Composite Scaffold for Optic Nerve Axon Regeneration

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Solution Overview

Problem

Current treatments for traumatic optic neuropathy (TON) face challenges in promoting effective regeneration of optic nerve axons due to internal factors like apoptosis and external barriers such as the glial scar, with existing methods like gene therapy, exogenous neurotrophic factors, and peripheral nerve transplantation showing limitations in safety and efficacy.

Innovation Solution

A composite scaffold made from gelatin A and sodium alginate, cross-linked with genipin, is developed to create a directional pipeline structure that supports and guides the regeneration of optic nerve axons by providing a conducive environment for growth and attachment, overcoming the limitations of existing treatments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If gene therapy modes such as AAV are used to promote regeneration of optic nerve axons, then proliferation inhibition of intracellular programs is opened, but safety needs to be verified

Engineering Contradiction:
ImprovesafetyVSAvoidverification difficulty
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses a physical scaffold structure as an intermediary carrier to deliver neurotrophic factors and create a favorable microenvironment, avoiding the safety concerns of gene therapy while achieving similar regenerative effects through biochemical and physical support mechanisms

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If exogenous neurotrophic factors are provided to improve neurotrophic factor deficiency, then regeneration of axons is promoted, but drug metabolism problem causes poor performance

Engineering Contradiction:
Improveregeneration effectVSAvoidperformance duration
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The scaffold is pre-loaded with neurotrophic factors before implantation, creating a sustained release system that maintains effective concentrations over time. The gradual degradation of the scaffold ensures continuous factor delivery, overcoming the rapid metabolism issue of exogenous factors

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the delivery parameters by using a controlled release system through scaffold degradation, transforming the rapid metabolism problem into a sustained release advantage that maintains therapeutic levels throughout the regeneration process

Inventive Principle:
Principle #35Parameter changes

3Reliability

If anti-inflammatory and anti-apoptotic drugs are applied to decrease apoptosis of RGCs, then inflammation and oxidative stress are reduced, but drug metabolism problem exists

Engineering Contradiction:
Improveapoptosis preventionVSAvoidprotection duration
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The scaffold material itself provides protective functions through its degradation products and structural properties, creating a self-sustaining protective environment that eliminates the need for continuous drug administration and overcomes metabolism limitations

Inventive Principle:
Principle #25Self-service

4Reliability

If peripheral nerves are transplanted to improve external inhibition environment, then regeneration of optic nerve axons is promoted, but limited sources and rejection in allograft exist

Engineering Contradiction:
Improveregeneration promotionVSAvoidmaterial availability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the material parameters by using synthetic or decellularized scaffold materials with controlled physical and chemical properties, eliminating source limitations and immunogenicity while maintaining the structural support function needed for axon regeneration

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The scaffold uses composite materials combining biodegradable polymers and biological components to achieve both structural integrity and biocompatibility, providing a versatile solution that avoids the limitations of single-material approaches and donor tissue variability

Inventive Principle:
Principle #40Composite materials

5Reliability

If optic canal decompression operation is performed to relieve compression, then blood supply is increased and swelling is reduced, but intrinsic apoptotic program cannot be prevented

Engineering Contradiction:
Improveblood supply improvementVSAvoidapoptosis
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The scaffold acts as an intermediary structure that delivers neurotrophic factors and creates a protective microenvironment, mediating between the mechanical decompression and the biological prevention of apoptosis to achieve comprehensive protection

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The scaffold provides self-sustaining neuroprotection through its gradual degradation and continuous release of protective factors, creating a long-term protective effect that extends beyond the immediate surgical intervention

Inventive Principle:
Principle #25Self-service

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 composite scaffold facilitates directional regeneration of optic nerve axons by offering a stable, biocompatible, and biomechanically suitable platform for axon growth and nutrient circulation, enhancing the regeneration process and serving as a potential clinical treatment for TON.

Implementation Method 1

dissolving Type A gelatin into deionized water at 70° C. to obtain a gelatin A solution; dissolving sodium alginate into the deionized water at 70° C. to obtain a sodium alginate solution; mixing the two solutions according to a ratio of 1:1

Methodology Applied
Scientific EffectFreezing: Freezing

Implementation Method 2

adding a gelatin A and sodium alginate composite scaffold into a genipin solution; and shaking the composite scaffold on a transfer membrane shaker for 24 hours for cross-linking

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Data Source

PatentUS11331413B1Preparation method and application of composite scaffold for directionally guiding regeneration of optic nerve axons
Publication Date: 2022.05.17 WENZHOU MEDICAL UNIV
  • US11331413B1 patent drawing
  • US11331413B1 patent drawing
  • US11331413B1 patent drawing

AI summary

A preparation method and an application of a composite scaffold for directionally guiding regeneration of optic nerve axons. A major component of the composite scaffold is prepared from one or more degradable biomedical materials combined according to different ratios by a gradient freezing method. To increase a mechanical property of the scaffold or prolong in-vivo degradation time, the scaffold may be cross-linked by a biological cross-linker. After a gelatin is added, the prepared composite scaffold exhibits excellent mechanical properties and biocompatibility. A problem of solubility differences of the gelatin A produced during gradient freezing can be regulated by sodium alginate, thereby facilitating regular directional pipeline morphology of the scaffold. After cross-linked with genipin, the composite scaffold significantly enhances stability, and the directional pipeline morphology of the scaffold cam provide attachment sites for regeneration of the optic nerve axons, thereby guiding directional regeneration of the optic nerve axons.