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International Journal of Bioprinting Exosome-based bioink for bioprinting

(Figure 6A). It provided a novel inspiration for bone biological activity. It was also a therapeutic strategy with a
regeneration and the design of therapeutic biomaterials high potential for treating bone defects.
with improved immune regulations. Exosomes are considered a powerful supplement for

Of the essential elements of tissue engineering, cell therapy in regenerative medicine for their excellent
cell seeding is important for inducing effective tissue biocompatibility, efficient cell internalization, and strong
regeneration. However, cell-based tissue engineering load capacities. However, exosomes still have some
approaches also have many drawbacks, such as limited shortcomings, such as low yield, unstable efficiency,
sources and restricted expansion capacities of donor cells, and lacking drug delivery routes, which can affect the
immune rejection, and many others. Thus, cell-free tissue further applications of biomolecular carriers. Zha et al.
engineering has been extensively explored in regenerative developed a novel exosome-mimetics, which had a similar
medicine as a safe, effective, and off-the-shelf strategy. Zha structure and biomarkers in comparison with the routine
et al. developed a cell-free tissue engineering system using exosomes . It can be generated with a high yield and has
[70]
functional exosomes instead of seeding cells . Gene- been applied to construct an engineered gene-activated
[67]
activated engineered exosomes were constructed by using matrix for local therapy, opening up a new idea for using
ATDC5-derived exosomes to encapsulate the VEGF gene. exosomes.
The specific exosomal-anchored peptide CP05 acted as a Furthermore, some researchers have also provided new
flexible linker, effectively linking the engineered exosome ideas to improve the therapeutic efficacy of exosomes. Li
nanoparticles with 3D-printed porous bone scaffolds et al. developed a stem cell-mediated gene therapy in which
(Figure 6B). The scaffolds were tested to effectively induce mediator MSCs were genetically engineered by the bone
the bulk of vascularized bone regeneration, illuminating morphogenetic protein-2 gene to produce exosomes with
the potential of functional exosomes in acellular tissue enhanced bone regeneration potency . The accelerating
[71]
engineering.
effect in bone healing and good biocompatibility suggested
MSCs have strong proliferative ability and multi- the potential clinical application of this strategy if applied
directional differentiation potential. It can secrete cytokines with bioprinting.
through paracrine effects to repair tissues. Zhang et al. In summary, though exosomes have been widely
developed a bioactive 3D PLA scaffold using an exosome- studied, the research of 3D bioprinting with exosomes has
based strategy . PLA-Exo scaffold can reduce the been initiated in bone tissue engineering and holds great
[40]
expression of the pro-inflammatory markers and limit the potential in tissue regeneration.
production of the ROS, indicating its immunoregulatory
potential. Meanwhile, the authors confirmed that it could 4.2. Vascular engineering
enhance osteogenic differentiation in the osteogenic tests, Exosome bioprinting technology has also been applied to
showing potential applications in bone tissue regeneration vascular engineering. The application of exosomes in 3D
(Figure 6C). printing can promote the sustained release of exosomes and
Similarly, Chen et al. also designed a bioscaffold for improve their biological activity. Sun et al. used 3D printing
delivering MSC exosomes. They fabricated a 3D-printed technology to construct porous scaffolds for macrophage
cartilage ECM/gelatin methacrylate/exosome scaffold with exosomes (BC-Exos) induced by β-tricalcium phosphate
radially oriented channels using desktop-stereolithography (phosphate bioceramics), and realized 3D-printed BC-
technology (Figure 6D), which significantly facilitated Exo scaffolds. The system had a predefined structure and
cartilage regeneration in the animal model . At the same enabled the continuous release of exosomes (Figure 7A) .
[36]
[68]
time, the 3D-printed radial exosome scaffolds also can be a It also showed significant immunomodulatory effects
promising strategy for early osteoarthritis treatment. and improved osteogenesis/angiogenesis properties. This
design of a cell-free 3D-printed scaffold using biomaterials
In addition to the direct combination of bone bioprinting
and osteogenic exosomes for bone tissue repair, the following to activate macrophage exosomes has increased the
application of immune cell-derived exosomes in tissue
system also offered new opportunities for the applications of regeneration and provided a new direction for the design
exosomes in bone bioprinting. Wu et al. added the Schwann of bioprinted systems. This study suggested that the 3D
cell-derived exosomes to bone marrow stromal cell culture printing of bioceramics-induced macrophage exosomes
environments and found they could effectively promote the can be a useful strategy for tissue engineering and
migration, proliferation, and differentiation of bone marrow regenerative medicine.
stromal cells (Figure 6E). In addition, the combination
[69]
of exosomes and porous Ti6Al4V implants provided both In terms of the clinical application of exosomes derived
mechanical support and open pores, exhibiting good from bone marrow MSCs, Zhang et al. developed a system

Volume 9 Issue 6 (2023) 118 https://doi.org/10.36922/ijb.0114