Applications of blood plasma derivatives for cutaneous wound healing: A mini-review of clinical studies.

Skin injuries are a global healthcare problem. Chronic ulcers do not heal in a timely fashion, so it is essential to help the body with skin repair. There are some treatments that have been applied to chronic ulcers. One of these treatments is growth factor (GF) therapy. Platelet-rich plasma (PRP) and Platelet-poor plasma (PPP) are two types of plasma derivatives containing many GFs important for wound healing. Several works have reported their application in wound healing and tissue regeneration. The use of autologous PRP is now an adequate alternative in regenerative medicine. It was also demonstrated that PPP is a hemostatic agent for wounds. This review has studied the latest clinical studies, which have applied PRP and PPP to patients with chronic wounds.

Collagen short nanofiber-embedded chondroitin sulfate-hyaluronic acid nanocomposite: A cartilage-mimicking in situ-forming hydrogel with fine-tuned properties.

In situ-forming hydrogels that possess the ability to be injected in a less invasive manner and mimic the biochemical composition and microarchitecture of the native cartilage extracellular matrix are desired for cartilage tissue engineering. Besides, gelation time and stiffness of the hydrogel are two interdependent factors that affect cells' distribution and fate and hence need to be optimized. This study presented a bioinspired in situ-forming hydrogel composite of hyaluronic acid (HA), chondroitin sulfate (CS), and collagen short nanofiber (CSNF). HA and CS were functionalized with aldehyde and amine groups to form a gel through a Schiff-base reaction. CSNF was fabricated via electrospinning, followed by fragmentation by ultrasonics. Gelation time (11-360 s) and compressive modulus (1.4-16.2 kPa) were obtained by varying the concentrations of CS, HA, CSNFs, and CSNFs length. The biodegradability and biocompatibility of the hydrogels with varying gelation and stiffness were also assessed in vitro and in vivo. At three weeks, the assessment of hydrogels' chondrogenic differentiation also yields varying levels of chondrogenic differentiation. The subcutaneous implantation of the hydrogels in a mouse model indicated no severe inflammation. Results demonstrated that the injectable CS/HA@CSNF hydrogel was a promising hydrogel for tissue engineering and cartilage regeneration.

Preparation of bilayer tissue-engineered polyurethane/poly-L-lactic acid nerve conduits and their in vitro characterization for use in peripheral nerve regeneration.

BACKGROUND: Due to loss of peripheral nerve structure and/or function resulting from trauma, accidents, and other causes, peripheral nerve injuries continue to be a major clinical problem. These injuries can cause partial or total loss of sensory, motor, and autonomic capabilities as well as neuropathic pain. PNI affects between 13 and 23 out of every 100,000 people annually in developed countries. Regeneration of damaged nerves and restoration of function after peripheral nerve injury remain significant therapeutic challenges. Although autologous nerve graft transplantation is a viable therapy option in several clinical conditions, donor site morbidity and a lack of donor tissue often hinder full functional recovery. Biomimetic conduits used in tissue engineering to encourage and direct peripheral nerve regeneration by providing a suitable microenvironment for nerve ingrowth are only one example of the cutting-edge methods made possible by this field. Many innate extracellular matrix (ECM) structures of different tissues can be successfully mimicked by nanofibrous scaffolds. Nanofibrous scaffolds can closely mimic the surface structure and morphology of native ECMs of many tissues. METHODS: In this study, we have produced bilayer nanofibrous nerve conduit based on poly-lactic acid/polyurethane/multiwall carbon nanotube (PLA/PU/MWCNT), for application as composite scaffolds for static nerve tissue engineering. The contact angle was indicated to show the hydrophilicity properties of electrospun nanofibers. The SEM images were analyzed to determine the fiber's diameters, scaffold morphology, and endometrial stem cell adhesion. Moreover, MTT assay and DAPI staining were used to show the viability and proliferation of endometrial stem cells. RESULTS: The constructed bilayer PLA/PU/MWCNT scaffolds demonstrated the capacity to support cell attachment, and the vitality of samples was assessed using SEM, MTT assay, and DAPI staining technique. CONCLUSIONS: According to an in vitro study, electrospun bilayer PLA/PU/MWCNT scaffolds can encourage the adhesion and proliferation of human endometrial stem cells (hEnSCs) and create the ideal environment for increasing cell survival.

Clinical Trials of Mesenchymal Stem Cells for the Treatment of COVID 19.

Mesenchymal Stem Cells (MSCs) are being investigated as a treatment for a novel viral disease owing to their immunomodulatory, anti-inflammatory, tissue repair and regeneration characteristics, however, the exact processes are unknown. MSC therapy was found to be effective in lowering immune system overactivation and increasing endogenous healing after SARS-CoV-2 infection by improving the pulmonary microenvironment. Many studies on mesenchymal stem cells have been undertaken concurrently, and we may help speed up the effectiveness of these studies by collecting and statistically analyzing data from them. Based on clinical trial information found on clinicaltrials. gov and on 16 November 2020, which includes 63 clinical trials in the field of patient treatment with COVID-19 using MSCs, according to the trend of increasing studies in this field, and with the help of meta-analysis studies, it is possible to hope that the promise of MSCs will one day be realized. The potential therapeutic applications of MSCs for COVID-19 are investigated in this study.

Enhanced spinal cord regeneration by gelatin/alginate hydrogel scaffolds containing human endometrial stem cells and curcumin-loaded PLGA nanoparticles in rat.

Spinal cord injury (SCI) is a serious problem with a high prevalence worldwide. The weak capability of the spinal cord for regeneration in association with upregulation of inflammatory factors is two key obstacles against a full SCI repair. Curcumin is a natural substance with anti-inflammatory and neuroprotective effects. Here, we have used a combined strategy using stem cells and hybrid hydrogel scaffolds loaded with curcumin for SCI repair. Curcumin-loaded PLGA nanoparticles were prepared, characterized, and encapsulated into gelatin/alginate hydrogel scaffolds, which were then seeded by human endometrial stem cells (hEnSCs). The resulting construct was studied using in vitro and in vivo experiments on rat models. DLS, SEM, Zeta potential, and FTIR data confirmed the successful addition of curcumin to PLGA nanoparticles. SEM analyses indicated the successful addition of curcumin-loaded nanoparticles into the gelatin/alginate scaffold, as well as the adherence of the seeded EnSCs. Based on the results, the prepared constructs not only allowed the controlled release of curcumin but also could support the survival and growth of hEnSCs. Based on the results of BBB and histological experiments, the highest BBB score was related to the combined strategy, consistent with histological outcomes, in which our hEnSC-seeded gelatin/alginate scaffold containing curcumin-loaded nanoparticles led to improved structures of the white and gray matters in the SCI site, being indicative of the superior nerve fiber regeneration, compared to other studied groups. These results indicate the efficiency of the proposed method for SCI repair and broaden the scope for subsequent studies on spinal cord regeneration.

Differentiation of human endometrial stem cells encapsulated in alginate hydrogel into oocyte-like cells.

Introduction: Human endometrial mesenchymal stem cells (hEnMSCs) are a rich source of mesenchymal stem cells (MSCs) with multi-lineage differentiation potential, making them an intriguing tool in regenerative medicine, particularly for the treatment of reproductive and infertility issues. The specific process of germline cell-derived stem cell differentiation remains unknown, the aim is to study novel ways to achieve an effective differentiation method that produces adequate and functioning human gamete cells. Methods: We adjusted the optimum retinoic acid (RA) concentration for enhancement of germ cell-derived hEnSCs generation in 2D cell culture after 7 days in this study. Subsequently, we developed a suitable oocyte-like cell induction media including RA and bone morphogenetic protein 4 (BMP4), and studied their effects on oocyte-like cell differentiation in 2D and 3D cell culture media utilizing cells encapsulated in alginate hydrogel. Results: Our results from microscopy analysis, real-time PCR, and immunofluorescence tests revealed that 10 µM RA concentration was the optimal dose for inducing germ-like cells after 7 days. We examined the alginate hydrogel structural characteristics and integrity by rheology analysis and SEM microscope. We also demonstrated encapsulated cell viability and adhesion in the manufactured hydrogel. We propose that in 3D cell cultures in alginate hydrogel, an induction medium containing 10 µM RA and 50 ng/mL BMP4 can enhance hEnSC differentiation into oocyte-like cells. Conclusion: The production of oocyte-like cells using 3D alginate hydrogel may be viable in vitro approach for replacing gonad tissues and cells.

Injectable hydrogels in central nervous system: Unique and novel platforms for promoting extracellular matrix remodeling and tissue engineering.

Repairing central nervous system (CNS) is difficult due to the inability of neurons to recover after damage. A clinically acceptable treatment to promote CNS functional recovery and regeneration is currently unavailable. According to recent studies, injectable hydrogels as biodegradable scaffolds for CNS tissue engineering and regeneration have exceptionally desirable attributes. Hydrogel has a biomimetic structure similar to extracellular matrix, hence has been considered a 3D scaffold for CNS regeneration. An interesting new type of hydrogel, injectable hydrogels, can be injected into target areas with little invasiveness and imitate several aspects of CNS. Injectable hydrogels are being researched as therapeutic agents because they may imitate numerous properties of CNS tissues and hence reduce subsequent injury and regenerate neural tissue. Because of their less adverse effects and cost, easier use and implantation with less pain, and faster regeneration capacity, injectable hydrogels, are more desirable than non-injectable hydrogels. This article discusses the pathophysiology of CNS and the use of several kinds of injectable hydrogels for brain and spinal cord tissue engineering, paying particular emphasis to recent experimental studies.

The Effect of Fetal Bovine Acellular Dermal Matrix Seeded with Wharton's Jelly Mesenchymal Stem Cells for Healing Full-Thickness Skin Wounds.

The treatment of full-thickness skin wounds is a problem in the clinical setting, as they do not heal spontaneously. Extensive pain at the donor site and a lack of skin grafts limit autogenic and allogeneic skin graft availability. We evaluated fetal bovine acellular dermal matrix (FADM) in combination with human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) to heal full-thickness skin wounds. FADM was prepared from a 6-month-old trauma-aborted fetus. WJ-MSCs were derived from a human umbilical cord and seeded on the FADM. Rat models of full-thickness wounds were created and divided into three groups: control (no treatment), FADM, and FADM-WJMSCs groups. Wound treatment was evaluated microscopically and histologically on days 7, 14, and 21 post-surgery. The prepared FADM was porous and decellularized with a normal range of residual DNA. WJ-MSCs were seeded and proliferated on FADM effectively. The highest wound closure rate was observed in the FADM-WJMSC group on days 7 and 14 post-surgery. Furthermore, this group had fewer inflammatory cells than other groups. Finally, in this study, we observed that, without using the differential cell culture media of fibroblasts, the xenogeneic hWJSCs in combination with FADM could promote an increased rate of full-thickness skin wound closure with less inflammation.

Enhanced sciatic nerve regeneration with fibrin scaffold containing human endometrial stem cells and insulin encapsulated chitosan particles: An in vivo study.

BACKGROUND: Based on recent advances in tissue engineering and stem cell therapy in nervous system diseases treatments, this study aimed to investigate sciatic nerve regeneration using human endometrial stem cells (hEnSCs) encapsulated fibrin gel containing chitosan nanoparticle loaded by insulin (Ins-CPs). Stem cells and also Insulin (Ins), which is a strong signaling molecule in peripheral nerve regeneration, play an important role in neural tissue engineering. METHODS: The fibrin hydrogel scaffold containing insulin loaded chitosan particles was synthesized and characterized. Release profiles of insulin from hydrogel was determined through UV-visible spectroscopy. Also, human endometrial stem cells encapsulated in hydrogel and its cell biocompatibility were assigned. Furthermore, the sciatic nerve crush injury was carried out and prepared fibrin gel was injected at the crush injury site by an 18-gage needle. Eight and twelve weeks later, the recovery of motor and sensory function and histopathological evaluation were assessed. RESULTS: The in vitro experiments showed that the insulin can promote hEnSCs proliferation within a certain concentration range. Animals' treatment confirmed that developed fibrin gel containing Ins-CPs and hEnSCs significantly improves motor function and sensory recovery. Hematoxylin and Eosin (H&E) images provided from cross-sectional and, longitudinal-sections of the harvested regenerative nerve showed that regenerative nerve fibers had been formed and accompanied with new blood vessels in the fibrin/insulin/hEnSCs group. CONCLUSION: Our results demonstrated that the prepared hydrogel scaffolds containing insulin nanoparticles and hEnSCs could be considered as a potential biomaterial aimed at regeneration of sciatic nerves.

Mesenchymal Stromal Cells and their EVs as Potential Leads for SARSCoV2 Treatment.

In December 2019, a betacoronavirus was isolated from pneumonia cases in China and rapidly turned into a pandemic of COVID-19. The virus is an enveloped positive-sense ssRNA and causes a severe respiratory syndrome along with a cytokine storm, which is the main cause of most complications. Therefore, treatments that can effectively control the inflammatory reactions are necessary. Mesenchymal Stromal Cells and their EVs are well-known for their immunomodulatory effects, inflammation reduction, and regenerative potentials. These effects are exerted through paracrine secretion of various factors. Their EVs also transport various molecules such as microRNAs to other cells and affect recipient cells' behavior. Scores of research and clinical trials have indicated the therapeutic potential of EVs in various diseases. EVs also seem to be a promising approach for severe COVID-19 treatment. EVs have also been used to develop vaccines since EVs are biocompatible nanoparticles that can be easily isolated and engineered. In this review, we have focused on the use of Mesenchymal Stromal Cells and their EVs for the treatment of COVID-19, their therapeutic capabilities, and vaccine development.

The Role of Advanced Technologies against COVID-19: Prevention, Detection, and Treatments.

Concurrent with the global outbreak of COVID-19, the race began among scientists to generate effective therapeutics for the treatment of COVID-19. In this regard, advanced technology such as nanotechnology, cell-based therapies, tissue engineering and regenerative medicine, nerve stimulation and artificial intelligence (AI) are attractive because they can offer new solutions for the prevention, diagnosis and treatment of COVID-19. Nanotechnology can design rapid and specific tests with high sensitivity for detecting infection and synthases new drugs and vaccines based on nanomaterials to directly deliver the intended antiviral agent to the desired site in the body and also provide new surfaces that do not allow virus adhesion. Mesenchymal stem cells and exosomes secreted from them apply in regenerative medicine and regulate inflammatory responses. Cell therapy and tissue engineering are combined to repair or substitute damaged tissues or cells. Tissue engineering using biomaterials, cells, and signaling molecules can develop new therapeutic and diagnostic platforms and help scientists fight viral diseases. Nerve stimulation technology can augment body's natural ability to modulate the inflammatory response and inhibit pro-inflammatory cytokines and consequently suppress cytokine storm. People can access free online health counseling services through AI and it helps very fast for screening and diagnosis of COVID-19 patients. This study is aimed first to give brief information about COVID-19 and the epidemiology of the disease. After that, we highlight important developments in the field of advanced technologies relevant to the prevention, detection, and treatment of the current pandemic.

The effect of decellularized cartilage matrix scaffolds combined with endometrial stem cell-derived osteocytes on osteochondral tissue engineering in rats.

Since decellularized tissues may offer the instructive niche for cell differentiation and function, their use as cell culture scaffolds is a promising approach for regenerative medicine. To repair osteochondral tissues, developing a scaffold with biomimetic structural, compositional, and functional characteristics is vital. As a result of their heterogeneous structure, decellularized articular cartilage matrix from allogeneic and xenogeneic sources are considered appropriate scaffolds for cartilage regeneration. We developed a scaffold for osteochondral tissue engineering by decellularizing sheep knee cartilage using a chemical technique. DNA content measurements and histological examinations revealed that this protocol completely removed cells from decellularized cartilage. Furthermore, SEM, MTS assay, and H&E staining revealed that human endometrial stem cells could readily adhere to the decellularized cartilage, and the scaffold was biocompatible for their proliferation. Besides, we discovered that decellularized scaffolds could promote EnSC osteogenic differentiation by increasing bone-specific gene expression. Further, it was found that decellularized scaffolds were inductive for chondrogenic differentiation of stem cells, evidenced by an up-regulation in the expression of the cartilage-specific gene. Also, in vivo study showed the high affinity of acellularized scaffolds for cell adhesion and proliferation led to an improved regeneration of articular lesions in rats after 4 weeks. Finally, a perfect scaffold with high fidelity is provided by the developed decellularized cartilage scaffold for the functional reconstruction of osteochondral tissues; these types of scaffolds are helpful in studying how the tissue microenvironment supports osteocytes and chondrocytes differentiation, growth, and function to have a good osteochondral repair effect.

Advanced approaches to regenerate spinal cord injury: The development of cell and tissue engineering therapy and combinational treatments.

Spinal cord injury (SCI) is a central nervous system (CNS) devastate event that is commonly caused by traumatic or non-traumatic events. The reinnervation of spinal cord axons is hampered through a myriad of devices counting on the damaged myelin, inflammation, glial scar, and defective inhibitory molecules. Unfortunately, an effective treatment to completely repair SCI and improve functional recovery has not been found. In this regard, strategies such as using cells, biomaterials, biomolecules, and drugs have been reported to be effective for SCI recovery. Furthermore, recent advances in combinatorial treatments, which address various aspects of SCI pathophysiology, provide optimistic outcomes for spinal cord regeneration. According to the global importance of SCI, the goal of this article review is to provide an overview of the pathophysiology of SCI, with an emphasis on the latest modes of intervention and current advanced approaches for the treatment of SCI, in conjunction with an assessment of combinatorial approaches in preclinical and clinical trials. So, this article can give scientists and clinicians' clues to help them better understand how to construct preclinical and clinical studies that could lead to a breakthrough in spinal cord regeneration.

Injectable nanocomposite hydrogels as an emerging platform for biomedical applications: A review.

Hydrogels have attracted much attention for biomedical and pharmaceutical applications due to the similarity of their biomimetic structure to the extracellular matrix of natural living tissues, tunable soft porous microarchitecture, superb biomechanical properties, proper biocompatibility, etc. Injectable hydrogels are an exciting type of hydrogels that can be easily injected into the target sites using needles or catheters in a minimally invasive manner. The more comfortable use, less pain, faster recovery period, lower costs, and fewer side effects make injectable hydrogels more attractive to both patients and clinicians in comparison to non-injectable hydrogels. However, it is difficult to achieve an ideal injectable hydrogel using just a single material (i.e., polymer). This challenge can be overcome by incorporating nanofillers into the polymeric matrix to engineer injectable nanocomposite hydrogels with combined or synergistic properties gained from the constituents. This work aims to critically review injectable nanocomposite hydrogels, their preparation methods, properties, functionalities, and versatile biomedical and pharmaceutical applications such as tissue engineering, drug delivery, and cancer labeling and therapy. The most common natural and synthetic polymers as matrices together with the most popular nanomaterials as reinforcements, including nanoceramics, carbon-based nanostructures, metallic nanomaterials, and various nanosized polymeric materials, are highlighted in this review.

Improving motor neuron-like cell differentiation of hEnSCs by the combination of epothilone B loaded PCL microspheres in optimized 3D collagen hydrogel.

Spinal cord regeneration is limited due to various obstacles and complex pathophysiological events after injury. Combination therapy is one approach that recently garnered attention for spinal cord injury (SCI) recovery. A composite of three-dimensional (3D) collagen hydrogel containing epothilone B (EpoB)-loaded polycaprolactone (PCL) microspheres (2.5 ng/mg, 10 ng/mg, and 40 ng/mg EpoB/PCL) were fabricated and optimized to improve motor neuron (MN) differentiation efficacy of human endometrial stem cells (hEnSCs). The microspheres were characterized using liquid chromatography-mass/mass spectrometry (LC-mas/mas) to assess the drug release and scanning electron microscope (SEM) for morphological assessment. hEnSCs were isolated, then characterized by flow cytometry, and seeded on the optimized 3D composite. Based on cell morphology and proliferation, cross-linked collagen hydrogels with and without 2.5 ng/mg EpoB loaded PCL microspheres were selected as the optimized formulations to compare the effect of EpoB release on MN differentiation. After differentiation, the expression of MN markers was estimated by real-time PCR and immunofluorescence (IF). The collagen hydrogel containing the EpoB group had the highest HB9 and ISL-1 expression and the longest neurite elongation. Providing a 3D permissive environment with EpoB, significantly improves MN-like cell differentiation and maturation of hEnSCs and is a promising approach to replace lost neurons after SCI.

Characterization of Macroporous Polycaprolactone/Silk Fibroin/Gelatin/Ascorbic Acid Composite Scaffolds and In Vivo Results in a Rabbit Model for Meniscus Cartilage Repair.

OBJECTIVE: Meniscus injuries in the inner avascular zone have weak intrinsic self-healing capacity and often progress to osteoarthritis. This study focused on evaluating the effects of polycaprolactone/silk fibroin/gelatin/ascorbic acid (PCL/SF/Gel/AA) composite scaffolds seeded with adipose-derived mesenchymal stem cells (ASCs), in the meniscus repair. DESIGN: To this end, composite scaffolds were cross-linked using N-hydroxysuccinimide and 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride. Scaffolds were then characterized by scanning electron microscope, mechanical tests, total antioxidant capacity, swelling, and toxicity tests. RESULTS: The PCL/SF/Gel/AA scaffolds exhibited suitable mechanical properties. Furthermore, vitamin C rendered them the highest antioxidant capacity. The PCL/SF/Gel/AA scaffolds also showed good biocompatibility and proliferation for chondrocytes. Moreover, the PCL/SF/Gel/AA scaffold seeded with allogeneic ASCs was engrafted in New Zealand rabbits who underwent unilateral punch defect in the medial meniscus of the right knee. After 2 months postimplantation, macroscopic and histologic studies for new meniscus cartilage were performed. CONCLUSIONS: Our results indicated that the PCL/SF/Gel/AA composite scaffolds seeded with allogeneic ASCs could successfully improve meniscus healing in damaged rabbits.

Defining the role of 17ß-estradiol in human endometrial stem cells differentiation into neuron-like cells.

Human endometrial stem cells (hEnSCs) that can be differentiated into various neural cell types have been regarded as a suitable cell population for neural tissue engineering and regenerative medicine. Considering different interactions between hormones, growth factors, and other factors in the neural system, several differentiation protocols have been proposed to direct hEnSCs towards specific neural cells. The 17ß-estradiol plays important roles in the processes of development, maturation, and function of nervous system. In the present research, the impact of 17ß-estradiol (estrogen, E2) on the neural differentiation of hEnSCs was examined for the first time, based on the expression levels of neural genes and proteins. In this regard, hEnSCs were differentiated into neuron-like cells after exposure to retinoic acid (RA), epidermal growth factor (EGF), and also fibroblast growth factor-2 (FGF2) in the absence or presence of 17ß-estradiol. The majority of cells showed a multipolar morphology. In all groups, the expression levels of nestin, Tuj-1 and NF-H (neurofilament heavy polypeptide) (as neural-specific markers) increased during 14 days. According to the outcomes of immunofluorescence (IF) and real-time PCR analyses, the neuron-specific markers were more expressed in the estrogen-treated groups, in comparison with the estrogen-free ones. These findings suggest that 17ß-estradiol along with other growth factors can stimulate and upregulate the expression of neural markers during the neuronal differentiation of hEnSCs. Moreover, our findings confirm that hEnSCs can be an appropriate cell source for cell therapy of neurodegenerative diseases and neural tissue engineering.

Enhanced sciatic nerve regeneration by poly-L-lactic acid/multi-wall carbon nanotube neural guidance conduit containing Schwann cells and curcumin encapsulated chitosan nanoparticles in rat.

The main aim of this study was to improve the efficacy of peripheral nerve regeneration by an artificial neural guidance conduit (NGC) as a carrier to transplant allogeneic Schwann cells (SCs) and curcumin encapsulated chitosan nanoparticles (nanocurcumin). The conduit was prepared by poly-L-lactic acid (PLLA) and surface-modified multi-wall carbon nanotubes (mMWCNT) and filled with SCs and nanocurcumin. SCs play an important role in the regeneration of injured peripheral nerve and controlled curcumin release can decrease SCs apoptosis, and enhance the regeneration and functional recovery of injured peripheral nerves. The mechanical properties, contact angle, and cell biocompatibility experiments showed that the optimized concentration of mMWCNT inside PLLA wall of conduits was 0.15 wt%. The drug release experiments showed slower release of curcumin from nanocurcumin samples compared to nanocurcumin encapsulated inside NGC wrapped fibrin gel sample. It was found that simultaneous using of both SCs and curcumin inside NGC had a significant role in sciatic nerve regeneration in vivo. Histological examination revealed a significant increase in the number of axons in injured sciatic nerve following treatment by SCs and nanocurcumin compared to negative control group. Histological evaluation also revealed a significant decrease in the number of vessels in fibrin groups compared to positive control group. The results showed that there was no significant difference between the reaction time and sciatic functional index (SFI) values of rats with injured sciatic nerve treated by NGC/SCs/nanocurcumin sample and autograft sample. In conclusion, our results strongly showed that PLLA/mMWCNT nanofibrous conduit filled with fibrin gel containing SCs and nanocurcumin is a proper strategy for improving nerve regeneration after a nerve transaction in the rat.

Microtubule stabilizer epothilone B as a motor neuron differentiation agent for human endometrial stem cells.

Microtubule-stabilizing agents (MSAs), until now, have primarily been considered for their anti-proliferative effects in the setting of cancer. However, recent studies have revealed that one particular MSA, epothilone B (EpoB), can promote axonal regeneration after traumatic spinal cord injuries (SCI) even in the presence of inhibitor molecules such as neurite outgrowth inhibitor-A (Nogo-A). On the basis of the importance of having an efficient motor neuron (MN) differentiation protocol for stem cell therapy and the attention of MSAs for SCI treatment, our study investigated the effect of EpoB on human endometrial stem cells (hEnSCs) differentiation into MN-like cells. hEnSCs were isolated and characterized by flow cytometry. The hEnSC cell viability was evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To mimic the in vivo inhibitory environment, hEnSCs were also differentiated in the presence of Nogo-A. After 15 days of differentiation, the expressions of MN-markers were evaluated by real-time reverse-transcriptase polymerase chain reaction and immunofluorescence. According to the MTT assay results, three doses (1, 5, and 10 nM) of EpoB were selected to evaluate their effect on MN-differentiation. All selected doses can increase the efficacy of hEnSCs differentiation into MN-like cells. In particular, the 10 nM EpoB dosage was shown to increase the axon elongation, cell alignment, and upregulation of these MN-markers compared with other doses. EpoB can improve MN differentiation from hEnSC and potentially provide a unique route for neuronal replacement in the setting of SCI.

A facile two step heat treatment strategy for development of bioceramic scaffolds for hard tissue engineering applications.

In the present study, a two-step sintering (TSS) method has been used to improve the mechanical properties, biocompatibility, drug release, and osteogenesis abilities of hardystonite (HT) ceramic scaffolds for tissue engineering and drug delivery applications. The average particle size of HT scaffold is kept lower than 80 nm and is reached higher than 130 nm by using two-step and conventional sintering methods, respectively. The compressive strengths of the prepared nanocrystalline HT scaffolds were found to be significantly higher than those of the micro-structure HT and currently available hydroxyapatite scaffolds. A comparative analysis of cell viability and live/dead staining of human mesenchymal stem cells (hMSCs) in nano- and micro-structured HT scaffolds and their drug release potentiation was carried out. The results showed that the nano-structured HT scaffolds have higher cell viability, biocompatibility and longer-term doxorubicin (DOX) release potential than the micro-structured ones. The results of quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) analyses showed that the expression of adhesion and differentiation supporting genes were significantly higher in nano-structured HT scaffolds as compared to the micro-structured ones. The results of qRT-PCR also showed that the mRNA expression level of ERK1/2 and P38 MAPK from hMSCs were significantly higher in nano-structured HT scaffolds than the micro-structured ones. These results potentially open new aspects for using nano-structured scaffolds in bone tissue engineering applications.