Decellularized Nerve Graft Using Low-Concentration Surfactant

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Solution Overview

Problem

Current decellularization methods for nerve grafts face challenges such as tissue structure collapse, incomplete cell removal, and residual surfactant toxicity, requiring lengthy washing processes and often resulting in damaged tissue and immune responses.

Innovation Solution

A method using a low-concentration basic solution and anionic surfactant with a peristaltic pump system for decellularization and delipidation, minimizing surfactant use and reducing processing time, while maintaining tissue structure and allowing for lyophilized or hydrated storage at room temperature.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high concentration surfactant or enzyme is used for decellularization, then cell removal efficiency is improved, but tissue structure is damaged

Engineering Contradiction:
Improvecell removal efficiencyVSAvoidtissue structure
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the concentration parameter of surfactant and enzyme to low levels, and extends the treatment time to achieve effective decellularization while preserving tissue structure. This resolves the contradiction by finding an optimal parameter combination that balances cell removal efficiency with tissue integrity maintenance.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs periodic treatment cycles with multiple washing steps interspersed between decellularization treatments. This periodic action allows gradual cell removal while continuously refreshing the solution to prevent tissue damage, maintaining both effectiveness and structural integrity.

Inventive Principle:
Principle #19Periodic action

2Reliability

If high concentration surfactant is used for decellularization, then cell removal is enhanced, but residual surfactant causes cell and tissue toxicity

Engineering Contradiction:
Improvecell removal efficiencyVSAvoidsurfactant residue toxicity
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses low concentration surfactant from the beginning, which inherently reduces the amount of residual toxic substance while still achieving effective decellularization through extended treatment time and periodic washing cycles.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent performs preliminary washing steps before complete decellularization is achieved, continuously removing surfactant residues during the process rather than allowing accumulation that would lead to toxicity.

Inventive Principle:
Principle #10Preliminary action

3Object-affected harmful factors

If thorough washing is performed to remove residual surfactant, then toxicity is reduced, but processing time increases to 3-4 days

Engineering Contradiction:
Improvesurfactant residue toxicityVSAvoidprocessing time
Core Design Contradiction:
Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The patent changes the surfactant concentration parameter to low levels from the start, which reduces the total amount of surfactant that needs to be removed, thereby shortening the washing time required while still achieving effective decellularization.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements continuous washing throughout the decellularization process rather than separate pre- and post-washing steps, maintaining constant removal of surfactant residues and reducing total processing time while ensuring low toxicity.

Inventive Principle:
Principle #20Continuity of useful action

4Reliability

If all processes are performed using a shaker for decellularization, then mixing is improved, but tissue structure can be damaged

Engineering Contradiction:
Improvedecellularization effectivenessVSAvoidtissue structure
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent uses periodic gentle shaking interspersed with static incubation periods, providing sufficient mixing for effective decellularization while allowing tissue structures to recover and maintain integrity during static phases.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent changes the mechanical agitation parameter from continuous strong shaking to gentle periodic shaking, reducing mechanical stress on tissue structures while maintaining sufficient mixing through extended treatment time.

Inventive Principle:
Principle #35Parameter changes

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 effectively removes cells and lipids, reduces tissue toxicity, shortens processing time, and maintains tissue structure, enabling the production of decellularized nerve grafts that can be stored and used for peripheral nerve regeneration with reduced immune response risk.

Implementation Method 1

a) and b) are performed using a peristaltic pump system

Methodology Applied
Scientific EffectPeristalsis: Peristalsis

Implementation Method 2

the nervous tissue is treated with a basic solution and an anionic surfactant

Methodology Applied
Scientific EffectSurfactant action: Surfactant

Implementation Method 3

cells are removed using a protease for removing a membrane protein and various surfactants for removing phospholipids

Methodology Applied
Scientific EffectChemical degradation: Decomposition (biological)

Implementation Method 4

allowing for lyophilized or hydrated storage at room temperature

Methodology Applied
Scientific EffectLyophilization: Freeze Drying

Data Source

PatentUS20230041245A1Decellularized Nerve Graft and Method of Manufacturing the Same
Publication Date: 2023.02.09 L&C BIO CO LTD
  • US20230041245A1 patent drawing
  • US20230041245A1 patent drawing
  • US20230041245A1 patent drawing

AI summary

The present invention relates to a decellularized nerve graft using allogeneic and heterologous nervous tissues and a method of manufacturing the same.In the present invention, by using a low-concentration basic solution and a surfactant as a decellularization solution, cell and tissue toxicity caused by a solvent or surfactant remaining in the tissue may be minimized by minimizing the use of a basic solution and an anionic surfactant in the entire manufacturing process. In addition, a peristaltic pump may be used to maintain the tissue structure and effectively remove lipid and cells.