Publications by authors named "Majid Salehi"

39 Publications

Synergic effects of nanoparticles-mediated hyperthermia in radiotherapy/chemotherapy of cancer.

Life Sci 2021 Mar 12;269:119020. Epub 2021 Jan 12.

Medical Technology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

The conventional cancer treatment modalities such as radiotherapy and chemotherapy suffer from several limitations; hence, their efficiency needs to be improved with other complementary modalities. Hyperthermia, as an adjuvant therapeutic modality for cancer, can result in a synergistic effect on radiotherapy (radiosensitizer) and chemotherapy (chemosensitizer). Conventional hyperthermia methods affect both tumoral and healthy tissues and have low specificity. In addition, a temperature gradient generates in the tissues situated along the path of the heat source, which is a more serious for deep-seated tumors. Nanoparticles (NPs)-induced hyperthermia can resolve these drawbacks through localization around/within tumoral tissue and generating local hyperthermia. Although there are several review articles dealing with NPs-induced hyperthermia, lack of a paper discussing the combination of NPs-induced hyperthermia with the conventional chemotherapy or radiotherapy is tangible. Accordingly, the main focus of the current paper is to summarize the principles of NPs-induced hyperthermia and more importantly its synergic effects on the conventional chemotherapy or radiotherapy. The heat-producing nanostructures such as gold NPs, iron oxide NPs, and carbon NPs, as well as the non-heat-producing nanostructures, such as lipid-based, polymeric, and silica-based NPs, as the carrier for heat-producing NPs, are discussed and their pros and cons highlighted.
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http://dx.doi.org/10.1016/j.lfs.2021.119020DOI Listing
March 2021

Improving sciatic nerve regeneration by using alginate/chitosan hydrogel containing berberine.

Drug Deliv Transl Res 2020 Oct 9. Epub 2020 Oct 9.

Tissue Engineering and Stem Cells Research Center, Shahroud University of Medical Sciences, Shahroud, Iran.

Peripheral nerve injuries are the common results of trauma that lead to pain and handicap in patients. Berberine due to its properties like antibiotic, immunostimulant, antitumor, antimotility, and positive effect on neurological disorders can be used to enhance peripheral nerve injuries. In this study, alginate/chitosan hydrogel containing different concentrations of berberine (0, 0.1, 1, 10% (w/v)) was created, evaluated, and applied as a scaffold for sciatic nerve regeneration. To prepare hydrogel, sodium alginate was dissolved in distilled water and cross-linked with CaCl2, and chitosan was dissolved in acetic acid and cross-linked with β-glycerol phosphate. The structure, release, swelling, weight loss, cytocompatibility, and hemocompatibility of the prepared hydrogels were assessed. The sciatic nerve crush was created in rats and fabricated hydrogels were injected, and functional analysis was used to evaluate their effectiveness. The results of physical characterization of the hydrogel indicated that the initial average pore size was about 39 μm and about 70% of the main weight of hydrogels was lost after incubation for 21 days and hemocompatibility of hydrogels was also confirmed. The MTT assay showed the cytocompatiblity of hydrogels and also indicated that berberine has dose-dependence effect on cell proliferation. The in vivo results showed the positive effect of berberine especially the hydrogel contained 1% of berberine on regeneration of sciatic nerve. Based on this study, Alg/Chit hydrogel can be applied as a treatment to heal peripheral nerve injuries. Graphical abstract.
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http://dx.doi.org/10.1007/s13346-020-00860-yDOI Listing
October 2020

Alginate hydrogel containing hydrogen sulfide as the functional wound dressing material: In vitro and in vivo study.

Int J Biol Macromol 2020 Dec 1;164:3323-3331. Epub 2020 Sep 1.

Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran; Tissue Engineering and Stem Cells Research Center, Shahroud University of Medical Sciences, Shahroud, Iran; Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran. Electronic address:

Functional and bioactive wound dressing materials are revolutionary for wound care and healing applications. In this concept, we fabricated alginate hydrogel (Alg) containing HS as the wound dressing materials and assessed the morphology, swelling, degradation, and release behavior, as well as the biocompatibility, cytocompatibility, and wound healing activity. The results depicted that the prepared hydrogels have a porous structure with the pore size in the range of 50 to 100 μm. Swelling and degradation studies showed that the hydrogel absorbed water about 179 ± 5% of initial dry weight during 96 h and loos about 80% of the initial dry weight after 7 days. The in vitro assessments illustrated that the optimum concentration of HS was 0.5% and the higher concentration induced hemolysis and cell toxicity. The in vivo study revealed that the treatment by Alg/HS 0.5% induced the highest wound closure percent with a value of 98 ± 1.22%. Moreover, the treatment by Alg/HS 0.5% elicited the formation of sebaceous glands, hair follicles, and complete epithelization without any fibroplasia or inflammation, revealed by the histopathological observations. Accordingly, these results illustrated that the prepared Alg/HS 0.5% could be applied as the functional and bioactive wound dressing materials.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.08.233DOI Listing
December 2020

A tailored polylactic acid/polycaprolactone biodegradable and bioactive 3D porous scaffold containing gelatin nanofibers and Taurine for bone regeneration.

Sci Rep 2020 08 7;10(1):13366. Epub 2020 Aug 7.

Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

The focus of the current study was to develop a functional and bioactive scaffold through the combination of 3D polylactic acid (PLA)/polycaprolactone (PCL) with gelatin nanofibers (GNFs) and Taurine (Tau) for bone defect regeneration. GNFs were fabricated via electrospinning dispersed in PLA/PCL polymer solution, Tau with different concentrations was added, and the polymer solution converted into a 3D and porous scaffold via the thermally-induced phase separation technique. The characterization results showed that the scaffolds have interconnected pores with the porosity of up to 90%. Moreover, Tau increased the wettability and weight loss rate, while compromised the compressive strengths. The scaffolds were hemo- and cytocompatible and supported cell viability and proliferation. The in vivo studies showed that the defects treated with scaffolds filled with new bone. The computed tomography (CT) imaging and histopathological observation revealed that the PLA/PCL/Gel/Tau 10% provided the highest new bone formation, angiogenesis, and woven bone among the treatment groups. Our finding illustrated that the fabricated scaffold was able to regenerate bone within the defect and can be considered as the effective scaffold for bone tissue engineering application.
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http://dx.doi.org/10.1038/s41598-020-70155-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414882PMC
August 2020

Electrospun cellulose acetate/gelatin nanofibrous wound dressing containing berberine for diabetic foot ulcer healing: in vitro and in vivo studies.

Sci Rep 2020 05 20;10(1):8312. Epub 2020 May 20.

Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

Functional wound dressing with tailored physicochemical and biological properties is vital for diabetic foot ulcer (DFU) treatment. Our main objective in the current study was to fabricate Cellulose Acetate/Gelatin (CA/Gel) electrospun mat loaded with berberine (Beri) as the DFU-specific wound dressing. The wound healing efficacy of the fabricated dressings was evaluated in streptozotocin-induced diabetic rats. The results demonstrated an average nanofiber diameter of 502 ± 150 nm, and the tensile strength, contact angle, porosity, water vapor permeability and water uptake ratio of CA/Gel nanofibers were around 2.83 ± 0.08 MPa, 58.07 ± 2.35°, 78.17 ± 1.04%, 11.23 ± 1.05 mg/cm/hr, and 12.78 ± 0.32%, respectively, while these values for CA/Gel/Beri nanofibers were 2.69 ± 0.05 MPa, 56.93 ± 1°, 76.17 ± 0.76%, 10.17 ± 0.21 mg/cm/hr, and 14.37 ± 0.42%, respectively. The antibacterial evaluations demonstrated that the dressings exhibited potent antibacterial activity. The collagen density of 88.8 ± 6.7% and the angiogenesis score of 19.8 ± 3.8 obtained in the animal studies indicate a proper wound healing. These findings implied that the incorporation of berberine did not compromise the physical properties of dressing, while improving the biological activities. In conclusion, our results indicated that the prepared mat is a proper wound dressing for DFU management and treatment.
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http://dx.doi.org/10.1038/s41598-020-65268-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239895PMC
May 2020

A promising wound dressing based on alginate hydrogels containing vitamin D3 cross-linked by calcium carbonate/d-glucono-δ-lactone.

Biomed Eng Lett 2020 May 19;10(2):309-319. Epub 2020 Mar 19.

8Department of Anatomical Sciences, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

In the present study, we fabricated vitamin D-loaded alginate hydrogel and assessed its wound healing capability in the animal model. The various concentrations of vitamin D3 were added to the pre-dissolved sodium alginate in deionized water and cross-linked by calcium carbonate in combination with d-glucono-δ-lactone. The microstructure, swelling behavior, weight loss, hemo- and cytocompatibility of the fabricated hydrogels were evaluated. In the last stage, the therapeutic efficacy of the prepared hydrogels was evaluated in the full-thickness dermal wound model. The scanning electron microscopy images showed that the prepared hydrogel was highly porous with the porosity of 89.2 ± 12.5% and contained the interconnected pores. Weight loss assessment showed that the prepared hydrogel is biodegradable with the weight loss percentage of about 89% in 14 days. The results showed that the prepared hydrogels were hemo- and cytocompatible. The animal study results implied that alginate hydrogel/3000 IU vitamin D group exhibited the highest wound closure present which was statistically significant than the control group ( < 0.05). Moreover, the histological examinations revealed that hydrogel containing 3000 IU vitamin D3 had the best performance and induced the highest re-epithelialization and granular tissue formation. All in all, this study suggests that alginate hydrogels with 3000 IU vitamin D can be exploited as a potential wound dressing in skin tissue engineering.
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http://dx.doi.org/10.1007/s13534-020-00155-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235134PMC
May 2020

Kaolin-loaded chitosan/polyvinyl alcohol electrospun scaffold as a wound dressing material: and studies.

J Wound Care 2020 May;29(5):270-280

Department of Tissue Engineering, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran.

Objective: To evaluate the application of a fabricated dressing containing kaolin for skin regeneration in a rat model of excisional wounds.

Method: In the present study, kaolin was loaded into electrospun polyvinyl alcohol (PVA)/chitosan polymer blend to develop a composite nanofibrous dressing. To make the yarns, kaolin with weight ratio of 5% was added to PVA/chitosan polymer blend and subsequently formed into nanofibres using the electrospinning method. Scaffolds were evaluated for to their microstructure, mechanical properties, surface wettability, water vapour transmission rate, water-uptake capacity, blood uptake capacity, blood compatibility, microbial penetration test, the number of colonies, and cellular response with the L929 cell line. Rats with full-thickness excisional wounds were treated with kaolin-containing and kaolin-free dressings.

Results: The study showed that rats treated with the kaolin-incorporated mats demonstrated a significant closure to nearly 97.62±4.81% after 14 days compared with PVA/chitosan and the sterile gauze, which showed 86.15±8.11% and 78.50±4.22% of wound closure, respectively. The histopathological studies showed that in the PVA/chitosan/kaolin group, dense and regular collagen fibres were formed, while wounds treated with sterile gauze or PVA/chitosan scaffolds had random and loose collagen fibres.

Conclusion: Our results show the potential applicability of PVA/chitosan/kaolin scaffolds as a wound care material.
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http://dx.doi.org/10.12968/jowc.2020.29.5.270DOI Listing
May 2020

Naturally occurring biological macromolecules-based hydrogels: Potential biomaterials for peripheral nerve regeneration.

Int J Biol Macromol 2020 Jul 18;154:795-817. Epub 2020 Mar 18.

Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Despite the recent advances in the treatment strategies of peripheral nerve system defects, peripheral nerve injury (PNI) is still one of the most important health issues with increasing incidence worldwide. The most commonly used treatment approaches are allografts, xenografts, and autologous, which have some drawbacks, including complications, limited source of the donor tissue, tubular collapse, and scar tissue formation. In this context, regenerative medicine has been introduced as a powerful approach to improve the healing process and obtain acceptable functional recovery in the injury site using living cells, scaffold, and bioactive (macro-) molecules. Amongst them, scaffold as a three-dimensional (3D) support biomaterial, structurally bridged the gap or site of injury in order to provide physical and chemical cues to promote correct reinnervation and functional regeneration. Amongst different scaffolding biomaterials, naturally occurring biological macromolecules (more especially proteins and polysaccharides)-based hydrogels exhibited promising results due to their fascinating physicochemical, as well as physiologically relevant properties. This review highlights the recent progress in the development of natural hydrogels-based neural scaffolds. Furthermore, PNI healing process, current status, and challenges are also shortly discussed.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.03.155DOI Listing
July 2020

Porous electrospun poly(ε-caprolactone)/gelatin nanofibrous mat containing cinnamon for wound healing application: in vitro and in vivo study.

Biomed Eng Lett 2020 Feb 18;10(1):149-161. Epub 2019 Nov 18.

1Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

In this study, cinnamon (cin) was loaded into poly(ε-caprolactone)/gelatin (PCL/Gel) nanofibrous matrices in order to fabricate an appropriate mat to improve wound healing. Mats were fabricated from PCL/COLL [1:1 (w/w)] solution with 1, 5 and 25% (w/v) of cinnamon. Prepared mats were characterized with regard to their microstructure, mechanical properties, porosity, surface wettability, water-uptake capacity, water vapor permeability, blood compatibility, microbial penetration and cellular response. The fabricated mats with and without cinnamon were used to treat the full-thickness excisional wounds in Wistar rats. The results indicated that the amount of cinnamon had a direct effect on porosity, mechanical properties, water uptake capacity, water contact angle, water vapor transmission rate and cell proliferation. In addition, the results of in vivo study indicated that after 14 days, the wounds which were treated with PCL/Gel 5%cin had better wound closure (98%) among other groups. Our results suggest that the cinnamon can be used as a suitable material for wound healing.
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http://dx.doi.org/10.1007/s13534-019-00138-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046867PMC
February 2020

Accelerating healing of excisional wound with alginate hydrogel containing naringenin in rat model.

Drug Deliv Transl Res 2021 Feb;11(1):142-153

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Wounds have always been considered as one of the most common physical damages. Therefore, various researches have been conducted to find an appropriate method to improve wound healing process. Among various materials, since hydrogels have appropriate properties for wound healing, they are widely used for this purpose. In this study, to develop a potential wound dressing, different concentrations of naringenin (0%, 1%, 10% and 20%) were incorporated in alginate hydrogel followed by evaluating its characters such as morphology, swelling properties, weight loss, antibacterial activity, releasing profile of the naringenin, hemo-, and cytocompatibility. Finally, to evaluate the effect of developed hydrogels on wound healing, the full-thickness dermal wound model in rat was used. Our results provided that the prepared hydrogels have appropriate porosity (86.7 ± 5.3%) with the interconnected pores. Moreover, weight loss assessment confirmed that fabricated hydrogels have suitable biodegradability (about 89% after 14 days). MTT assay also revealed the positive effect of hydrogels on cell viabilities, and they have no toxicity effect on cells. In vivo study indicated that the prepared hydrogels had better wound closure than the gauze-treated wound (the control), and alginate/20% naringenin group had the best wound closure among other groups. All in all, this study concluded that alginate/naringenin hydrogel has positive effect on wound healing process, and it can be used to treat skin injuries in the clinic. Graphical abstract.
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http://dx.doi.org/10.1007/s13346-020-00731-6DOI Listing
February 2021

Sophisticated polycaprolactone/gelatin nanofibrous nerve guided conduit containing platelet-rich plasma and citicoline for peripheral nerve regeneration: In vitro and in vivo study.

Int J Biol Macromol 2020 May 11;150:380-388. Epub 2020 Feb 11.

Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran; Tissue Engineering and Stem Cells Research Center, Shahroud University of Medical Sciences, Shahroud, Iran. Electronic address:

Peripheral nerve injury (PNI) is a devastating condition that may result in loss of sensory function, motor function, or both. In the present study, we construct an electrospun nerve guide conduit (NGC) based on polycaprolactone (PCL) and gelatin filled with citicoline bearing platelet-rich plasma (PRP) gel as a treatment for PNI. The NGCs fabricated from PCL/Gel polymeric blend using the electrospinning technique. The characterizations demonstrated that the fabricated nanofibers were straight with the diameter of 708 ± 476 nm, the water contact angle of 78.30 ± 2.52°, the weight loss of 41.60 ± 6.94% during 60 days, the tensile strength of 5.31 ± 0.97 MPa, and the young's modulus of 3.47 ± 0.10 GPa. The in vitro studies revealed that the PCL/Gel/PRP/Citi NGC was biocompatible and hemocompatible. The in vivo studies conducted on sciatic nerve injury in rats showed that the implantation of PCL/Gel/PRP/Citi NGC induced regeneration of nerve tissue, demonstrated with histopathological assessments. Moreover, the sciatic function index (SFI) value of -30.3 ± 3.5 and hot plate latency time of 6.10 ± 1.10 s revealed that the PCL/Gel/PRP/Citi NGCs recovered motor and sensory functions. Our findings implied that the fabricated NGC exhibited promising physicochemical and biological activates favorable for PNI treatment.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.02.102DOI Listing
May 2020

A novel polycaprolactone/carbon nanofiber composite as a conductive neural guidance channel: an in vitro and in vivo study.

Prog Biomater 2019 Dec 12;8(4):239-248. Epub 2019 Dec 12.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

The current study aimed to investigate the potential of carbon nanofibers to promote peripheral nerve regeneration. The carbon nanofiber-imbedded scaffolds were produced from polycaprolactone and carbon nanofibers using thermally induced phase separation method. Electrospinning technique was utilized to fabricate polycaprolactone/collagen nanofibrous sheets. The incorporation of carbon nanofibers into polycaprolactone's matrix significantly reduced its electrical resistance from 4.3 × 10 ± 0.34 × 10 Ω to 8.7 × 10 ± 1.2 × 10 Ω. Further in vitro studies showed that polycaprolactone/carbon nanofiber scaffolds had the porosity of 82.9 ± 3.7% and degradation rate of 1.84 ± 0.37% after 30 days and 3.58 ± 0.39% after 60 days. The fabricated scaffolds were favorable for PC-12 cells attachment and proliferation. Neural guidance channels were produced from the polycaprolactone/carbon nanofiber composites using water jet cutter machine then incorporated with PCL/collagen nanofibrous sheets. The composites were implanted into severed rat sciatic nerve. After 12 weeks, the results of histopathological examinations and functional analysis proved that conductive conduit out-performed the non-conductive type and induced no toxicity or immunogenic reactions, suggesting its potential applicability to treat peripheral nerve damage in the clinic.
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http://dx.doi.org/10.1007/s40204-019-00121-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930318PMC
December 2019

Sciatic nerve regeneration by using collagen type I hydrogel containing naringin.

J Mater Sci Mater Med 2019 Sep 11;30(9):107. Epub 2019 Sep 11.

Department of Physiology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

In the present study, collagen hydrogel containing naringin was fabricated, characterized and used as the scaffold for peripheral nerve damage treatment. The collagen was dissolved in acetic acid, naringin added to the collagen solution, and cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide powder (EDC; 0.10 mM) to form the hydrogel. The microstructure, swelling behavior, biodegradation, and cyto/hemocompatibility of the fabricated hydrogels were assessed. Finally, the healing efficacy of the prepared collagen hydrogel loaded with naringin on the sciatic nerve crush injury was assessed in the animal model. The characterization results showed that the fabricated hydrogels have a porous structure containing interconnected pores with the average pore size of 90 µm. The degradation results demonstrated that about 70% of the primary weight of the naringin loaded hydrogel had been lost after 4 weeks of storage in PBS. The in vitro study showed that the proliferation of Schwann cells on the collagen/naringin hydrogel was higher than the control group (tissue culture plate) at both 48 and 72 h after cell seeding and even significantly higher than pure collagen 72 h after cell seeding (*p < 0.005, **p < 0.001). The animal study implied that the sciatic functional index reached to -22.13 ± 3.00 at the end of 60th days post-implantation which was statistically significant (p < 0.05) compared with the negative control (injury without the treatment) (-82.60 ± 1.06), and the pure collagen hydrogel (-59.80 ± 3.20) groups. The hot plate latency test, the compound muscle action potential, and wet weight-loss of the gastrocnemius muscle evaluation confirmed the positive effect of the prepared hydrogels on the healing process of the induced nerve injury. In the final, the histopathologic examinations depicted that the collagen/naringin hydrogel group reduced all the histological changes induced from the nerve injury and showed more resemblance to the normal sciatic nerve, with well-arranged fibers and intact myelin sheath. The overall results implied that the prepared collagen/naringin hydrogel can be utilized as a sophisticated alternative to healing peripheral nerve damages.
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http://dx.doi.org/10.1007/s10856-019-6309-8DOI Listing
September 2019

A collagen-based hydrogel containing tacrolimus for bone tissue engineering.

Drug Deliv Transl Res 2020 02;10(1):108-121

Faculty of Dentistry, Shahed University of Medical Sciences, Tehran, Iran.

Bone tissue engineering aims to develop bone graft structure that can heal bone defects without using autografts or allografts. The current study was conducted to promote bone regeneration using a collagen type I hydrogel containing tacrolimus. For this purpose, different amounts of tacrolimus (10 μg/ml, 100 μg/ml, and 1000 μg/ml) were loaded into the hydrogel. The resulting drug-loaded hydrogels were characterized for their porosity, swelling capacity, weight loss, drug release, blood compatibility, and cell proliferation (MTT). For functional analysis, the developed hydrogel surrounded by a film made of gelatin and polycaprolactone (PCL) was administrated in the calvarias defect of Wistar rats. The results indicated that the hydrogel has a porosity of 89.2 ± 12.5% and an appropriate swelling, drug release, and blood compatibility behavior. The in vitro results indicated that the collagen hydrogel containing 1000 μg tacrolimus was adequate in terms of cell proliferation. Finally, in vivo studies provided some evidence of the potential of the developed hydrogel for bone healing.
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http://dx.doi.org/10.1007/s13346-019-00666-7DOI Listing
February 2020

Nesfatin-1 protects PC12 cells against high glucose-induced cytotoxicity via inhibiting oxidative stress, autophagy and apoptosis.

Neurotoxicology 2019 09 16;74:196-202. Epub 2019 Jul 16.

School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. Electronic address:

Objective: Diabetic neuropathy (DN) is the most common complication of diabetes mellitus. It is thought that neuronal cell death which is mainly due to reactive oxygen species (ROS) overproduction in the cells is responsible for most symptoms of this disorder. Nesfatin-1 has identified recently as a novel endogenous neuropeptide which recent studies have shown that it may have a protective effect. Therefore, we postulated that Nesfatin-1 might adequately prevent from high glucose-induced cell injury via inhibition of apoptotic, autophagy, and ROS responses.

Methods: In this study, PC12 cells were pretreated with different concentrations of Nesfatin-1 (1-100 ng/ml) and then co-treated with Nesfatin-1 and glucose (125 mM) for 48 h, and downstream pathways then were evaluated to investigate ROS, apoptosis, and autophagy.

Results: Results of this study showed that Nesfatin-1 can not only inhibit from intracellular ROS overproduction-induced by high glucose in PC12 cells (p < 0.0001) but also reduce the apoptotic cell death in PC12 cells following high glucose exposure by increasing cell viability and reducing apoptotic rates (p < 0.05). Furthermore, Nesfatin-1 decreased the LC3-II levels by western blotting (p < 0.0001), which showed a reduction in autophagy.

Conclusion: These results support the idea that Nasfatin-1can protect PC12 cells against high glucose-induced cell injury by inhibition of apoptosis, autophagy and ROS production and can be considered as a potential drug for treatment of diabetic neuropathy.
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http://dx.doi.org/10.1016/j.neuro.2019.07.001DOI Listing
September 2019

Will Nanotechnology Bring New Hope for Stem Cell Therapy?

Cells Tissues Organs 2018 9;206(4-5):229-241. Epub 2019 Jul 9.

Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

The potential of stem cell therapy has been shown in preclinical trials for the treatment of damage and replacement of organs and degenerative diseases. After many years of research, its clinical application is limited. Currently there is not a single stem cell therapy product or procedure. Nanotechnology is an emerging field in medicine and has huge potential due to its unique characteristics such as its size, surface effects, tunnel effects, and quantum size effect. The importance of application of nanotechnology in stem cell technology and cell-based therapies has been recognized. In particular, the effects of nanotopography on stem cell differentiation, proliferation, and adhesion have become an area of intense research in tissue engineering and regenerative medicine. Despite the many opportunities that nanotechnology can create to change the fate of stem cell technology and cell therapies, it poses several risks since some nanomaterials are cytotoxic and can affect the differentiation program of stem cells and their viability. Here we review some of the advances and the prospects of nanotechnology in stem cell research and cell-based therapies and discuss the issues, obstacles, applications, and approaches with the aim of opening new avenues for further research.
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http://dx.doi.org/10.1159/000500517DOI Listing
July 2019

Design and characterization of biodegradable multi layered electrospun nanofibers for corneal tissue engineering applications.

J Biomed Mater Res A 2019 10 17;107(10):2340-2349. Epub 2019 Jun 17.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran.

Tissue engineering is one of the most promising areas for treatment of various ophthalmic diseases particularly for patients who suffer from limbal stem cell deficiency and this is due to the lack of existence of appropriate matrix for stem cell regeneration. The aim of this research project is to design and fabricate triple layered electrospun nanofibers as a suitable corneal tissue engineering scaffold and the objective is to investigate and perform various in vitro tests to find the most optimum and suitable scaffold for this purpose. Electrospun scaffolds were prepared in three layers. Poly(d, l-lactide-co-glycolide; PLGA, 50:50) nanofibers were electrospun as outer and inner layers of the scaffold and aligned type I collagen nanofibers were electrospun in the middle layer. Furthermore, the scaffolds were cross-linked by 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide hydrochloride and glutaraldehyde. Structural, physical, and mechanical properties of scaffolds were investigated by using N adsorption/desorption isotherms, Fourier transform infrared spectroscopy, contact angle measurement, tensile test, degradation, shrinkage analysis, and scanning electron microscopy (SEM). In addition, capability to support cell attachment and viability were characterized by SEM, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and 4',6-diamidino-2-phenylindole staining. According to the result of Brunauer-Emmett-Teller analysis, specific surface area of electrospun scaffold was about 23.7 m g . Tensile tests on cross-linked scaffolds represented more suitable hydrophilicity and tensile behavior. In addition, degradation rate analysis indicated that noncross-linked scaffolds degraded faster than cross-linked one and cross-linking led to controlled shrinkage in the scaffold. The SEM analysis depicted nano-sized fibers in good shape. Also, the in vitro study represented an improved cell attachment and proliferation in the presence of human endometrial stem cells for both cross-linked and noncross-linked samples. The current study suggests the possibility of producing an appropriate substrate for successful cornea tissue engineering with a novel design.
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http://dx.doi.org/10.1002/jbm.a.36742DOI Listing
October 2019

Fabrication of Poly(L-Lactic Acid)/Chitosan Scaffolds by Solid-Liquid Phase Separation Method for Nerve Tissue Engineering: An In Vitro Study on Human Neuroblasts.

J Craniofac Surg 2019 May/Jun;30(3):784-789

Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences.

Polymeric scaffolds that support neural cell behaviors are attracting more attention. In the present study, solid-liquid phase separation technique is used to fabricate scaffolds made of poly(L-lactic acid) (PLLA) and chitosan (CS) blends to mimic both cellular microenvironment and anatomical structure of nerve tissue. The fabricated scaffolds favor characteristics of both natural and synthetic polymers. Different tests and assays including physical and mechanical ones (in vitro degradation rate, free radical release, hydrophilicity, and porosity measurements, microstructure observation, and mechanical tests) and cellular assays (cell attachment measurement and viability assessment) suggest that blend scaffolds prepared with this method support nerve cells for tissue engineering applications adequately and even better than scaffolds prepared with the same method but from pure PLLA or CS.
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http://dx.doi.org/10.1097/SCS.0000000000005398DOI Listing
July 2019

Alginate/chitosan hydrogel containing olfactory ectomesenchymal stem cells for sciatic nerve tissue engineering.

J Cell Physiol 2019 Jan 31. Epub 2019 Jan 31.

Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Regeneration and functional recovery after peripheral nerve damage still remain a significant clinical problem. In this study, alginate/chitosan (alg/chit) hydrogel was used for the transplantation of olfactory ectomesenchymal stem cells (OE-MSCs) to promote peripheral nerve regeneration. The OE-MSCs were isolated from olfactory mucosa biopsies and evaluated by different cell surface markers and differentiation capacity. After creating sciatic nerve injury in a rat model, OE-MSCs were transplanted to the injured area with alg/chit hydrogel which was prepared and well-characterized. The prepared hydrogel had the porosity of 91.3 ± 1.27%, the swelling ratio of 379% after 240 min, weight loss percentages of 80 ± 5.56% after 14 days, and good blood compatibility. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4',6-diamidino-2-phenylindole, and LIVE/DEAD staining were done to assay the behavior of OE-MSCs on alg/chit hydrogel and the results confirmed that the hydrogel can provide a suitable substrate for cell survival. For functional analysis, alg/chit hydrogel with and without OE- MSCs was injected into a 3-mm sciatic nerve defect of Wistar rats. The results of the sciatic functional index, hot plate latency, electrophysiological assessment, weight-loss percentage of wet gastrocnemius muscle, and histopathological examination using hematoxylin-eosin and Luxol fast blue staining showed that utilizing alg/chit hydrogel with OE-MSCs to the sciatic nerve defect enhance regeneration compared to the control group and hydrogel without cells.
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http://dx.doi.org/10.1002/jcp.28183DOI Listing
January 2019

Extracellular micro/nanovesicles rescue kidney from ischemia-reperfusion injury.

J Cell Physiol 2019 08 4;234(8):12290-12300. Epub 2019 Jan 4.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Acute renal failure (ARF) is a clinical challenge that is highly resistant to treatment, and its high rate of mortality is alarming. Ischemia-reperfusion injury (IRI) is the most common cause of ARF. Especially IRI is implicated in kidney transplantation and can determine graft survival. Although the exact pathophysiology of renal IRI is unknown, the role of inflammatory responses has been elucidated. Because mesenchymal stromal cells (MSCs) have strong immunomodulatory properties, they are under extensive investigation as a therapeutic modality for renal IRI. Extracellular vesicles (EVs) play an integral role in cell-to-cell communication. Because the regenerative potential of the MSCs can be recapitulated by their EVs, the therapeutic appeal of MSC-derived EVs has dramatically increased in the past decade. Higher safety profile and ease of preservation without losing function are other advantages of EVs compared with their producing cells. In the current review, the preliminary results and potential of MSC-derived EVs to alleviate kidney IRI are summarized. We might be heading toward a cell-free approach to treat renal IRI.
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http://dx.doi.org/10.1002/jcp.27998DOI Listing
August 2019

Promotion of excisional wound repair by a menstrual blood-derived stem cell-seeded decellularized human amniotic membrane.

Biomed Eng Lett 2018 Nov 11;8(4):393-398. Epub 2018 Sep 11.

4Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

This is the first study demonstrating the efficacy of menstrual blood-derived stem cell (MenSC) transplantation via decellularized human amniotic membrane (DAM), for the promotion of skin excisional wound repair. The DAM was seeded with MenSCs at the density of 3 × 10 cells/cm and implanted onto a rat's 1.50 × 1.50 cm full-thickness excisional wound defect. The results of wound closure and histopathological examinations demonstrated that the MenSC-seeded DAM could significantly improve the wound healing compared with DAM-treatment. All in all, our data indicated that the MenSCs can be a potential source for cell-based therapies to regenerate skin injuries.
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http://dx.doi.org/10.1007/s13534-018-0084-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209087PMC
November 2018

Unrestricted Somatic Stem Cells Loaded in Nanofibrous Conduit as Potential Candidate for Sciatic Nerve Regeneration.

J Mol Neurosci 2019 Jan 27;67(1):48-61. Epub 2018 Nov 27.

Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Motor and sensory recovery following critical size peripheral nerve defects is often incomplete. Although nerve grafting has been proposed as the gold standard, it is associated with several disadvantages. Here we report a novel approach to peripheral nerve repair using Human Unrestricted Somatic Stem Cells (USSC) delivered through an electrospun neural guidance conduit. Conduits were produced from PCL and gelatin blend. Several in vitro methods were utilized to investigate the conduit's physicochemical and biological characteristics. Nerve regeneration was studied across a 10-mm sciatic nerve gap in Wistar rats. For functional analysis, the conduits were seeded with 3 × 10 USSCs and implanted into a 10-mm sciatic nerve defect. After 14 weeks, the results of functional recovery analysis and histopathological examinations showed that animals implanted with USSC containing conduits exhibited improved functional and histopathological recovery which was more close to the autograft group compared to other groups. Our results support the potential applicability of USSCs to treat peripheral nerve injury in the clinic.
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http://dx.doi.org/10.1007/s12031-018-1209-9DOI Listing
January 2019

Fabrication and characterization of collagen-hydroxyapatite-based composite scaffolds containing doxycycline via freeze-casting method for bone tissue engineering.

J Biomater Appl 2018 10;33(4):501-513

1 Faculty of dentistry, Shahed University, Tehran, Iran.

In this study, hydroxyapatite nanoparticles containing 10% doxycycline, a structural isomer of tetracycline, was prepared by the co-precipitation method. It was added to collagen solution for the preparation of the scaffold with freeze-casting method in order to develop a composite scaffold with both antibacterial and osteoinductive properties for repairing bone defects. The scaffolds were evaluated regarding their morphology, porosity, degradation and cellular response. The scaffolds for further investigation were added in a rat calvaria defect model. The study showed that after eight weeks, the bone formation was relatively higher in the collagen/nano-hydroxyapatite/doxycycline group with completely filled defect when compared with other groups. Histopathological evaluation showed that the defect in the collagen/nano-hydroxyapatite/doxycycline group was fully replaced by the new bone and connective tissue. Our results provide evidence supporting the possible applicability of doxycycline-containing scaffolds for successful bone regeneration.
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http://dx.doi.org/10.1177/0885328218805229DOI Listing
October 2018

In vitro and in vivo investigation of PLA/PCL scaffold coated with metformin-loaded gelatin nanocarriers in regeneration of critical-sized bone defects.

Nanomedicine 2018 10 28;14(7):2061-2073. Epub 2018 Jun 28.

Department of Radiology, School of Medicine, AJA University of Medical Science, Tehran, Iran. Electronic address:

Large bone defects constitute a major challenge in bone tissue engineering and usually fail to heal due to the incomplete differentiation of recruited mesenchymal stem cells (MSCs) into osteogenic precursor cells. As previously proposed, metformin (MET) induces differentiation of MSCs into osteoblastic lineages in vitro. We fabricated a Poly (lactic acid) and Polycaprolactone (PLA/PCL) scaffold to deliver metformin loaded gelatin nanocarriers (MET/GNs) to critical-sized calvarial bone defects in a rat model. The scaffolds were evaluated regarding their morphology, porosity, contact angle, degradation rate, blood compatibility, biomechanical, cell viability and their osteogenic differentiation. In animal study, the defects were filled with autograft, scaffolds and a group was left empty. qRT-PCR analyses showed the expression level of osteogenic and angiogenic markers considerably increased in MET/GNs-PLA/PCL. The in vivo results showed that MET/GNs-PLA/PCL improved bone ingrowth, angiogenesis and defect reconstruction. Our results represent the applicability of MET/GNs-PLA/PCL for successful bone regeneration.
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http://dx.doi.org/10.1016/j.nano.2018.06.007DOI Listing
October 2018

Mechanical, material, and biological study of a PCL/bioactive glass bone scaffold: Importance of viscoelasticity.

Mater Sci Eng C Mater Biol Appl 2018 Sep 26;90:280-288. Epub 2018 Apr 26.

Department of Oral Pathology and Maxillofacial, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Microsphere sintering method was used to fabricate bone tissue engineering scaffolds made of polycaprolactone (PCL)/bioactive glass 58S5Z (58S modified with 5 wt% Zinc). First, the effect of PCL/58S5Z ratio on the mechanical properties (elastic modulus and yield strength) was investigated. It was found that samples with 5 wt% 58S5Z (named 5%BG) had the highest elastic modulus and yield strength among all samples, i.e., with 0, 5, 10, and 20 wt% bioactive glass. Then, considering the importance of viscoelastic properties of bone, the viscoelastic behavior of 0%BG (scaffold with only PCL) and 5%BG samples was determined by performing compressive stress relaxation test and subsequently a Generalized Maxwell model was developed. Findings indicated a similar amount and pattern of predicted storage and loss moduli and loss factor of the composite scaffolds to those of the bone. In the next step, the analysis of biological behavior of the scaffolds using MTT assay, DAPI and Alizarin red staining demonstrated that 5%BG scaffolds had higher in vitro cell viability and bone formation compared to 0%BG ones. Furthermore, in vivo study employing H&E staining of the scaffolds implanted in rats' calvarium for 50 days, confirmed the earlier findings and showed that 5%BG-filled defects had higher and more uniform bone formation compared to both 0%BG-filled and empty defects.
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http://dx.doi.org/10.1016/j.msec.2018.04.080DOI Listing
September 2018

In vitro and in vivo study of PCL/COLL wound dressing loaded with insulin-chitosan nanoparticles on cutaneous wound healing in rats model.

Int J Biol Macromol 2018 Oct 25;117:601-609. Epub 2018 May 25.

Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

In the current study, insulin delivering chitosan nanoparticles were coated onto the electrospun poly (ε-caprolactone) (PCL)/Collagen (COLL) to produce a potential wound care material. Electrospun matrices were fabricated from PCL/COLL (1:1 (w/w)) solution. The insulin-loaded chitosan nanoparticles were produced by ionic gelation process and then attached onto the yarns. The dressings were investigated regarding their surface wettability, microstructure, the capacity to absorb water, water vapour permeability, mechanical properties, blood compatibility, microbial penetration, and cellular behavior. Full-thickness excisional wound model was used to assess the in vivo healing capacity of the dressings. Our data showed that after 14 days the wounds covered with PCL/COLL/Cs-Ins wound dressing could reach to nearly full wound closure compared with the sterile gauze which exhibited nearly 45% of wound size reduction. Our results suggest that fabricated scaffolds can be potentially applied in clinical practice for wound treatment.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.05.184DOI Listing
October 2018

In vitro and in vivo evaluation of electrospun cellulose acetate/gelatin/hydroxyapatite nanocomposite mats for wound dressing applications.

Artif Cells Nanomed Biotechnol 2018 19;46(sup1):964-974. Epub 2018 Feb 19.

g Department of Anatomical Sciences, School of Medical Sciences , Tarbiat Modares University , Tehran , Iran.

The present study aimed to evaluate the efficacy of cellulose acetate/gelatin/nanohydroxyapatite (CA/Gel/nHA) nanocomposite mats as the wound dressing. The dressings were prepared with electrospinning of CA/Gel solutions containing 12.5, 25 and 50 mg nHA. The dressings were evaluated regarding their water uptake capacity, morphology, tensile strength, water vapour transmission rate, wettability and cellular response with L929 cell line. The results showed that the concentration of nHA had a direct correlation with porosity, water contact angle, water uptake, water vapor transmission rate and proliferation. In vivo studies showed that all dressings had higher wound closure percent than the sterile gauze, as the control. The highest wound closure value was achieved in the CA/Gel +25 mg nHA group, which showed 93.5 ± 1.6%. The histological and the histomorphometric examinations of the wounds revealed that the CA/Gel +25 mg nHA dressing had the greatest collagen synthesis, re-epithelialization, neovascularization and also the best cosmetic appearance. Based on our finding, it could be concluded the applicability of electrospun nanofibrous CA/Gel/nHA dressings for successful wound treatment.
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http://dx.doi.org/10.1080/21691401.2018.1439842DOI Listing
April 2019

Enhanced sciatic nerve regeneration by human endometrial stem cells in an electrospun poly (ε-caprolactone)/collagen/NBG nerve conduit in rat.

Artif Cells Nanomed Biotechnol 2018 Dec 8;46(8):1731-1743. Epub 2017 Nov 8.

a Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine , Tehran University of Medical Sciences , Tehran , Iran.

In recent years, for neurodegenerative diseases therapy, research has focused on the stem cells therapy. Due to promising findings in stem cell therapy, there are various sources of stem cells for transplantation in human. The aim of this study was to evaluate sciatic nerve regeneration in the rat after nerve transaction followed by human endometrial stem cells (hEnSCs) treatment into poly (e-caprolactone)/collagen/nanobioglass (PCL/collagen/NBG) nanofibrous conduits. After treatment of animals, the performance in motor and sensory tests, showed significant improvement in rats treated with hEnSCs as an autograft. H&E images provided from cross-sectional and, longitudinal-sections of the harvested regenerative nerve as well as immunohistochemistry results indicated that regenerative nerve fibres had been formed and accompanied with new blood vessels in the conduit cell group. Due to the advantage of high surface area for cell attachment, it is reported that this electrospun nerve conduit could find more application in cell therapy for nerve regeneration in future, to further improve the functional regeneration outcome, especially for longer nerve defect restoration. In conclusion, our results suggest that the PCL/collagen/NBG nanofibrous conduit filled with hEnSCs is a suitable strategy to improve nerve regeneration after a nerve transaction in rat.
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http://dx.doi.org/10.1080/21691401.2017.1391823DOI Listing
December 2018

Can gray values derived from CT and cone beam CT estimate new bone formation? An in vivo study.

Oral Maxillofac Surg 2018 Mar 31;22(1):13-20. Epub 2017 Oct 31.

Department of Oral Radiology, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objectives: The main aim of this study was to investigate whether Hounsfield unit derived from computed tomography (HU/CT) and gray value derived from cone beam computed tomography (GV/CBCT) can predict the amount of new bone formation (NBF) in the defects after bone reconstruction surgeries.

Materials And Methods: Thirty calvaria defects created in 5 rabbits and grafted with both radiolucent (RL, n = 15) and radiopaque (RO, n = 15) bone substitute materials were evaluated, 8 weeks postoperatively. The defects were scanned by multislice computed tomography (Somatom®, Siemens Healthineers, Erlangen, Germany) and CBCT (NewTom VG®, Qualitative Radiology, Verona, Italy). MSCT and CBCT scans were matched to select the exact region of interest (ROI, diameter = 5 mm and height = 1 mm). HU/CT and GV/CBCT of each ROI were obtained. Mean amount of NBF in whole of the defects was measured using serial histomorphometric assessment. We investigated the correlation between HU/CT and GV/CBCT, HU/CT and NBF, and GV/CBCT and NBF generally, and separately among the RL or RO grafted defects, by linear generalized estimating equation modeling. Receiver operation characteristic analysis was performed to check the accuracy of HU/CT and GV/CBCT in diagnosing more than 10% NBF in the samples.

Results: There were linear correlations between HU/CT and GV/CBCT, HU/CT and NBF, and GV/CBCT and NBF.

Conclusion: According to the results, both HU/CT and GV/CBCT can be considered as fairly good predictors for assessment of the amount of NBF following bone reconstruction surgeries.
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http://dx.doi.org/10.1007/s10006-017-0657-7DOI Listing
March 2018

Sciatic nerve regeneration by transplantation of menstrual blood-derived stem cells.

Mol Biol Rep 2017 Oct 4;44(5):407-412. Epub 2017 Oct 4.

Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, 3613773955, Iran.

This is the first study demonstrating the efficacy of menstrual blood-derived stem cell (MenSC) transplantation via a neural guidance conduit, for peripheral nerve regeneration. The synthesized poly (ɛ-caprolactone)/Gelatin conduit, filled with collagen type I and seeded with 3 × 10 MenSCs, was implanted into a rat's 10 mm sciatic nerve defect. The results of hot plate latency, sciatic functional index and weight-loss percentage of wet gastrocnemius muscle demonstrated that the MenSC transplantation had comparable nerve regeneration outcome to autograft, as the gold standard of nerve bridging. The transplantation of MenSCs via a synthetic conduit could ameliorate the functional recovery of sciatic nerve-injured rats which make them a potential candidate for cell therapy of peripheral nervous system disorders.
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http://dx.doi.org/10.1007/s11033-017-4124-1DOI Listing
October 2017