Gas Vesicle Nanoparticles Enhance Oxygen Diffusion in 3D Bioprinted Tissue

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Solution Overview

Problem

Current 3D bioprinting technologies face challenges in nutrient diffusion within tissue constructs due to diffusion barriers, and existing oxygen-releasing biomaterials are not biodegradable and lack natural occurrence in the human body, while gas vesicle nanoparticles production is hindered by slow growth rates and genetic instability.

Innovation Solution

The development of a method for high-yielding production of gas vesicle nanoparticles using a genetically encoded system in Haloferax volcanii, combined with ultrashort peptide scaffolds to create 3D tissue constructs that enhance oxygen diffusion by incorporating air-loaded gas vesicles, which are biodegradable and biocompatible.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Use of energy by moving object

If oxygen-releasing biomaterials are used to promote nutrient diffusion, then oxygen delivery is improved, but biodegradability and biocompatibility are compromised

Engineering Contradiction:
Improveoxygen deliveryVSAvoidbiodegradability
Core Design Contradiction:
Use of energy by moving objectVSReliability

Solution Approach 1:

The patent changes the chemical composition parameters of oxygen-releasing materials from synthetic peroxides and fluorinated compounds to biodegradable compounds such as organic peroxides, hydroperoxides, and carbonate polymers. This parameter change maintains oxygen delivery functionality while improving biodegradability and biocompatibility, allowing the materials to be safely metabolized or excreted by the body.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite material strategies by combining biodegradable oxygen-releasing compounds with bio-compatible scaffolding materials. The composite structure integrates oxygen-generating capabilities with biodegradable matrices, creating materials that simultaneously provide oxygen delivery and exhibit proper biodegradation behavior in physiological environments.

Inventive Principle:
Principle #40Composite materials

2Strength

If conventional bioink scaffolding materials are used, then structural integrity is maintained, but nutrient diffusion to the center is hindered

Engineering Contradiction:
Improvestructural integrityVSAvoidnutrient diffusion
Core Design Contradiction:
StrengthVSProductivity

Solution Approach 1:

The patent applies local quality by incorporating oxygen-releasing compounds specifically at strategic locations within the scaffolding structure, such as at the center or in regions with anticipated nutrient deprivation. This localized placement ensures that oxygen is generated where it is most needed to overcome diffusion limitations, while maintaining overall structural integrity of the bioink scaffold.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The oxygen-releasing compounds act as intermediary substances that facilitate nutrient diffusion by creating oxygen gradients and enhancing mass transport within the scaffold. These intermediary materials bridge the gap between the external environment and the central regions of the construct, enabling efficient nutrient delivery without compromising the scaffolding's structural properties.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If Halobacterium expression host is used for GVPN production, then gas vesicle nanoparticles are produced, but slow growth rates and genetic instability occur

Engineering Contradiction:
Improvegas vesicle nanoparticle productionVSAvoidgrowth rate
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent uses copying strategies by transferring the gas vesicle gene cluster from Halobacterium into more productive expression hosts such as Escherichia coli or Bacillus subtilis. The genetic blueprint for gas vesicle production is copied and adapted to hosts with faster growth rates and better genetic stability, enabling high-yield GVPN production while overcoming the limitations of the original Halobacterium system.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent changes the biological parameters of the expression system by selecting alternative host organisms with superior growth characteristics. This parameter change involves transitioning from slow-growing Halobacterium to fast-growing bacterial hosts, thereby increasing productivity and genetic stability while maintaining the ability to produce functional gas vesicle nanoparticles through genetic engineering and optimization of expression conditions.

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

This approach improves cell viability and proliferation in 3D bioprinted constructs by overcoming the diffusion barrier, ensuring efficient oxygen delivery and maintaining structural integrity, thus promoting the growth and survival of cells within the constructs.

Implementation Method 1

oxygen-releasing biomaterials have been explored as a means of promoting its diffusion throughout the construct

Methodology Applied
Scientific EffectOxygen diffusion: Diffusion

Data Source

PatentUS20230279344A1Air-loaded gas vesicle nanoparticles for promoting cell growth in 3D bioprinted tissue constructs
Publication Date: 2023.09.07 KING ABDULLAH UNIV OF SCI & TECH
  • US20230279344A1 patent drawing
  • US20230279344A1 patent drawing
  • US20230279344A1 patent drawing

AI summary

The present disclosure relates to a method of high yielding production of gas vesicle nanoparticles (GVNPs) and genetic tools used for high-yielding GVNPs production. The present disclosure further relates to a method of creating 3D tissue constructs with improved cell viability and proliferation and the resulting 3D tissue constructs. The GVNPs can promote cell growth and proliferation in 3D constructs and are suitable bioinks components for a bioprinter to build 3D structures through 3D printing as well as other applications.