Double-Network Hydrogel for Sequential Drug Release in Corneal Repair

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Solution Overview

Problem

Current hydrogel-based corneal substitutes primarily focus on promoting single stages of corneal regeneration, which is insufficient to address the complex needs of severe infectious keratitis, including multiple stages of corneal wound healing.

Innovation Solution

A double-network versatile hydrogel (SQPV) with antibacterial and drug sequential release capabilities is developed using silk fibroin (SF) and chitosan (CS) as main raw materials, enabling spatiotemporal drug release and realizing antimicrobial, anti-inflammatory, proliferative, and remodeling functions at different stages of corneal infection repair.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If hydrogel corneas are designed to promote single stage of corneal regeneration, then the structure is simple and easy to manufacture, but the functional versatility is insufficient to meet complex clinical needs of infectious keratitis

Engineering Contradiction:

Improvefunctional versatilityVSAvoidstructure complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The hydrogel cornea is designed to perform multiple functions simultaneously: antibacterial activity through chitosan, anti-inflammatory effects through PDRN, and promotion of corneal regeneration through GelMA. This multi-functional design allows a single hydrogel system to address the complex needs of infectious keratitis, including infection control, inflammation reduction, and tissue repair, without requiring multiple separate treatments

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The hydrogel cornea combines multiple materials with complementary properties: GelMA provides corneal-like structure and cell adhesion, chitosan contributes antibacterial activity and mechanical strength, and PDRN adds anti-inflammatory and regenerative capabilities. This composite material approach enables the hydrogel to achieve functional versatility while maintaining structural integrity

Inventive Principle:

Principle #40Composite materials

2Reliability

If drug-loaded micelles are incorporated into hydrogel for sequential release, then the therapeutic effect is enhanced through spatiotemporal control, but the manufacturing process becomes more complex

Engineering Contradiction:

Improvetherapeutic effectVSAvoidmanufacturing process

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

Drugs are pre-loaded into micelles during the hydrogel fabrication process, allowing the therapeutic agents to be positioned and protected before implantation. The micelles are formed and drug-loaded in advance, then integrated into the hydrogel network, ensuring controlled release kinetics and protecting drugs from degradation until delivery

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The structure employs a nested configuration where drugs are encapsulated within micelles, which are then incorporated into the hydrogel matrix. This multi-level nesting (drugs inside micelles, micelles inside hydrogel) provides hierarchical control over drug release, with micelles offering first-level encapsulation and the hydrogel providing second-level control through its mesh structure

Inventive Principle:

Principle #7Nested doll (Nesting)

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 SQPV hydrogel effectively eliminates residual bacteria, reduces inflammation, promotes regeneration of the corneal epithelium and stroma, prevents scar formation, and accelerates wound healing, demonstrating potential as an ideal substitute material for corneal transplantation in severe bacterial keratitis.

Implementation Method 1

The SQPV hydrogel effectively eliminates residual bacteria

Methodology Applied

Scientific EffectAntibacterial action:

Implementation Method 2

reduces inflammation

Methodology Applied

Scientific EffectAnti-inflammatory action:

Implementation Method 3

promotes regeneration of the corneal epithelium and stroma

Methodology Applied

Scientific EffectTissue regeneration:

Implementation Method 4

prevents scar formation

Methodology Applied

Scientific EffectTissue remodeling:

Implementation Method 5

accelerates wound healing

Methodology Applied

Scientific EffectWound healing acceleration:

Implementation Method 6

realizing controllable spatiotemporal sequential administration of the drug

Methodology Applied

Scientific EffectDrug release: Diffusion

Data Source

PatentUS12324769B1Double-network versatile hydrogel with antibacterial and drug sequential release capabilities

Publication Date: 2025.06.10 EYE INST OF SHANDONG FIRST MEDICAL UNIV

AI summary

A preparation method of a double-network versatile hydrogel with antibacterial and drug sequential release capabilities is provided in the present disclosure, belonging to the technical field of biological corneas. The preparation method includes the following steps: mixing filipin protein-methacrylate, glycidyl methacrylate functionalized quaternized chitosan, polydeoxyribonucleotide, and lithium phenyl(2,4,6-trimethylbenzoyl) phosphinate with drug-loaded micelles, followed by cross-linking under irradiation of ultraviolet to construct a double-network versatile hydrogel with antibacterial and drug sequential release capabilities.