Enzymatic Tissue Pliability via Proteolytic Digestion

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Solution Overview

Problem

Tissue-derived products often exhibit undesirable mechanical properties such as stiffness and elicit an excessive immune response when implanted, leading to scar tissue formation and impaired tissue regeneration.

Innovation Solution

Treating collagen-containing tissue matrices with proteolytic enzymes like bromelain under controlled conditions to enhance pliability and porosity, thereby reducing immunogenicity and improving mechanical properties without compromising biological functionality.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If tissue products are used for surgical applications, then they provide structural support and tissue replacement, but they are undesirably stiff and have an unnatural feel

Engineering Contradiction:
Improvemechanical strengthVSAvoidpliability
Core Design Contradiction:
StrengthVSEase of operation

Solution Approach 1:

The patent applies parameter changes by treating the tissue matrix with proteolytic enzymes under controlled conditions (pH 6.0-8.0, temperature 20-40°C, treatment time 1-24 hours) to selectively modify the collagen structure. This enzymatic treatment alters the physical-chemical parameters of the tissue, reducing cross-linking and improving pliability while preserving sufficient mechanical strength for surgical applications

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent extracts excess collagen and interfacial material from the tissue matrix through enzymatic digestion. By removing surplus collagen that contributes to stiffness while maintaining the essential structural framework, the tissue achieves improved pliability and a more natural feel without compromising the mechanical support needed for surgical use

Inventive Principle:
Principle #2Taking out (Extraction)

2Strength

If tissue products are derived from exogenous materials, then they provide structural support for tissue replacement, but they elicit an excessive immune response causing scar tissue formation

Engineering Contradiction:
Improvestructural supportVSAvoidimmune response
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful immune response into a beneficial outcome by using controlled enzymatic treatment to modify the tissue matrix. The proteolytic enzyme treatment reduces immunogenicity by degrading antigenic epitopes and creating a more biocompatible surface, thereby converting the potential harm of immune rejection into improved biocompatibility and reduced scar formation

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent introduces proteolytic enzymes as an intermediary agent between the exogenous tissue material and the host immune system. These enzymes modify the tissue surface properties and collagen structure, creating an intermediate state that reduces immunogenicity while preserving the structural support function, thereby mediating between the foreign material and the host's immune response

Inventive Principle:
Principle #24Intermediary (Mediator)

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 treatment method significantly increases tissue pliability and porosity, reduces immune response, and maintains mechanical strength, promoting natural tissue feel and regeneration without adverse effects like inflammation or scar formation.

Implementation Method 1

contacting the tissue matrix with a proteolytic enzyme under conditions sufficient to produce a desired level of pliability in the tissue matrix

Methodology Applied
Scientific EffectProteolysis: Hydrolysis

Data Source

PatentUS9957477B2Method for enzymatic treatment of tissue products
Publication Date: 2018.05.01 LIFECELL CORP
  • US9957477B2 patent drawing
  • US9957477B2 patent drawing
  • US9957477B2 patent drawing

AI summary

Methods for treating tissue matrices and tissue matrices produced according to the methods are provided. The methods can include treating a tissue matrix with a proteolytic enzyme to produce a desired pliability of the tissue matrix and/or to control the immunogenicity of the tissue matrix. The methods can also comprise performing an assay to determine if contacting the at least one collagen-containing tissue matrix with a proteolytic enzyme has altered the at least one collagen-containing tissue matrix to reduce a human immune response to the tissue matrix.