Double Crosslinked Biopolymer Membrane for Corneal Repair

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Solution Overview

Problem

Current methods for ocular trauma repair, particularly for corneal trauma, lack a biopolymer membrane that can be effectively double cross-linked using two natural cross-linkers, which is essential for creating a durable and biocompatible temporary implant.

Innovation Solution

A two-step process involving a mixed solution of collagen and chitosan biopolymers, where tannic acid is used as the primary cross-linker followed by genipin as the secondary cross-linker, forming a thin, porous membrane with hydrogen bonding and covalent crosslinking, applied at room temperature over 48 to 72 hours.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If a single cross-linking agent is used to create a biopolymer membrane, then the membrane formation process is simple, but the membrane lacks sufficient durability and structural stability for corneal trauma repair

Engineering Contradiction:
Improvesimplicity of membrane formation processVSAvoiddurability and structural stability of membrane
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The cross-linking process is divided into two distinct stages: first cross-linking with tannic acid to form an initial membrane structure, then second cross-linking with genipin to enhance structural stability. This segmentation allows each cross-linking agent to perform a specific function, with tannic acid providing initial framework and genipin reinforcing the structure for durability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent combines two different natural cross-linking agents (tannic acid and genipin) to create a composite cross-linking system. This composite approach leverages the complementary properties of both agents: tannic acid provides initial cross-linking and the genipin enhances structural stability, resulting in a more durable membrane than either agent could achieve alone.

Inventive Principle:
Principle #40Composite materials

2Reliability

If multiple cross-linking stages are implemented to enhance membrane durability, then the structural stability improves, but the manufacturing process complexity increases

Engineering Contradiction:
Improvestructural stability of membraneVSAvoidcomplexity of cross-linking process
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The complex cross-linking process is segmented into two simple, sequential stages that can be performed in succession. Each stage uses a single cross-linking agent with a specific function, making the overall process manageable despite the two-step nature. The first stage creates the basic structure while the second stage reinforces it, with each step being straightforward and repeatable.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The first cross-linking stage with tannic acid serves as a preliminary action that prepares the membrane structure for the second cross-linking stage with genipin. By establishing the initial framework first, the subsequent genipin cross-linking can focus on enhancing structural stability without requiring complete process complexity from the outset.

Inventive Principle:
Principle #10Preliminary action

3Ease of operation

If the membrane is made thin for corneal application, then the biocompatibility and healing properties improve, but the membrane strength and durability are reduced

Engineering Contradiction:
Improvebiocompatibility and healing propertiesVSAvoidmembrane strength and durability
Core Design Contradiction:
Ease of operationVSStrength

Solution Approach 1:

The dual cross-linking system creates a composite structural framework within the thin membrane. The tannic acid-crosslinked network provides the basic structural integrity while the genipin-crosslinked network reinforces it, allowing the membrane to maintain both thinness for biocompatibility and sufficient strength for durability.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The cross-linking density and type vary within different regions of the membrane structure. The dual cross-linking creates localized regions of enhanced strength where needed, while maintaining overall thinness. This local variation in cross-linking quality allows the membrane to be thin enough for corneal application yet strong enough for functional durability.

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 resulting double cross-linked membrane is non-transparent, dark-colored, and maintains porosity, providing a suitable temporary implant for corneal trauma repair with enhanced biocompatibility and healing properties.

Implementation Method 1

hydrogen bonding is primarily formed by the action of tannic acid

Methodology Applied
Scientific EffectHydrogen bonding: Van der Waals Force

Implementation Method 2

covalent crosslinking between the amino groups of the biopolymer and the secondary cross-linker by genipin

Methodology Applied
Scientific EffectCovalent crosslinking: Chemical Bonding

Data Source

PatentEP3664857B1A process for producing a two-stage crosslinked biopolymer membrane and a biopolymer membrane made in this process
Publication Date: 2022.12.21 UNIVERZITA TOMASE BATI VE ZLINE
  • EP3664857B1 patent drawingFigure 1(a)~2

AI summary

The fabrication of a double/two-step crosslinked biopolymer membrane for eye trauma repair lies in preparation of a mixed solution of biopolymers consisting of collagen and chitosan, dropwise adding a solution of the primary crosslinking agent from the group of tannins and pouring the solution onto a flat pad and then drying to form a thin primary cross-linked chitosan-collagen membrane with a thickness after drying of 5 to 10 μm. This is then crosslinked in the second stage with a solution of genipin as a secondary crosslinking agent.