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Identifying communities is one of the hardest tasks in network analysis, and it is critical in various fields, including computer science, biology, sociology, and physics. It aims to partition the graph of a network into groups/clusters of nodes (communities) according to the graph topology. Because determining the optimal partition is a computationally difficult task, it is usually carried out using optimization methods. Most optimization methods proposed for this problem have considered network modularity as the objective function. This article proposes a new evolutionary algorithm called LGA to tackle the community detection problem through modularity optimization. In LGA, learning automata are utilized in the evolution process of the genetic algorithm. Utilizing learning automata in the evolution process of the genetic algorithm largely prevents getting stuck in local optima and premature convergence of the genetic algorithm. It has been tested on different examples of the community detection problem to assess the performance of the LGA. The experiment results showed that the LGA efficiently detects communities within networks. On average, its performance is 26.47% better in real-world networks and 48.32% better in synthetic networks than in compared algorithms.

In this article, high frequency power amplifier is designed based on monolithic microwave integrated circuit (MMIC) technology. For this design the process of GaN transistors with high electron mobility has been used and its length gate technology is 150nm central frequency of the amplifier is 2.5GHz. the maximum gain of the amplifier is approximately equal to 12.76dB and is designed in one stage. At this frequency, the maximum output power of the amplifier is about 39.196 dBm in 30dBm input. In the maximum output power, PAE is about 41.25% that this is maximum amount of PAE .The final area of the circuit for embedding on the chip is 25.903mm by 19.346mm.the maximum values of AM/PM and AM/AM are 2.38deg/db and 1.66dB/dB respectively. For the 3-rd intermodulation distortion (IMD3) is about -20 dBc at the center of frequency. To design this amplifier, Loadpull analysis of ADS software was used to obtain the appropriate output power.

Community detection is crucial for analyzing the structure of social networks and extracting hidden information from them. The goal is to find groups of nodes (communities) with high intra-group and low inter-group communications. This problem is NP-hard, and most existing algorithms are global with high computational complexity, especially for large networks. Recently, local methods with acceptable computational complexity have been developed, but many have low accuracy and are non-deterministic. This paper introduces a new local algorithm, LCD-SN, which identifies communities based on first- and second-degree neighbor nodes. Unlike other local algorithms, LCD-SN is highly accurate, definitive, and not dependent on initial seed nodes. Additionally, a new index is proposed to determine the importance of network nodes using their local characteristics (first- and second-degree neighbors). Using this index, LCD-SN first identifies important nodes, forms initial communities with these nodes and their first-degree neighbors, and then obtains final communities through post-processing. Experiments show that LCD-SN is effective in identifying communities in social networks.

Network analysis involves using graph theory to understand networks. This knowledge is valuable across various disciplines like marketing, management, epidemiology, homeland security, and psychology. An essential task within network analysis is deciphering the structure of complex networks including technological, informational, biological, and social networks. Understanding this structure is crucial for comprehending network performance and organization, shedding light on their underlying structure and potential functions. Community structure detection aims to identify clusters of nodes with high internal link density and low external link density. While there has been extensive research on community structure detection in single-layer networks, the development of methods for detecting community structure in multilayer networks is still in its nascent stages. In this paper, a new method, namely, IGA-MCD, has been proposed to tackle the problem of community structure detection in multiplex networks. IGA-MCD consists of two general phases: flattening and community structure detection. In the flattening phase, the input multiplex network is converted to a weighted monoplex network. In the community structure detection phase, the community structure of the resulting weighted monoplex network is determined using the Improved Genetic Algorithm (IGA). The main aspects that differentiate IGA from other algorithms presented in the literature are as follows: (a) instead of randomly generating the initial population, it is smartly generated using the concept of diffusion. This makes the algorithm converge faster. (b) A dedicated local search is employed at the end of each cycle of the algorithm. This causes the algorithm to come up with better new solutions around the currently found solutions. (c) In the algorithm process, chaotic numbers are used instead of random numbers. This ensures that the diversity of the population is preserved, and the algorithm does not get stuck in the local optimum. Experiments on the various benchmark networks indicate that IGA-MCD outperforms state-of-the-art algorithms.

Study region: Six wetland sites around Iran (Gavkhoni and Hur al-Azim wetlands, Gorgan Bay, and Namak, Urmia, and Maharloo & Bakhtegan lakes) and their associated hydrological basins. Study focus: The aim was to distinguish the contributions of climatic and non-climatic changes (including land-use/land-cover, LULC) to areal decline in six Iranian wetlands. This was done using data-driven quantification methodology that combined comparative change correlation and Budyko-based analyses of evapotranspiration (ETb), and runoff (Rb) changes in the hydrological basin of each wetland, extended to consider explicitly climate-driven change in evaporation rate (Ew) from the wetland area and the shift from previous Ew to ETb caused by the wetland decline itself. New hydrological insights for the region: Comparative correlation analysis revealed an overall stronger correlation of wetland decline with LULC changes (mainly cropland, urban land) than with changes in temperature (T) or precipitation (P) across all wetland sites. The extended Budyko-based analysis revealed that the predominant cause of wetland decline across all sites was increased ETb, with related decrease in Rb from basin to wetland, whereas changes in Ew and in wetland decline shifting Ew to ETb had only a weak influence. In line with the correlation analysis results, non-climatic drivers were revealed as causing ETb increases and Rb decreases, leading to wetland decline to a greater degree than climate change (T, P).

Necessity of the human to the safe and permanent water sources is one of the important problems today, especially in Iran that is a buried region. One of the permanent water sources is groundwater. In the last decades, soft rock aquifers of country mainly are used; therefore, this causes to exploration the groundwater in the hard rocks. Tectonics and faults one of the important factors to crush the rocks and formations and make and develop the faulted aquifers. Therefore in this study the role of the structures is researched in development of the water sources in Kelvanaq city area. This city is in the South of Heris city that located in the North of the Ajichai River and its main subdivisions are middle part sources of this river that itself sourced from Ghare-Dagh Mountains. In this study, first field studies, geological maps and search in remote sensing and photo maps help to select area have active tectonics in relation by active faults. Study the hydrologic specifications of the basin, in connection by high potential regions of groundwater are guided. After, geophysical methods helps exploration, and geoelectrical sections and pseudo-sections are shown the fault related aquifers and their developments. Research and compare the resistivity maps and sections in this study, shown the extent of aquifers and shown that in the eastern and north-eastern part of the study area, resistivity are mainly very low and are in 10-15 Ὡm range, that are in relation by impermeable clay and marl stones of Red-Formation. Geophysical exploration results have shown that the northern part of the study area mainly formed by impermeable or low-permeable hard rocks, and faults of the study area mainly are impermeable or low-permeable fault zones. But study and compare the results have shown that high potential regions are in the southern parts of the region. Finally in relation by the explored aquifers, location of the number 26 and 30 geoelectric wells, respectively proposed for drilling. Large thickness of the explored faulted aquifer and its specifications, promising good Q for the proposed wells.

Estimating evapotranspiration (ET), the main water output flux within basins, is an important step in assessing hydrological changes and water availability. However, direct measurements of ET are challenging, especially for large regions. Global products now provide gridded estimates of ET at different temporal resolution, each with its own method of estimating ET based on various data sources. This study investigates the differences between ERA5, GLEAM, and GLDAS datasets of estimated ET at gridded points across Iran, and their accuracy in comparison with reference ET. The spatial and temporal discrepancies between datasets are identified, as well as their co-variation with forcing variables. The ET reference values used to check the accuracy of the datasets were based on the water balance (ETwb) from Iran’s main basins, and co-variation of estimated errors for each product with forcing drivers of ET. The results indicate that ETERA5 provides higher base average values and lower maximum annual average values than ETGLEAM. Temporal changes at the annual scale are similar for GLEAM, ERA5, and GLDAS datasets, but differences at seasonal and monthly time scales are identified. Some discrepancies are also recorded in ET spatial distribution, but generally, all datasets provide similarities, e.g., for humid regions basins. ETERA5 has a higher correlation with available energy than available water, while ETGLEAM has higher correlation with available water, and ETGLDAS does not correlate with none of these drivers. Based on the comparison of ETERA5 and ETGLEAM with ETwb, both have similar errors in spatial distribution, while ETGLDAS provided over and under estimations in northern and southern basins, respectively, compared to them (ETERA5 and ETGLEAM). All three datasets provide better ET estimates (values closer to ETWB) in hyper-arid and arid regions from central to eastern Iran than in the humid areas. Thus, the GLEAM, ERA5, and GLDAS datasets are more suitable for estimating ET for arid rather than humid basins in Iran.

Background: This study aimed to evaluate possible predictors for postoperative outcome in patients with tumor-associated epilepsy. Methods: In this study, patients with tumor-associated epilepsy who were candidates for epilepsy surgery were included. After required presurgical evaluations, they underwent surgical resection of the tumor. Patients were followed 24-57 months after the surgery and were divided to two groups of seizure-free and not-seizure-free. Demographic data, medical history, seizure characteristics and tumor features were compared between the two groups to find possible predictors. Findings: Thirty-five patients (17 men and 18 women) with the mean age of 22.8 years (8 to 45 years) were enrolled this study. Most of the patients had temporal lobe tumors (68.0%) followed by frontal and parietal lobe tumors. Ganglioglioma was seen in 62.9% of the patients, followed by astrocytoma and dysembryoplastic neuroepithelial tumour (DNET). We found a non-significant positive correlation between better surgical outcome and being male, younger age at epilepsy onset, longer duration of epilepsy, more seizure frequency, tumors in right hemisphere, tumor type of ganglioglioma, and seizures with secondary generalization. Furthermore, we found that history of head trauma, infection of centeral nervous system (CNS), febrile convulsion, natural vaginal delivery, familial history of epilepsy, tumors in temporal lobe, having auras, developing more seizure types and ipsilateral temporal spikes on preoperative electroencephalogram (EEG) were associated with worst surgical outcome (P > 0.05 for all). Conclusion: In this study, we found no statistically significant predicting factor for surgical outcome; however, we found that being male, smaller ages at seizure onset, longer duration of epilepsy, higher seizure frequency before surgery, involvement of right hemisphere, ganglioglioma, and secondary generalization are more seen in patients with better surgical outcome while history of head trauma, CNS infection, family history of epilepsy, temporal lobe tumors, presence of aura, having multiple types of seizures, and epileptic discharges from temporal lobe in preoperative EEG were seen more in patients with poor outcome. Studies with larger sample sizes are suggested to confirm these findings.

Background: Median neuropathy due to nerve compression in the wrist, or carpal tunnel syndrome (CTS), is the most common entrapment neuropathy. Incidence of CTS is high at an estimated value of 280.6 per 100,000 patients per year. Accurate diagnosis of CTS is essential for treatment and preventing disability and morbidity. Methods: 64 patients with clinical diagnosis of CTS from the out-patient clinic of Alzahra Hospital, Isfahan, Iran were evaluated between January and March 2013. All the patients (54 women and 10 men) underwent nerve conduction study (NCS) and ultrasonography. The cross sectional area of the median nerve at the level of pisiform bone and 12cm proximal to that in elbow was estimated via ultrasonography which were used to calculate wrist/forearm ratio(WFR). The cut-off point value for WFR of median nerve was assessed and sensitivity and specificity of ultrasonography for CTS diagnosis was also determined. Findings: The optimal diagnostic cut-off values of CTS that we obtained by ROC curve was 2.07 and the areas under the ROC curve, was 0.8. This cut-off value had a sensitivity of 76%, specificity of 83%, positive predictive value (PPV) of 95% and negative predictive value (NPV) of 45%. Conclusion: The WFR is a new option in the ultra-sonographic diagnosis of CTS. This technique does not add significant time to routine ultra-sonographic examination .The use of a ratio also helps to omit the variability between populations and anatomic variation. Our initial findings suggest a high sensitivity for this method, but study of a larger population is needed for confirmation.

Background: Electrophysiologic (EDX) study is the most valuable method in grading the severity of carpal tunnel syndrome (CTS), but it is invasive and painful. We evaluated the efficacy of ultrasound for this purpose. Materials and Methods: Eighty-one wrists of 52 consecutive patients with clinical evidences of CTS, confirmed and graded by EDX as mild, moderate, and severe, were examined by ultrasonography. Cross-sectional area (CSA) of the median nerve was measured at the distal wrist (CSA-D), and proximal forearm (CSA-P), and wrist-to-forearm ratio (WFR) was calculated for each hand. Results: The mean CSA-D was 0.12 cm 2 ± 0.03, 0.15 cm 2 ± 0.03 and 0.19 cm 2 ± 0.06 and the mean WFR was 2.77 ± 1.14, 3.07 ± 1.07 and 4.07 ± 1.61 in mild, moderate and severe groups respectively. WFR showed significant differences between the severe and none severe CTS groups (P < 0.001), but there was no significant difference between mild and moderate CTS groups (P < 0.381). CSA-D showed a significant difference between all groups (P < 0.0001). In the Receiver Operating Characteristic curve analysis, the optimal cut-off value of the CSA-D and WFR for detecting severe CTS were 0.15 (area under the curve 0.784, 95% confidence interval (CI): 0.662-0.898, P < 0.001, sensitivity of 68.2% and specificity of 70.9%) and 3 (area under the curve 0.714, 95% CI: 0.585-0.84, P = 0.001, sensitivity of 68.2% and specificity of 64.8%) respectively. All values were superior in CSA-D. Conclusion: Ultrasonography, can be complementary but not conclusive to the classification of CTS severities. CSA-D and WFR both increased in proportion to CTS severity, but neither parameter exhibited excellent performance in grading the severities.

We have developed an innovative peripheral nerve tissue repair approach by designing biomimetic microparticles loaded with cannabidiol (CBD) using horseradish peroxidase-mediated crosslinking within a microfluidic device. This method utilizes a water-in-oil emulsion system where a mixture of phenol-substituted hyaluronic acid (HAPh), CBD, and laccase is channeled into oil flow, forming hydrogel microparticles. The physical properties, such as their swelling rate, mechanical strength, and the sustained release of CBD, emphasize their potential in tissue engineering and drug delivery applications. Cellular proliferation studies within the microparticles demonstrate their cytocompatibility, making them suitable for developing microtissues. The microparticles also served as a controlled release mechanism for CBD-targeted delivery to the injured locations, showcasing the effectiveness and ability to aid in the regeneration of the sciatic nerve tissue. In vivo, histopathological analysis of treated sciatic nerve injuries showed enhanced axonal restoring and remyelination with HAPh microparticles containing CBD in contrast to control groups. Furthermore, microparticles enhanced various functional aspects of locomotor activities, such as functional sciatic index (SFI) values, response to heat stimulation, and muscle mass retention. In conclusion, results indicate that these composite biomimetic microparticles with CBD effectively promote nerve structural restoration and increase the reconstruction process in a sciatic nerve injury model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gelatin-based biomaterials are widely acknowledged as a promising choice for wound dressings, given their similarity to the extracellular matrix and biocompatibility. However, the challenge of cross-linking gelatin while preserving its biocompatibility and cost-effectiveness persists. This study aimed to enhance the properties of gelatin by incorporating the oxidized lignosulfonate (OLS) biopolymer as an inexpensive and biocompatible natural material. The polyphenolic structure of OLS acts as both a cross-linking agent and an antibacterial component. The OLS/gelatin films were prepared using a casting method with varying weight ratios (0.1, 0.2, 0.3, 0.4, and 0.5 w/w). FTIR analysis confirmed the formation of Schiff-base and hydrogen bonds between gelatin and OLS. The resulting films exhibited enhanced mechanical properties (Young's modulus ∼40 MPa), no cytotoxicity, and excellent cell adhesion and morphology. Antimicrobial tests showed significant activity against Escherichia coli and Staphylococcus aureus, with higher activity against S. aureus (17 mm inhibition zone and 99 % bactericidal rate). In vivo studies in a mouse model demonstrated that the gelatin/0.2OLS dressing significantly improved wound healing, including re-epithelialization, collagen formation, inflammation reduction, and blood vessel density, compared to untreated wounds. These findings suggest that the synthesized novel gelatin/OLS wound dressing has promising healing and antibacterial properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This study was supported by the Iran University of Medical Sciences (IUMS) through research Grant Nos. 1401-3-14-23834. The cell culture was performed by the Cellular and Molecular Research Center at IUMS, which the authors gratefully acknowledge., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sensorineural hearing loss (SNHL), often stemming from reactive oxygen species (ROS) generation due to various factors such as ototoxic drugs, acoustic trauma, and aging, remains a significant health concern. Oxidative stress-induced damage to the sensory cells of the inner ear, particularly the non-regenerating hair cells, is a critical pathologic mechanism leading to SNHL. Despite the proven efficacy of antioxidants in mitigating oxidative stress, their clinical application for otoprotection is hindered by the limitations of conventional drug delivery methods. This review highlights the challenges associated with systemic and intratympanic administration of antioxidants, including the blood-labyrinthine barrier, restricted permeability of the round window membrane, and inadequate blood flow to the inner ear. To overcome these hurdles, the application of nanoparticles as a delivery platform for antioxidants emerges as a promising solution. Nanocarriers facilitate indirect drug delivery to the cochlea through the round and oval window membrane, optimising drug absorption while reducing dosage, Eustachian tube clearance, and associated side effects. Furthermore, the development of nanoparticles carrying antioxidants tailored to the intracochlear environment holds immense potential. This literature research aimed to critically examine the root causes of SNHL and ROS overproduction in the inner ear, offering insights into the application of nanoparticle-based drug delivery systems for safeguarding sensorineural hair cells. By focusing on the intricate interplay between oxidative stress and hearing loss, this research aims to contribute to the advancement of innovative therapeutic strategies for the prevention of SNHL., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cardiovascular diseases (CDs) are the foremost cause of death worldwide. Several promising therapeutic methods have been developed for this approach, including pharmacological, surgical intervention, cell therapy, or biomaterial implantation since heart tissue is incapable of regenerating and healing on its own. The best treatment for heart failure to date is heart transplantation and invasive surgical intervention, despite their invasiveness, donor limitations, and the possibility of being rejected by the patient's immune system. To address these challenges, research is being conducted on less invasive and efficient methods. Consequently, graphene-based materials (GBMs) have attracted a great deal of interest in the last decade because of their exceptional mechanical, electrical, chemical, antibacterial, and biocompatibility properties. An overview of GBMs' applications in the cardiovascular system has been presented in this article. Following a brief explanation of graphene and its derivatives' properties, the potential of GBMs to improve and restore cardiovascular system function by using them as cardiac tissue engineering, stents, vascular bypass grafts,and heart valve has been discussed.

Bone tissue engineering (BTE) provides the treatment possibility for segmental long bone defects that are currently an orthopedic dilemma. This review explains different strategies, from biological, material, and preparation points of view, such as using different stem cells, ceramics, and metals, and their corresponding properties for BTE applications. In addition, factors such as porosity, surface chemistry, hydrophilicity and degradation behavior that affect scaffold success are introduced. Besides, the most widely used production methods that result in porous materials are discussed. Gene delivery and secretome-based therapies are also introduced as a new generation of therapies. This review outlines the positive results and important limitations remaining in the clinical application of novel BTE materials and methods for segmental defects., (© 2024 IOP Publishing Ltd.)

Exosomes are among the most effective therapeutic tools for tissue engineering. This study demonstrates that a 3D composite scaffold containing exosomes can promote regeneration in rat tympanic membrane perforation (TMP). The scaffolds were characterized using scanning electron microscopy (SEM), degradation, PBS adsorption, swelling, porosity, and mechanical properties. To confirm the isolation of exosomes from human adipose-derived mesenchymal stem cells (hAMSCs), western blot, SEM, and dynamic light scattering (DLS) were performed. The Western blot test confirmed the presence of exosomal surface markers CD9, CD81, and CD63. The SEM test revealed that the isolated exosomes had a spherical shape, while the DLS test indicated an average diameter of 82.5 nm for these spherical particles. MTT assays were conducted to optimize the concentration of hAMSCs-exosomes in the hydrogel layer of the composite. Exosomes were extracted on days 3 and 7 from an alginate hydrogel containing 100 and 200 μg/mL of exosomes, with 100 μg/mL identified as the optimal value. The optimized composite scaffold demonstrated improved growth and migration of fibroblast cells. Animal studies showed complete tympanic membrane regeneration (TM) after five days. These results illustrate that a scaffold containing hAMSC-exosomes can serve as an appropriate tissue-engineered scaffold for enhancing TM regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we fabricated a novel multilayer polyvinyl alcohol (PVA)/alginate sulfate (ALG-S) nanofiber/decellularized Wharton's Jelly ECM (d-ECM) composite for tympanic membrane perforations (TMPs) tissue engineering (TE). Initially, electrospun PVA/ALG-S scaffolds with different blend ratios were fabricated. The influence of ALG-S ratio on surface morphology, mechanical, physical and biological properties of the nanofibers was studied. Secondly, 3-layer composites were developed as a combination of PVA/ALG-S nanofibers and d-ECM to take synergic advantages of electrospun mats and d-ECM. As part of the evaluation of the effects of d-ECM incorporation, the composite's mechanical properties, in vitro degradation, swelling ratio, and biological activities were assessed. The MTT assay showed that PVA/ALG-S nanofibers with 50:50 ratio provided a more desirable environment to support cell growth. A composite containing 25 mg/cm 2 d-ECM was determined as the optimal composite through MTT assay, and this composite was used for animal studies inducing TMP regeneration. According to the in vivo studies, the optimal composite not only stimulated the healing of TMPs but also shortened the healing period. These results suggest that a multilayer nanofiber/hydrogel composite could be a potential platform for regenerating TMPs., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Male survivors of childhood cancer have been known to be afflicted with azoospermia. To combat this, the isolation and purification of spermatogonial stem cells (SSCs) are crucial. Implementing scaffolds that emulate the extracellular matrix environment is vital for promoting the regeneration and proliferation of SSCs. This research aimed to evaluate the efficiency of nanocomposite scaffolds based on alginate, chitosan, and graphene oxide (GO) in facilitating SSCs proliferation. To analyze the cytotoxicity of the scaffolds, an MTT assay was conducted at 1, 3, and 7 days, and the sample containing 30 µg/mL of GO (ALGCS/GO30) exhibited the most favorable results, indicating its optimal performance. The identity of the cells was confirmed using flow cytometry with C-Kit and GFRα1 markers. The scaffolds were subjected to various analyses to characterize their properties. FTIR was employed to assess the chemical structure, XRD to examine crystallinity, and SEM to visualize the morphology of the scaffolds. To evaluate the proliferation of SSCs, qRT-PCR was used. The study's results demonstrated that the ALGCS/GO30 nanocomposite scaffold exhibited biocompatibility and facilitated the attachment and proliferation of SSCs. Notably, the scaffold displayed a significant increase in proliferation markers compared to the control group, indicating its ability to support SSC growth. The expression level of the PLZF protein was assessed using the Immunocytochemistry method. The observations confirmed the qRT-PCR results, which indicated that the nanocomposite scaffolds had higher levels of PLZF protein expression than scaffolds without GO. The biocompatible ALGCS/GO30 is a promising alternative for promoting SSC proliferation in in vitro applications.

Stem cell therapy is a promising strategy for cartilage tissue engineering, and cell transplantation using polymeric scaffolds has recently gained attention. Herein, we encapsulated human adipose-derived stem cells (hASCs) within the alginate sulfate hydrogel and then added them to polycaprolactone/gelatin electrospun nanofibers and extracellular matrix (ECM) powders to mimic the cartilage structure and characteristic. The composite hydrogel scaffolds were developed to evaluate the relevant factors and conditions in mechanical properties, cell proliferation, and differentiation to enhance cartilage regeneration. For this purpose, different concentrations (1-5 % w/v) of ECM powder were initially loaded within an alginate sulfate solution to optimize the best composition for encapsulated hASCs viability. Adding 4 % w/v of ECM resulted in optimal mechanical and rheological properties and better cell viability. In the next step, electrospun nanofibrous layers were added to the alginate sulfate/ECM composite to prepare different layered hydrogel-nanofiber (2, 3, and 5-layer) structures with the ability to mimic the cartilage structure and function. The 3-layer structure was selected as the optimum layered composite scaffold, considering cell viability, mechanical properties, swelling, and biodegradation behavior; moreover, the chondrogenesis potential was assessed, and the results showed promising features for cartilage tissue engineering application., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Silk fibroin (SF), extracted from Bombyx mori, has unique physicochemical properties to achieve an efficient wound dressing. In this study, reduced graphene oxide (RGO)/ZnO NPs/silk fibroin nanocomposite was made, and an innovative nanofiber of SF/polyvinyl alcohol (PVA)/RGO/ZnO NPs was ready with the electrospinning technique and successfully characterized. The results of MIC and OD analyses were used to investigate the synthesized materials' antibacterial effects and displayed that the synthesized materials could inhibit growth against Staphylococcus aureus and Escherichia coli bacteria. However, both in vitro cytotoxicity (MTT) and scratch wound studies have shown that RGO/ZnO NPs and SF/PVA/RGO/ZnO NPs are not only non-toxic to NIH 3T3 fibroblasts, but also can cause cell viability, cell proliferation, and cell migration. Furthermore, improving the synthesized nanofiber's structural properties in the presence of RGO and ZnO NPs has been confirmed by performing tensile strength, contact angle, and biodegradation analyses. Also, in a cell attachment analysis, fibroblast cells had migrated and expanded well in the nanofibrous structures. Moreover, in vivo assay, SF/PVA/RGO/ZnO NPs nanofiber treated rats and has been shown significant healing activity and tissue regeneration compared with other treated groups. Therefore, this study suggests that SF/PVA/RGO/ZnO NPs nanofiber is a hopeful wound dressing for preventing bacteria growth and improving superficial wound repair., (© 2023 American Institute of Chemical Engineers.)

Introduction: Strategies of Schwann cell (SC) transplantation for regeneration of peripheral nerve injury involve many limitations. Stem cells can be used as alternative cell source for differentiation into Schwann cells. Given the high potential of neural crest-derived stem cells for the generation of multiple cell lineages, in this research, we considered whether olfactory ectomesenchymal stem cells (OE-MSCs) derived from neural crest can spontaneously differentiate into SC lineage., Methods: OE-MSCs were isolated from human nasal mucosa and characterized by the mesenchymal and neural crest markers. The cells were cultured in glial growth factors-free medium and further investigated in terms of the phenotypic and functional properties., Results: Immunocytochemical staining and real-time PCR analysis indicated that the cultured OE-MSCs expressed SCs markers, SOX10, p75, S100, GFAP and MBP, differentiation indicative. It was found that the cells could secrete neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Furthermore, after co-cultured with PC12, the mean neurite length was enhanced by OE-MSCs., Conclusion: The findings indicated that OE-MSCs could be differentiated spontaneously into SC-like phenotypes, suggesting their applications for transplantation in peripheral nerve injuries., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2023 Iranian Neuroscience Society.)

Objective: Animal-free scaffolds have emerged as a potential foundation for consistent, chemically defined, and low-cost materials. Because of its good potential for high biocompatibility with reproductive tissues and well-characterized scaffold design, we investigated whether polyglycolic acid (PGA) could be used as an animal-free scaffold instead of natural fibrin-agarose, which has been used successfully for three-dimensional human endometrial cell culture., Methods: Isolated primary endometrial cells was cultured on fibrin-agarose and PGA polymers and evaluated various design parameters, such as scaffold porosity and mean fiber diameter. Cytotoxicity, scanning electron microscopy (SEM), and immunostaining experiments were conducted to examine cell activity on fabricated scaffolds., Results: The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and SEM results showed that endometrial cells grew and proliferated on both scaffolds. Immunostaining showed cytokeratin and vimentin expression in seeded cells after 7 days of culture. On both scaffolds, an epithelial arrangement of cultured cells was found on the top layer and stromal arrangement matrix on the bottom layer of the scaffolds. Therefore, fibrin-agarose and PGA scaffolds successfully mimicked the human endometrium in a way suitable for in vitro analysis., Conclusion: Both fibrin-agarose and PGA scaffolds could be used to simulate endometrial structures. However, because of environmental and ethical concerns and the low cost of synthetic polymers, we recommend using PGA as a synthetic polymer for scaffolding in research instead of natural biomaterials.

Bioactive glasses are highly reactive surface materials synthesized by melting or sol-gel techniques. In this study, mesoporous bioactive glass-ceramics doped with different amounts of vanadium and iron ((60-( x + y )) SiO 2 -36CaO-4P 2 O 5 - x V 2 O 5 - y Fe 2 O 3 , x and y between 0, 5 and, 10 mole%) were synthesized using a sol-gel method. Then, their effects on particle morphology and the biomineralization process were examined in simulated body fluid (SBF). N2 adsorption isotherm analysis proved that the samples have a mesoporous structure. In addition, the Fourier-transform infrared spectroscopy (FTIR) spectra of the samples after soaking in SBF for various periods (7, 14, and 21 days) confirmed the presence of new chemical bonds related to the apatite phase, which is in accordance with scanning electron microscopy (SEM) observations. X-ray diffraction (XRD) patterns of the samples after SBF soaking showed that lower amounts of vanadium and iron were associated with the formation of a stable and more crystalline phase of hydroxyapatite. The MTT results showed that the cell viability of mesoporous bioactive glass containing 5% V 2 O 5 remains more than 90% over 7 days, which indicates the biocompatibility of the samples. To conclude, further studies on these formulations are going to be carried out in future investigations for chemohyperthermia application., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: Maintenance of neurogenesis depends on the function of some histone-modifying enzymes; including Enhancer of zeste homolog 2 (EZH2) and histone acetyltransferases (P300). The mechanism of epigenetic regulation and gene expression underlying the transition of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) into MNs has not been fully clarified., Methods: Two morphogens; sonic hedgehog (Shh: 100 ng/mL) and retinoic acid (RA: 0.01 mM) were involved in the specification of hUCB-MSCs into MNs after MSC characterization using Flow cytometry. Real time-quantitative PCR and immunocytochemistry were performed to find the expression of the genes at the level of mRNA and protein., Results: The expression of MN-related markers was confirmed at the level of mRNA and protein by induction of differentiation. The results were confirmed by immunocytochemistry and showed those mean cell percentages of 55.33%±15.885% and 49.67%±13.796% could express Islet-1 and ChAT, respectively. The gene expression level of Islet-1 and ChAT was significantly increased in the first and second week of exposure, respectively. After two weeks, the expression level of P300 and EZH-2 genes increased remarkably. No significant expression of Mnx-1 was detected when compared to the control sample., Conclusion: MN-related markers, Islet-1 and ChAT, were detected in differentiated cells of hUCB-MSCs, supporting the potency of cord blood cells in the regeneration of MN-related disorders. Assessing these epigenetic regulatory genes at the protein level can be suggested to confirm their functional epigenetic modifying effects during motor neuron differentiation., Competing Interests: Conflict of interest The authors declared no competing interest., (Copyright© 2022 Iranian Neuroscience Society.)

Background: Mutations in NARS2 (MIM: 612803) are associated with combined oxidative phosphorylation deficiency 24 (COXPD24; MIM: 616239) that is a rare mitochondrial and a multisystem autosomal recessive disorder., Aims: We aimed to detect the underlying genetic factors in two siblings with progressive ataxia, epilepsy, and severe-to-profound hearing impairment., Methods: After doing medical assessments and pertinent tests (i.e., auditory brainstem responses, pure tone otoacoustic emission test, cardiac examinations, computed tomography, and electroencephalogram), because of the clinical and probable genetic heterogeneity, whole-exome sequencing was performed, and co-segregation analysis was confirmed by Sanger sequencing. Biological impacts of the novel variant were evaluated using sequence-to-function bioinformatics tools., Results: A novel homozygous missense variant, NM&#95;024678.6:c.545 T > A; p.(Ile182Lys), in exon 5 of NARS2 was identified in both patients and verified by Sanger sequencing. In silico analyses introduced this variant as pathogenic. Mitral valve prolapses with mild regurgitation, brachymetatarsia, severe hallux valgus, and clubbed fingers were reported as novel manifestations in association with NARS2 gene. By doing a literature review, we also underscored the high heterogeneity of disease phenotype., Conclusions: Herein, we report some novel phenotype and genotype features of two female patients in an Iranian consanguineous family with COXPD24, caused by a variant in NARS2-NM&#95;024678.6: c.545 T > A; p.(Ile182Lys). Moreover, our data expanded the phenotype and genotype spectrum of NARS2-related disorder and confirmed an unpredictable nature of genotype-phenotype correlation in COXPD24., (© 2021. Royal Academy of Medicine in Ireland.)

Various composite scaffolds with different fabrication techniques have been applied in cartilage tissue engineering. In this study, poly ɛ-caprolactone (PCL) was printed by fused deposition modeling method, and the prepared scaffold was filled with Alginate (Alg): Alginate-Sulfate (Alg-Sul) hydrogel to provide a better biomimetic environment and emulate the structure of glycosaminoglycans properly. Furthermore, to enhance chondrogenesis, different concentrations of decellularized extracellular matrix (dECM) were added to the hydrogel. For cellular analyses, the adipose-derived mesenchymal stem cells were seeded on the hydrogel and the results of MTT assay, live/dead staining, and SEM images revealed that the scaffold with 1% dECM had better viscosity, cell viability, and proliferation. The study was conducted on the optimized scaffold (1% dECM) to determine mechanical characteristics, chondrogenic differentiation, and results demonstrated that the scaffold showed mechanical similarity to the native nasal cartilage tissue along with possessing appropriate biochemical features, which makes this new formulation based on PCL/dECM/Alg:Alg-Sul a promising candidate for further in-vivo studies., (© 2022 Wiley Periodicals LLC.)

Implantation of a suitable nerve guide conduit (NGC) seeded with sufficient Schwann cells (SCs) is required to improve peripheral nerve regeneration efficiently. Given the limitations of isolating and culturing SCs, using various sources of stem cells, including mesenchymal stem cells (MSCs) obtained from nasal olfactory mucosa, can be desirable. Olfactory ecto-MSCs (OE-MSCs) are a new population of neural crest-derived stem cells that can proliferate and differentiate into SCs and can be considered a promising autologous alternative to produce SCs. Regardless, a biomimetic physicochemical microenvironment in NGC such as electroconductive substrate can affect the fate of transplanted stem cells, including differentiation toward SCs and nerve regeneration. Therefore, in this study, the effect of 3D printed polycaprolactone (PCL)/polypyrrole (PPy) conductive scaffolds on differentiation of human OE-MSCS into functional SC-like phenotypes was investigated. Biological evaluation of 3D printed scaffolds was examined by in vitro culturing the OE-MSCs on samples surfaces, and conductivity showed no effect on increased cell attachment, proliferation rate, viability, and distribution. In contrast, immunocytochemical staining and real-time polymerase chain reaction analysis indicated that 3D structures coated with PPy could provide a favorable microenvironment for OE-MSCs differentiation. In addition, it was found that differentiated OE-MSCs within PCL/PPy could secrete the highest amounts of nerve growth factor and brain-derived neurotrophic factor neurotrophic factors compared to pure PCL and 2D culture. After co-culturing with PC12 cells, a significant increase in neurite outgrowth on PCL/PPy conductive scaffold seeded with differentiated OE-MSCs. These findings indicated that 3D printed PCL/PPy conductive scaffold could support differentiation of OE-MSCs into SC-like phenotypes to promote neurite outgrowth, suggesting their potential for neural tissue engineering applications., (© 2022 Wiley Periodicals LLC.)

Motor neuron diseases such as spinal cord injuries and amyotrophic lateral sclerosis are known as the most common disorders worldwide. Using stem cells (e.g., human umbilical cord blood mesenchymal stem cells) is currently a potent medical approach for modulating the impact of neural damages and regeneration of spinal cord injuries. MicroRNAs (miRNA) are taken into account as principal regulators during differentiation. The miRNAs play a significant role in stem cell self-renewal and fate determination. There are few studies on how miRNAs regulate neural differentiation in stem cells. The purpose of this study is to explore miRNA profiles of CB-MSCs during differentiation into motor neuron-like cells. Human CB-MSCs were isolated and characterized using flow cytometry. Cell differentiation has been induced by combining retinoic acid (RA) and sonic hedgehog (Shh) in a two-step protocol for 14 days. Then, cell differentiation was confirmed by immunocytochemistry and flow cytometry. The miRNA was analyzed using Illumina/Solexa sequencing platform. In this regard, three libraries were prepared to investigate the effect of these two biological morphogens on the miRNA profile of the differentiating cells. These libraries were Control (non-treated CB-MSCs), Test 1 (RA + /Shh +), and Test 2 (RA-/Shh-). Quantitative RT-PCR was employed to verify miRNA expression. CB-MSCs were spindle-shaped in morphology, and they did not express hematopoietic markers. After differentiation, the cells expressed motor neuron markers (i.e., Islet-1, SMI-32, and ChAT) at the protein level after 14 days. The analysis of miRNA sequencing demonstrated a significant up-regulation of miR-9-5p and miR-324-5p in Test 1 (RA + /Shh +). Also, there is a considerable down-regulation of mir-137 and let-7b in Test 2 (RA-/Shh-). These results have been obtained by comparing them with the Control library. Indeed, they were responsible for neuron and motor neuron differentiation and suppression of proliferation in neural progenitor cells. Furthermore, significant up-regulation was detected in some novel microRNAs involved in cholinergic, JAK-STAT, and Hedgehog and MAPK signaling pathways. CB-MSCs are potent to express motor neuron markers. This procedure has been performed by developing a two-week protocol and employing Shh and RA. The miRNA profile analysis showed a significant up-regulation in the expression of some miRs involved in neuron differentiation and motor neuron maturation. MiR-9-5p and miR-324-5p were up-regulated at the early stage of differentiation. Also, miR-137 and miR-let-7b were downregulated in the absence of RA and Shh. Furthermore, several novel miRNAs involved in cholinergic, Hedgehog, MAPK, and JAK-STAT signaling pathways have been detected. However, further studies are still necessary to validate their functions during motor neuron generation and maturation., (© 2022. The Author(s).)

Peripheral nerve injury is a common medical condition that has a great impact on patient quality of life. Currently, surgical management is considered to be a gold standard first-line treatment; however, is often not successful and requires further surgical procedures. Commercially available FDA- and CE-approved decellularized nerve conduits offer considerable benefits to patients suffering from a completely transected nerve but they fail to support neural regeneration in gaps > 30 mm. To address this unmet clinical need, current research is focused on biomaterial-based therapies to regenerate dysfunctional neural tissues, specifically damaged peripheral nerve, and spinal cord. Recently, attention has been paid to the capability of graphene-based materials (GBMs) to develop bifunctional scaffolds for promoting nerve regeneration, often via supporting enhanced neural differentiation. The unique features of GBMs have been applied to fabricate an electroactive conductive surface in order to direct stem cells and improve neural proliferation and differentiation. The use of GBMs for nerve tissue engineering (NTE) is considered an emerging technology bringing hope to peripheral nerve injury repair, with some products already in preclinical stages. This review assesses the last six years of research in the field of GBMs application in NTE, focusing on the fabrication and effects of GBMs for neurogenesis in various scaffold forms, including electrospun fibres, films, hydrogels, foams, 3D printing, and bioprinting.

The tympanic membrane (TM), more commonly known as the eardrum, consists of a thin layer of tissue in the human ear that receives sound vibrations from outside of the body and transmits them to the auditory ossicles. The TM perforations (TMPs) are a common ontological condition, which in some cases can result in permanent hearing loss. Despite the spontaneous healing capacity of the TM to regenerate in the majority of cases of acute perforation, chronic perforations require surgical interventions. However, the disadvantages of the surgical procedure include infection, anesthetic risks, and high failure of graft patency. The tissue engineering strategy, which includes the applications of a three-dimensional (3D) scaffold, cells, and biomolecules or a combination of them for the closure of chronic perforation, has been considered as an emerging treatment. Using this approach, emerging products are currently under development to regenerate the TM structure and its properties. This research aimed to highlight the problems with the current methods of TMP treatment, and critically evaluate the tissue engineering approaches, which may overcome these drawbacks. The focus of this review is on recent literature to critically discuss the emerging advanced materials used as a 3D scaffold in the development of a TM with cellular engineering, biomolecules, cells, and the fabrications of the TM and its pathway to the clinical application. In this review, we discuss the properties of TM and the advantages and disadvantages of the current clinical products for repair and replacement of the TM. Furthermore, we provide an overview of the in vitro and preclinical studies of emerging products over the past 5 years. The results of recent preclinical studies suggest that the tissue engineering field holds significant promise.

The modification of poly ( l -lactic acid) (PLLA) electrospun nanofibrous scaffolds was carried out by blending with second-generation poly amidoamine (PAMAM) for enhancement of their ionic conductivity. The samples containing PLLA and various amounts of PAMAM (1%, 3%, 5%, and 7% by wt.) were fabricated by electrospinning techniques. The electrospun fibers were characterized using scanning electron microscopy (SEM), porosity, Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry, contact angle measurement, water uptake measurement, mechanical properties, and electrical properties. Furthermore, in vitro degradation study and cell viability assay were investigated in biomaterial applications. Creating amide groups through aminolysis reaction was confirmed by FTIR analysis successfully. The results reveal that adding PAMAM caused an increase in fiber diameter, crystallinity percentage, hydrophilicity, water absorption, elongation-at-break, and OE-mesenchymal stem cell viability. It is worth mentioning that this is the first report investigating the conductivity of PLLA/PAMAM nanofiber. The results revealed that by increasing the amount of PAMAM, the ionic conductivity of scaffolds was enhanced by about nine times. Moreover, the outcomes indicated that the presence of PAMAM could improve the limitations of PLLA like hydrophobicity, lack of active group, and poor cell adhesion., (© 2021 IOP Publishing Ltd.)

The occurrence of anosmia, the loss or change in sense of smell, is one of the most common symptoms of COVID-19 experienced by almost 53% of those affected. Several hypotheses explain the mechanism of anosmia in patients suffering from COVID-19. This study aims to review the related mechanisms and answer the questions regarding COVID-19-related anosmia as well as propose a new strategy for treatment of long-term anosmia as a result of COVID-19 infection. This paper covers all of the studies investigating olfactory disorders following COVID-19 infection and explains the possible reasons for the correlated anosmia, including olfactory cleft syndrome, local inflammation in the nasal epithelium, early apoptosis of olfactory cells, changes in olfactory cilia and odor transmission, damage to microglial cells, effect on olfactory bulbs, epithelial olfactory injury, and impairment of olfactory neurons and stem cells. The key questions that arise in this field have been discussed, such as why prevalent anosmia is varied among the age categories and among sexes and the correlation of anosmia with mild or severe COVID-19 infection. The angiotensin-converting enzyme 2 receptor is a significant player in the mechanism of anosmia in COVID-19 patients. Based on current studies, a novel approach to treat long-COVID-19 with ongoing anosmia has been proposed. The fields of smart drug delivery, tissue engineering, and cell therapy provide a hypothesized strategy that can minimize the side effects of current treatments and support efficient recovery of the olfactory system.

Background: Therapy based stem cells have offered a novel therapeutic approach for the improvement of neurodegenerative diseases, specially Parkinson. Hence, developing a well-established culture model with appropriate stem cells is extremely crucial in regenerative engineering to provide efficient targeted cells. Human adult mesenchymal stem cells derived from adipose tissue (hADSCs) have emerged as a promising source of stem cells due to their unique potentials of self-renewal and differentiation into other stem cells. The purpose of this study was to investigate the differentiation capacity of hADSCs into dopaminergic and neuron-like cells in the 3D culture plate (Matrigel)., Methods and Materials: hADSCs were obtained from adipose tissues of patients and then characterized morphologically with flowcytometry. Isolated cells were harvested to perform differentiation on Matrigel and tissue culture plate (TCP) supplemented with induction factors. The survival rate of cells during neural induction was monitored by MTT. The expression of specific cell markers was analyzed by QRT-PCR and immunocytochemistry on days 2, 8 and 14. The level of released dopamine was measured using HPLC technique., Results: Matrigel had a positive effect on maintaining cell growth compared to those on TCP. Moreover, the number of TH and MAPII positive cells is substantially higher in Matrigel than in TCP. Sox2 and Nestin had a prominent expression in hADSCs within the first days of differentiation. The gene expression of neural markers such as TH, Nurr1, LMX1A and DAT was detected and increased after day 8. Moreover, the dopamine released in the cell harvested on Matrigel was greater than those seeded on TCP., Conclusions: Overall, hADSCs could generate dopaminergic cells, which suggest its strong capability to serve as a tool for Parkinson disease model in the regenerative medicine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, we fabricated two different arrangements of laminated composite scaffolds based on Alginate:Alginate sulfate hydrogel, PCL:Gelatin electrospun mat, and Kartogenin-PLGA nanoparticles (KGN-NPs). The optimized composite scaffold revealed a range of advantages such as improved mechanical features as well as less potential of damage (less dissipated energy), interconnected pores of hydrogel and fiber with adequate pore size, excellent swelling ratio, and controlled biodegradability. Furthermore, the synthesized KGN-NPs with spherical morphology were incorporated into the composite scaffold and exhibited a linear and sustained release of KGN within 30 days with desirable initial burst reduction (12% vs. 20%). Additionally, the cytotoxicity impact of the composite was evaluated. Resazurin assay and Live/Dead staining revealed that the optimized composite scaffold has no cytotoxic effect and could improve cell growth. Overall, according to the enhanced mechanical features, suitable environment for cellular growth, and sustained drug release, the optimized scaffold would be a good candidate for tissue regeneration., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Among the various therapeutic procedures used for improving PD, stem cell-based therapy has been shown to be a promising method. Olfactory ectomesenchymal stem cells (OE-MSCs) are a great source of stem cells for PD. Also, the intranasal administration (INA) of stem cells to the neural lesion has several advantages over the other approaches to cellular injections. However, improving the efficacy of INA to produce the highest number of cells at the lesion site has always been a controversial issue. For this purpose, this study was designed to apply the magnetically targeted cell delivery (MTCD) approach to OE-MSCs in the injured striatum area through the IN route in order to explore their outcomes in rat models of PD. Animals were randomly classified into four groups including control, PD model, treatment-NTC (treated with INA of non-target cells), and treatment-TC (treated with INA of target cells). The Alg-SPIONs-labeled OE-MSCs were stained successfully using the Prussian blue method with an intracellular iron concentration of 2.73 pg/cell. It was able to reduce signal intensity in the striatum region by increasing the number of these cells, as shown by the magnetic resonance imaging (MRI). Behavioral evaluation revealed that the administration of OE-MSCs with this novel advanced stem cell therapy alleviated Parkinson's motor dysfunction. Further, histological evaluations confirmed the functional enhancement of dopaminergic neuron cells by the expression of Nurr1, Dopamine transporter (DAT), and paired-like homeodomain transcription factor 3 (TH). Overall, this study showed that INA of OE-MSCs in the MTCD approach enhanced stem cells' therapeutic effects in PD models., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

For bone tissue engineering, stem cell-based therapy has become a promising option. Recently, cell transplantation supported by polymeric carriers has been increasingly evaluated. Herein, we encapsulated human olfactory ectomesenchymal stem cells (OE-MSC) in the collagen hydrogel system, and their osteogenic potential was assessed in vitro and in vivo conditions. Collagen type I was composed of four different concentrations of (4 mg/mL, 5 mg/mL, 6 mg/mL, 7 mg/mL). SDS-Page, FTIR, rheologic test, resazurin assay, live/dead assay, and SEM were used to characterize collagen hydrogels. OE-MSCs encapsulated in the optimum concentration of collagen hydrogel and transplanted in rat calvarial defects. The tissue samples were harvested after 4- and 8-weeks post-transplantation and assessed by optical imaging, micro CT, and H&E staining methods. The highest porosity and biocompatibility were confirmed in all scaffolds. The collagen hydrogel with 7 mg/mL concentration was presented as optimal mechanical properties close to the naïve bone. Furthermore, the same concentration illustrated high osteogenic differentiation confirmed by real-time PCR and alizarin red S methods. Bone healing has significantly occurred in defects treated with OE-MSCs encapsulated hydrogels in vivo. As a result, OE-MSCs with suitable carriers could be used as an appropriate cell source to address clinical bone complications.

One of the complex neurodegenerative disorders is Parkinson disease (PD). PD is mainly caused by dopaminergic (DAergic) neuron degeneration in the midbrain. The loss of DAergic neurons is considered as a key reason of motor functional defects in PD patients. Cell replacement strategies are considered as an alternative remedy to effectively address neurodegeneration in PD. In this report, we evaluated the restorative effect of human olfactory ecto-mesenchymal stem cells (OE-MSCs) in rat models of PD. Accordingly, human OE-MSCs were isolated and phenotypically characterized by flow cytometry and immunocytochemistry. Next, the undifferentiated OE-MSCs were unilaterally transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-lesioned rat models, followed by molecular and histological analyzes as well as assessment of motor skills. Our results displayed that the grafting of OE-MSCs increased the expression of DAergic markers namely dopamine transporter (DAT), tyrosine hydroxylase (TH), nuclear receptor related-1 (Nurr1) in a 6-OHDA model compared with that of control, detected by immunohistochemical staining and western blot. Moreover, noticeable improvements in motor coordination, muscle activity and locomotor performance were observed in 6-OHDA model of PD following OE-MSCs transplantation. Taken together, our finding indicates that undifferentiated OE-MSCs might be counted as an appropriate source for cell replacement therapy particularly aimed at PD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which is caused by the loss of dopaminergic (DAergic) neurons. Thus, cell replacement therapy (CRT) might be regarded as an alternative therapy to effectively treat motor functional defects in PD patients. Human olfactory ectomesenchymal stem cells (OE-MSCs) are a novel type of mesenchymal stem cells (MSCs) with a strong tendency to differentiate into DAergic neurons. However, there are various barriers to successful CRT including the proliferation capacity of stem cells at higher passage numbers as well as the route of stem cell delivery. In this regard, we aimed to explore the efficacy of late passage OE-MSC administration through the intranasal (IN) route in PD rat models. Herein, the proliferation capacity of OE-MSCs was compared at early and late passage numbers; then, the results were validated via RNA sequencing analysis. Subsequently, the efficacy of IN injection of late passage OE-MSC in PD models was evaluated. The results manifested the absence of noticeable differences in proliferation capacity and signaling pathways in OE-MSCs at early and late passage numbers. Moreover, it was found that the IN administration of OE-MSCs with a high passage number substantially increased the levels of DAergic markers and improved the motor function in rat models of PD. Overall, our findings suggested that OE-MSCs with a high passage number are a promising CRT candidate due to their fundamental potential to provide a large number of cells with an enormous proliferation capacity. Moreover, they exhibit the high efficiency of IN administration as a noninvasive route of late-passage OE-MSC delivery for CRT, particularly for PD.

Regenerative medicine offers the potential to repair or substitute defective tissues by constructing active tissues to address the scarcity and demands for transplantation. The method of forming 3D constructs made up of biomaterials, cells, and biomolecules is called bioprinting. Bioprinting of stem cells provides the ability to reliably recreate tissues, organs, and microenvironments to be used in regenerative medicine. 3D bioprinting is a technique that uses several biomaterials and cells to tailor a structure with clinically relevant geometries and sizes. This technique's promise is demonstrated by 3D bioprinted tissues, including skin, bone, cartilage, and cardiovascular, corneal, hepatic, and adipose tissues. Several bioprinting methods have been combined with stem cells to effectively produce tissue models, including adult stem cells, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and differentiation techniques. In this review, technological challenges of printed stem cells using prevalent naturally derived bioinks (e.g., carbohydrate polymers and protein-based polymers, peptides, and decellularized extracellular matrix), recent advancements, leading companies, and clinical trials in the field of 3D bioprinting are delineated.

Human olfactory ecto-mesenchymal stem cells (hOE-MSCs) derived from the human olfactory mucosa (OM) can be easily isolated and expanded in cultures while their immense plasticity is maintained. To mitigate ethical concerns, the hOE-MSCs can be also transplanted across allogeneic barriers, making them desirable cells for clinical applications. The main purpose of this study was to evaluate the effects of administering the hOE-MSCs on a spinal cord injury (SCI) model of rats. These cells were accordingly isolated and cultured, and then treated in the neurobasal medium containing serum-free Dulbecco's Modified Essential Medium (DMEM) and Ham's F-12 Medium (DMEM/F12) with 2% B27 for two days. Afterwards, the pre-induced cells were incubated in N2B27 with basic fibroblast growth factor (bFGF), fibroblast growth factor 8b (FGF8b), sonic hedgehog (SHH), and ascorbic acid (vitamin C) for six days. The efficacy of the induced cells was additionally evaluated using immunocytochemistry (ICC) and real-time polymerase chain reaction (RT-PCR). The differentiated cells were similarly transplanted into the SC contusions. Functional recovery was further conducted on a weekly basis for eight consecutive weeks. Moreover, cell integration was assessed via conventional histology and ICC, whose results revealed the expression of choline acetyltransferase (ChAT) marker at the induction stage. According to the RT-PCR findings, the highest expression level of insulin gene-enhancer protein (islet-1), oligodendrocyte transcription factor (Olig2), and homeobox protein HB9 was observed at the induction stage. The number of engraftment cells also rose (approximately by 2.5 % ± 0.1) in the motor neuron-like cells derived from the hOE-MSCs-grafted group compared with the OE-MSCs-grafted one. The functional analysis correspondingly revealed that locomotor and sensory scores considerably improved in the rats in the treatment group. These findings suggested that motor neuron-like cells derived from the hOE-MSCs could be utilized as an alternative cell-based therapeutic strategy for SCI., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Current hyaluronic acid-based hydrogels often cause cytotoxicity to encapsulated cells and lack the adhesive property required for effective biomedical and tissue engineering applications. Provision of the cell-adhesive surface is an important requirement to improve its biocompatibility. An aqueous solution of hyaluronic acid possessing phenolic hydroxyl (HA-Ph) moieties is gellable via a horseradish peroxidase (HRP)-catalyzed oxidative cross-linking reaction. This study evaluates the effect of different degrees of cross-linked Ph moieties on cellular adhesiveness and proliferation on the resultant enzymatically cross-linked HA-Ph hydrogels. Mechanical characterization demonstrated that the compression force of engineered hydrogels could be tuned in the range of 0.05-35 N by changing conjugated Ph moieties in the precursor formulation. The water contact angle and water content show hydrophobicity of hydrogels increased with increasing content of cross-linked Ph groups. The seeded mouse embryo fibroblast-like cell line and human cervical cancer cell line, on the HA-Ph hydrogel, proved cell attachment and spreading with a high content of cross-linked Ph groups. The HA-Ph with a higher degree of Ph moieties shows the maximum degree of cell adhesion, spreading, and proliferation which presents this hydrogel as a suitable biomaterial for biomedical and tissue engineering applications., (© 2020 Wiley Periodicals LLC.)

Introduction: Cholinergic-associated diseases currently constitute a significant cause of neurological and neurodegenerative disabilities. As the drugs are not efficient in improving the suffered tissues, stem cell treatment is considered an effective strategy for substituting the lost cells., Methods: In the current study, we set out to investigate the differentiation properties of human Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) into cholinergic-like cells by two morphogens of Retinoic Acid (RA) and Sonic Hedgehog (Shh) using a three-step in vitro procedure. The results were evaluated using real-time PCR, flow cytometry, and immunocytochemistry for two weeks., Results: Our data showed that the cells could express cholinergic specific markers, including Islet-1, Acetylcholinesterase (AChE), SMI-32, and Nestin, at mRNA and protein levels. We could also quantitatively evaluate the expression of Islet-1, AChE, and Nestin at 14 days post-induction using flow cytometry., Conclusion: Human AD-MSCs are potent cells to differentiate into cholinergic-like cells in the presence of RA and Shh through a three-step protocol. Thus, they could be a suitable cell candidate for the regeneration of cholinergic-associated diseases. However, more functional and electrophysiological analyses are needed in this regard., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2021 Iranian Neuroscience Society.)

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.

Cellular transplant therapy is one of the most common therapeutic strategies used to mitigate symptoms of neurodegenerative diseases such as Huntington's disease (HD). Briefly, the main goal of the present study was to investigate HD's motor deficits through the olfactory ecto-mesenchymals stem cells (OE-MSC) secretome. OE-MSCs were characterized immunophenotypically by the positive expression of CD73, CD90 and CD105. Also, three specific markers of OE-MSCs were obtained from the nasal cavity of human volunteers. The main features of OE-MSCs are their high proliferation, ease of harvesting and growth factor secretion. All animals were randomly assigned to three groups: control, 3-NP + vehicle treated and 3-NP + Cell groups. In both experimental groups, the subjects received intraperitoneal 3-NP (30 mg/kg) injections once a day for five consecutive days, followed by the bilateral intra-striatal implantation of OE-MSCs in the 3-NP + Cell group. Muscular function was assessed by electromyography and rotarod test, and the locomotor function was evaluated using the open field test. According to our findings, striatal transplants of OE-MSCs reduced microglial inflammatory factor, the tumor necrosis factor (TNFα) in the 3-NP + Cell group, with a significant reduction in RIP3, the markers of necroptosis in striatum. In addition to the remarkable recovery of the striatal volume after engraftment, the motor activities were enhanced in the 3-NP + cell group compared to the 3-NP + vehicle group. Taken together, our results demonstrated the in vivo advantages of OE-MSCs treatment in an HD rat model with numerous positive paracrine effects including behavioral and anatomical recovery., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Functional improvement after spinal cord injury remains an unsolved difficulty. Glial scars, a major component of SCI lesions, are very effective in improving the rate of this recovery. Such scars are a result of complex interaction mechanisms involving three major cells, namely, astrocytes, oligodendrocytes, and microglia. In recent years, scientists have identified two subtypes of reactive astrocytes, namely, A1 astrocytes that induce the rapid death of neurons and oligodendrocytes, and A2 astrocytes that promote neuronal survival. Moreover, recent studies have suggested that the macrophage polarization state is more of a continuum between M1 and M2 macrophages. M1 macrophages that encourage the inflammation process kill their surrounding cells and inhibit cellular proliferation. In contrast, M2 macrophages promote cell proliferation, tissue growth, and regeneration. Furthermore, the ability of oligodendrocyte precursor cells to differentiate into adult oligodendrocytes or even neurons has been reviewed. Here, we first scrutinize recent findings on glial cell subtypes and their beneficial or detrimental effects after spinal cord injury. Second, we discuss how we may be able to help the functional recovery process after injury., Competing Interests: I wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. I confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. I further confirm that the order of authors listed in the manuscript has been approved by all of authors. I confirm that the authors have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing I confirm that we have followed the regulations of our institutions concerning intellectual property., (© 2021 The Authors.)

The design of 3D hydrogel constructs to elicit highly controlled cell response is a major field of interest in developing tissue engineering. The bioactivity of encapsulated cells inside pure alginate hydrogel is limited by its relatively inertness. Combining short nanofibers within a hydrogel serves as a promising method to develop a cell friendly environment mimicking the extracellular matrix. In this paper, we fabricated alginate hydrogels incorporating different magnetic short nanofibers (M.SNFs) content for olfactory ecto-mesenchymal stem cells (OE-MSCs) encapsulation. Wet-electrospun gelatin and superparamagnetic iron oxide nanoparticles (SPIONs) nanocomposite nanofibers were chopped using sonication under optimized conditions and subsequently embedded in alginate hydrogels. The storage modulus of hydrogel without M.SNFs as well as with 1 and 5 mg/mL of M.SNFs were in the range of nerve tissue. For cell encapsulation, OE-MSCs were used as a new hope for neuronal regeneration due to their neural crest origin. Resazurin analyses and LIVE/DEAD staining confirmed that the composite hydrogels containing M.SNFs can preserve the cell viability after 7 days. Moreover, the proliferation rate was enhanced in M.SNF/hydrogels compared to alginate hydrogel. The presence of SPIONs in the short nanofibers can accelerate neural-like differentiation of OE-MSCs rather than the sample without SPIONs., (Copyright © 2020 Elsevier B.V. All rights reserved.)

One of the most effective approaches for treatment of chronic rhinosinusitis is the use of hydrogel scaffolds with the sustained release of a given required drug. With this in mind, first, we synthesized and characterized poly (lactide-co-glycolide) (PLGA) micro and nano particles loaded with dexamethasone (DEX). We observed a 7-day release of DEX from nanoparticles, while the microparticles showed a 22-day release profile. Due to their slower rate of release, the PLGA microparticles loaded with DEX (PLGADEX microparticles) were specifically chosen for this study. As a second step, chitosan/polyvinylpyrrolidone (PVP) based hydrogels were prepared in various weight ratios and the PLGADEX microparticles were optimized in their structure based on variable gelation times. The morphological studies showed PLGADEX microparticles homogenously dispersed in the hydrogels. Moreover, the effect of weight ratio in the presence and absence of optimum percentage of PLGADEX microparticles was studied. The resultant hydrogels demonstrated a range of advantages, including good mechanical strength, porous morphology, amorphous structure, high swelling ratio, controlled biodegradability rate, and antibacterial activity. Additionally, a cytotoxicity analysis confirmed that the hydrogel scaffolds do not have adverse effects on the cells; our release studies in the hydrogel with the highest PVP content also showed 80% release after 30 days. Based on these results we were able to predict and control some of the mechanical properties, including the microstructure of the scaffolds, as well as the drug release, by optimizing the polymers - microparticle concentration, plus their resulting interactions. This optimized hydrogel can become part of a suitable alternative for treatment of allergic rhinitis and chronic sinusitis., (Copyright © 2020 Elsevier B.V. All rights reserved.)