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International Journal of Bioprinting 3D printed topographically fabricated micron track peripheral nerve conduit

changes in axons and vice versa . In this work, the rapid hypothesized that the nerve conduit with tracks could
[49]
directional migration of Schwann cells might provide promote faster regeneration of the severed sciatic nerve, thus
scaffolding and protection from the misgrowth of nerve achieving reinnervation of the putative muscle earlier and
axons . further serving to maintain the appearance and morphology
[50]
of the target muscle. In week 12, we can see a similar pattern
To further verify the ability of MTC to promote
peripheral nerve regeneration, we stained nerve myelin (Figure S6 in Supplementary File). To further demonstrate
that CC with MTC does not cause excessive inflammation,
with toluidine blue (Figure 4C). Figure 4D shows that we performed HE staining and TNF-α immunofluorescence
the density of myelinated nerve fibers in MTC@NT3 was staining of the surrounding tissue 1 week after subcutaneous
statistically higher than both the MTC and the CC groups implantation (Figure S7 in Supplementary File), which
and that the MTC group was statistically higher than the showed no significant difference between the CC and
CC group, indicating that MTC was able to promote myelin MTC groups (Figure S8 in Supplementary File). As an
regeneration. Since the myelin sheath of myelinated nerve important target organ of the sciatic nerve, maintaining
fibers is mainly composed of Schwann cells, this result is the condition of the gastrocnemius muscle often affects
consistent with Figure 3C.
functional recovery. Muscle wet weight, cross-sectional area,
We also evaluated the electrical conductivity of the and muscle fiber density are the indicators of muscle status.
regenerated nerves using neurophysiological instruments MTC and MTC@NT3 can better maintain target muscle
(Figure 4E). The results show that in terms of CAMP size and lay the foundation for functional recovery after
amplitude, the MTC@NT3 group was higher than the nerve reinnervation.
MTC and CC groups and was close to the Autologous
group level (Figure 4F), and in terms of CAMP latency, 3.7. Functional evaluation of regenerative nerves
the MTC group was shorter than the CC group, while the To further evaluate how well MTC promotes functional
MTC@NT3 group was similar to the Autologous group recovery, we used the CatWalk instrument to analyze
(Figure 4G). This may be because NT3 promoted axonal plantar pressures and footprints in model rats . Although
[55]
regeneration and never had a higher amplitude of nerve the MTC@NT3 and MTC groups had significantly
electrical conduction. Moreover, the presence of micron improved function compared to the CC group, there
tracks promoted the orderly regeneration of myelin, thus were still differences compared to the uninjured sham
reducing the neuroelectric conduction delay. It is well group (Figure 5E and F). As shown in Figure 5G, SFI was
known that the conduction velocity of myelinated nerve better in the MTC@NT3 group compared with the MTC
fibers is much higher than that of unmyelinated nerve and CC groups, suggesting that MTC@NT3 effectively
fibers, and the degree of integrity of the myelin sheath promoted functional recovery in the 15-mm sciatic nerve
greatly affects the electrical conduction performance injury model in SD rats. We can conclude that the targeted
of nerves [51,52] . By increasing myelin orientation and guidance of MTC and the release of NT-3 factor enhance
thickness, nerve conduction is moderately enhanced . the regeneration of the sciatic nerve.
[53]
The difference in electrical conduction in regenerating
nerves is mainly due to the directional and rapid growth Three-dimensional printing technology has been
of Schwann cells that wrap around nerve axons to form widely used in the field of tissue engineering and
myelin sheaths. regenerative medicine to create custom-made scaffolds
that can support the growth and differentiation of cells. The
3.6. Gastrocnemius maintenance scaffolds are designed to mimic the structure and function
As shown in Figure S5 (Supplementary File), the complete of natural tissues, providing a framework for new tissue
degradation of CC and MTC took more than 36 weeks, growth and regeneration [56–60] . PNI is a common problem
enough time to support the reinnervation of the regenerated that can lead to the loss of motor and sensory function.
nerve to the target muscle. The rat gastrocnemius muscle Regenerating damaged peripheral nerves is a major
was collected, weighed, and Masson-stained 8 weeks after challenge in the field of regenerative medicine [15,61–63] . One
the implantation surgery to verify the maintenance effect promising approach is to use neurotrophic factors, such
of different materials on the target organ . As shown in as neurotrophin-3 (NT-3), which promotes nerve growth
[54]
Figure 5A, we induced a 15-mm long-distance sciatic nerve and regeneration [64–68] . Chitosan is a natural polysaccharide
injury model in SD rats and repaired them with CC, MTC, widely used as a biomaterial in tissue engineering and
MTC@NT3, and Autologous, respectively, and the MTC regenerative medicine. It has been shown to have excellent
and MTC@NT3 groups had higher muscle cross-sectional biocompatibility and biodegradability, making it an ideal
area and wet weight than the CC group (Figure 5D). This material for scaffold fabrication and other biomedical
is also consistent with the results in Figure 5B and C. We applications [69–72] . Recent studies have investigated the

Volume 9 Issue 5 (2023) 426 https://doi.org/10.18063/ijb.770