Focused Ultrasound Crosslinked Granular Hydrogels for High Porosity

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Solution Overview

Problem

Existing granular hydrogels face challenges in maintaining stability and desirable mechanical properties at high porosity, which limits their applications in therapeutic delivery and tissue engineering.

Innovation Solution

A method involving the mixing of hydrogel microparticles and polymeric fibers with crosslinking groups, followed by focused ultrasound (FUS) to crosslink them, optionally with removable particles and viscosity promoters, to create a stable granular hydrogel with adjustable porosity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If porosity is increased in granular hydrogels, then tissue regeneration capability is improved, but mechanical integrity deteriorates

Engineering Contradiction:
ImproveporosityVSAvoidmechanical integrity
Core Design Contradiction:
Quantity of substanceVSStrength

Solution Approach 1:

The hydrogel is segmented into discrete microparticles (200 μm or less) that form a granular structure. This segmentation allows high porosity between particles while maintaining mechanical integrity through interparticle crosslinks, resolving the contradiction between porosity and strength

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses composite granular hydrogels combining multiple microparticle types with different properties. The composite structure enables tuning of both porosity and mechanical properties by adjusting particle composition, size distribution, and crosslinking density

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If porosity is increased to enable cell incorporation, then tissue engineering application is improved, but structural stability deteriorates

Engineering Contradiction:
ImproveporosityVSAvoidstructural stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

Crosslinks are formed between microparticles before cell incorporation to pre-establish structural stability. This preliminary crosslinking ensures the granular hydrogel maintains its composition and structure even at high porosity levels required for cell embedding and tissue growth

Inventive Principle:
Principle #10Preliminary action

3Stability of the object's composition

If particle concentration is increased to improve mechanical properties, then structural stability is improved, but porosity deteriorates

Engineering Contradiction:
Improvestructural stabilityVSAvoidporosity
Core Design Contradiction:
Stability of the object's compositionVSQuantity of substance

Solution Approach 1:

The invention changes key parameters including particle size distribution, crosslinking density, and particle concentration to achieve optimal balance. By adjusting these parameters, the system can maintain structural stability while preserving sufficient porosity for tissue engineering applications

Inventive Principle:
Principle #35Parameter changes

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 a crosslinked granular hydrogel that maintains stability and mechanical integrity at high porosity, enabling applications in 3D bioprinting and regenerative medicine.

Implementation Method 1

applying focused ultrasound (FUS) to the precursor composition, whereby each of the first crosslinking group and the second crosslinking group reacts with the crosslinker

Methodology Applied
Scientific EffectUltrasound: Ultrasound

Implementation Method 2

each of the first crosslinking group and the second crosslinking group reacts with the crosslinker, thereby the hydrogel microparticle and the polymeric fiber are crosslinked

Methodology Applied
Scientific EffectCrosslinking: Chemical Bonding

Implementation Method 3

a viscosity promotor, which increases viscosity upon FUS-induced heating

Methodology Applied
Scientific EffectHeating: Heating

Implementation Method 4

the precursor composition further includes a removable particle, which upon removal changes the porosity of the granular hydrogel

Methodology Applied
Scientific EffectPorosity: Porosity

Data Source

PatentUS20250361368A1Focused ultrasound (FUS) crosslinking and pore-generation in granular hydrogels
Publication Date: 2025.11.27 UNIV OF VIRGINIA PATENT FOUND
  • US20250361368A1 patent drawing
  • US20250361368A1 patent drawing
  • US20250361368A1 patent drawing

AI summary

Provided herein is a method of preparing a crosslinked granular hydrogel, the method includes mixing a hydrogel microparticle having a first crosslinking group, a polymeric fiber having a second crosslinking group, an initiator, and a crosslinker to form a precursor composition. The method also includes applying focused ultrasound (FUS) to the precursor composition, whereby each of the first crosslinking group and the second crosslinking group reacts with the crosslinker, thereby the hydrogel microparticle and the polymeric fiber are crosslinked to form the granular hydrogel.