Biomimicry in 3D printing design: implications for peripheral nerve regeneration

2021 ◽  
Author(s):  
Zhiwen Yan ◽  
Yun Qian ◽  
Cunyi Fan

Nerve guide conduits (NGCs) connect dissected nerve stumps and effectively repair short-range peripheral nerve defects. However, for long-range defects, autografts show better therapeutic effects, despite intrinsic limitations. Recent evidence shows that biomimetic design is essential for high-performance NGCs, and 3D printing is a promising fabricating technique. The current work includes a brief review of the challenges for peripheral nerve regeneration. The authors propose a potential solution using biomimetic 3D-printed NGCs as alternative therapies. The assessment of biomimetic designs includes microarchitecture, mechanical property, electrical conductivity and biologics inclusion. The applications of 3D printing in preparing NGCs and present strategies to improve therapeutic effects are also discussed.

2006 ◽  
Vol 10 (03) ◽  
pp. 131-140 ◽  
Author(s):  
Yasushi Morisawa ◽  
Shinichiro Takayama ◽  
Kazuhiko Okushi ◽  
Toshiyasu Nakamura ◽  
Keiichi Fukuda ◽  
...  

Peripheral nerve injury changes the kinetics of neurotrophins. The production of several neurotrophins increases at the site of injury. Although numerous reports have described changes in neurotrophins over time in areas of nerve injury, neurotrophin mRNA is present at very low levels in target tissues, making accurate quantitation difficult. We developed a reverse transcription–polymerase chain reaction/high-performance liquid chromatography (RT-PCR/HPLC) method that enables accurate quantitation of neurotrophin mRNA. We then attempted to quantitate mRNA levels for nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) produced by skeletal muscle innervated by the sciatic nerve following transection and reattachment of the nerve in mice. In addition, wet weights of the muscle were measured and changes in weight over time were determined. The results indicated that neurotrophin production in muscle increases as a result of peripheral nerve denervation due to transection, and decreases with nerve regeneration and reinnervation resulting from reattachment.


2020 ◽  
Vol 8 (22) ◽  
pp. 6261-6271
Author(s):  
Jin Yoo ◽  
Ji Hun Park ◽  
Young Woo Kwon ◽  
Justin J. Chung ◽  
In Cheul Choi ◽  
...  

Longitudinally oriented, 3D printed collagen hydrogel-grafted elastic nerve guidance conduits to promote nerve regeneration in peripheral nerve defects.


2015 ◽  
Vol 43 (02) ◽  
pp. 215-230 ◽  
Author(s):  
Han-Chung Lee ◽  
Yuan-Man Hsu ◽  
Chin-Chuan Tsai ◽  
Cherng-Jyh Ke ◽  
Chun-Hsu Yao ◽  
...  

We assessed the therapeutic effects of lumbrokinase, a group of enzymes extracted from the earthworm, on peripheral-nerve regeneration using well-defined sciatic nerve lesion paradigms in diabetic rats induced by the injection of streptozotocin (STZ). We found that lumbrokinase therapy could improve the rats' circulatory blood flow and promote the regeneration of axons in a silicone rubber conduit after nerve transection. Lumbrokinase treatment could also improve the neuromuscular functions with better nerve conductive performances. Immunohistochemical staining showed that lumbrokinase could dramatically promote calcitonin gene-related peptide (CGRP) expression in the lamina I–II regions in the dorsal horn ipsilateral to the injury and cause a marked increase in the number of macrophages recruited within the distal nerve stumps. In addition, the lumbrokinase could stimulate the secretion of interleukin-1 (IL-1), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) in dissected diabetic sciatic nerve segments. In conclusion, the administration of lumbrokinase after nerve repair surgery in diabetic rats was found to have remarkable effects on promoting peripheral nerve regeneration and functional recovery.


Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 370
Author(s):  
Jan Krieghoff ◽  
Johannes Rost ◽  
Caroline Kohn-Polster ◽  
Benno Müller ◽  
Andreas Koenig ◽  
...  

The performance of artificial nerve guidance conduits (NGC) in peripheral nerve regeneration can be improved by providing structures with multiple small channels instead of a single wide lumen. 3D-printing is a strategy to access such multi-channeled structures in a defined and reproducible way. This study explores extrusion-based 3D-printing of two-component hydrogels from a single cartridge printhead into multi-channeled structures under aseptic conditions. The gels are based on a platform of synthetic, anhydride-containing oligomers for cross-linking of gelatinous peptides. Stable constructs with continuous small channels and a variety of footprints and sizes were successfully generated from formulations containing either an organic or inorganic gelation base. The adjustability of the system was investigated by varying the cross-linking oligomer and substituting the gelation bases controlling the cross-linking kinetics. Formulations with organic N‑methyl-piperidin-3-ol and inorganic K2HPO4 yielded hydrogels with comparable properties after manual processing and extrusion-based 3D-printing. The slower reaction kinetics of formulations with K2HPO4 can be beneficial for extending the time frame for printing. The two-component hydrogels displayed both slow hydrolytic and activity-dependent enzymatic degradability. Together with satisfying in vitro cell proliferation data, these results indicate the suitability of our cross-linked hydrogels as multi-channeled NGC for enhanced peripheral nerve regeneration.


2021 ◽  
Vol 10 (1) ◽  
pp. 50-61
Author(s):  
Liling Zhang ◽  
Tiantian Zheng ◽  
Linliang Wu ◽  
Qi Han ◽  
Shiyu Chen ◽  
...  

Abstract Peripheral nerve injury has seriously affected patient’s health and life. Schwann cells play an important role in peripheral nerve regeneration. However, the effect of the current tissue engineered scaffolds for promoting Schwann cells growth is still not as good as that of autologous graft. In this study, new developed three-dimensional gellan gum/starch (GG/ST) scaffolds with various printing gap for Schwann cells growth were prepared by 3D printing technology. Various physiochemical characterizations of the printed scaffolds were performed including morphology, rheological behavior, swelling ratio, and degradation behavior. The cytotoxicity and biocompatibility of the scaffolds were evaluated using L929 fibroblasts and RSC96 Schwann cells, respectively. The results displayed that the GG/ST scaffold exhibited a porous network structure. The cross-sectional pore density of the hydrogel had a tendency to increase with the ascending printing gap. The swelling rate and degradation rate of the hydrogel gradually increased and eventually reached an equilibrium state. The rheological test results showed that the scaffolds had good printability. MTT cytotoxicity test and CCK-8 cell proliferation test displayed that the scaffold was nontoxic, and Schwann cells could grow well on the scaffold after 5 days of culture, whereas the number of cells on the scaffold with the printing gap of 3 mm was the largest. These results indicated that the GG/ST scaffold prepared by 3D printing technology may have a potential application in peripheral nerve regeneration.


2018 ◽  
Vol 10 (3) ◽  
pp. 032001 ◽  
Author(s):  
Eugen B Petcu ◽  
Rajiv Midha ◽  
Erin McColl ◽  
Aurel Popa-Wagner ◽  
Traian V Chirila ◽  
...  

Polymers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 3957
Author(s):  
Ci Li ◽  
Meng Zhang ◽  
Song-Yang Liu ◽  
Feng-Shi Zhang ◽  
Teng Wan ◽  
...  

Peripheral nerve injury (PNI) is an unresolved medical problem with limited therapeutic effects. Epineurium neurorrhaphy is an important method for the treatment of PNI in clinical application, but it is accompanied by inevitable complications such as the misconnection of nerve fibers and neuroma formation. Conduits small gap tubulization has been proved to be an effective suture method to replace the epineurium neurorrhaphy. In this study, a chitin conduit was used to bridge the peripheral nerve stumps. The micromorphology, mechanical property, and biocompatibility of chitin conduits were characterized. The results showed chitin was a high-quality biological material for constructing nerve conduits. In addition, previous reports demonstrated that mesenchymal stem cells culture as spheroids can improve the therapeutic potential. In the present study, we used a hanging drop protocol to prepare bone mesenchymal stem cells (BMSCs) spheroids. Meanwhile, spherical stem cells could express higher stemness-related genes. In the PNI rat models with small gap tubulization, the transformation of BMSCs spheroids, but not BMSCs monolayer, improved sciatic nerve regeneration. Therefore, combining BMSCs spheroids with chitin nerve conduits shows application potential in promoting peripheral nerve regeneration.


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