Page 183 - IJB-10-6

International Journal of Bioprinting 3D-printed EVs for nasal septal defects

1. Introduction Extracellular vesicles (EVs) are conventionally obtained
via 2D extraction, which entails the monolayer culture of
Nasal septal cartilage is hyaline cartilage, a specialized stem cells. However, studies have indicated that the growth
connective tissue that is devoid of blood vessels, nerves, environment of MSCs in 2D conditions differs significantly
1
and lymphatics. Nasal septal cartilage is composed of from that of natural stem cells in vivo, resulting in limited
17
approximately 1% chondrocytes and 99% extracellular stemness and functionality of the EVs secreted by MSCs.
18
3
matrix, which imparts specific mechanical properties. In recent years, numerous studies have demonstrated that
2
Nasal deformities caused by congenital nasal septal defects EVs secreted by MSCs cultured in a 3D environment exhibit
are rare. Most common nasal septal defects are caused significantly enhanced abilities to promote cell proliferation
4
by tumor resection and trauma. These defects are often and cell communication. For instance, Chen et al.
19
20
accompanied by facial deformities, which can significantly designed a method to culture MSCs in hollow alginate
impact the patient’s quality of life and psychological hydrogel microfibers using coaxial printing technology,
well-being. Due to the poor self-repair ability of septal significantly enhancing the enrichment efficiency and
5
cartilage, it is difficult for the defected cartilage to rely on stemness of extracted EVs. Thus, this method can provide an
surrounding normal chondrocytes for repair. As a result, ample supply of raw materials for regenerative EV treatment.
the defect often leads to varying degrees of nose deformity
and dysfunction. Currently, the most commonly used Injecting EVs into the damaged area often leads to
6
methods for repairing nasal septal defects include significant loss, resulting in short residence time and low
prosthesis implantation or autologous rib cartilage and ear utilization of the target site. Therefore, there is a need for
7
cartilage. However, using these materials for defect repair a tool that can retain EVs at the damaged site for a longer
21
can easily compress the lower part of the nose and lead period. Additionally, an ideal biological scaffold should
8
22
to poor ventilation. Additionally, the use of autologous maintain its shape and size, which is why we focused on
cartilage as graft material for repair poses challenges such tissue-engineered biomaterials. Gelatin methacrylic acid
as secondary damage, difficult shaping, easy deformation, (GelMA) is a widely used biomaterial in soft tissue repair
and easy absorption after implantation. In contrast, the use due to its good biocompatibility, degradability, tunable
of allogeneic cartilage for repair may be affected by immune mechanical properties, and drug-loading capabilities,
rejection and the risk of related disease, causing significant thereby promoting cartilage repair and serving as an
2
23
concerns for both doctors and patients. Although artificial excellent carrier for sustained release of EVs. . However,
materials are easy to shape and resistant to absorption, GelMA alone has relatively poor mechanical properties,
their implantation in vivo can induce rejection reactions making it difficult to simulate the mechanical modulus
24
and secondary infections, and their stability in the human of the nasal septum. Furthermore, due to the small
body remains inadequate. 9,10 number of cells in the nasal septal cartilage, achieving
rapid defect healing is challenging, even with the support
The use of extracellular vesicles (EVs) for filling is 25
a potential treatment for cartilage defects. These tiny of EVs. Therefore, we utilized polylactic acid-glycolic
acid (PLGA) in combination with electrospinning
vesicles, typically measuring 30–150 nm in diameter, are technology to fabricate biological scaffolds for promoting
primarily produced by mesenchymal stem cell (MSC)- chondrocyte adhesion and proliferation at the defect site.
derived paracrine and have demonstrated promise in The PLGA electrospun membrane, when combined with
treating cartilage damage. EVs are primarily composed hydrogel, offers mechanical support to better mimic the
11
of lipid molecular layers that encapsulate various mechanical properties of nasal septal cartilage. Research
nucleic acids, proteins, and molecules, promoting cell has indicated that the 3D arrangement of electrospun
communication. Due to their nano-sized structure, EVs fibers closely resembles natural collagen fibers in the
can be easily taken up by cells, allowing them to release extracellular matrix, effectively promoting chondrocyte
their contents within the cell and play a role in promoting adhesion, proliferation, and migration. PLGA is a
26
cell communication, as well as tissue regeneration and synthetic biomaterial with excellent biocompatibility
repair. EVs have been utilized in the treatment of various and mechanical properties, which helps maintain the
12
clinical diseases, particularly cardiovascular diseases and functional morphology of cartilage and promotes the
13
skin wound repair. 14,15 Studies have demonstrated that EVs synthesis of cartilage extracellular matrix. 27
can effectively enhance the proliferation and migration
of chondrocytes, as well as the deposition of cartilage Currently, there is no effective engineering method for
extracellular matrix, thereby facilitating the repair of repairing nasal septal defects. In this study, we developed
cartilage defects. This indicates the significant potential a composite PLGA-electrospun scaffold hydrogel
16
for using EVs in repairing nasal septal defects, though for the sustained release of 3D EVs to promote nasal
none has been reported to date. septum repair. The composite hydrogel scaffold serves as

Volume 10 Issue 6 (2024) 175 doi: 10.36922/ijb.4118