Tropoelastin Elastic Material Formation Without Cross-Linkers

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Solution Overview

Problem

Current methods for forming stable three-dimensional elastic structures from tropoelastin monomers face challenges due to the dissociation of cross-linked monomers in physiological conditions, use of non-biocompatible cross-linking agents, and limitations in shaping robust structures, particularly in tissue engineering applications.

Innovation Solution

A method involving heating a solution of tropoelastin monomers on a surface to a specific temperature range that allows the monomers to bind irreversibly, forming an elastic material that maintains its structure in aqueous environments without the need for cross-linking agents, enabling the creation of biocompatible, elastic materials suitable for tissue repair and engineering.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If cross-linking agents are used to form stable three-dimensional elastic structures from tropoelastin monomers, then the stability and structural integrity of the material is improved, but the biocompatibility and safety of the material deteriorates due to toxicity of cross-linking agents

Engineering Contradiction:
Improvestability of elastic structureVSAvoidtoxicity of cross-linking agents
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and eliminates the harmful cross-linking agents from the system by using a purely thermal process. Tropoelastin monomers are heated to undergo spontaneous cross-linking without any chemical cross-linking agents, thereby removing the source of toxicity while maintaining structural stability.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The tropoelastin monomers perform self-cross-linking through thermal activation alone. The monomers themselves provide the necessary chemical groups and reactivity to form cross-links when heated, eliminating the need for external cross-linking agents and their associated toxicity.

Inventive Principle:
Principle #25Self-service

2Stability of the object's composition

If heating is applied to evaporate solvent and enable cross-linking, then the formation of stable elastic structures is improved, but the complexity of the manufacturing process worsens due to additional heating steps and temperature control requirements

Engineering Contradiction:
Improvestability of elastic structureVSAvoidcomplexity of heating and temperature control
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The invention merges two separate functions into one unified heating step: solvent evaporation and cross-linking activation both occur simultaneously during the same heating process. This eliminates the need for separate drying and cross-linking steps, reducing overall process complexity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention uses a specific temperature range (60-100°C) that simultaneously achieves solvent evaporation and activates cross-linking of tropoelastin monomers. By optimizing this parameter, the process achieves multiple objectives without requiring complex multi-step temperature protocols.

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If cross-linked tropoelastin monomers are formed to prevent dissociation in physiological conditions, then the stability of the material in aqueous environments is improved, but the ability to form preferred three-dimensional shapes deteriorates because the material solidifies quickly and cannot be conformed

Engineering Contradiction:
Improvestability in physiological conditionsVSAvoidpreferred three-dimensional structure
Core Design Contradiction:
Stability of the object's compositionVSShape

Solution Approach 1:

The invention applies preliminary thermal treatment to induce cross-linking while the material is still in a workable state on the substrate. This preliminary cross-linking provides sufficient stability to prevent dissociation in physiological conditions while maintaining enough flexibility during the process to allow shaping and conforming to three-dimensional structures.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The cross-linking process is applied locally on the substrate surface where the tropoelastin solution is deposited. This localized cross-linking creates stable elastic structures at the deposition site while allowing controlled shaping and manipulation before complete solidification, enabling formation of preferred three-dimensional shapes.

Inventive Principle:
Principle #3Local quality

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 method produces biocompatible, elastic materials with retained mechanical properties, allowing for the formation of stable three-dimensional structures that can be used in tissue engineering and in vitro assays without toxicity concerns, offering a scalable and cost-effective solution for tissue repair and regeneration.

Implementation Method 1

The cross-linking of tropoelastin monomers, whether in coacervated form or otherwise, leads to a covalent bonding of tropoelastin monomers that ostensibly represents an association of tropoelastin monomers that cannot be dissociated by pH, salt or temperature adjustment.

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 2

cross-linking of tropoelastin monomers... leads to a covalent bonding of tropoelastin monomers

Methodology Applied
Scientific EffectCross-linking:

Implementation Method 3

heating the solution on the surface to a temperature sufficient to enable the tropoelastin monomers to bind to each other

Methodology Applied
Scientific EffectThermal energy: Heating

Implementation Method 4

Generally the heating step is required to evaporate solvent, and/or to provide the required temperature condition for the cross-linking reaction.

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 5

The process is known as coacervation, in which tropoelastin monomers associate with each other by contact of hydrophobic regions of one tropoelastin monomer with the like regions of another monomer.

Methodology Applied
Scientific EffectCoacervation: Coacervate

Data Source

PatentUS11077226B2Scalable three-dimensional elastic construct manufacturing
Publication Date: 2021.08.03 ALLERGAN PHARMACEUTICALS INTERNATIONAL LTD
  • US11077226B2 patent drawing
  • US11077226B2 patent drawing
  • US11077226B2 patent drawing

AI summary

Tissue repair and restoration can be performed using an elastic material formed from tropoelastin. The elastic material can be formed by providing a solution of tropoelastin monomers, applying the solution to a surface, and heating the solution on the surface in absence of a cross-linking agent to enable the tropoelastin monomers to bind to each other to form an elastic material that does not dissociate into tropoelastin monomers when the elastic material is contacted with an aqueous solution.