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International Journal of Bioprinting 3D-bioprinted peripheral nerve scaffold
Electrospinning and other technologies can be used to dual printing with two nozzles, the combination of
construct PCL filaments with exceptional fineness, and hydrogel and PCL could enhance the physical performance
their biocompatibility has been demonstrated in various of the scaffold. The combination of the scSHED-laden
configurations, whether ordered or disordered. When hydrogel and PCL promoted recovery of the sciatic nerve
combined with cells or drugs, PCL filaments effectively defect model in a manner generally comparable to that
promote tissue regeneration. Furthermore, the gradual of autografting during in vivo experiments, suggesting an
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degradation of PCL in vivo and nerve regeneration are both approach to better manage peripheral nerve injury.
relatively slow, thereby potentially creating an improved
barrier environment. Moreover, acid production in the 5. Conclusion
microenvironment during PCL degradation also restricts
the placement position of PCL during scaffold construction. In this study, we applied 3D bioprinting to construct a nerve
Therefore, we primarily focused on the physical properties scaffold with RGD-Alg/GelMA/PCL laden with induced
of PCL in this study. In vivo, the PCL group had better scSHEDs. SHEDs could be stably induced into scSHEDs,
functional recovery than the hydrogel group. Compared as indicated by enhanced immunofluorescence staining
to traditional hydrogels, we posit that PCL offered a better of the S-100β, GFAP, and P0 proteins. The 6% RGD-
in vivo barrier environment, heightened resistance against Alg/5% GelMA hydrogel displayed decent mechanical and
potential bending, and more importantly, facilitated suture rheological properties for 3D bioprinting, and the addition
fixation during clinical repair. of a PCL layer greatly enhanced the physical properties
of the scaffold. Moreover, the 3D-bioprinted scaffold
In the present study, the scSHED-laden hydrogel was
combined with PCL scaffolds to develop a therapeutic demonstrated enhanced proliferation and adhesion of the
scSHEDs for optimal biological functions. The scaffold
approach. The scaffold was transplanted into the injury also improved sciatic nerve regeneration in rats. Overall,
site of sciatic nerve-injured rats, facilitating the continuous this study demonstrated the potential of 3D bioprinting to
release of neurotrophic factors through scSHEDs. This
innovative therapy significantly improved gait recovery and manage peripheral nerve defects, and the 3D-bioprinted
promoted nerve regeneration in rats. Electrophysiological composite scaffold is expected to provide new insights
analysis also demonstrated that the scSHED group into peripheral nerve regeneration applications with broad
exhibited superior CMAP recovery compared to the clinical prospects.
PCL and hydrogel scaffold groups. We hypothesized that
scSHEDs played an important role in contributing to Acknowledgments
neurofiber regeneration by simulating the Schwann cells. None.
Nonetheless, further investigation is warranted to evaluate
the survival of scSHEDs in vivo and their implications in Funding
sciatic nerve repair.
This study was supported by the National Natural Science
The involvement of GAP43 in the regulation of neurite Foundation of China (Grant No. 81870781), Capital’s Funds
outgrowth during nerve regeneration was observed. Our for Health Improvement and Research (Grant No. 2022-2-
findings reported an upregulation of GAP43 expression 4102), and the Peking University School of Stomatology
in the scSHED group, suggesting a favorable impact Youth Research Fund (Grant No. PKUSS20220108).
on axonal extension. The NF200 protein effectively
reflects the structural integrity and regeneration of Conflict of interest
nerves. The elevated expression of NF200 in the scSHED
group signifies a heightened rate of nerve regeneration. The authors declare no conflicts of interest.
Furthermore, the expression of S-100β reflects the
proliferation and functional status of Schwann cells. Our Author contributions
study demonstrated that scaffolds in the scSHED group Conceptualization: Shijun Li, Zongxi Wu
induced the upregulation of S-100β expression, leading to Formal analysis: Shang Xie, Xiaofeng Shan
improved recovery of the injured rat sciatic nerves after Investigation: Shijun Li, Zichao Wang, Shang Xie
8 weeks. Methodology: Shijun Li, Zichao Wang, Qing Li
In summary, the present study demonstrated that Project Administration: Zhigang Cai
SHEDs could differentiate into scSHEDs, and the RGD- Validation: Qing Li, Zhigang Cai
Alg/GelMA hydrogel would be suitable for facilitating Writing – original draft: Shijun Li, Zichao Wang
adhesion and functional expression of scSHEDs. Through Writing – review & editing: Qing Li, Zhigang Cai
Volume 10 Issue 4 (2024) 471 doi: 10.36922/ijb.2908

