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International Journal of Bioprinting Exosome-based bioink for bioprinting
formation and collagen deposition, driving wound re- studies have found that exosomes secreted from dental
epithelization and significantly increasing the regeneration pulp stem cells (DPSCs-E) inhibited the differentiation of
of skin appendages. In addition, it also reduces the CD4 T cells into T helper 17 cells (Th17) and reduced the
+
formation of scar tissue. Exosome-loaded FEP hydrogels secretions of pro-inflammatory factors IL-17 and TNF-α,
have shown great potential in promoting diabetic wound while promoted the polarization of CD4 T cells into Treg
+
healing, providing strong evidence for their clinical and increased the release of anti-inflammatory factors IL-10
potential in skin regeneration. and TGF-β . Wei et al. used stem cells from human
[96]
Exosomes combined with bioprinting for skin tissue exfoliated deciduous teeth (SHED)-derived exosomes
engineering may mainly refer to the exosome-contained, (SHED-Exo) in the bone loss area caused by periodontitis
[97]
bioprinted scaffolds to aid wound closure and promote the in a mouse model . SHED-Exo specifically promoted
stable release of therapeutic exosomes in predesigned areas. BMSCs osteogenesis and inhibited adipogenesis. In
The combination improves therapeutic efficacy and further addition, SHED-Exo can further promote osteogenic
takes advantage of the high bioactivity of exosomes . differentiation and bone formation in BMSCs.
[91]
Although it is still at an early stage of development Meanwhile, in dental medicine, biological 3D printing
and more focus on the research is needed, based on the technology has been widely used to cure diseases such as
current demonstrated examples about the combination tooth osteo-deficiency. Tian et al. mixed sodium alginate
of exosomes and hydrogels, it may be possible to modify (SA), gelatin (Gel), and nano-hydroxyapatite (na-HA)
the designs of exosome-loaded hydrogels and apply them to prepare a hydrogel composite . Human periodontal
[98]
to the preparation of bioinks, thus building high-activity ligament stem cells (HPDLSCs) were mixed with SA/Gel/
exosome-bioprinting systems, which will be one of the na-HA printing slurry to create a “bioink” to prepare SA/
promising research directions in the field of regenerative Gel/na-HA/hPDLSCs cell bioscaffolds. The results showed
medicine in the near future. that the SA/GEL/N-HA composite hydrogel had good
streaming performance and was suitable for printing.
4.5. Other applications Cell biological stent had good biocompatibility and was
4.5.1. Corneal repair conducive to the osteoma of HPDLSCs.
Currently, bioprinting with exosomes has not yet been In all, there have been great potential for the use of
systematically studied in the field of corneal repair. However, exogenous biological printing for corneal repair and oral
there has been relatively in-depth research on using repair, while the current research applications still have great
exosomes for the treatment of corneal injury. For instance, challenges from the perspective of real clinical applications.
Samaeekia et al. isolated corneal mesenchymal stem cell
(cMSCs) exosomes from humans and found a significant
healing effect of the exosomes on corneal epithelial cell 5. Summary
damage . Shojaati et al. demonstrated that exosomes 3D bioprinting technology is a new field that has emerged
[92]
produced by corneal stromal stem cells (CSSC) inhibited in recent years. However, their translational application
the formation of fibrotic scarring after corneal injury and in the clinic is still lagging due to their limited ability
stimulated the regeneration of transparent stromal tissue . to produce bioprinted constructs with the necessary
[93]
Several different 3D bioprinting strategies have been biological activities to integrate with host tissues. Exosomes
developed for the fabrication of corneal donor graft have high biological activity as an important medium of
materials. Sorkio et al. used stem cells and laser-assisted information transmission in organisms. They have become
bioprinting to produce a 3D corneal tissue that mimicked one of the potential materials for application in bioprinting
the structure of natural corneal tissue. The cells in the systems. Combining exosomes as bioink with bioprinting
structure maintained good viability . Isaacson et al. technology can compensate for the lack of biological
[94]
used a low-viscosity bioink made from sodium alginate activity of traditional 3D bioprinting. Traditional 3D
and methacrylated type I collagen to produce an artificial bioprinting bioinks for scaffold manufacturing include
corneal substitute by 3D bioprinting, which also had good alginate, gelatin, and collagen. Gelatin is a soluble protein
biocompatibilities and bioactivities . compound obtained by partial hydrolysis of collagen,
[95]
which is the main fibrin component in bone, cartilage, and
4.5.2. Oral repair skin , while natural alginate is a bioinert material (i.e., it
[99]
The oral cavity contains various tissues, such as teeth, jaw, lacks cell adhesion part) with limited biodegradation [100-102] .
gums, oral mucosa, gland, and cartilage. Stem cells in these Compared with the above biological materials, exosomes
tissues can secrete different functional exosomes, and these have shown higher biological activity and targeting in cell
exosomes have different biological effects. For example, signaling and drug release [103] . Therefore, exosomes can
Volume 9 Issue 6 (2023) 121 https://doi.org/10.36922/ijb.0114

