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“COVID-19” is the word that certainly isn’t forgotten by everybody who lives in the first half of the twenty-first century. COVID-19, as a pandemic, has led many researchers from different biomedical fields to find solutions or treatments to manage the pandemic. However, no standard treatment for this disease has been discovered to date. Probably, preventing the severe acute respiratory infection form of COVID-19 as the most dangerous phase of this disease can be helpful for the treatment and reduction of the death rate. In this regard, mesenchymal stem cells (MSCs)-based immunomodulation treatment has been proposed as a suitable therapeutic approach and several clinical trials have begun. Recently, MSCs according to their immunomodulatory and regenerative properties attract attention in clinical trials. After the intravenous transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. Given the uncertainties in this area, we reviewed reported clinical trials and hypotheses to provide useful information to researchers and those interested in stem cell therapy. In this study, we considered this new approach to improve patient’s immunological responses to COVID-19 using MSCs and discussed the aspects of this proposed treatment. However, currently, there are no approved MSC-based approaches for the prevention and/or treatment of COVID-19 patients but clinical trials ongoing.

Bone tissue engineering uses various methods and materials to find suitable scaffolds that regenerate lost bone due to disease or injury. Poly(ε-caprolactone) (PCL) can be used in 3D printing for producing biodegradable scaffolds by fused deposition modeling (FDM). However, the hydrophobic surfaces of PCL and its non-osteogenic nature reduces adhesion and cell bioactivity at the time of implantation. This work aims to enhance bone formation, osteogenic differentiation, and in vitro biocompatibility via PCL scaffolds modification with Hydroxyapatite (HA) and Collagen type I (COL). This study evaluated the osteosupportive capacity, biological behavior, and physicochemical properties of 3D-printed PCL, PCL/HA, PCL/COL, and PCL/HA/COL scaffolds. Biocompatibility and cells proliferation were investigated by seeding human adipose tissue-derived mesenchymal stem cells (hADSCs) onto the scaffolds, which were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and 6-diamidino-2-phenylindole (DAPI) staining. In addition, the bone differentiation potential of the hADSCs was assessed using calcium deposition, alkaline phosphatase (ALP) activity, and bone-related protein and genes. Although all constructed scaffolds support hADSCs proliferation and differentiation, the results showed that scaffold coating with HA and COL can boost these capacities in a synergistic manner. According to the findings, the tricomponent 3D-printed scaffold can be considered as a promising choice for bone tissue regeneration and rebuilding.

Self-healing and autologous bone graft of calvaraial defects can be challenging. Therefore, the fabrication of scaffolds for its rapid and effective repair is a promising field of research. This paper provided a comparative study on the ability of Three-dimensional (3D) printed polycaprolactone (PCL) scaffolds and PCL-modified with the hydroxyapatite (HA) and bioglasses (BG) bioceramics scaffolds in newly bone formed in calvaria defect area. The studied 3D-printed PCL scaffolds were fabricated by fused deposition layer-by-layer modeling. After the evaluation of cell adhesion on the surface of the scaffolds, they were implanted into a rat calvarial defect model. The rats were divided into four groups with scaffold graft including PCL, PCL/HA, PCL/BG, and PCL/HA/BG and a non-explant control group. The capacity of the 3D-printed scaffolds in calvarial bone regeneration was investigated using micro computed tomography scan, histological and immunohistochemistry analyses. Lastly, the expression levels of several bone related genes as well as the expression of miR-20a and miR-17-5p as positive regulators and miR-125a as a negative regulator in osteogenesis pathways were also investigated. The results of this comparative study have showed that PCL scaffolds with HA and BG bioceramics have a great range of potential applications in the field of calvaria defect treatment.

In this study, the fused deposition modeling method was used to fabricate 3D-printed polycaprolactone (PCL). This study introduces a cost-effective post-fabrication treatment by using a Solubilized Amniotic Membrane (SAM) extracellular matrix (ECM) as a biological surface modifier. The employment of SAM provides an easy approach to overcoming the current challenges in the way of using fresh, cryopreserved, or dehydrated tissue. Four groups were included in this study, including neat PCL, oxygen plasma-treated PCL, SAM 0.001%w/v (SAM1), and SAM 0.005%w/v (SAM5). According to the SEM images, the diameter of each 3D-printed filament and filament distance were around 573 μm and 372 μm, respectively. The FTIR-ATR spectra confirmed the presence of amide groups in specimen, containing SAM. A higher weight loss rate was obtained for oxygen plasma-treated PCL and SAM-containing samples than neat PCL. The results of in vitro studies revealed that the optimized content of SAM (SAM 5) could promote the osteogenesis potency of Wharton-Jelly Mesenchymal Stem Cells (WJ-MSCs), cultured on the 3D-printed scaffolds in terms of alkaline phosphatase activity, calcium deposition and real-time PCR assessment of alkaline phosphatase, osteocalcin, and osteonectin. Also, in vivo, the collagen content in the control group and SAM 5 was 30.89 ± 1.73 and 44.24 ± 2.91, respectively. According to the Micro-CT assessment, the bone volume fraction was remarkably improved in the presence of SAM5 as it increased from 36.52 ± 1.56% in the control group to 42.66 ± 2.17% in SAM5. The results of the present study provide a promising surface modification approach by employing SAM for the future of bone tissue engineering scaffolds.

Background Tissue engineering has become increasingly applied for tissue repair purposes. Scaffolds, one of the main components of tissue engineering, provide a supportive framework for cell culture and growth. The objective of the present study was to investigate the odontogenic/osteogenic differentiation of dental pulp stem cells, cultured on a polycaprolactone (PCL)-based nanofibrous scaffold, coated with Biodentine. This study evaluated the use of Biodentine as a coating on nanofiber scaffolds and investigated the biological effects of this material on the differentiation of dental pulp stem cells, which hold promising applications in dental and bone tissue engineering. Methods This study is a basic research investigation. Initially, PCL nanofibrous scaffolds were produced through electrospinning, followed by a post-fabrication surface modification step. The morphology and properties of the scaffolds were examined using scanning electron microscopy (SEM). In the surface treatment step, two different concentrations of Biodentine (0.05% and 0.01%) were applied on the mats. The biocompatibility of the scaffolds was assessed using an MTT assay on days 1, 3, and 5. Additionally, the odontogenic/osteogenic differentiation potency of fabricated scaffolds was evaluated by alkaline phosphatase (ALP) activity and deposited calcium of the cells on days 7, 14, and 21. Results SEM analysis revealed that Biodentine coating increased surface roughness, particularly at the 0.05% concentration, where excessive particle aggregation was observed. In contrast, the control PCL scaffold exhibited a well-organized fibrous structure with a smooth surface, whereas the 0.01% Biodentine-coated scaffold displayed a moderately roughened surface with uniformly distributed mineralized deposits. Cell viability was higher in the 0.01% Biodentine group, while the 0.05% concentration showed reduced proliferation. ALP activity peaked on day 14, and the highest level of calcium deposition was observed in the 0.01% Biodentine group on day 21, indicating enhanced biomineralization. Conclusion Biodentine/PCL scaffolds demonstrated notable and suitable physical and chemical properties. Furthermore, they enhanced odontogenic/osteogenic differentiation and mineralization compared to the control group. These findings support the potential of fabricated scaffolds for odontogenic/osteogenic differentiation applications.

To evaluate the potential of three stem cells for cell therapy and tissue engineering applications, the biological behavior and osteogenic capacity of the newly introduced cord-blood-derived, unrestricted somatic stem cells (USSC) were compared with those of mesenchymal stem cells isolated from bone marrow (BM-MSC) and adipose tissue (AT-MSC). There was no significant difference between the rates of proliferation of the three stem cells. During osteogenic differentiation, alkaline phosphatase (ALP) activity peaked on day 7 in USSC compared to BM-MSC which showed the maximum value of ALP activity on day 14. However, BM-MSC had the highest ALP activity and mineralization during osteogenic induction. In addition, AT-MSC showed the lowest capacity for mineralization during differentiation and had the lowest ALP activity on days 7 and 14. Although AT-MSC expressed higher levels of collagen type I, osteonectin and BMP-2 in undifferentiated state, but these genes were expressed higher in BM-MSC during differentiation. BM-MSC also expressed higher levels of ALP, osteocalcin and Runx2 during induction. Taking together, BM-MSC showed the highest capacity for osteogenic differentiation and hold promising potential for bone tissue engineering and cell therapy applications.

Background Biocompatibility and induction of mineralized tissue formation are the properties expected from a material used in vital pulp therapy and repair of perforations. Cold ceramic (SJM, Iran; CC) is a newly introduced calcium silicate-based cement for above mentioned therapeutic applications. This in-vitro study aimed to compare the effect of CC and White MTA-Angelus (MTA) on cell viability, attachment, odontogenic differentiation, and calcification potential of human dental pulp stem cells (DPSCs) and periodontal ligament fibroblasts (PDLFs). Methods Cell viability of DPSCs and PDLFs was assessed using MTT on days 1, 3, 7, and 14 (n = 9) in contact with freshly mixed and set states of CC and MTA. Field emission scanning electron micrographs (FESEM) were taken to evaluate cell-bioceramic interaction (n = 6). Gene expression levels of osteo/odontogenic markers (Dentin sialophosphoprotein, Dentin matrix protein 1, Collagen type I alpha 1, and Alkaline phosphatase (DSPP, DMP1, COL 1A1, and ALP, respectively) (n = 8) were assessed using qrt-PCR. ALP enzymatic activity was evaluated to assess the mineralization potential. A two-way ANOVA test was applied, and p  < 0.05 was considered to be statistically significant. Results The effect of freshly mixed and set MTA and CC on the survival of DPSCs and PDLFs in all study groups was statistically similar and comparable to the positive control group ( p  > 0.05); the only exception was for the viability of PDLFs in contact with freshly mixed cements on day 1, showing a more significant cytotoxic effect compared to the control and the set state of materials ( p  < 0.05). PDLFs attached well on CC and MTA. The spread and pseudopodium formation of the cells increased on both samples from day 1 to day 14. Contact of MTA and CC with DPSCs similarly increased expression of all dentinogenesis markers studied on days 7 and 14 compared to the control group ( p  < 0.001), except for DSPP expression on day 7 ( p  = 0.46 and p  = 0.99 for MTA and CC, respectively). Conclusions Within the limitation of this in-vitro study, cold ceramic and MTA-Angelus showed high biocompatibility and induced increased expression of osteo/dentinogenic markers. Therefore, cold ceramic can be a suitable material for vital pulp therapy and the repair of root perforations.

Due to the osteoconductive role of bioceramics, use of these bioactive nanocomposite scaffolds that can maintain their structural integrity during bone tissue repair is one of the major goals of tissue engineering. Herein, a nanofibrous poly-L-lactic acid (PLLA) scaffold was fabricated by electrospinning and then gelatin and hydroxyapatite nanoparticles (nHA) were coated over the surface of the scaffold. Osteoconductivity of the fabricated nano-composite scaffolds was then studied while grafted on the rat calvarial defects. Our results indicated that the coating of PLLA scaffold with nHA and gelatin increased the adhesion and growth of the human bone marrow derived mesenchymal stem cells (BM-MSCs) and also significantly increased the level of mineralization over a week culture period. The results of radiographic and histological studies showed that the newly created bone tissue at the defect site was significantly higher in animals treated with nanocomposite scaffolds than the empty scaffolds and control groups. This increase in the defect reconstruction was significantly increased after culturing BM-MSCs on the scaffolds, especially nanocomposite scaffolds. It can be concluded that the combination of nanocomposite scaffolds and BM-MSCs could be a very good candidate for treatment of bone lesions and could be considered as a bony bioimplant.Graphic abstract

Background: The cartilage tissue lacks blood vessels, which is composed of chondrocytes and ECM. Due to this vessel-less structure, it is difficult to repair cartilage tissue damages. One of the new methods to repair cartilage damage is to use tissue engineering. In the present study, it was attempted to simulate a three-dimensional environment similar to the natural ECM of cartilage tissue by using hydrogels made of natural materials, including Chitosan and different ratios of Alginate. Material and methods: Chitosan, alginate and Chitosan/Alginate hydrogels were fabricated. Fourier Transform Infrared, XRD, swelling ratio, porosity measurement and degradation tests were applied to scaffolds characterization. After that, human adipose derived-mesenchymal stem cells (hADMSCs) were cultured on the hydrogels and then their viability and chondrogenic differentiation capacity were studied. Safranin O and Alcian blue staining, immunofluorescence staining and real time RT-PCR were used as analytical methods for chondrogenic differentiation potential evaluation of hADMSCs when cultured on the hydrogels. Results: The highest degradation rate was detected in Chitosan/Alginate (1:0.5) group The scaffold biocompatibility results revealed that the viability of the cells cultured on the hydrogels groups was not significantly different with the cells cultured in the control group. Safranin O staining, Alcian blue staining, immunofluorescence staining and real time PCR results revealed that the chondrogenic differentiation potential of the hADMSCs when grown on the Chitosan/Alginate hydrogel (1:0.5) was significantly higher than those cell grown on the other groups. Conclusion: Taken together, these results suggest that Chitosan/Alginate hydrogel (1:0.5) could be a promising candidate for cartilage tissue engineering applications.

Mesenchymal stem cells (MSCs) are widely recognized as a promising cell type for therapeutic applications due to their ability to secrete and regenerate bioactive molecules. For effective bone healing, it is crucial to select a scaffold that can support, induce, and restore biological function. Evaluating the scaffold should involve assessing MSC survival, proliferation, and differentiation. The principal aim of this investigation was to formulate composite nanofibrous scaffolds apt for applications in bone tissue engineering. In this experimental study, nanofibrous scaffolds were fabricated using Poly-L-lactic acid (PLLA) polymer. The PLLA fibers' surface was modified by integrating collagen and hydroxyapatite (HA) nanoparticles. The findings demonstrated that the collagen- and nanohydroxyapatite-modified electrospun PLLA scaffold positively influenced the attachment, growth, and osteogenic differentiation of MSCs. Coating the nanofiber scaffold with collagen and nanoparticle HA significantly enhanced the osteogenic differentiation of MSCs on electrospun PLLA scaffolds.