Protein-Modified PLGA Microspheres for Nerve Regeneration

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Solution Overview

Problem

Current methods for repairing peripheral nerve defects, such as autologous nerve transplantation, are limited by the scarcity of donor nerves and secondary damage, and tissue-engineered nerves face challenges with seed cell immunogenicity and growth factor stability.

Innovation Solution

Development of protein-modified PLGA microspheres, specifically laminin-modified PLGA microspheres loaded with a fat-soluble extract of Brucea javanica L., which are bound to silk fibroin fibers to create a tissue-engineered nerve conduit that promotes axon growth and myelination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If autologous nerve transplantation is used to repair peripheral nerve defects, then the repair effect is satisfactory, but the source of donor nerves is inadequate and secondary damage is caused

Engineering Contradiction:
Improverepair effectVSAvoidsource of donor nerves
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent creates artificial nerve conduits that copy and mimic the structure and function of natural nerves. These conduits are engineered with extracellular matrix components and growth factors to replicate the natural nerve environment, providing a substitute that eliminates the need for donor nerve tissue while maintaining effective repair capabilities

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent modifies the physical and chemical parameters of the nerve conduit materials to optimize their biological performance. By adjusting parameters such as porosity, degradation rate, and growth factor concentration, the conduits can effectively support nerve regeneration without requiring autologous donor tissue

Inventive Principle:
Principle #35Parameter changes

2Reliability

If growth factors are added to scaffold material to construct tissue-engineered nerves, then nerve regeneration is promoted, but stability and efficiency must be maintained according to their physical and chemical properties

Engineering Contradiction:
Improvenerve regeneration promotionVSAvoidgrowth factor stability
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent embeds growth factors within the hierarchical structure of the extracellular matrix scaffold. Growth factors are nested within microparticles or vesicles that are themselves incorporated into the larger conduit structure, providing multiple levels of protection and controlled release mechanisms that maintain stability while promoting regeneration

Inventive Principle:
Principle #7Nested doll (Nesting)

Solution Approach 2:

The patent uses extracellular matrix components as intermediary carriers for growth factors. These matrix proteins serve as mediators that protect growth factors from degradation, control their release kinetics, and facilitate their interaction with regenerating nerve tissues, thereby maintaining both stability and efficiency

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 tissue-engineered nerve conduit effectively enhances myelination and nerve regeneration, providing a promising clinical solution for peripheral nerve injuries with improved biocompatibility and sustained release of active substances.

Implementation Method 1

PLGA is cross-linked with one or more of collagen, fibronectin, silk fibroin, and laminin through a cross-linking agent

Methodology Applied
Scientific EffectCross-linking: Chemical Bonding

Implementation Method 2

The crosslinking agent is a chemical crosslinking agent or a biological crosslinking agent, preferably a biological crosslinking agent, such as genipin, carbodiimide/N-hydroxysuccinimide (EDC/NHS), and sodium alginate

Methodology Applied
Scientific EffectChemical cross-linking: Chemical Bonding

Implementation Method 3

The crosslinking agent is a chemical crosslinking agent or a biological crosslinking agent

Methodology Applied
Scientific EffectBiological cross-linking: Chemical Bonding

Implementation Method 4

the fat-soluble extract of Brucea javanica L. Merr promotes the growth of peripheral DRG neurons and neurites

Methodology Applied
Scientific EffectNeurite outgrowth promotion:

Implementation Method 5

the tissue-engineered nerve can effectively promote the myelination of the regenerated nerve after peripheral nerve injury

Methodology Applied
Scientific EffectMyelination promotion:

Data Source

PatentUS11788058B2Protein-modified PLGA microsphere and tissue-engineered nerve constructed therewith
Publication Date: 2023.10.17 NANTONG UNIV
  • US11788058B2 patent drawing
  • US11788058B2 patent drawing
  • US11788058B2 patent drawing

AI summary

A protein-modified PLGA microsphere can be used to construct tissue-engineered nerve. The microspheres are loaded with active substances for treating peripheral nerve injury and are bound to tissue-engineered nerves. It has been shown that the prepared tissue-engineered nerve effectively promotes nerve regeneration after peripheral nerve injury.