Decellularized Nerve Allografts for Motor Function Restoration

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Solution Overview

Problem

Current methods for nerve reconstruction, such as autografts, are limited by supply, diameter, and length, and result in donor site morbidity, making it difficult to reconstruct nerves with multiple segmental defects effectively.

Innovation Solution

Decellularized nerve allografts prepared using elastase and stored under cold conditions without freezing can be used to repair nerve injuries or bridge severed nerves, restoring motor function by reducing immunogenicity and maintaining structural integrity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If autograft is used for nerve reconstruction, then motor function restoration is achieved, but donor site morbidity and limited supply occur

Engineering Contradiction:
Improvemotor function restorationVSAvoiddonor site morbidity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses decellularized nerve allograft as an intermediary material between the damaged nerve ends. This allograft has been treated to remove immunogenic cellular components while preserving the extracellular matrix structure, serving as a mediator that facilitates nerve regeneration without requiring donor site harvesting from the patient.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a copy of the native nerve structure by using decellularized allograft that replicates the extracellular matrix architecture. This copied structure provides the necessary scaffolding for regenerating nerve fibers without requiring actual autograft tissue, thereby avoiding donor site morbidity while maintaining functional restoration capabilities.

Inventive Principle:
Principle #26Copying

2Reliability

If autograft is used for nerve reconstruction, then motor function restoration is achieved, but limited length and diameter availability occur

Engineering Contradiction:
Improvemotor function restorationVSAvoidnerve graft length
Core Design Contradiction:
ReliabilityVSLength of stationary object

Solution Approach 1:

The patent employs nerve allografts that can serve multiple length and diameter requirements from a single donor source. The decellularized allografts can be sectioned and configured to match various defect sizes without being constrained by the limited dimensions of autograft harvests, providing universal applicability across different nerve injury scenarios.

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Duration of action of stationary object

If nerve allograft is frozen for storage, then long-term preservation is achieved, but structural integrity deteriorates

Engineering Contradiction:
Improvestorage durationVSAvoidstructural integrity
Core Design Contradiction:
Duration of action of stationary objectVSStrength

Solution Approach 1:

The patent changes the storage parameter from freezing to cold storage at refrigerated temperatures (2-8°C). This parameter modification preserves the structural integrity of the nerve allograft extracellular matrix while still allowing for long-term preservation. The decellularized state of the graft enables this cold storage approach without requiring freezing, thereby maintaining both duration of storage and structural strength.

Inventive Principle:
Principle #35Parameter changes

4Object-affected harmful factors

If decellularization is performed to reduce immunogenicity, then immune rejection is reduced, but processing complexity increases

Engineering Contradiction:
ImproveimmunogenicityVSAvoidprocessing complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent applies decellularization processes that extract and remove immunogenic cellular components (such as nuclei and cytoplasmic elements) from the nerve allograft while leaving the extracellular matrix intact. This extraction of harmful cellular material reduces immunogenicity and subsequent immune rejection, while the standardized decellularization protocols manage processing complexity through established methods.

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 use of decellularized nerve allografts allows for effective nerve reconstruction with reduced immunogenicity and preserved structural properties, enabling restored motor function in injured or severed nerves, evident at 12 weeks or longer post-implantation.

Implementation Method 1

contacting nerve tissue with from about 0.01 units/mL to about 1 unit/mL (e.g., about 0.05 units/mL) of elastase for at least about four hours (e.g., about 16 hours) to prepare the decellularized nerve graft

Methodology Applied
Scientific EffectEnzyme: Enzyme

Implementation Method 2

the decellularized nerve graft was not frozen and was stored under cold conditions of from about 1.5 °C to about 6.5 °C

Methodology Applied
Scientific EffectCold storage: Cooling

Data Source

PatentEP3302353B1Decellularized nerve allografts
Publication Date: 2020.08.26 MAYO FOUNDATION FOR MEDICAL EDUCATION & RESEARCH
  • EP3302353B1 patent drawingFigure 1
  • EP3302353B1 patent drawingFigure 2
  • EP3302353B1 patent drawingFigure 3

AI summary

This document relates to decellularized nerve allografts. For example, decellularized nerve allografts and methods and materials for using decellularized nerve allografts to repair nerve injuries or bridge a severed nerve are provided.