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RESEARCH ARTICLE

Air-loaded Gas Vesicle Nanoparticles Promote Cell

Growth in Three-dimensional Bioprinted Tissue Constructs

Salwa Alshehri 1,2† , Ram Karan , Sarah Ghalayini , Kowther Kahin , Zainab Khan ,
3†
1
1
1∞
Dominik Renn , Sam Mathew , Magnus Rueping *, Charlotte A. E. Hauser *
3
1,5
3,4
3
1 Laboratory for Nanomedicine, Division of Biological and Environmental Science and Engineering, King Abdullah
University of Science and Technology, 23955 Thuwal, Kingdom of Saudi Arabia
2 Department of Biochemistry, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia
3 KAUST Catalysis Center, Division of Physical Sciences and Engineering, King Abdullah University of Science and
Technology, 23955 Thuwal, Kingdom of Saudi Arabia
4 Institute for Experimental Molecular Imaging, University Clinic, RWTH Aachen University, Forckenbeckstrasse 55,
D52074 Aachen, Germany
5 Computational Bioscience Research Center, King Abdullah University of Science and Technology, Thuwal 23955-6900,
Kingdom of Saudi Arabia
∞ McGovern Medical School, Houston, TX, USA & The University of Texas MD Anderson Cancer Center UTHealth
Graduate School of Biomedical Sciences, Houston, TX, USA.
† These authors contributed equally to this work
∞ Current affiliation

Abstract: Three-dimensional (3D) bioprinting has emerged as a promising method for the engineering of tissues and organs.
Still, it faces challenges in its widespread use due to issues with the development of bioink materials and the nutrient diffusion
barrier inherent to these scaffold materials. Herein, we introduce a method to promote oxygen diffusion throughout the printed
constructs using genetically encoded gas vesicles derived from haloarchaea. These hollow nanostructures are composed of
a protein shell that allows gases to permeate freely while excluding the water flow. After printing cells with gas vesicles of
various concentrations, the cells were observed to have increased activity and proliferation. These results suggest that air-filled
gas vesicles can help overcome the diffusion barrier throughout the 3D bioprinted constructs by increasing oxygen availability
to cells within the center of the construct. The biodegradable nature of the gas vesicle proteins combined with our promising
results encourage their potential use as oxygen-promoting materials in biological samples.
Keywords: Three-dimensional bioprinting; Gas vesicles; Halobacterium; Haloferax; Tissue engineering

*Correspondence to: Charlotte A. E. Hauser, Laboratory for Nanomedicine, Division of Biological and Environmental Science and Engineering,
King Abdullah University of Science and Technology, 23955 Thuwal, Kingdom of Saudi Arabia; charlotte.hauser@kaust.edu.sa; Magnus
Rueping, KAUST Catalysis Center, Division of Physical Sciences and Engineering, King Abdullah University of Science and Technology, 23955
Thuwal, Kingdom of Saudi Arabia; magnus.rueping@kaust.edu.sa

Received: February 10, 2022; Accepted: March 16, 2022; Published Online: June 1, 2022
Citation: Alshehri S, Karan R, Ghalayini S, et al., 2022, Air-loaded Gas Vesicle Nanoparticles Promote Cell Growth in Three-dimensional
Bioprinted Tissue Constructs. Int J Bioprint, 8(3):489. http://doi.org/10.18063/ijb.v8i3.489
1. Introduction engineering, whereby scaffolds, cells, and biologically
active molecules are combined to assemble functional
Human organs are defined by their complex, functional constructs. The goal is to develop constructs capable of
organization of diverse, specialized cells, and tissues . The restoring, improving, or maintaining damaged tissues and
[1]
rising incidence rates of disease and injury leading to organ organs . Of the many methods to generate these functional
[2]
failure have led to increased demand for tissue and organ three-dimensional (3D) structures, 3D bioprinting is the most
transplants. This growing demand has given rise to tissue promising due to its ability to produce complex, scalable

© 2022 Author(s). This is an Open-Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
reproduction in any medium, provided the original work is properly cited.
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