scholarly journals Functional Tissue-engineered Microtissue Formed by Self-aggregation of Cells for Peripheral Nerve Regeneration

Author(s):  
Jian Zhang ◽  
Chaochao Li ◽  
Fanqi Meng ◽  
Yanjun Guan ◽  
Tieyuan Zhang ◽  
...  

Abstract Background: Peripheral nerve injury (PNI) is one of the essential causes of physical disability with a high incidence rate. The traditional tissue engineering strategy, Top-Down strategy, has some limitations. A new tissue-engineered strategy, Bottom-Up strategy (tissue-engineered microtissue strategy), has emerged and made significant research progress in recent years. However, to the best of our knowledge, microtissues are rarely used in neural tissue engineering, thus we intended to use microtissues to repair PNI.Methods: We used a low-adhesion cell culture plate to construct adipose-derived mesenchymal stem cells (ASCs) into microtissues in vitro, explored the physicochemical properties and microtissues components, compared the expression of cytokines related to nerve regeneration between microtissues and the same amount of two-dimension (2D)-cultured cells, co-cultured directly microtissues with dorsal root ganglion (DRG) or Schwann cells (SCs) to observe the interaction between them using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA). We used grafts constructed by microtissues and polycaprolactone (PCL) nerve conduit to repair sciatic nerve defects in rats.Results: The present study results indicated that compared with the same number of 2D-cultured cells, microtissue could secrete more nerve regeneration related cytokines to promote SCs proliferation and axons growth. Moreover, in the direct co-culture system of microtissue and DRG or SCs, axons of DRG grown in the direction of microtissue, and there seems to be a cytoplasmic exchange between SCs and ASCs around microtissue. Furthermore, microtissues could repair sciatic nerve defects in rat models more effectively than traditional 2D cultured-ASCs. Conclusion: Tissue-engineered microtissue is an effective strategy for stem cell culture and therapy in nerve tissue engineering.

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jian Zhang ◽  
Chaochao Li ◽  
Fanqi Meng ◽  
Yanjun Guan ◽  
Tieyuan Zhang ◽  
...  

Abstract Background Peripheral nerve injury (PNI) is one of the essential causes of physical disability with a high incidence rate. The traditional tissue engineering strategy, Top-Down strategy, has some limitations. A new tissue-engineered strategy, Bottom-Up strategy (tissue-engineered microtissue strategy), has emerged and made significant research progress in recent years. However, to the best of our knowledge, microtissues are rarely used in neural tissue engineering; thus, we intended to use microtissues to repair PNI. Methods We used a low-adhesion cell culture plate to construct adipose-derived mesenchymal stem cells (ASCs) into microtissues in vitro, explored the physicochemical properties and microtissues components, compared the expression of cytokines related to nerve regeneration between microtissues and the same amount of two-dimension (2D)-cultured cells, co-cultured directly microtissues with dorsal root ganglion (DRG) or Schwann cells (SCs) to observe the interaction between them using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA). We used grafts constructed by microtissues and polycaprolactone (PCL) nerve conduit to repair sciatic nerve defects in rats. Results The present study results indicated that compared with the same number of 2D-cultured cells, microtissue could secrete more nerve regeneration related cytokines to promote SCs proliferation and axons growth. Moreover, in the direct co-culture system of microtissue and DRG or SCs, axons of DRG grown in the direction of microtissue, and there seems to be a cytoplasmic exchange between SCs and ASCs around microtissue. Furthermore, microtissues could repair sciatic nerve defects in rat models more effectively than traditional 2D-cultured ASCs. Conclusion Tissue-engineered microtissue is an effective strategy for stem cell culture and therapy in nerve tissue engineering.


2015 ◽  
Vol 15 (6) ◽  
pp. 612-621 ◽  
Author(s):  
Lorena R. Lizarraga-Valderrama ◽  
Rinat Nigmatullin ◽  
Caroline Taylor ◽  
John W. Haycock ◽  
Frederik Claeyssens ◽  
...  

2011 ◽  
Vol 175-176 ◽  
pp. 220-223 ◽  
Author(s):  
Ai Jun Hu ◽  
Bao Qi Zuo ◽  
Feng Zhang ◽  
Qing Lan ◽  
Huan Xiang Zhang

Schwann cells (SCs) are primary structural and functional cells in peripheral nervous system and play a crucial role in peripheral nerve regeneration. Current challenge in peripheral nerve tissue engineering is to produce an implantable scaffold capable of bridging long nerve gaps and assist Scs in directing the growth of regenerating axons in nerve injury recovery. Electrospun silk fibroin nanofibers, fabricated for the cell culture in vitro, can provide such experiment support. Silk fibroin scaffolds (SFS) were fabricated with formic acid (FA), and the average fiber diameter was 305 ± 24 nm. The data from microscopic, immunohistochemical and scanning electron micrograph confirmed that the scaffold was beneficial to the adherence, proliferation and migration of SCs without exerting any significant cytotoxic effects on their phenotype. Thus, providing an experimental foundation accelerated the formation of bands of Bünger to enhance nerve regeneration. 305 nm SFS could be a candidate material for nerve tissue engineering.


2020 ◽  
Vol 209 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Zohreh Jahromi ◽  
Fahimeh Mohammadghasemi ◽  
Farshad Moharrami Kasmaie ◽  
Arash Zaminy

Peripheral nerve injury is a common clinical issue induced by trauma, tumor, and damage caused by treatment. Such factors create chemical and inflammatory alterations at the injury site, which increase nerve deterioration. Thus, minimizing these modifications can lead to nerve protection after injury. The present study sought to evaluate the possible improvement in nerve regeneration and enhancement of functional outcomes by cinnamaldehyde (Cin) administration following sciatic nerve crush in a rat model. Rats (n = 48) were distributed into 6 groups, including sham, injury, DMSO (vehicle group), and Cin groups (10, 30, and 90 mg/kg/day). Using small hemostatic forceps, crush injury was induced in the left sciatic nerve. Thereafter, Cin was administered for 28 successive days. Weekly records were taken for sciatic functional index (SFI) measurements. Further assessments including electrophysiological and histomorphometric evaluations, gastrocnemius muscle wet weight measurements, and estimation of the serum total oxidant status were performed. According to the results, Cin could accelerate sciatic nerve recovery after crush injury, and the dose of 30 mg/kg/day of Cin had better impacts on SFI recovery, muscle mass ratio, and myelin content. The current research demonstrated that Cin positively affects peripheral nerve restoration. Therefore, Cin therapy could be considered as a potential treatment method for peripheral nerve regeneration and its functional recovery. However, more investigations are required to further validate the study results and evaluate the optimal dose of Cin.


Author(s):  
Hongyu Liu ◽  
Yanan Zhao ◽  
Jun Tong ◽  
Xiaowen Shi ◽  
Yun Chen ◽  
...  

The development of peripheral nerve tissue engineering requires safe and reliable methodology to construct biodegradable conduits. Herein, a new type of chitosan-based nerve-guide hydrogel conduit (CNHC) with enhanced mechanical flexibility...


2018 ◽  
Vol 34 (2) ◽  
pp. 190-208 ◽  
Author(s):  
Xing-Lei Guo ◽  
Hai-Xing Xu ◽  
Qun-Di He ◽  
Yun-Xuan Yu ◽  
Xiao-Fei Ming ◽  
...  

Defected peripheral nerve regeneration is still a challenge in clinical treatment. Conductive polymers show great potential in nerve tissue engineering because of their electrical property based on bioelectricity in vivo. In this study, conductive composite nerve conduit was synthesized with tetra-aniline and poly-dl-lactic acid. Their properties and the differentiation of rat pheochromocytoma 12 (PC12) cells in vitro stimulated with 200 mV for 1 h were investigated. Different amounts of tetra-aniline (0%, 5%, 10%, and 15%) were used to synthesize the conduits with different conductivities (0, 0.00625, 0.01, and 0.025 s/m, respectively), tensile strengths (2.45, 3.40, 4.45, and 5.50 MPa, respectively), and contact angles (80°, 78.5°, 62.5°, and 61.5°, respectively). The percentage of neurite-bearing cells and the median neurite length increased with an obvious raise of the content of tetra-aniline. In addition, the conduit with subcutaneous implantable experiments in vivo showed less inflammatory response. These promising results illustrated that this poly-dl-lactic acid/tetra-aniline conductive composite conduit had potential for nerve tissue engineering.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yin Li ◽  
Zhenjiang Ma ◽  
Ya Ren ◽  
Dezhi Lu ◽  
Tao Li ◽  
...  

A peripheral nerve injury (PNI) has severe and profound effects on the life of a patient. The therapeutic approach remains one of the most challenging clinical problems. In recent years, many constructive nerve regeneration schemes are proposed at home and abroad. Nerve tissue engineering plays an important role. It develops an ideal nerve substitute called artificial nerve. Given the complexity of nerve regeneration, this review summarizes the pathophysiology and tissue-engineered repairing strategies of the PNI. Moreover, we discussed the scaffolds and seed cells for neural tissue engineering. Furthermore, we have emphasized the role of 3D printing in tissue engineering.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Shih-Tien Hsu ◽  
Chun-Hsu Yao ◽  
Yuan-Man Hsu ◽  
Jia-Horng Lin ◽  
Yung-Hsiang Chen ◽  
...  

Abstract Recent studies describe taxol as a candidate treatment for promoting central nerve regeneration. However, taxol has serious side effects including peripheral neurotoxicity, and little information is known about the effect of taxol on peripheral nerve regeneration. We investigated the effects of taxol on regeneration in a rat sciatic nerve transection model. Rats were divided into four groups (n = 10): normal saline (i.p.) as the control, Cremophor EL vehicle, and 2 or 6 mg/kg of taxol in the Cremophor EL solution (four times in day-2, 4, 6, and 8), respectively. We evaluated neuronal electrophysiology, animal behaviour, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors and immunoregulatory factors. In the high-dose taxol group (6 mg/kg), neuronal electrophysiological function was significantly impaired. Licking latencies were significantly changed while motor coordination was unaffected. Neuronal connectivity, macrophage density, and expression levels of CGRP was dramatically reduced. Expression levels of nerve growth factors and immunoregulatory factors was also reduced, while it was increased in the low-dose taxol group (2 mg/kg). These results indicate that taxol can modulate local inflammatory conditions, impair nerve regeneration, and impede recovery of a severe peripheral nerve injury.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feixiang Chen ◽  
Weihuang Liu ◽  
Qiang Zhang ◽  
Ping Wu ◽  
Ao Xiao ◽  
...  

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.


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