Hydrothermally reinforcing hydroxyaptatite and bioactive glass on carbon nanofiber scafold for bone tissue engineering.

As a bone tissue engineering scaffold, the objective of this study was to design hierarchical bioceramics based on an electrospun composite of carbon nanofibers (CNF) reinforced with hydroxyapatite (HA) and bioactive glasses (BGs) nanoparticles. The performance of the nanofiber as a scaffold for bone tissue engineering was enhanced by reinforcing it with hydroxyapatite and bioactive glass nanoparticles through a hydrothermal process. The influence of HA and BGs on the morphology and biological properties of carbon nanofibers was examined. The prepared materials were evaluated for cytotoxicity in vitro using the water-soluble tetrazolium salt assay (WST-assay) on Osteoblast-like (MG-63) cells, and oste-ocalcin (OCN), alkaline phosphatase (ALP) activity, total calcium, total protein, and tar-trate-resistant acid phosphatase (TRAcP) were measured. The WST-1, OCN, TRAcP, total calcium, total protein, and ALP activity tests demonstrated that scaffolds reinforced with HA and BGs had excellent in vitro biocompatibility (cell viability and proliferation) and were suitable for repairing damaged bone by stimulating bioactivity and biomarkers of bone cell formation.

Cellulose Acetate Nanofibers: Incorporating Hydroxyapatite (HA), HA/Berberine or HA/Moghat Composites, as Scaffolds to Enhance In Vitro Osteoporotic Bone Regeneration.

The specific objective of this study was to stabilize a simple valid method to prepare pure nanorod hydroxyapatite (HA) mixed with berberine chloride (BER) and Moghat water extract (ME) as composites for incorporation into cellulose acetate (CA) nanofibers to be used as novel bone scaffolds and to determine their efficacy in bone regeneration process In Vitro. Preparation of HA/BER and HA/ME composites were performed by mixing powders using the ball-milling machine. The HA, HA/BER, and HA/ME composites at a concentration of 6.25, 12.5, 25, 50, 100, and 200 mg were mixed with CA solution (13%), then the fiber was formed using electrospinning technique. The properties of the obtained CA fibers were investigated (SEM, TEM, EDX, FTIR, TGA, water uptake, porosity, and mechanical tests). The efficacy of HA and HA composites loaded into CA nanofiber on osteoblast and osteoclast differentiation were measured by tacking ALP, osteocalcin, TRAcP, calcium, and total protein concentration. Moreover, their effects on cell differentiation (CD90 and PARP- É£) and death markers (GSK3b, MAPK, Wnt-5 and ß-catenin) were evaluated by using ELISA and qPCR. The obtained TEM results indicated that the continuous CA and CA/HA composites electrospun fibers have ultrafine fiber diameters of about 200 nm and uniform distribution of discrete n-HA clusters throughout. In addition, hydrocortisone (HCT) was found to increase the formation of adipocytes and osteoclastic markers CD90 and p38-MAPK which indicated the bone lose process take placed. Treatment with CA loaded with HA, HA/BER or HA/ME decreased CD90, Wnt-5, PARP- É£, GSK3b and p38-MAPK associated elevation of osteogenic markers: ALP and osteocalcin. Moreover, HCT overexpressed RANKL and down expressed Osterix gene. Treatment with CA/HA/BER or CA/HA/ME downregulated RANKL and upregulated Osterix associated with a reduction in RANKL/OPG ratio, at p < 0.05. In conclusion, novel CA composite nanofibers (CA/HA/BER and CA/HA/ME) reversed the HCT adverse effect on osteoblast cell death through canonical and non-canonical pathways regulated by Wnt/ß-catenin and Wnt/Ca(2+) pathways. Furthermore, our data confirmed that the novel scaffolds create a crosstalk between RUNX-2, RANKL, p38-MAPK, and Wnt signals which positively impact bone regeneration process. Treatment with CA/HA/BER is better compared to the treatment with CA/HA/ME. Nevertheless, both are considered as alternative biomaterial scaffolds with a potential for biomedical applications in the field of bone tissue engineering.

Synthesized Nanorods Hydroxyapatite by Microwave-Assisted Technology for In Vitro Osteoporotic Bone Regeneration through Wnt/ß-Catenin Pathway.

This research presents an optimal and inexpensive, without any additives, method for the synthesis and sintering of hydroxyapatite (HA) by microwave-assisted technology (MAT) furnace. The target sintering temperature of the furnace (1100 ℃) was held for one and two hours for conventional sintering. With regard to the microwave hybrid sintering, it was held at 100%MW for 20 and 30 min. FTIR, XRD, TGA, SEM/EDS, and TEM were assessed to determine HA phase composition, and structural as well as thermal decomposition behavior. The in vitro effects of sintered HA discs on cultured aged mice-isolated osteoblast cells and hydrocortisone-induced osteoclast cells were assessed by measuring ALP, osteocalcin, TRAP, calcium, and Alizarin red S staining. Moreover, their effects on cell differentiation (CD90 and CD 105 and PARR- É£) and death markers (GSK3b, MAPK, and ß-catenin) were evaluated. The results demonstrate the production of ≈35 nm crystal-sized pure hydroxyapatite nanorod-like particles with a high degree of crystallinity and no impurities as required for biomedical application. HA increased osteogenesis (ALP, osteocalcin, and calcium) markers and decreased cell resorption markers. In addition, HA nanorods reversed the effect of cortisone on cell differentiation and death markers. In conclusion, microwave hybrid sintered HA is a potential nanomaterial for osteoporotic bone regeneration as HA reversed the cortisone adverse effect on osteoblast cell death through canonical and non-canonical pathways.

Nanoparticles of ZnO/Berberine complex contract COVID-19 and respiratory co-bacterial infection in addition to elimination of hydroxychloroquine toxicity.

Purpose: A novel coronavirus (COVID-19) that has not been previously identified in humans and has no specific treatment has recently spread. Treatment trials using antiviral and immune-modulating drugs such as hydroxychloroquine (HCQ) were used to control this viral outbreak however several side effects have emerged. Berberine (BER) is an alkaloid that has been reported to reveal some pharmacological properties including antioxidant and antimicrobial activities. Additionally, Zinc oxide nanoparticles (ZnO-NPs) possess potent antioxidant and anti-inflammatory properties. Therefore, this study was undertaken to estimate the efficiency of both BER and synthetic ZnO/BER complex as an anti-COVID-19 therapy. Methods: First, the ZnO/BER complex was prepared by the facile mixing method. Then in vitro studies on the two compounds were conducted including VeroE6 toxicity, anti-COVID-19 activity, determination of inhibitory activity towards papain-like proteinase (PL pro) and spike protein- and receptor- binding domain (RBD) as well as assessment of drug toxicity on RBCs. Results: The results showed that ZnO/BER complex acts as an anti-COVID-19 by inhibiting spike protein binding with angiotensin-converting enzyme II (ACE II), PL pro activity, spike protein and E protein levels, and expression of both E-gene and RNA dependent RNA polymerase (RdRp) at a concentration lower than that of BER or ZnO-NPs alone. Furthermore, ZnO/BER complex had antioxidant and antimicrobial properties where it prevents the auto oxidation of 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the culture of lower respiratory system bacteria that affected Covid 19 patients. The ZnO/BER complex prevented as well the HCQ cytotoxic effect on both RBC and WBC (in vitro) and hepatotoxicity, nephrotoxicity and anemia that occurred after HCQ long administration in vivo. Conclusion: The ZnO/BER complex can be accounted as promising anti-COVID 19 candidate because it inhibited the virus entry, replication, and assembly. Furthermore, it could be used to treat a second bacterial infection that took place in hospitalized COVID 19 patients. Moreover, ZnO/BER complex was found to eliminate the toxicity of long-term administration of HCQ in vivo.

Potential therapeutic and pharmacological strategies for SARS-CoV2.

BACKGROUND: At the end of 2019, the new Coronavirus disease 2019 (COVID-19) strain causing severe acute respiratory syndrome swept the world. From November 2019 till February 2021, this virus infected nearly 104 million, with more than two million deaths and about 25 million active cases. This has prompted scientists to discover effective drugs to combat this pandemic. AREA COVERED: Drug repurposing is the magic bullet for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Therefore, several drugs have been investigated in silico, in vitro, as well as through human trials such as anti-SARS-CoV2 agents, or to prevent the complications resulting from the virus. In this review, the mechanisms of action of different therapeutic strategies are summarized. According to the WHO, different classes of drugs can be used, including anti-malarial, antiviral, anti-inflammatory, and anti-coagulant drugs, as well as angiotensin-converting enzyme inhibitors, antibiotics, vitamins, zinc, neutralizing antibodies, and convalescent plasma therapy. Recently, there are some vaccines which are approved against SARS-CoV2. EXPERT OPINION: A complete understanding of the structure and function of all viral proteins that play a fundamental role in viral infection, which contribute to the therapeutic intervention and the development of vaccine in order to reduce the mortality rate. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40005-021-00520-4.