Page 468 - IJB-10-4

International Journal of Bioprinting 3D-bioprinted peripheral nerve scaffold

1. Introduction by providing mechanical support. Li et al. successfully
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constructed a network scaffold with a fine structure and
Peripheral nerve injury is a prevalent clinical dilemma, adequate mechanical strength for treating nerve defects.
particularly facial nerve injury which is common in oral The structure of the PCL scaffold effectively accommodated
1
and maxillofacial surgery. Clinical manifestations 2,3 the positioning and spatial requirements for axial cell
of facial nerve injury (e.g., dysfunction in eye closure, growth, resulting in an optimal outcome.
smiling, and severe permanent facial paralysis) can result
4
in corneal damage. Although autologous nerve graft is Reasonable loading of biological factors 25-27 (e.g.,
widely acknowledged as the gold standard for treating extracellular matrix and stem cells) can effectively improve
peripheral nerve defects, limited reanimation and donor nerve regeneration. Adipose-derived mesenchymal stem
5,6
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site loss of nerve function may still occur. Thus, tissue cells 28,29 (ADMSCs), bone marrow stem cells (BMSCs),
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engineering currently focuses on producing nerve guide and dental pulp stem cells (DPSCs) are commonly used
conduits to address these limitations. for tissue regeneration. However, it remains challenging to
determine the differentiation potential, therapeutic effects,
With the aid of computer-aided design and and survival duration of implanted stem cells in vivo.
advancements in printed materials, three-dimensional Following specific induction protocols, stem cells can be
(3D) bioprinting techniques have become extensively applied in specific scenarios, such as bone defect repair,
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utilized for fabricating tissue regeneration structures, nerve injury restoration, and dental pulp regeneration.
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offering the distinct advantage of highly personalized Stem cells from human-exfoliated deciduous teeth
and precise internal architectures. 8-10 For peripheral (SHEDs) are readily available, and these cells exhibit
nerve injury, an ideal nerve guide conduit should possess low immunogenicity. 34,35 SHEDs have been reported to
optimal mechanical strength and flexibility, appropriate enhance dental pulp regeneration and nerve regeneration,
permeability, as well as incorporate slow-release factors as they originate from neural crest cells and exhibit a high
to induce directional regeneration of nerve fibers. potential for differentiation into Schwann-like cells. 36,37
11
Recently, various studies 12-17 have fabricated nerve conduits While mesenchymal stem cells (MSCs) are known to
composed of diverse materials, such as collagen, gelatin, differentiate into Schwann-like cells 38-40 for peripheral
gelatin methacrylate (GelMA), chitosan, sodium alginate nerve repair, there is a lack of studies on the induction of
(SA), polycaprolactone (PCL), graphene, etc., along with SHED into Schwann-like SHEDs (scSHEDs).
auxiliary nanomaterials, combined with 3D-printing and
electrospinning technologies. Herein, we used a double-nozzle collaborative
3D-printing technology to construct PCL-hydrogel
Wu et al. constructed a gelatin/SA hydrogel conduit composite scaffolds that were then combined with
containing rat Schwann cells, as well as a GelMA/SA/ scSHEDs for 3D bioprinting. Cell viability and proliferation
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bacterial nanocellulose (BNC) hydrogel scaffold. These assessments, immunofluorescence assay, enzyme-linked
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two 3D-bioprinted scaffolds enhanced cell-oriented immunosorbent assay (ELISA), and quantitative real-time
proliferation, attachment, and the release of associated polymerase chain reaction (qRT-PCR) were performed to
factors. The mechanical properties of biocompatible validate the impact of the hydrogel on scSHEDs. Ultimately,
hydrogels can be improved by incorporating nanomaterials the nerve repair effect of the scaffold was verified in a rat
like BNC, which could also facilitate the directional sciatic nerve defect model (Figure 1).
alignment of cells. It has been reported that dual-nozzle
bioprinting can be used to construct structures using 2. Methods
different materials simultaneously. This method combines
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the advantages of various materials and holds promising 2.1. Physicochemical nature of the materials
application prospects.
2.1.1. Material preparation
Polycaprolactone (PCL) has been approved by the The sources of all materials can be found in Table S1
FDA for clinical use due to its excellent biocompatibility, (Supplementary File). We synthesized arginine-glycine-
absorbability, low melting point, and rheological properties. aspartic acid-modified sodium alginate (RGD-Alg) based
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Scaffolds of various shapes can be constructed through on previously reported carbodiimide chemistry. In brief,
electrospinning or coating techniques after modification 1% w/v of SA was dissolved in 0.1 M 2-(N-morpholino)
with organic solvents, or by direct 3D printing with high- ethanesulfonic acid (MES) buffer (pH 6.5; 0.3 M NaCl)
temperature printing nozzles. At present, PCL is widely and stirred overnight. Thereafter, 48.42 mg N-(3-
used as a scaffold material to guide bone regeneration 22,23 dimethylaminopropyl)-N’-ethylcarbodiimide (EDC), 27.4

Volume 10 Issue 4 (2024) 460 doi: 10.36922/ijb.2908