Biodegradable Nerve Conduit with Pre-seeded Stem Cells

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Solution Overview

Problem

Current methods for peripheral nerve injury repair, such as nerve autografts and guidance tubes, are inadequate for significant nerve trauma, leading to low success rates in restoring motor and sensory function due to issues like scar tissue interference, foreign body reactions, and limited axon regeneration distance.

Innovation Solution

A biodegradable and biocompatible nerve conduit/matrix is developed using cultured human mesenchymal stem cells, differentiated Schwann cells, and neuronal cells on a composite polymer scaffold with glutaraldehyde cross-linking, allowing for direct implantation and promoting synergistic nerve regeneration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Length of moving object

If nerve autograft is used for major nerve trauma, then nerve continuity is restored, but the treatment is largely ineffective for large nerve segments (>5 cm) due to limited axon regeneration distance

Engineering Contradiction:
Improveaxon regeneration distanceVSAvoidnerve regeneration success rate
Core Design Contradiction:
Length of moving objectVSReliability

Solution Approach 1:

The patent applies preliminary action by pre-seeding Schwann cells and other supportive cells onto the nerve conduit scaffold before implantation. This pre-preparation creates a pro-regenerative environment in advance, allowing axons to regenerate over longer distances by providing guidance cues and supportive factors along the entire conduit length, thus overcoming the limitation of limited axon regeneration distance in traditional autografts.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses a biodegradable nerve conduit as an intermediary structure between the proximal and distal nerve stumps. This conduit serves as a mediator that provides physical support, cellular guidance, and biochemical cues to facilitate axon regeneration across large gaps, effectively extending the functional regeneration distance beyond what is achievable with direct autografting alone.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If traditional nerve repair strategies are used, then surgical intervention is provided, but scar tissue interference and foreign body reactions reduce the success rate of restoring motor and sensory function

Engineering Contradiction:
Improverestoration of motor and sensory functionVSAvoidscar tissue interference and foreign body reactions
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by using biodegradable materials for the nerve conduit that gradually decompose over time, changing from a foreign structure to integrated tissue. The scaffold material transitions from intact to degraded state, eliminating foreign body reactions while maintaining structural support during regeneration. This temporal parameter change allows the conduit to serve its function and then disappear without causing chronic inflammation or scarring.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs discarding and recovering by designing a biodegradable scaffold that is temporarily discarded (degraded) after serving its regenerative function. The scaffold provides essential support and guidance during the regeneration process, then deliberately degrades and is absorbed by the body, eliminating foreign body reactions and scar tissue formation while the regenerated nerve tissue takes over the functional role.

Inventive Principle:
Principle #34Discarding and recovering

3Reliability

If nerve guidance tubes are used for peripheral nerve injury, then some structural support is provided, but the success rate remains low due to inadequate support for significant nerve trauma

Engineering Contradiction:
Improvenerve regeneration success rateVSAvoidconduit structure simplicity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies composite materials by combining biodegradable polymer scaffold with pre-seeded Schwann cells, growth factors, and extracellular matrix components. This composite structure integrates multiple functional elements (structural support, cellular guidance, biochemical signaling) into a single conduit system, providing comprehensive support for significant nerve trauma while maintaining a unified device architecture that does not substantially increase complexity.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent merges multiple previously separate components (nerve conduit, Schwann cells, growth factors, ECM) into a single integrated pre-seeded nerve graft. This combination consolidates the regenerative support system into one implantable unit, improving reliability for significant nerve trauma while avoiding the need for multiple separate surgical steps or complex multi-component assemblies.

Inventive Principle:
Principle #5Merging (Combining)

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 nerve conduit/matrix enables efficient nerve repair and regeneration, restoring motor and sensory functions in a shorter timeframe with reduced complications and morbidity, capable of spanning longer nerve gaps and maintaining pro-regenerative environments.

Implementation Method 1

a biodegradable and biocompatible nerve conduit/matrix is developed using cultured human mesenchymal stem cells, differentiated Schwann cells, and neuronal cells on a composite polymer scaffold with glutaraldehyde cross-linking

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Implementation Method 2

The final product obtained is transported in semi-solid medium wherein the semi-solid medium is agar medium 1% to 3% and cell culture medium with essential growth factors

Methodology Applied
Scientific EffectGel structure: Gel

Data Source

PatentUS11957815B2Ready to use biodegradable and biocompatible cell-based nerve conduit for nerve injury and a method of preparation thereof
Publication Date: 2024.04.16 DATT LIFE SCI PVT LTD
  • US11957815B2 patent drawing
  • US11957815B2 patent drawing
  • US11957815B2 patent drawing

AI summary

An artificial tissue construct for nerve repair and regeneration includes a biocompatible and biodegradable nerve guidance matrix comprising a plurality of biopolymers that include chitosan, gelatin, collagen and hyaluronic acid. A cross-linker includes glutaraldehyde. The nerve guidance matrix is formed as a three-dimensional scaffold polyelectrolyte complex (PEC). A subconfluent and grown monolayer of at least one of human mesenchymal stem cells, mesenchymal stem cells, differentiated Schwann cells and neuronal cells is on the biocompatible and biodegradable nerve guidance matrix for direct implantation or delivery. A method of making the artificial tissue construct is disclosed.