Nanowarming Vitrification for Large Tissue Rewarming Uniformity

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Solution Overview

Problem

Existing methods for large volume tissue preservation face challenges in achieving uniform heating rates and avoiding thermal stresses during rewarming, leading to potential damage and reduced cell viability.

Innovation Solution

Supplementation of ice-free vitrification formulations with magnetic nanoparticles (mNPs) and sugars, such as 2 mg/mL Fe mNPs, combined with nanowarming procedures, to enhance cell survival and tissue functions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional heating methods are used for rewarming large volume tissue samples, then the rewarming process is simple to implement, but thermal gradients cause thermal stresses that lead to fractures or cracks and reduced cell viability

Engineering Contradiction:
Improvecell viabilityVSAvoidrewarming process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The tissue sample is divided into multiple segments by inserting heating elements (needles) at various locations throughout the sample volume. Each heating element independently controls the temperature in its local region, ensuring uniform heating throughout the entire sample and eliminating thermal gradients that cause stress and damage.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The heating approach transitions from external surface heating to internal volumetric heating by inserting heating elements throughout the sample. This three-dimensional distribution of heating sources eliminates thermal gradients by heating from the interior outward simultaneously, preventing thermal stress and fractures.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Reliability

If high concentrations of cryoprotectants are used for ice-free vitrification, then ice formation is prevented during cooling and storage, but cell viability is reduced due to cryoprotectant toxicity

Engineering Contradiction:
Improveice formation preventionVSAvoidcryoprotectant toxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Cryoprotectants are removed from the tissue sample before the rewarming process begins. This preliminary removal eliminates the source of toxicity that would otherwise damage cells during and after rewarming, while the tissue remains protected during storage in the vitrified state.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The protocol includes preliminary steps to remove cryoprotectants and prepare the tissue for rewarming before the actual heating process. This cushioning approach prevents cryoprotectant toxicity from affecting cell viability during the critical rewarming phase.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Reliability

If rapid heating rates are applied during rewarming to prevent ice crystallization, then ice formation is avoided, but thermal stresses increase causing fractures or cracks

Engineering Contradiction:
Improveice crystallization preventionVSAvoidtissue structural integrity
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

Multiple heating elements distributed throughout the sample enable simultaneous heating at many locations. This segmentation allows the tissue to be warmed rapidly overall while maintaining uniform temperature distribution, preventing both ice crystallization and thermal stress-induced fractures.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The heating rate and temperature distribution are dynamically controlled by adjusting the power output of individual heating elements. This parameter control enables rapid rewarming while maintaining uniform temperatures that prevent ice formation without creating excessive thermal gradients that would cause structural damage.

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 improves cell survival and maintains tissue integrity by reducing ice formation and thermal stresses during cooling and rewarming, achieving high cell viability and functional preservation.

Implementation Method 1

Volumes up to 80 ml were placed in a uniform alternating magnetic field (AMF) to heat the nanoparticles by magnetic hysteresis in a process known as nanowarming.

Methodology Applied
Scientific EffectMagnetic hysteresis: Magnetic Hysteresis

Implementation Method 2

In ice-free cryopreservation by vitrification the formation of ice is prevented by the presence of high concentrations of chemicals known as cryoprotectants that both interact with and replace water and, therefore, prevent water molecules from forming ice.

Methodology Applied
Scientific EffectVitrification: Vitrification

Data Source

PatentUS20250374916A1Ice-free vitrification and nano-warming of large tissue samples
Publication Date: 2025.12.11 LIFENET HEALTH
  • US20250374916A1 patent drawing
  • US20250374916A1 patent drawing
  • US20250374916A1 patent drawing

AI summary

Large volume cellular material may be preserved by combining the cellular material with a cryoprotectant formulation/medium/solution containing at least one mNP and then subjecting the cellular material to a vitrification preservation protocol including nanowarming. This preservation method is particularly effective for cartilage tissues.