Page 122 - IJB-9-6

International Journal of Bioprinting Exosome-based bioink for bioprinting

2.3. Exosomes and decellularized extracellular promoting a variety of tissue remodeling processes . The
[49]
matrix (dECM) dECMs from different sources of the tissues have shown
Recently, there has been another biologically derived higher tissue-specific heterogeneities for their potential
material widely used in bioprinting called decellularized applications compared to the applications of exosomes.
ECM (dECM). It is a combination of 3D scaffolds, proteins, Currently, many dECM inks are derived from porcine
and bioactive small molecules that remain after removing tissues [50,51] , raising questions about their biocompatibilities
all or part of the cellular and nucleic acid components. It is for later clinical applications. Additionally, their overall
typically derived from animal, human, or plant tissues . biocompatibilities also require further investigation since
[31]
While dECM can be used as a bioink in bioprinting, it dECM materials are extracted from real biological tissues
differs significantly from exosomes due to the variations that are influenced by age, health status, and environmental
in their sources, collection methods, bioink preparation factors. Batch variations and instabilities are also issues
processes, and ink properties. Common methods for that need addressing.
preparing dECM involve either vascular system perfusion In summary, both dECM and exosomes have the
or immersion/stirring . During printing, collagen cross- potential for applications in tissue engineering. However,
[32]
linking serves as the primary mechanism of solidification. further research is needed to explore their applications and
Therefore, it is mainly compatible with digital light overcome their respective limitations.
processing or extrusion-based approaches .
[33]
Unlike dECM, exosomes can be collected using 3. Bioprinting
centrifugation techniques and subjected to surface
processing . By adding specific scaffolding proteins, 3D printing technology, as an emerging field in regenerative
[34]
cytokines, hydrogels, or other materials, exosomes can medicine, is showing great potential compared to
be turned into bioinks that primarily deliver signaling traditional technologies. It has offered a huge possibility
molecules, proteins, and nucleic acids. Exosomes for digital designs with low manufacturing costs. Derived
contain signaling molecules that play a significant role from 3D printing technology, bioprinting, especially organ
in tissue repair, giving them potential for applications in printing, has developed rapidly in recent years. With
bioprinting . Compared to dECM, exosome therapy technological advances, plenty of great demonstrations
[35]
has fewer ethical limitations, lower immunogenicity, and have been fulfilled in various fields, such as bone
reduced risks of ectopic transplantation . Therefore, engineering, artificial vascular, nerve injury treatment,
[36]
it has been applied to the bioprinting of different tissues skin regeneration, and so on. In order to meet the distinct
or organs, such as blood vessels [37-39] , bones [36,40] , skin , functions required in these different applications, the
[41]
nerves [42-44] , corneas , etc. For instance, Zhang et al. appropriate bioinks and printing methods need to be
[45]
developed a 3D PLA scaffold based on MSC exosomes . designed and engineered.
[40]
It reduced pro-inflammatory markers and ROS (reactive 3.1. Bioink
oxygen species), showing immune regulation potential, Bioink is an important factor that directly affects cell
and enhanced osteogenic differentiation, contributing to survival and biomaterial constituent in tissue engineering
bone formation. Shafei et al. used an alginate hydrogel and regenerative medicine. Hydrogel is a commonly used
with Adipose-derived Stem Cells (ASC) exosomes bioink which can mimic the physical characteristics of
as a bioactive scaffold . It had beneficial effects on ECMs in the body. Generally, two types of hydrogels are
[46]
wound closure and promoted re-epithelialization. The used for bioink: natural-derived hydrogels and synthetic
applications of exosomes in different tissues will be hydrogels. The materials of natural-derived hydrogels are
discussed in detail later in the text. However, it should be mainly generated from the body of the organisms, such
noted that exosomes are highly sensitive to environmental as collagen, alginate, agarose, hyaluronic acid, etc. On the
factors such as temperature and pressure since they exist as other hand, a synthetic hydrogel is usually synthesized by
extracellular vesicles, causing their storage and transport chemical methods. Its physical and chemical properties
more challenging. Further explorations are also needed to are usually controllable to meet specific requirements
understand the functional mechanisms of exosomes. for bioprinting, such as good biocompatibility for a high
Similar to exosomes, dECM may also contain signaling cell survival rate and optimal viscosity for high printing
molecules that can regulate cell behaviors and promote resolution. Commonly used synthetic bioink includes
cell adhesion, migration, and differentiation [47,48] . In polyethylene glycol (PEG) and Pluronics F127. For the
addition, research has demonstrated that dECM materials specific introductions of bioinks, please refer to the review
have potential applications in tissue remodeling and by Barrs et al. In addition, according to the preparation
[52]
organ regeneration by enhancing cellular functions and methods of hydrogels, they can be divided into physically

Volume 9 Issue 6 (2023) 114 https://doi.org/10.36922/ijb.0114