scholarly journals Differential Effects of Encapsulation of Rat ADSCs in Fibrin Matrix and Combination Delivery of BDNF and Gold Nanoparticles on Peripheral Nerve Regeneration

2020 ◽  
Author(s):  
Shahnaz Razavi ◽  
Maliheh Jahromi ◽  
Elham Vatankhah ◽  
Reihaneh Seyedebrahimi
Keyword(s):  
Gold Nanoparticles ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
Chitosan Nanoparticles ◽  
Nerve Fibers ◽  
Matrix Group ◽  
Differential Effects ◽  
Fibrin Matrix ◽  
Autograft Group

Abstract Background: Fibrin as an extracellular matrix feature like biocompatibility, creates a favorable environment for proliferation and migration of cells and acts as a reservoir for storage and release of growth factors in tissue engineering. Methods: In this study, the inner surface electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibrous conduit was biofunctionalized with laminin containing brain derived neurotrophic factor (BDNF) and gold nanoparticles in chitosan nanoparticle. The rats were randomly divided into five groups, including autograft group as the positive control, PLGA conduit coated by laminin and filled with DMEM/F12, PLGA conduit coated by laminin and filled with adipose-derived stem cells (rADSCs) , PLGA conduit coated by laminin containing gold-chitosan nanoparticles (AuNPs-CNPs), BDNF-chitosan nanoparticles (BDNF-CNPs) and filled with rADSCs or filled with rADSCs suspended in fibrin matrix, and they were implanted to bridge a 10 mm rat sciatic nerve gap. Eventually, axonal regeneration and functional recovery were assessed after 12 weeks.Results: After 3months post-surgery period, the results showed that in the PLGA conduit filled with rADSCs without fibrin matrix group, positive effects were obtained as compared to other implanted groups by increasing the sciatic functional index significantly (p < 0.05). In addition, the diameter nerve fibers had a significant difference mean in the PLGA conduit coated by laminin and conduit filled with rADSCs in fibrin matrix groups relative to the autograft group (p< 0.001). However, G-ratio and amplitude (AMP) results showed that fibrin matrix might have beneficial effects on nerve regeneration but, immunohistochemistry and real-time PCR outcomes indicated that the implanted conduit which filled with rADSCs with or without BDNF-CNPs and AuNPs-CNPs had significantly higher expression of S100, MBP and NF200 markers than other conduit implanted groups (p< 0.05).Conclusions: It seems, in this study differential effects of fibrin matrix, could be interfered it with other factors thereby and further studies are required to determine the distinctive effects of fibrin matrix combination with other exogenous factors in peripheral nerve regeneration.

scholarly journals Differential effects of rat ADSCs encapsulation in fibrin matrix and combination delivery of BDNF and Gold nanoparticles on peripheral nerve regeneration

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shahnaz Razavi ◽  
Maliheh Jahromi ◽  
Elham Vatankhah ◽  
Reihaneh Seyedebrahimi
Keyword(s):  
Gold Nanoparticles ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
Chitosan Nanoparticles ◽  
Nerve Fibers ◽  
Matrix Group ◽  
Differential Effects ◽  
Fibrin Matrix ◽  
Autograft Group

Abstract Background Fibrin as an extracellular matrix feature like biocompatibility, creates a favorable environment for proliferation and migration of cells and it can act as a reservoir for storage and release of growth factors in tissue engineering. Methods In this study, the inner surface of electrospun poly (lactic-co-glycolic acid) (PLGA) nanofibrous conduit was biofunctionalized with laminin containing brain derived neurotrophic factor (BDNF) and gold nanoparticles in chitosan nanoparticle. The rats were randomly divided into five groups, including autograft group as the positive control, PLGA conduit coated by laminin and filled with DMEM/F12, PLGA conduit coated by laminin and filled with rat-adipose derived stem cells (r-ADSCs), PLGA conduit coated by laminin containing gold-chitosan nanoparticles (AuNPs-CNPs), BDNF-chitosan nanoparticles (BDNF-CNPs) and filled with r-ADSCs or filled with r-ADSCs suspended in fibrin matrix, and they were implanted into a 10 mm rat sciatic nerve gap. Eventually, axonal regeneration and functional recovery were assessed after 12 weeks. Results After 3 months post-surgery period, the results showed that in the PLGA conduit filled with r-ADSCs without fibrin matrix group, positive effects were obtained as compared to other implanted groups by increasing the sciatic functional index significantly (p < 0.05). In addition, the diameter nerve fibers had a significant difference mean in the PLGA conduit coated by laminin and conduit filled with r-ADSCs in fibrin matrix groups relative to the autograft group (p < 0.001). However, G-ratio and amplitude (AMP) results showed that fibrin matrix might have beneficial effects on nerve regeneration but, immunohistochemistry and real-time RT-PCR outcomes indicated that the implanted conduit which filled with r-ADSCs, with or without BDNF-CNPs and AuNPs-CNPs had significantly higher expression of S100 and MBP markers than other conduit implanted groups (p < 0.05). Conclusions It seems, in this study differential effects of fibrin matrix, could be interfered it with other factors thereby and further studies are required to determine the distinctive effects of fibrin matrix combination with other exogenous factors in peripheral nerve regeneration.

scholarly journals Nogo-C Inhibits Peripheral Nerve Regeneration by Regulating Schwann Cell Apoptosis and Dedifferentiation

2021 ◽  
Vol 14 ◽  
Author(s):  
Bo Jia ◽  
Wei Huang ◽  
Yu Wang ◽  
Peng Zhang ◽  
Zhiwei Wang ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Cell Apoptosis ◽  
Peripheral Nerve Regeneration ◽  
Nerve Fibers ◽  
Cell Dedifferentiation

While Nogo protein demonstrably inhibits nerve regeneration in the central nervous system (CNS), its effect on Schwann cells in peripheral nerve repair and regeneration following sciatic nerve injury remains unknown. In this research, We assessed the post-injury expression of Nogo-C in an experimental mouse model of sciatic nerve-crush injury. Nogo-C knockout (Nogo-C–/–) mouse was generated to observe the effect of Nogo-C on sciatic nerve regeneration, Schwann cell apoptosis, and myelin disintegration after nerve injury, and the effects of Nogo-C on apoptosis and dedifferentiation of Schwann cells were observed in vitro. We found that the expression of Nogo-C protein at the distal end of the injured sciatic nerve increased in wild type (WT) mice. Compared with the injured WT mice, the proportion of neuronal apoptosis was significantly diminished and the myelin clearance rate was significantly elevated in injured Nogo-C–/– mice; the number of nerve fibers regenerated and the degree of myelination were significantly elevated in Nogo-C–/– mice on Day 14 after injury. In addition, the recovery of motor function was significantly accelerated in the injured Nogo-C–/– mice. The overexpression of Nogo-C in primary Schwann cells using adenovirus-mediated gene transfer promoted Schwann cells apoptosis. Nogo-C significantly reduced the ratio of c-Jun/krox-20 expression, indicating its inhibition of Schwann cell dedifferentiation. Above all, we hold the view that the expression of Nogo-C increases following peripheral nerve injury to promote Schwann cell apoptosis and inhibit Schwann cell dedifferentiation, thereby inhibiting peripheral nerve regeneration.

scholarly journals Peripheral Nerve Regeneration and Muscle Reinnervation

2020 ◽  
Vol 21 (22) ◽  
pp. 8652 ◽  
Author(s):  
Tessa Gordon
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Low Frequency ◽  
Nerve Fibers ◽  
Target Organs ◽  
Neuronal Soma ◽  
Original Target ◽  
Surgical Manipulations

Injured peripheral nerves but not central nerves have the capacity to regenerate and reinnervate their target organs. After the two most severe peripheral nerve injuries of six types, crush and transection injuries, nerve fibers distal to the injury site undergo Wallerian degeneration. The denervated Schwann cells (SCs) proliferate, elongate and line the endoneurial tubes to guide and support regenerating axons. The axons emerge from the stump of the viable nerve attached to the neuronal soma. The SCs downregulate myelin-associated genes and concurrently, upregulate growth-associated genes that include neurotrophic factors as do the injured neurons. However, the gene expression is transient and progressively fails to support axon regeneration within the SC-containing endoneurial tubes. Moreover, despite some preference of regenerating motor and sensory axons to “find” their appropriate pathways, the axons fail to enter their original endoneurial tubes and to reinnervate original target organs, obstacles to functional recovery that confront nerve surgeons. Several surgical manipulations in clinical use, including nerve and tendon transfers, the potential for brief low-frequency electrical stimulation proximal to nerve repair, and local FK506 application to accelerate axon outgrowth, are encouraging as is the continuing research to elucidate the molecular basis of nerve regeneration.

Platelet-Rich Fibrin Conduits as an Alternative to Nerve Autografts for Peripheral Nerve Repair

2017 ◽  
Vol 33 (08) ◽  
pp. 549-556 ◽  
Author(s):  
Marcela Fernandes ◽  
Sandra Valente ◽  
João Santos ◽  
Rebeca Furukawa ◽  
Carlos Fernandes ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Motor Neurons ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Nerve Fibers ◽  
Nerve Graft ◽  
Platelet Rich Fibrin ◽  
Significant Difference ◽  
Autogenous Vein

Background Peripheral nerves have limited regeneration capacity despite best efforts. Platelet-rich fibrin (PRF) contains growth factors that may stimulate peripheral nerve regeneration. This study verified whether nerve regeneration using autogenous vein conduits filled with PRF is comparable to autologous nerve graft, which is the standard treatment. Methods The sciatic nerve of the right paw of inbred rats was dissected, and a 10-mm segment was removed from rats randomized to receive autologous nerve graft (GRAFT) or vein conduit filled with PRF (PRF). A third group (SHAM) underwent surgery without nerve resection. The sciatic functional index (SFI) was measured 0, 30, 60, and 90 days postsurgery. Morphometry and morphology of the distal nerve injury were examined. Motor neurons in the anterior horn of spinal cord stained with FluoroGold and counted. Results No significant difference in SFI was observed between the GRAFT and PRF groups at any time point (all p > 0.05); however, SFI was lower in both groups compared with SHAM (p < 0.05). Morphometric and morphologic indexes were not significantly different between the GRAFT and PRF groups (p > 0.05); however, nerve fibers, axons, and myelin sheaths were thinner in both groups compared with SHAM (p = 0.0001). Average motor neurons' count was similar between the GRAFT and PRF groups (p = 0.91); the count was lower in both groups compared with SHAM (p = 0.002 and p = 0.001), respectively. Conclusion Autologous nerve GRAFT and PRF-filled autogenous vein conduits were associated with similar outcomes, and worse than those observed in SHAM controls. Vein conduits filled with PRF may be a favorable alternative treatment to nerve grafts.

scholarly journals Chitin Nerve Conduits with Three-Dimensional Spheroids of Mesenchymal Stem Cells from SD Rats Promote Peripheral Nerve Regeneration

Polymers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 3957
Author(s):  
Ci Li ◽  
Meng Zhang ◽  
Song-Yang Liu ◽  
Feng-Shi Zhang ◽  
Teng Wan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Therapeutic Potential ◽  
Peripheral Nerve Regeneration ◽  
Nerve Fibers ◽  
Therapeutic Effects ◽  
Bone Mesenchymal Stem Cells ◽  
Nerve Conduits

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.

scholarly journals The Mechanisms Mediated by α7 Acetylcholine Nicotinic Receptors May Contribute to Peripheral Nerve Regeneration

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7668
Author(s):  
Michael Sebastian Salazar Intriago ◽  
Roberta Piovesana ◽  
Alessandro Matera ◽  
Marilena Taggi ◽  
Rita Canipari ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nicotinic Acetylcholine Receptors ◽  
Partial Agonist ◽  
Peripheral Nerve Regeneration ◽  
Transcript Level ◽  
Nerve Fibers ◽  
Inflammatory Microenvironment ◽  
Α7 Nachrs

Due to the microenvironment created by Schwann cell (SC) activity, peripheral nerve fibers are able to regenerate. Inflammation is the first response to nerve damage and the removal of cellular and myelin debris is essential in preventing the persistence of the local inflammation that may negatively affect nerve regeneration. Acetylcholine (ACh) is one of the neurotransmitters involved in the modulation of inflammation through the activity of its receptors, belonging to both the muscarinic and nicotinic classes. In this report, we evaluated the expression of α7 nicotinic acetylcholine receptors (nAChRs) in rat sciatic nerve, particularly in SCs, after peripheral nerve injury. α7 nAChRs are absent in sciatic nerve immediately after dissection, but their expression is significantly enhanced in SCs after 24 h in cultured sciatic nerve segments or in the presence of the proinflammatory neuropeptide Bradykinin (BK). Moreover, we found that activation of α7 nAChRs with the selective partial agonist ICH3 causes a decreased expression of c-Jun and an upregulation of uPA, MMP2 and MMP9 activity. In addition, ICH3 treatment inhibits IL-6 transcript level expression as well as the cytokine release. These results suggest that ACh, probably released from regenerating axons or by SC themselves, may actively promote through α7 nAChRs activation an anti-inflammatory microenvironment that contributes to better improving the peripheral nerve regeneration.

scholarly journals Challenges for Nerve Repair Using Chitosan-Siloxane Hybrid Porous Scaffolds

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Yuki Shirosaki ◽  
Satoshi Hayakawa ◽  
Akiyoshi Osaka ◽  
Maria A. Lopes ◽  
José D. Santos ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Nerve Fibers ◽  
Porous Scaffolds ◽  
Hybrid Membranes ◽  
Nerve Injuries ◽  
Myelinated Nerve ◽  
Nerve Guides

The treatment of peripheral nerve injuries remains one of the greatest challenges of neurosurgery, as functional recover is rarely satisfactory in these patients. Recently, biodegradable nerve guides have shown great potential for enhancing nerve regeneration. A major advantage of these nerve guides is that no foreign material remains after the device has fulfilled its task, which spares a second surgical intervention. Recently, we studied peripheral nerve regeneration using chitosan-γ-glycidoxypropyltrimethoxysilane (chitosan-GPTMS) porous hybrid membranes. In our studies, these porous membranes significantly improved nerve fiber regeneration and functional recovery in rat models of axonotmetic and neurotmetic sciatic nerve injuries. In particular, the number of regenerated myelinated nerve fibers and myelin thickness were significantly higher in rat treated with chitosan porous hybrid membranes, whether or not they were used in combination with mesenchymal stem cells isolated from the Wharton’s jelly of the umbilical cord. In this review, we describe our findings on the use of chitosan-GPTMS hybrids for nerve regeneration.

Effects of Hedysari Polysaccharides on Regeneration and Function Recovery Following Peripheral Nerve Injury in Rats

2009 ◽  
Vol 37 (01) ◽  
pp. 57-67 ◽  
Author(s):  
Shao-Yin Wei ◽  
Pei-Xun Zhang ◽  
Na Han ◽  
Yu Dang ◽  
Hong-Bo Zhang ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Peripheral Nerve Regeneration ◽  
Nerve Fibers ◽  
Myelinated Nerve ◽  
Function Index ◽  
Main Component ◽  
And Function

It has been demonstrated that aqueous extract of Radix Hedysari Prescription and modified Radix Hedysari Prescription could improve the regeneration of injured peripheral nerve. Radix Hedysari is a main component in these two formulas. We hypothesized that Hedysari polysaccharides (HPS), a main active ingredient, could also enhance peripheral nerve regeneration after nerve injury in adult animals. In the present study, we examined the effects of HPS on sciatic nerve regeneration for 6 weeks following clamping in rats (administrated orally of 2 ml HPS liquid daily, 0.25 g/ml). The results showed that HPS was able to enhance sciatic function index (SFI) value, tibial function index (TFI) value, peroneal nerve function index (PFI) value, conduction velocity, and the number of regenerated myelinated nerve fibers, suggesting the potential clinical application of HPS for the treatment of peripheral nerve injury in humans.

scholarly journals Development of Multi-channel Electro-conductive Nanofibrous Conduits for Peripheral Nerve Regeneration

2021 ◽  
Author(s):  
Niloofar Nazeri ◽  
Mohammad Ali Derakhshan ◽  
Korosh Mansoori ◽  
Hossein Ghanbari
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Cell Attachment ◽  
Peripheral Nerve Regeneration ◽  
Nerve Fibers ◽  
Cross Sectional ◽  
Nerve Conduits ◽  
Mean Diameter ◽  
Sciatic Nerve Regeneration

Abstract Multichannel structures in the design of nerve conduits offer potential advantages for regeneration of damaged nerves due to their bio-mimicking architecture. However, lack of biochemical cues and electrical stimulation could hamper satisfactory nerve regeneration. The aim of this study was to simultaneously evaluate the effects of topographical, biological and electrical cues on sciatic nerve regeneration in a rat model. Accordingly, a series of multichannel nanofibrous nerve conduit was made using longitudinally-aligned laminin-coated electrospun PLGA/CNT nanofibers (NF, mean diameter: 455 ± 362 nm) in the lumen and randomly-oriented PCL NF (mean diameter: 340 ± 200 nm) on the outer surface. In vitro studies revealed that both materials were nontoxic to Schwann cells and able to promote cell attachment and proliferation. To determine the influence of topographical, biological and electrical cues on nerve regeneration, either of hollow PCL conduits, PLGA NF-embedded, PLGA/CNT NF-embedded or laminin-coated PLGA/CNT NF-embedded PCL conduits were implanted in rats. A new surgery method was utilized and results were compared with an autograft. After animal treatments, motor and sensory tests showed significant improvement in the rats treated with NF-embedded PCL conduits. H&E images obtained from cross-sectional and, longitudinal-sections of the regenerated nerves demonstrated the formation of regenerative nerve fibers and also, angiogenesis in laminin-coated PLGA/CNT NF-embedded PCL conduits. Results suggested that these conduits have the potential for clinical application to reconstruct peripheral nerve defects.

scholarly journals Bioabsorbable nerve conduits three-dimensionally coated with human induced pluripotent stem cell-derived neural stem/progenitor cells promote peripheral nerve regeneration in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ema Onode ◽  
Takuya Uemura ◽  
Kiyohito Takamatsu ◽  
Takuya Yokoi ◽  
Kosuke Shintani ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerve Regeneration ◽  
Induced Pluripotent Stem Cell ◽  
Control Group ◽  
Nerve Conduit ◽  
Nerve Conduits ◽  
Neural Stem Progenitor Cells ◽  
G Ratio ◽  
Autograft Group

AbstractPeripheral nerve regeneration using nerve conduits has been less effective than autogenous nerve grafts. To overcome this hurdle, we developed a tissue-engineered nerve conduit coated with mouse induced pluripotent stem cell (iPSC)-derived neurospheres, for the first time, which accelerated nerve regeneration in mice. We previously demonstrated the long-term efficacy and safety outcomes of this hybrid nerve conduit for mouse peripheral nerve regeneration. In this study, we investigated the therapeutic potential of nerve conduits coated with human iPSC (hiPSC)-derived neurospheres in rat sciatic nerve defects, as a translational preclinical study. The hiPSC-derived quaternary neurospheres containing neural stem/progenitor cells were three-dimensionally cultured within the nerve conduit (poly l-lactide and polycaprolactone copolymer) for 14 days. Complete 5-mm defects were created as a small size peripheral nerve defect in sciatic nerves of athymic nude rats and reconstructed with nerve conduit alone (control group), nerve conduits coated with hiPSC-derived neurospheres (iPS group), and autogenous nerve grafts (autograft group) (n = 8 per group). The survival of the iPSC-derived neurospheres was continuously tracked using in vivo imaging. At 12 weeks postoperatively, motor and sensory function and histological nerve regeneration were evaluated. Before implantation, the hiPSC-derived quaternary neurospheres that three-dimensional coated the nerve conduit were differentiated into Schwann-like cells. The transplanted hiPSC-derived neurospheres survived for at least 56 days after implantation. The iPS group showed non-significance higher sensory regeneration than the autograft group. Although there was no actual motor functional nerve regeneration in the three groups: control, iPS, and autograft groups, the motor function in the iPS group recovered significantly better than that in the control group, but it did not recover to the same level as that in the autograft group. Histologically, the iPS group demonstrated significantly higher axon numbers and areas, and lower G-ratio values than the control group, whereas the autograft group demonstrated the highest axon numbers and areas and the lowest G-ratio values. Nerve conduit three-dimensionally coated with hiPSC-derived neurospheres promoted axonal regeneration and functional recovery in repairing rat sciatic nerve small size defects. Transplantation of hiPSC-derived neurospheres with nerve conduits is a promising clinical iPSC-based cell therapy for the treatment of peripheral nerve defects.

Sign in / Sign up

Export Citation Format

Share Document