive ingredients, leading to potential immune reactions and reduced tissue regeneration capabilities.

Innovation Solution

A method involving pretreatment, degreasing, disinfection, decellularization with alkaline protease, removal of α-Gal antigen, and sterilization is employed, using specific reagents and conditions to preserve the ECM's structural integrity and bioactivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If strong decellularizing reagents (detergents, NaOH, trypsin) are used to remove immunogenic ingredients, then decellularization effect is improved, but the three-dimensional structure of ECM is damaged and bioactive ingredients are lost

Engineering Contradiction:
Improvedecellularization effectVSAvoidECM structure and bioactive ingredients
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the parameters of the decellularization process by using mild detergents (Triton X-100, CHAPS) at controlled concentrations (0.01-0.1%) and temperatures (4-37°C), replacing strong reagents like NaOH and trypsin. This parameter optimization achieves effective decellularization while preserving ECM structure and bioactive ingredients such as collagen, glycosaminoglycan, and laminin.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces an intermediary washing step using PBS buffer between the decellularization treatment and subsequent processing steps. This intermediary step removes residual detergent while preserving the intact ECM structure, acting as a protective mediator that prevents further damage to the matrix.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If repeated freeze-thaw method is used for decellularization, then physical decellularization is achieved, but treatment period becomes excessively long

Engineering Contradiction:
Improvedecellularization effectVSAvoidtreatment period
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent replaces the mechanical freeze-thaw method with a chemical decellularization approach using mild detergents (Triton X-100, CHAPS). This substitution eliminates the need for repeated freezing and thawing cycles, significantly reducing the treatment time while maintaining effective decellularization through chemical action on cell membranes.

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

3Reliability

If animal-derived biomaterials are used to provide biological induction function, then tissue regeneration ability is improved, but immunogenic ingredients (residual DNA, fat) cause immune reactions

Engineering Contradiction:
Improvetissue regeneration abilityVSAvoidimmunogenic ingredients
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes immunogenic ingredients from the animal-derived biomaterial through a optimized decellularization process. Mild detergents selectively remove cell membranes, residual DNA, and fat while preserving the ECM structure. The subsequent washing steps further eliminate traces of immunogenic components, reducing immune reaction risks while maintaining the biological induction function for tissue regeneration.

Inventive Principle:
Principle #2Taking out (Extraction)

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 method effectively removes immunogenic ingredients, retains bioactive components like collagen, glycosaminoglycan, and laminin, resulting in a decellularized matrix biomaterial with low immunogenicity and high bioactivity, suitable for tissue repair and regeneration.

Implementation Method 1

enzymatic methods: include protease digestion, nuclease digestion, and the use of calcium chelate reagents, and the like. Trypsin is the most commonly used enzyme in the decellularizing process.

Methodology Applied
Scientific EffectProtease digestion: Enzyme

Implementation Method 2

physical methods: repeated freeze-thaw method, for example, is a physical method of decellularizing

Methodology Applied
Scientific EffectFreeze-thaw: Freezing

Implementation Method 3

chemical methods: mainly include using acids, bases, detergents (also known as surfactants). Detergents such as SDS, Triton X-100, and CHAPS, are chemically synthesized or semi-synthesized, with strong stain removal effect and good decellularizing effect.

Methodology Applied
Scientific EffectDetergent action: Surfactant

Implementation Method 4

enzymatic methods: include protease digestion, nuclease digestion, and the use of calcium chelate reagents

Methodology Applied
Scientific EffectNuclease digestion: Enzyme

Data Source

PatentEP4272773B1Preparation method for decellularized matrix biomaterial
Publication Date: 2025.12.03 HANGZHOU HUAMAI MEDICAL DEVICES CO LTD
  • EP4272773B1 patent drawingFigure 1A~2
  • EP4272773B1 patent drawingFigure 3A~3C
  • EP4272773B1 patent drawingFigure 3D~4

AI summary

The present application provides a preparation method for a decellularized matrix biomaterial, which combines specific pretreatment, degreasing, disinfection, decellularization, α-Gal antigen removal and sterilization, and reserves the integrity of bioactive components and structures in a material to the maximum extent while effectively removing an antigenic substance of an animal tissue, so that a decellularized matrix biomaterial having low immunogenicity and high biological activity is obtained. In addition, the decellularized matrix biomaterial prepared by the method provided by the present application effectively reduces immunogen components, has good biocompatibility and biological safety, is beneficial to cell adhesion, aggregation and proliferation on the surface, and can be used as a high-activity biological matrix material to be applied to skin soft tissue defect, gingival recession and periodontal soft tissue repair.