Publications by authors named "Alexander M Seifalian"

315 Publications

The risk of pancreatic adenocarcinoma following SARS-CoV family infection.

Sci Rep 2021 06 21;11(1):12948. Epub 2021 Jun 21.

Nanotechnology and Regenerative Medicine Commercialization Centre (Ltd), London BioScience Innovation Centre, London, UK.

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was "double-stranded RNA binding" and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.
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http://dx.doi.org/10.1038/s41598-021-92068-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217230PMC
June 2021

Vitamin E at a high dose as an anti-ferroptosis drug and not just a supplement for COVID-19 treatment.

Biotechnol Appl Biochem 2021 May 2. Epub 2021 May 2.

Nanotechnology and Regenerative Medicine Commercialization Centre (NanoRegMed Ltd), London BioScience Innovation Centre, London, UK.

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http://dx.doi.org/10.1002/bab.2176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239546PMC
May 2021

Graphene Oxide: Opportunities and Challenges in Biomedicine.

Nanomaterials (Basel) 2021 Apr 22;11(5). Epub 2021 Apr 22.

Nanotechnology and Regenerative Medicine Commercialisation Centre (NanoRegMed Ltd.), London BioScience Innovation Centre, London NW1 0NH, UK.

Desirable carbon allotropes such as graphene oxide (GO) have entered the field with several biomedical applications, owing to their exceptional physicochemical and biological features, including extreme strength, found to be 200 times stronger than steel; remarkable light weight; large surface-to-volume ratio; chemical stability; unparalleled thermal and electrical conductivity; and enhanced cell adhesion, proliferation, and differentiation properties. The presence of functional groups on graphene oxide (GO) enhances further interactions with other molecules. Therefore, recent studies have focused on GO-based materials (GOBMs) rather than graphene. The aim of this research was to highlight the physicochemical and biological properties of GOBMs, especially their significance to biomedical applications. The latest studies of GOBMs in biomedical applications are critically reviewed, and in vitro and preclinical studies are assessed. Furthermore, the challenges likely to be faced and prospective future potential are addressed. GOBMs, a high potential emerging material, will dominate the materials of choice in the repair and development of human organs and medical devices. There is already great interest among academics as well as in pharmaceutical and biomedical industries.
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http://dx.doi.org/10.3390/nano11051083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143506PMC
April 2021

Preparation of internally-crosslinked alginate microspheres: Optimization of process parameters and study of pH-responsive behaviors.

Carbohydr Polym 2021 Mar 5;255:117336. Epub 2020 Nov 5.

Nanotechnology and Regenerative Medicine Centre (Ltd), London BioScience Innovation Centre, London, United Kingdom.

In this study, the effects of various parameters of the water-in-oil emulsification/internal gelation method on the properties of calcium-alginate microparticles were evaluated and optimized. Results showed that the spherical-shaped microparticles with the highest circularity and high production yield can be produced by alginate solution with a concentration of 2 wt.%, calcium carbonate/alginate ratio of 10/1 (w/w), water/oil volume ratio of 1/20, emulsifier concentration of 5 % (v/v), and emulsification speed of 1000 rpm. Two model drugs including simvastatin lactone and simvastatin β-hydroxyacid were loaded into the microspheres with promising encapsulation efficiencies of 73 % and 69 %, respectively. The microspheres showed a pH-responsive swelling behavior with a percentage of 10.60 %, 352.65 %, 690.03 %, and 1211.46 % at the pH values of 2.0, 4.5, 7.4, and 8.5, respectively. The microspheres showed an increasing trend of release rate in direct proportion to pH. These findings would be useful for therapeutic applications which need pH-responsive drug carriers.
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http://dx.doi.org/10.1016/j.carbpol.2020.117336DOI Listing
March 2021

Gelatin Electrospun Mat as a Potential Co-culture System for Production of Sperm Cells from Embryonic Stem Cells.

ACS Biomater Sci Eng 2020 10 18;6(10):5823-5832. Epub 2020 Sep 18.

Cellular and Molecular Research Centre, Iran University of Medical Sciences, 14496-14535 Tehran, Iran.

Engineering of 3D substrates with maximum similarity to seminiferous tubules would help to produce functional sperm cells from stem cells. Here, we present a 3D electrospun gelatin (EG) substrate seeded with Sertoli cells and determine its potential for guided differentiation of embryonic stem cells (ESCs) toward germline cells. The EG was fabricated by electrospinning, and its morphology under SEM, as well as cytobiocompatibility for Sertoli cells and ESCs, was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and cell attachment assay. Embryoid bodies (EBs) were formed from ESCs and co-cultured with Sertoli cells, induced with BMP4 for 3 and 7 consecutive days to induce the differentiation of EBs toward germline cells. The differentiation was investigated by immunocytochemistry (ICC), flow cytometry, and RT-PCR in four experimental groups of EBs (EBs cultured in gelatin-coated cell culture plates); Scaffold/EB (EBs cultured on EG); ESCs/Ser (EBs and Sertoli cells co-cultured on gelatin-coated cell culture plates without EG); and Scaffold/EB/Ser (EBs and Sertoli cells co-cultured on EG). All experimental groups exhibited a significantly increased MVH (germline-specific marker) and decreased c-KIT (stemness marker) expression when compared with the EB group. ICC and flow cytometry revealed that Scaffold/EB/Ser had the highest level of MVH and the lowest c-KIT expression at both 3 and 7 days postdifferentiation compared with other groups. RT-PCR results showed a significant increase in the germline marker () and a significant decrease in the ESC stemness marker () in Scaffold/EB compared to the EB group. The germline markers , , , , , and were significantly increased in Scaffold/EB/Ser compared to the Scaffold/EB group. Our findings revealed that the EG scaffold can provide an excellent substrate biomimicking the micro/nanostructure of native seminiferous tubules and a platform for Sertoli cell-EB communication required for growth and differentiation of ESCs into germline cells.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00893DOI Listing
October 2020

COVID-19 Vaccines in Clinical Trials and their Mode of Action for Immunity against the Virus.

Curr Pharm Des 2021 ;27(13):1553-1563

Nanotechnology and Regenerative Medicine Commercialization Centre (NanoRegMed Ltd), London BioScience Innovation Centre, London, United Kingdom.

For nearly two decades, coronaviruses have caused many health and economic problems, while no effective commercial vaccine has yet been developed. It is worth mentioning that despite some mutations and recombination in SARS-CoV-2, its genotype is very close to the original strain from Wuhan, China. Therefore, the development of an effective vaccine would be promising. It might be hypothesized that BCG vaccination is performed in high-risk populations before the commercialization of an effective SARS-CoV-2 vaccine. However, the development of an effective vaccine without considering the adverse immune reactions derived from antibody-dependent or cell-based immune enhancement may threaten vaccinated people's lives and long-term side effects must be considered. To this end, targeting of the receptor-binding domain (RBD) in spike and not whole spike, glycolization of FC receptors, PD-1 blockers, CPPs, etc., are promising. Therefore, the subunit vaccines or RNA vaccines that encode the RBP segment of the spike are of interest. To enhance the vaccine efficacy, its co-delivery with an adjuvant has been recommended. Nanoparticles modulate immune response with higher efficiency than the soluble form of antigens and can be functionalized with the positively charged moieties and ligands of targeted cells, such as dendritic cells, to increase cellular uptake of the antigens and their presentation on the surface of immune cells. This research aimed to discuss the COVID-19 vaccines entering the clinical trial and their mode of action effective immunity against the virus and discusses their advantages compared to each other.
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http://dx.doi.org/10.2174/1381612826666201023143956DOI Listing
June 2021

Thermo-responsive chitosan hydrogel for healing of full-thickness wounds infected with XDR bacteria isolated from burn patients: In vitro and in vivo animal model.

Int J Biol Macromol 2020 Dec 1;164:4475-4486. Epub 2020 Sep 1.

Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Treatment of non-healing skin wounds infected with extensively drug-resistant (XDR) bacteria remains as a big challenge. To date, different biomaterials have been applied for treatment of post-wound infections, nevertheless their efficacy for treatment of the wounds infected with XDR isolates has not been determined yet. In this study, the potential of the thermo-responsive chitosan (TCTS) hydrogel for protection of full-thickness wounds XDR bacteria isolated from burn patients was evaluated both in vitro and in vivo in a rat model. Antibacterial activity of the TCTS hydrogel against standard strain and clinical isolates of Acinetobacter baumannii, cytobiocompatibility for Hu02 fibroblast cells, degradation rate and swelling ratio were determined in vitro. MTT assay and disk diffusion test indicated no detectable cytotoxicity and antibacterial activity in vitro, respectively. In vivo study showed significant acceleration of wound healing, re-epithelialization, wound closure, and decreased colony count in the TCTS hydrogel group compared with control. This study suggests TCTS hydrogel as an excellent wound dressing for management of the wounds infected with XDR bacteria, and now promises to proceed with clinical investigations.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.08.239DOI Listing
December 2020

Platelet-rich plasma fibrin glue for treatment of chylothorax following cavopulmonary connections.

Eur J Cardiothorac Surg 2020 12;58(6):1269-1273

Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Objectives: The postoperative persistence of chylothorax is a fatal complication of paediatric cardiac surgery. There is an urgent need for an effective treatment of chylothorax. This study reports the application of allogenic platelet-rich plasma fibrin glue (PRP-FG) as a conservative therapy before reoperation.

Methods: Over a 9-year period, from 2010 to 2019, 27 patients with persistent chylothorax following a cavopulmonary connection, with a mean latency period of 11 days (range 10-15 days), were treated with PRP-FG. These patients were selected because they had not responded positively to initial conservative management plans. The patients were followed up for 9 years.

Results: Twenty-five patients (92%) responded positively to treatment with PRP-FG; 2 patients did not respond to the treatment and died after reoperation. All of the successfully treated patients in follow-up continued to live a healthy life without further complications.

Conclusions: Recalcitrant chylothorax that persists after paediatric cardiac surgery responded positively to treatment with PRP-FG. This technique precluded the need for another operation and significantly decreased the morbidity and mortality rates.
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http://dx.doi.org/10.1093/ejcts/ezaa243DOI Listing
December 2020

A New Nanocomposite Copolymer Based On Functionalised Graphene Oxide for Development of Heart Valves.

Sci Rep 2020 03 24;10(1):5271. Epub 2020 Mar 24.

Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation.

Polymeric heart valves seem to be an attractive alternative to mechanical and biological prostheses as they are more durable, due to the superior properties of novel polymers, and have the biocompatibility and hemodynamics comparable to tissue substitutes. This study reports a comprehensive assessment of a nanocomposite based on the functionalised graphene oxide and poly(carbonate-urea)urethane with the trade name "Hastalex" in comparison with GORE-TEX, a commercial polymer routinely used for cardiovascular medical devices. Experimental data have proved that GORE-TEX has a 2.5-fold (longitudinal direction) and 3.5-fold (transverse direction) lower ultimate tensile strength in comparison with Hastalex (p < 0.05). The contact angles of Hastalex surfaces (85.2 ± 1.1°) significantly (p < 0.05) are lower than those of GORE-TEX (127.1 ± 6.8°). The highest number of viable cells Ea.hy 926 is on the Hastalex surface exceeding 7.5-fold when compared with the GORE-TEX surface (p < 0.001). The platelet deformation index for GORE-TEX is 2-fold higher than that of Hastalex polymer (p < 0.05). Calcium content is greater for GORE-TEX (8.4 mg/g) in comparison with Hastalex (0.55 mg/g). The results of this study have proven that Hastalex meets the main standards required for manufacturing artificial heart valves and has superior mechanical, hemocompatibility and calcific resistance properties in comparison with GORE-TEX.
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http://dx.doi.org/10.1038/s41598-020-62122-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093488PMC
March 2020

Engineered skin graft with stromal vascular fraction cells encapsulated in fibrin-collagen hydrogel: A clinical study for diabetic wound healing.

J Tissue Eng Regen Med 2020 03 17;14(3):424-440. Epub 2020 Jan 17.

Applied Cell Sciences Department, Kashan University of Medical Science, Kashan, Iran.

Despite the abundance of skin substitutes in the worldwide market, major hurdles in developing more complex tissues include the addition of skin appendages and vascular networks as the most important structure. The aim of this research was a clinical feasibility study of a novel prevascularized skin grafts containing the dermal and epidermal layer using the adipose stromal vascular fraction (SVF)-derived endothelial cell population for vascular network regeneration. Herein, we characterized hydrogel with emphasis on biological compatibility and cell proliferation, migration, and vitality. The therapeutic potential of the prevascularized hydrogel transplanted on five human subjects as an intervention group with diabetic wounds was compared with nonvascularized skin grafts as the control on five patients. Wound planimetric and biometric analysis was performed using a Mann-Whitney nonparametric t-test (p ≤ .05). The fibrin-collagen hydrogel was suitable for skin organotypic cell culture. There was a significant (p ≤ .05) increased in skin thickness and density in the vascular beds of the hypodermis measured with skin scanner compared with that in the control group. No significant macroscopic differences were observed between the intervention and control groups (p ≤ .05). In summary, we report for the first time the use of autologous dermal-epidermal skin grafts with intrinsic vascular plexus in a clinical feasibility study. The preliminary data showed that SVF-based full-thickness skin grafts are safe and accelerate the wound healing process. The next stage of the study is a full-scale randomized clinical trial for the treatment of patients with chronic wounds.
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http://dx.doi.org/10.1002/term.3003DOI Listing
March 2020

Skin regenerative medicine advancements in the Islamic Republic of Iran: a concise review.

Regen Med 2019 11 13;14(11):1047-1056. Epub 2019 Nov 13.

Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.

In the last decade, the Islamic Republic of Iran has witnessed significant improvement and growth in the field of interdisciplinary medicine and in its translation to patients, including the field of cell and stem cell therapy. The main aim of this report is to highlight various advances in regenerative medicine for skin and dermatology using stem cell technology, and its translation to clinic in the past two decades, in Iranian academic centers, clinical institutes and hospitals. While there have been numerous positive advances in clinical outcomes reported in Iran, there is no comparative analytical information on these studies. Here we present a historical overview of the progress and key advancements seen in skin regeneration in this country, review the research frameworks, regulatory approach and pathways and offer perspectives for the future.
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http://dx.doi.org/10.2217/rme-2018-0170DOI Listing
November 2019

Argon plasma modification promotes adipose derived stem cells osteogenic and chondrogenic differentiation on nanocomposite polyurethane scaffolds; implications for skeletal tissue engineering.

Mater Sci Eng C Mater Biol Appl 2019 Dec 26;105:110085. Epub 2019 Aug 26.

Stem Cells and Regenerative Medicine Section, UCL Institute of Child Health, University College London, London WC1N 1EH, United Kingdom. Electronic address:

Bone and cartilage craniofacial defects due to trauma or congenital deformities pose a difficult problem for reconstructive surgeons. Human adipose stem cells (ADSCs) can differentiate into bone and cartilage and together with suitable scaffolds could provide a promising system for skeletal tissue engineering. It has been suggested that nanomaterials can direct cell behavior depending on their surface nanotopographies. Thus, this study examined whether by altering a nanoscaffold surface using radiofrequency to excite gases, argon (Ar), nitrogen (N) and oxygen (O) with a single step technique, we could enhance the osteogenic and chondrogenic potential of ADSCs. At 24 h, Ar modification promoted the highest increase in ADSCs adhesion as indicated by upregulation of vinculin and focal adhesion kinase (FAK) expression compared to O and N scaffolds. Furthermore, ADSCs on Ar-modified nanocomposite polymer POSS-PCU scaffolds upregulated expression of bone markers, alkaline phosphatase, collagen I and osteocalcin after 3 weeks. Cartilage markers, aggrecan and collagen II, were also upregulated on Ar-modified scaffolds at the mRNA and protein level. Finally, all plasma treated scaffolds supported tissue ingrowth and angiogenesis after grafting onto the chick chorioallantoic membrane. Ar promoted greater expression of vascular endothelial growth factor and laminin in ovo compared to O and N scaffolds as shown by immunohistochemistry. This study provides an important understanding into which surface chemistries best support the osteogenic and chondrogenic differentiation of ADSCs that could be harnessed for regenerative skeletal applications. Argon surface modification is a simple tool that can promote ADSC skeletal differentiation that is easily amenable to translation into clinical practice.
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http://dx.doi.org/10.1016/j.msec.2019.110085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892254PMC
December 2019

Ultra-low percolation threshold POSS-PCL/graphene electrically conductive polymer: Neural tissue engineering nanocomposites for neurosurgery.

Mater Sci Eng C Mater Biol Appl 2019 Nov 25;104:109915. Epub 2019 Jun 25.

Nanotechnology and Regenerative Medicine Commercialisation Centre (NanoRegMed Ltd.), The London BioScience Innovation Centre, London, UK. Electronic address:

An ultra-low percolation threshold electrically conductive polymer nanocomposite incorporating graphene into a polyhedral oligomeric silsesquioxane polycaprolactone (POSS-PCL/graphene) is described in this paper. Multilayer graphene flakes were homogeneously dispersed into POSS-PCL at 0.08, 0.4, 0.8, 1.6, and 4.0 wt% concentrations. The impedance spectroscopy of 0.08 wt% and higher concentration of graphene in POSS-PCL represented major improvement in conductivity over pristine POSS-PCL. The percolation threshold occurred at 0.08 wt% graphene concentration, and at 4.0 wt% the electrical conductivity exceeded 10 Scm. Furthermore, the chemical, morphological, and mechanical of the POSS-PCL/graphene with various graphene concentrations were investigated. Finally, neural cells cultured on all POSS-PCL/graphene constructs indicated higher metabolic activity and cell proliferation in comparison with pristine POSS-PCL. Herein, we demonstrate a method of developing a neural-compatible and electrically conductive polymer nanocomposite that could potentially function as a neural tissue engineered platform technology for neurological and neurosurgical applications.
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http://dx.doi.org/10.1016/j.msec.2019.109915DOI Listing
November 2019

Emerging roles of exosomal miRNAs in breast cancer drug resistance.

IUBMB Life 2019 11 19;71(11):1672-1684. Epub 2019 Jul 19.

Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Breast cancer (BC), as a heterogeneous disease, is considered as one of the most common malignancies in women worldwide. The resistance of BC cells to therapeutic agents has remained a big challenge in the treatment of BC patients. Some factors such as cytokines, exosomes, and soluble receptors were recognized as crucial agents involved in the development of drug resistance. However, the exact mechanisms underlying the drug resistance is still unknown. There is growing evidence to support the emerging roles of exosomes, especially exosomal miRNAs, in tumor initiation, angiogenesis, proliferation, migration, invasion, metastasis, and drug resistance. Therefore, identification of BC-specific exosomal miRNAs and their underlying mechanisms would be helpful to define sensitivity to therapeutic drugs and establish an appropriate therapeutic strategy. This review focuses mainly on the roles of exosomal miRNAs and their associated mechanisms in the resistance of BC cells to therapeutic agents, as well as critically examines the potential of these macromolecules as a treatment biomarker in BC patients.
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http://dx.doi.org/10.1002/iub.2116DOI Listing
November 2019

Relaxivity and toxicological properties of manganese oxide nanoparticles for MRI applications.

RSC Adv 2019 May 10;6(51):45462-45474. Epub 2016 May 10.

NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (NUS), Singapore.

Manganese oxide nanoparticles (MONs) have received growing attention as alternative MRI contrast agents due to the association of commercial gadolinium-based contrast agents with nephrogenic systemic fibrosis. Since the seminal publication first describing the use of MONs as positive contrast agents, there is an ongoing impetus to develop MONs of higher signal intensity for better diagnostic efficacy. Indeed, various MON-based nanoprobe designs have been proposed, such as the employment of a mesoporous nanomaterial with MONs evenly dispersed within, or the traditional coating of a biocompatible layer onto the surface of MONs to form a core-shell configuration. Recent advances in this field also propose stimuli-responsive MONs that capitalize on an acidic dissolution or reduction to release Mn ions for a multi-fold increase in MRI contrast. However, the potential nanotoxicity of MONs remains a key obstacle to the clinical translation of MON-based contrast agents. Due to the wide variety of functionalities and physicochemical properties of MONs, there is also a lack of consensus on the toxicological properties of MONs. In addition, the relaxivity of MRI contrast agents typically decreases at higher field strength. Hence, it highlights the need to develop MON-based contrast agents with higher relaxivities. In this regard, this article aims to present a thorough review of MONs for MRI applications, with particular emphasis on their relaxivity and toxicological properties. In order to systematically review the current state-of-the-art for the development of MONs for MRI applications, the MON-based contrast agents are categorized based on the structure of the nanomaterial system. Key parameters that influence the nanotoxicity of MONs are also examined while the absorption, distribution, metabolism and excretion of MON are evaluated to discern how long the nanoparticles will be present within the body, as well as to predict the organs or tissues in which they distribute.
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http://dx.doi.org/10.1039/C6RA04421BDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542684PMC
May 2019

Effect of Laser Irradiation on Cell Cycle and Mitosis.

J Lasers Med Sci 2018 17;9(4):249-253. Epub 2018 Sep 17.

Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran.

In this research, low-level helium-neon (He-Ne) laser irradiation effects on monkey kidney cells (Vero cell line) mitosis were studied. The experiment was carried out on a monkey kidney cell line "Vero (CCL-81)". This is a lineage of cells used in cell cultures and can be used for efficacy and media testing. The monolayer cells were formed on coating glass in a spectral cuvette (20×20×30 mm). The samples divided into two groups. The first groups as irradiated monolayer cells were exposed by a He-Ne laser (PolyaronNPO, L'vov, Ukraine) with λ=632.8 nm, max power density (P) = 10 mW/cm2 , generating linearly polarized and the second groups as the control monolayer cells were located in a cuvette protected by a lightproof screen from the first cuvette and also from the laser exposure. Then, changing functional activity of the monolayer cells, due to the radiation influence on some physical factors were measured. The results showed that low-intensity laser irradiation in the range of visible red could make meaningful changes in the cell division process (the mitosis activity). These changes depend on the power density, exposure time, the presence of a magnetic field, and the duration of time after exposure termination. The stimulatory effects on the cell division within the power density of 1-6 mW/(cm2 ) and exposure time in the range of 1-10 minutes was studied. It is demonstrated that the increase in these parameters (power density and exposure time) leads to destructing the cell division process. The results are useful to identify the molecular mechanisms caused by low-intensity laser effects on the biological activities of the cells. Thus, this study helps to optimize medical laser technology as well as achieving information on the therapeutic effects of low-intensity lasers.
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http://dx.doi.org/10.15171/jlms.2018.45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6499552PMC
September 2018

Human Adipose-Derived Stem Cells with Great Therapeutic Potential.

Curr Stem Cell Res Ther 2019 ;14(7):532-548

Nanotechnology and Regenerative Medicine Centre (Ltd), The London Innovation BioScience Centre, London, United Kingdom.

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in regenerative medicine. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. While clinically, adipose-derived stem cells (ADSCs) are one of the most widely used types of stem cells used more than five years in clinically setting. It has many advantages including; yields a high number of ADSCs per volume of tissue, high rate of proliferation, anti-fibrotic, anti-apoptotic, anti-inflammation, immunomodulation, and paracrine mechanisms have been demonstrated in various preclinical studies. It is much easier to harvest compared with bone marrow stem cells. Results of clinical studies have demonstrated the potentials of ADSCs for stem cells therapy for a number of clinical disorders. The aim of this paper was to provide an update on the most recent developments of ADSCs, by highlighting the properties and features of ADSCs, critically discussing its clinical benefit and its clinical trials in treatment and regeneration. This is a multi-billion dollars industry with huge interest to clinician, academia and industries.
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http://dx.doi.org/10.2174/1574888X14666190411121528DOI Listing
April 2020

Evaluation of Sterilisation Techniques for Regenerative Medicine Scaffolds Fabricated with Polyurethane Nonbiodegradable and Bioabsorbable Nanocomposite Materials.

Int J Biomater 2018 3;2018:6565783. Epub 2018 Oct 3.

Director/Professor Nanotechnology & Regenerative Medicine, NanoRegMed Ltd., The London BioScience Innovation Centre, London NW1 0NH, UK.

An effective sterilisation technique that maintains structure integrity, mechanical properties, and biocompatibility is essential for the translation of new biomaterials to the clinical setting. We aimed to establish an effective sterilisation technique for a biodegradable (POSS-PCL) and nonbiodegradable (POSS-PCU) nanocomposite scaffold that maintains stem cell biocompatibility. Scaffolds were sterilised using 70% ethanol, ultraviolet radiation, bleach, antibiotic/antimycotic, ethylene oxide, gamma irradiation, argon plasma, or autoclaving. Samples were immersed in tryptone soya broth and thioglycollate medium and inspected for signs of microbial growth. Scaffold surface and mechanical and molecular weight properties were investigated. AlamarBlue viability assay of adipose derived stem cells (ADSC) seeded on scaffolds was performed to investigate metabolic activity. Confocal imaging of rhodamine phalloidin and DAPI stained ADSCs was performed to evaluate morphology. Ethylene oxide, gamma irradiation, argon plasma, autoclaving, 70% ethanol, and bleach were effective in sterilising the scaffolds. Autoclaving, gamma irradiation, and ethylene oxide led to a significant change in the molecular weight distribution of POSS-PCL and gamma irradiation and ethylene oxide to that of POSS-PCU (p<0.05). UV, ethanol, gamma irradiation, and ethylene oxide caused significant changes in the mechanical properties of POSS-PCL (p<0.05). Argon was associated with significantly higher surface wettability and ADSC metabolic activity (p<0.05). In this study, argon plasma was an effective sterilisation technique for both nonbiodegradable and biodegradable nanocomposite scaffolds. Argon plasma should be further investigated as a potential sterilisation technique for medical devices.
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http://dx.doi.org/10.1155/2018/6565783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192142PMC
October 2018

In vivo toxicological evaluation of graphene oxide nanoplatelets for clinical application.

Int J Nanomedicine 2018 22;13:4757-4769. Epub 2018 Aug 22.

NanoRegMed ltd, Nanotechnology and Regenerative Medicine Commercialization Centre, The London Bioscience Innovation Centre, London, UK.

Background: Graphene is considered as a wonder material; it is the strongest material on the planet, super-elastic, and conductive. Its application in biomedicine is huge, with a multibillion-dollar industry, and will revolutionize the diagnostic and treatment of diseases. However, its safety and potential toxicity is the main challenge.

Methods: This study assessed the potential toxicity of graphene oxide nanoplatelets (GONs) in an in vivo animal model using systemic, hematological, biochemical, and histopathological examinations. Normal saline (control group) or GONs (3-6 layers, lateral dimension=5-10 μm, and thickness=0.8-2 nm) at dose rate of 50, 150, or 500 mg/kg were intraperitoneally injected into adult male Wistar rats (n=5) every 48 hours during 1 week to receive each animal a total of four doses. The animals were allowed 2 weeks to recover after the last dosing. Then, animals were killed and the blood was collected for hematological and biochemical analysis. The organs including the liver, kidney, spleen, lung, intestine, brain, and heart were harvested for histopathological evaluations.

Results: The results showed GONs prevented body weight gain in animals after 21 days, treated at 500 mg/kg, but not in the animals treated at 150 or 50 mg/kg GONs. The biochemical analysis showed a significant increase in total bilirubin, with a significant decrease in triglycerides and high-density lipoprotein in animals treated at 500 mg/kg. Nonetheless, other hematological and biochemical parameters remained statistically insignificant in all GONs treated animals. The most common histopathological findings in the visceral organs were granulomatous reaction with giant cell formation and accumulation of GONs in capsular regions. Also, small foci of neuronal degeneration and necrosis were the most outstanding findings in the brain, including the cerebellum.

Conclusion: In conclusion, this study shows that GONs without functionalization are toxic. The future study is a comparison of the functionalized with non-functionalized GONs.
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http://dx.doi.org/10.2147/IJN.S168731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110298PMC
October 2018

Comparison of the antibacterial effects of a short cationic peptide and 1% silver bioactive glass against extensively drug-resistant bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii, isolated from burn patients.

Amino Acids 2018 Nov 25;50(11):1617-1628. Epub 2018 Aug 25.

Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran.

We have already established that a short cationic peptide (CM11) has high antimicrobial activity against a number of bacterial pathogens. Considering the untreatable problem of burn infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii, this study evaluated and compared antibacterial effects of the CM11 peptide and 1% silver-doped bioactive glass (AgBG) against extensively drug-resistant strains of these bacteria which were isolated from burn patients. Accordingly, the bacteria were isolated from burn patients and their antibiotic resistance patterns and mechanisms were fully determined. The isolated bacterial from patients were resistant to almost all commonly used antibiotics and silver treatment. The isolates acquired their resistance through inactivation of their porin, the overexpression of efflux pump, and beta-lactamase. CM11 peptide and 1% AgBG had minimum inhibitory concentration (MIC) of ≥ 16 μg ml and ≥ 4 mg ml for clinical isolates, respectively. The minimum bactericidal concentration (MBC) of peptide and 1% AgBG for resistant bacteria was ≥ 32 μg ml and ≥ 4 mg ml, respectively. Among the clinical isolates, two P. aeruginosa isolates and one A. baumannii isolate were resistant to 1% AgBG disk. The CM11 peptide also showed high biocompatibility in vivo and no cytotoxicity against fibroblasts and adipose-derived mesenchymal stem cells in concentrations ≤ 64 μg ml and ≤ 32 μg ml, respectively, while the safe concentration of 1% AgBG for these cells was ≤ 16 μg ml. In conclusion, these findings indicated that the 1% silver is not safe and effective for treatment of such infections. The data suggest that CM11 peptide therapy is a reliable and safe strategy that can be used for the treatment of burn infections caused by antimicrobial-resistant isolates. The next stage of the study will be a multicenter clinical trial.
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http://dx.doi.org/10.1007/s00726-018-2638-zDOI Listing
November 2018

Conductive Polymers: Opportunities and Challenges in Biomedical Applications.

Chem Rev 2018 07 3;118(14):6766-6843. Epub 2018 Jul 3.

NanoRegMed Ltd. (Nanotechnology and Regenerative Medicine Commercialization Centre) , The London Innovation BioScience Centre , London NW1 0NH , United Kingdom.

Research pertaining to conductive polymers has gained significant traction in recent years, and their applications range from optoelectronics to material science. For all intents and purposes, conductive polymers can be described as Nobel Prize-winning materials, given that their discoverers were awarded the Nobel Prize in Chemistry in 2000. In this review, we seek to describe the chemical forms and functionalities of the main types of conductive polymers, as well as their synthesis methods. We also present an in-depth analysis of composite conductive polymers that contain various nanomaterials such as graphene, fullerene, carbon nanotubes, and paramagnetic metal ions. Natural polymers such as collagen, chitosan, fibroin, and hydrogel that are structurally modified for them to be conductive are also briefly touched upon. Finally, we expound on the plethora of biomedical applications that harbor the potential to be revolutionized by conductive polymers, with a particular focus on tissue engineering, regenerative medicine, and biosensors.
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http://dx.doi.org/10.1021/acs.chemrev.6b00275DOI Listing
July 2018

Translational Regenerative Therapies for Chronic Spinal Cord Injury.

Int J Mol Sci 2018 Jun 15;19(6). Epub 2018 Jun 15.

NanoRegMed Ltd. (Nanotechnology & Regenerative Medicine Commercialization Centre), The London BioScience Innovation Centre, London NW1 0NH, UK.

Spinal cord injury is a chronic and debilitating neurological condition that is currently being managed symptomatically with no real therapeutic strategies available. Even though there is no consensus on the best time to start interventions, the chronic phase is definitely the most stable target in order to determine whether a therapy can effectively restore neurological function. The advancements of nanoscience and stem cell technology, combined with the powerful, novel neuroimaging modalities that have arisen can now accelerate the path of promising novel therapeutic strategies from bench to bedside. Several types of stem cells have reached up to clinical trials phase II, including adult neural stem cells, human spinal cord stem cells, olfactory ensheathing cells, autologous Schwann cells, umbilical cord blood-derived mononuclear cells, adult mesenchymal cells, and autologous bone-marrow-derived stem cells. There also have been combinations of different molecular therapies; these have been either alone or combined with supportive scaffolds with nanostructures to facilitate favorable cell⁻material interactions. The results already show promise but it will take some coordinated actions in order to develop a proper step-by-step approach to solve impactful problems with neural repair.
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http://dx.doi.org/10.3390/ijms19061776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032191PMC
June 2018

3D Protein-Based Bilayer Artificial Skin for the Guided Scarless Healing of Third-Degree Burn Wounds in Vivo.

Biomacromolecules 2018 07 18;19(7):2409-2422. Epub 2018 Apr 18.

3Bs Research Group, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine , University of Minho , 4805-017 Barco, Guimaraes , Portugal.

Severe burn injuries can lead to delays in healing and devastating scar formation. Attempts have been made to develop a suitable skin substitute for the scarless healing of such skin wounds. Currently, there is no effective strategy for completely scarless healing after the thermal injuries. In our recent work, we fabricated and evaluated a 3D protein-based artificial skin made from decellularized human amniotic membrane (AM) and electrospun nanofibrous silk fibroin (ESF) in vitro. We also characterized both biophysical and cell culture investigation to establish in vitro performance of the developed bilayer scaffolds. In this report, we evaluate the appropriate utility of this fabricated bilayered artificial skin in vivo with particular emphasis on healing and scar formation due to the biochemical and biomechanical complexity of the skin. For this work, AM and AM/ESF membranes alone or seeded with adipose-tissue-derived mesenchymal stem cells (AT-MSCs) are implanted on full-thickness burn wounds in mice. The healing efficacy and scar formation are evaluated at 7, 14, and 28 days post-implantation in vivo. Our data reveal that ESF accelerates the wound-healing process through the early recruitment of inflammatory cells such as macrophages into the defective site as well as the up-regulation of angiogenic factors from the AT-MSCs and the facilitation of the remodeling phase. In vivo application of the prepared AM/ESF membrane seeded with the AT-MSCs reduces significantly the post-burn scars. The in vivo data suggest that the potential applications of the AM/ESF bilayered artificial skin may be considered a clinical translational product with stem cells to guide the scarless healing of severe burn injuries.
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http://dx.doi.org/10.1021/acs.biomac.7b01807DOI Listing
July 2018

Emerging In Vitro 3D Tumour Models in Nanoparticle-Based Gene and Drug Therapy.

Trends Biotechnol 2018 05 27;36(5):477-480. Epub 2018 Feb 27.

Nanotechnology and Regenerative Medicine Centre (Ltd), The London BioScience Innovation Centre, London, UK. Electronic address:

3D models are emerging as valuable tools for personalised nanoparticle-based cancer treatments. 3D models represent in vivo cancers more realistically than 2D patterns that are grown in Petri dishes. However, creating a 3D cancer model that mimics the complexity and heterogeneity of cancers in vivo remains difficult.
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http://dx.doi.org/10.1016/j.tibtech.2018.02.002DOI Listing
May 2018

Stem cells for spinal cord injuries bearing translational potential.

Neural Regen Res 2018 Jan;13(1):35-42

Nanotechnology & Regenerative Medicine Commercialisation Centre (Ltd.), The London BioScience Innovation Centre, London, UK.

Spinal cord injury (SCI) is a highly debilitating neurological disease, which still lacks effective treatment strategies, causing significant financial burden and distress to the affected families. Nevertheless, nanotechnology and regenerative medicine strategies holding promise for the development of novel therapies that would reach from bench to bedside to serve the SCI patients. There has already been significant progress in the field of cell-based therapies, with the clinical application for SCI, currently in phase II of the clinical trial. Stem cells (e.g., induced pluripotent stem cells, fetal stem cells, human embryonic stem cells, and olfactory ensheathing cells) are certainly not to be considered the panacea for neural repair but, especially when combined with rehabilitation or other combinatorial approaches using the help of nanotechnology, they seem to be the source of some of the most promising and clinical translatable cell-based therapies that could help solving impactful problems on neural repair.
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http://dx.doi.org/10.4103/1673-5374.224360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840986PMC
January 2018

Silk fibroin/amniotic membrane 3D bi-layered artificial skin.

Biomed Mater 2018 02 20;13(3):035003. Epub 2018 Feb 20.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Cellular & Molecular Biology Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.

Burn injuries have been reported to be an important cause of morbidity and mortality and they are still considered as unmet clinical need. Although there is a myriad of effective stem cells that have been suggested for skin regeneration, there is no one ideal scaffold. The aim of this study was to develop a three-dimensional (3D) bi-layer scaffold made of biological decellularized human amniotic membrane (AM) with viscoelastic electrospun nanofibrous silk fibroin (ESF) spun on top. The fabricated 3D bi-layer AM/ESF scaffold was submerged in ethanol to induce β-sheet transformation as well as to get a tightly coated and inseparable bi-layer. The biomechanical and biological properties of the 3D bi-layer AM/ESF scaffold were investigated. The results indicate significantly improved mechanical properties of the AM/ESF compared with the AM alone. Both the AM and AM/ESF possess a variety of suitable adhesion cells without detectable cytotoxicity against adipose tissue-derived mesenchymal stem cells (AT-MSCs). The AT-MSCs show increased expression of two main pro-angiogenesis factors, vascular endothelial growth factor and basic fibroblast growth factor, when cultured on the AM/ESF for 7 days, when comparing with AM alone. The results suggest that the AM/ESF scaffold with autologous AT-MSCs has excellent cell adhesion and proliferation along with production of growth factors which serves as a possible application in a clinical setting for skin regeneration.
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http://dx.doi.org/10.1088/1748-605X/aa999bDOI Listing
February 2018

Nanoparticles in wound healing; from hope to promise, from promise to routine.

Front Biosci (Landmark Ed) 2018 Jan 1;23:1038-1059. Epub 2018 Jan 1.

Nanotechnology & Regenerative Medicine Commercialisation Centre, The London BioScience Innovation Centre, London, UK,

Chronic non-healing wounds represent a growing problem due to their high morbidity and cost. Despite recent advances in wound healing, several systemic and local factors can disrupt the weighed physiologic healing process. This paper critically reviews and discusses the role of nanotechnology in promoting the wound healing process. Nanotechnology-based materials have physicochemical, optical and biological properties unique from their bulk equivalent. These nanoparticles can be incorporated into scaffolds to create nanocomposite smart materials, which promote wound healing through their antimicrobial, as well as selective anti- and pro-inflammatory, and pro-angiogenic properties. Owed to their high surface area, nanoparticles have also been used for drug delivery as well as gene delivery vectors. In addition, nanoparticles affect wound healing by influencing collagen deposition and realignment and provide approaches for skin regeneration and wound healing.
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http://dx.doi.org/10.2741/4632DOI Listing
January 2018

Limitations in Clinical Translation of Nanoparticle-Based Gene Therapy.

Trends Biotechnol 2017 12 17;35(12):1124-1125. Epub 2017 Aug 17.

Nanotechnology and Regenerative Medicine Centre (Ltd), The London BioScience Innovation Centre, London, UK. Electronic address:

Organic nanoparticle-based (ONP) gene therapy is a potential strategy to cure human cancer. However, there are still many practical barriers before the promising results from in vitro and preclinical studies can be translated to clinical success. We discuss the reasons behind the hesitant uptake by the clinic.
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http://dx.doi.org/10.1016/j.tibtech.2017.07.009DOI Listing
December 2017

Nanohydroxyapatite Effect on the Degradation, Osteoconduction and Mechanical Properties of Polymeric Bone Tissue Engineered Scaffolds.

Open Orthop J 2016 30;10:900-919. Epub 2016 Dec 30.

John Scales Centre for Biomedical Engineering, Institute of Orthopaedics and Musculoskeletal Science, Division of Surgery and Interventional Science, University College London, Royal National Orthopaedic Hospital, Stanmore HA7 4LP, United Kingdom.

Background: Statistical reports show that every year around the world approximately 15 million bone fractures occur; of which up to 10% fail to heal completely and hence lead to complications of non-union healing. In the past, autografts or allografts were used as the "gold standard" of treating such defects. However, due to various limitations and risks associated with these sources of bone grafts, other avenues have been extensively investigated through which bone tissue engineering; in particular engineering of synthetic bone graft substitutes, has been recognised as a promising alternative to the traditional methods.

Methods: A selective literature search was performed.

Results: Bone tissue engineering offers unlimited supply, eliminated risk of disease transmission and relatively low cost. It could also lead to patient specific design and manufacture of implants, prosthesis and bone related devices. A potentially promising building block for a suitable scaffold is synthetic nanohydroxyapatite incorporated into synthetic polymers. Incorporation of nanohydroxyapatite into synthetic polymers has shown promising bioactivity, osteoconductivity, mechanical properties and degradation profile compared to other techniques previously considered.

Conclusion: Scientific research, through extensive physiochemical characterisation, and assessment has brought together the optimum characteristics of nanohydroxyapatite and various types of synthetic polymers in order to develop nanocomposites of suitable nature for bone tissue engineering. The aim of the present article is to review and update various aspects involved in incorporation of synthetic nanohydroxyapatite into synthetic polymers, in terms of their potentials to promote bone growth and regeneration , and consequently in clinical applications.
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http://dx.doi.org/10.2174/1874325001610010900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299581PMC
December 2016

Chitosan-Intercalated Montmorillonite/Poly(vinyl alcohol) Nanofibers as a Platform to Guide Neuronlike Differentiation of Human Dental Pulp Stem Cells.

ACS Appl Mater Interfaces 2017 Apr 27;9(13):11392-11404. Epub 2017 Mar 27.

Cellular and Molecular Research Center, Iran University of Medical Sciences (IUMS) , Tehran, Iran.

In this study, we present a novel chitosan-intercalated montmorillonite/poly(vinyl alcohol) (OMMT/PVA) nanofibrous mesh as a microenvironment for guiding differentiation of human dental pulp stem cells (hDPSCs) toward neuronlike cells. The OMMT was prepared through ion exchange reaction between the montmorillonite (MMT) and chitosan. The PVA solutions containing various concentrations of OMMT were electrospun to form 3D OMMT-PVA nanofibrous meshes. The biomechanical and biological characteristics of the nanofibrous meshes were evaluated by ATR-FTIR, XRD, SEM, MTT, and LDH specific activity, contact angle, and DAPI staining. They were carried out for mechanical properties, overall viability, and toxicity of the cells. The hDPSCs were seeded on the prepared scaffolds and induced with neuronal specific differentiation media at two differentiation stages (2 days at preinduction stage and 6 days at induction stage). The neural differentiation of the cells cultured on the meshes was evaluated by determining the expression of Oct-4, Nestin, NF-M, NF-H, MAP2, and βIII-tubulin in the cells after preinduction, at induction stages by real-time PCR (RT-PCR) and immunostaining. All the synthesized nanofibers exhibited a homogeneous morphology with a favorable mechanical behavior. The population of the cells differentiated into neuronlike cells in all the experimental groups was significantly higher than that in control group. The expression level of the neuronal specific markers in the cells cultured on 5% OMMT/PVA meshes was significantly higher than the other groups. This study demonstrates the feasibility of the OMMT/PVA artificial nerve graft cultured with hDPSCs for regeneration of damaged neural tissues. These fabricated matrices may have a potential in neural tissue engineering applications.
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http://dx.doi.org/10.1021/acsami.6b14283DOI Listing
April 2017
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