Injectable Porous Hydrogels via Enzymatic Microgel Cross-Linking

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Solution Overview

Problem

Injectable hydrogels lack inherent pore structures, limiting their interactions with surrounding tissues and reducing their clinical efficacy in wound healing applications.

Innovation Solution

A method for producing injectable porous hydrogels by preparing gelatin microgels, mixing them with a cross-linking enzyme like transglutaminase, and curing them, optionally with a photoinitiator and UV light, to create a matrix that supports cell migration and proliferation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If injectable hydrogels are used for wound healing, then they conform to irregular wound shapes, but they lack inherent pore structures which limits interactions with surrounding tissues

Engineering Contradiction:
Improveconformability to wound shapesVSAvoidclinical efficacy
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent applies porous materials by incorporating pre-formed microgels with inherent porous structures into the injectable hydrogel formulation. These microgels maintain their porous architecture after injection and curing, providing channels for cell migration and tissue interaction while preserving the hydrogel's conformability to irregular wound shapes.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent uses composite materials by combining microgels with hydrogel matrix components to create a composite injectable formulation. The microgels serve as porous building blocks that provide structural pathways for tissue integration, while the hydrogel matrix provides conformability and structural support, achieving both adaptability and clinical efficacy.

Inventive Principle:
Principle #40Composite materials

2Adaptability or versatility

If microgels are mixed with cross-linking enzyme to form porous hydrogel, then pore structure is created for cell migration, but additional curing steps are required

Engineering Contradiction:
Improvecell migration supportVSAvoidcuring process complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent uses cross-linking enzymes as intermediaries that naturally catalyze the formation of porous hydrogel structures from microgels. The enzymes facilitate cross-linking reactions between microgel components, creating stable porous networks without requiring complex external curing equipment or multiple processing steps.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies self-service by utilizing the inherent enzymatic activity present in the microgel formulation to automatically cross-link and stabilize the porous structure after injection. The cross-linking enzyme performs the curing function autonomously under physiological conditions, eliminating the need for external curing interventions.

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 resulting hydrogels exhibit enhanced cellular proliferation and tissue adhesion, allowing for effective wound healing and tissue engineering by providing a porous structure for cell migration and growth.

Implementation Method 1

mixing the gelatin microgels with a cross-linking enzyme to produce the injectable porous hydrogel; the cross-linking enzyme includes a transglutaminase

Methodology Applied
Scientific EffectEnzymatic cross-linking: Enzyme

Implementation Method 2

curing the injectable porous hydrogel includes: mixing the gelatin microgels with a photoinitiator; the photoinitiator includes at least one of Irgacure 2959, vitamin B12, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP); contacting the mixture that includes the gelatin microgels and the photoinitiator with ultraviolet (UV) light

Methodology Applied
Scientific EffectPhotopolymerization: Photopolymerisation

Implementation Method 3

The macroporous hydrogels may be prepared in a manner that includes live cells and can be used to deliver live cells to tissues and subjects

Methodology Applied
Scientific EffectHydrogel swelling: Absorption (physical)

Data Source

PatentUS11998658B2Injectable porous hydrogels
Publication Date: 2024.06.04 UNIVERSITY OF NEW HAMPSHIRE
  • US11998658B2 patent drawing
  • US11998658B2 patent drawing
  • US11998658B2 patent drawing

AI summary

Injectable macroporous hydrogels, and methods of producing same, are described. The injectable macroporous hydrogels may be formed by mixing gelatin microgels with an enzyme. In at least some embodiments, the enzyme may be transglutaminase, and more specifically microbial transglutaminase (mTG).