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International Journal of Bioprinting Exosome-based bioink for bioprinting

effectively affect the activity of cells and the development that exosomes cannot exert sustained function due to their
of tissues through multiple signaling pathways without short half-life. Although the combination of exosomes and
causing immune responses. In addition, some stem cell- liposomes can complement each other, sustained release of
derived exosomes also have exhibited immunomodulatory exosomes has not been demonstrated to accumulate in the
and tissue regeneration abilities [104] . From the perspective bone marrow [109] . In the area of angiogenesis, there have been
of enhancing the biological activity of biological ink by cases in which chitosan hydrogels have been used to improve
exosomes, this paper briefly introduced exosomes and 3D the stability of proteins and microRNAs in exosomes
bioprinting technology and summarized the application significantly. However, the release of exosomes depended
and progress of exosomes and 3D bioprinting technology on the permeation and biodegradation of chitosan hydrogel,
in bone, blood vessel, nerve, and skin in recent years. which made this process difficult to control . A class of
[72]
At present, there have been many studies on the use of peptide-modified adhesive hydrogels (Exo-pGel) therapies
exosome hydrogels for the treatment of diseases. This provided a promising strategy for the effective treatment
paper briefly combed them and outlined their advantages of central nervous system diseases based on exosome
and disadvantages, as detailed in Table 1. implantation. In another study, the combination of size

However, despite the exciting progress to date, several exclusion chromatography and ultracentrifugation was used,
challenges remain. Firstly, good-quality exosomes should and before ultracentrifugation, the qEV column was used to
be obtained before printing. However, the current challenge exclude microvesicles from the total extracellular vesicles
lies not only in the isolation of exosomes before preparing (EVs), and the highly bioactive exosomes were successfully
[77]
exosome-rich bioinks. At present, the methods for extracting isolated and purified . The exosomes, after being added
exosomes mainly include differential centrifugation [105] , to biomaterials, can enhance the osteogenic ability of the
volume exclusion chromatography [106] , and immunoaffinity body and treat neurological diseases. However, maintaining
capture [107] . Each method has advantages and disadvantages, the biological activity of exosomes is still a great challenge.
but the extraction method to be used is determined by the Thirdly, 3D printing can print a variety of tissues and organs,
sample source and the intended use of exosomes. A few but the current applications of exosomes are limited, and
studies have been conducted on the rapid and accurate the studies on their functions and clinical applications are
preparation of bioactive exosomes with a low loss rate [108] . inadequate. This paper mainly focuses on the fields of bone
Secondly, during the printing process, it is necessary to engineering, vascular engineering, nerve injury treatment,
ensure that the exosomes are put into the bioprinting and skin regeneration. In conclusion, the applications of
system while maintaining sufficient biological activity. For exosomes to promote bioprinting in tissue engineering and
instance, integrating exosomes with bone tissue engineering regenerative medicine in other fields such as liver tissue
materials gives rise to a favorable environment for exosomes regeneration, kidney tissue regeneration, and lung tissue
to exert their functions . However, it has also been found regeneration have great potential and need to be developed.
[24]

Volume 9 Issue 6 (2023) 122 https://doi.org/10.36922/ijb.0114