Summary The development of effective and safe COVID‐19 vaccines is a major move forward in our global effort to control the SARS‐CoV‐2 pandemic. The aims of this study were (1) to develop an inactivated whole‐virus SARS‐CoV‐2 candidate vaccine named BIV1‐CovIran and (2) to determine the safety and potency of BIV1‐CovIran inactivated vaccine candidate against SARS‐CoV‐2. Infectious virus was isolated from nasopharyngeal swab specimen and propagated in Vero cells with clear cytopathic effects in a biosafety level‐3 facility using the World Health Organization’s laboratory biosafety guidance related to COVID‐19. After characterisation of viral seed stocks, the virus working seed was scaled‐up in Vero cells. After chemical inactivation and purification, it was formulated with alum adjuvant. Finally, different animal species were used to determine the toxicity and immunogenicity of the vaccine candidate. The study showed the safety profile in studied animals including guinea pig, rabbit, mice and monkeys. Immunisation at two different doses (3 or 5 μg per dose) elicited a high level of SARS‐CoV‐2 specific and neutralising antibodies in mice, rabbits and nonhuman primates. Rhesus macaques were immunised with the two‐dose schedule of 5 or 3 μg of the BIV1‐CovIran vaccine and showed highly efficient protection against 10 4 TCID50 of SARS‐CoV‐2 intratracheal challenge compared with the control group. These results highlight the BIV1‐CovIran vaccine as a potential candidate to induce a strong and potent immune response that may be a promising and feasible vaccine to protect against SARS‐CoV‐2 infection.

There is an urgent demand to manufacture an effective and safe vaccine to prevent SARS-CoV2 infection, which resulted in a global pandemic. In this study, we developed an inactivated whole-virus SARS-CoV-2 candidate vaccine named COVIran Barekat. Immunization at two different doses (3 microgram or 5 microgram per dose) elicited a high level of SARS-CoV-2 specific neutralizing antibodies in mice, rabbits, and non-human primates. The results show the safety profile in studied animals (include guinea pig, rabbit, mice, and monkeys). Rhesus macaques were immunized with the two-dose of 5 microgram and microgram of the COVIran Barekat vaccine and showed highly efficient protection against 104 TCID50 of SARS-CoV-2 intratracheal challenge compared with the control group. These results highlight the COVIran Barekat vaccine as a potential candidate to induce a strong and potent immune response which may be a promising and feasible vaccine to protect against SARS-CoV2 infection.

Magnesium (Mg) plays an important role in controlling bone apatite structure and density and is a potential bioactive material in repairing critical‐sized bone defects. In this study, we aimed to evaluate the effect of adding NanoMgO to polycaprolactone/beta‐tricalcium phosphate (PCL/β‐TCP) scaffolds on bone regeneration. Novel 3D‐printed porous PCL/β‐TCP composite scaffolds containing 10% nanoMgO were fabricated by fused deposition modeling (FDM) and compared with PCL/β‐TCP (1:1) scaffolds (control). The morphology and physicochemical properties of the scaffolds were characterized by ATR‐FTIR, XRD, scanning electron microscope‐energy dispersive X‐ray analysis (SEM–EDX), transmission‐electron‐microscopy (TEM), water contact angle, and compressive strength tests and correlated to its cytocompatibility and osteogenic capacity in‐vitro. To evaluate in‐vivo osteogenic capacity, bone‐marrow‐derived stem cell (BMSC)‐loaded scaffolds were implanted into 8 mm rat critical‐sized calvarial defects for 12 weeks. The hydrophilic scaffolds showed 50% porosity (pore size = 504 μm). MgO nanoparticles (91.5 ± 27.6 nm) were homogenously dispersed and did not adversely affect BMSCs' viability and differentiation. Magnesium significantly increased elastic modulus, pH, and degradation. New bone formation (NBF) in Micro‐CT was 30.16 ± 0.31% and 23.56 ± 1.76% in PCL/β‐TCP/nanoMgO scaffolds with and without BMSCs respectively, and 19.38 ± 2.15% and 15.75 ± 2.24% in PCL/β‐TCP scaffolds with and without BMSCs respectively. Angiogenesis was least remarkable in PCL/β‐TCP compared with other groups (p < .05). Our results suggest that the PCL/β‐TCP/nanoMgO scaffold is a more suitable bone substitute compared to PCL/β‐TCP in critical‐sized calvarial defects.

Bone-marrow mesenchymal stem cells (BM-MSCs) have not yet proven any significant therapeutic efficacy in spinal cord injury (SCI) clinical trials, due to the hostile microenvironment of the injured spinal cord at the acute phase. This study aims to modulate the inflammatory milieu by lipopolysaccharide (LPS) and granulocyte colony-stimulating factor (G-CSF) to improve the BM-MSCs therapy. For this purpose, we determined the optimum injection time and sub-toxic dosage of LPS following a T10 contusion injury. Medium-dose LPS administration may result in a local anti-inflammatory beneficial role. This regulatory role is associated with an increase in NF-200-positive cells, significant tissue sparing, and improvement in functional recovery compared to the SCI control group. The second aim was to examine the potential ability of LPS and LPS + G-CSF combination therapy to modulate the lesion site before BM-MSC (1 × 105 cells) intra-spinal injection. Our results demonstrated combination therapy increased potency to enhance the anti-inflammatory response (IL-10 and Arg-1) and decrease inflammatory markers (TNF-α and CD86) and caspase-3 compared to BM-MSC monotherapy. Histological analysis revealed that combination groups displayed better structural remodeling than BM-MSC monotherapy. In addition, Basso–Beattie–Bresnahan (BBB) scores show an increase in motor recovery in all treatment groups. Moreover, drug therapy shows faster recovery than BM-MSC monotherapy. Our results suggest that a sub-toxic dose of LPS provides neuroprotection to SCI and can promote the beneficial effect of BM-MSC in SCI. These findings suggest that a combination of LPS or LPS + G-CSF prior BM-MSC transplantation is a promising approach for optimizing BM-MSC-based strategies to treat SCI. However, because of the lack of some methodological limitations to examine the survival rate and ultimate fate of transplanted BM-MSCs followed by LPS administration in this study, further research needs to be done in this area. The presence of only one-time point for evaluating the inflammatory response (1 week) after SCI can be considered as one of the limitations of this study. We believed that the inclusion of additional time points would provide more information about the effect of our combination therapy on the microglia/macrophage polarization dynamic at the injured spinal cord.

In this study, polyvinyl alcohol hydrogel chains were crosslinked by polyurethane in order to synthesize a suitable substrate for cartilage lesions. The substrate was fully characterized, and in vitro and in vivo investigations were conducted based on a sheep model. In vitro tests were performed based on the chondrocyte cells with the Alcian Blue and safranin O staining in order to prove the presence of proteoglycan on the surface of the synthesized substrate, which has been secreted by cultures of chondrocytes. Furthermore, the expression of collagen type I, collagen type II, aggrecan, and Sox9 was presented in the chondrocyte cultures on the synthesized substrate through RT-PCR. In addition, the H&E analysis and other related tests demonstrated the formation of neocartilage tissue in a sheep model. The results were found to be promising for cartilage tissue engineering and verified that the isolated chondrocyte cultures on the synthesized substrate retain their original composition. K E Y W O R D S cartilage tissue engineering, polyvinyl alcohol-polyurethane composite, sheep model 1 | INTRODUCTION Joint problems such as traumatic lesions of articular hyaline cartilages in athletes and people have created a major challenge in the general public health. Cartilage damages in both severe injuries and osteoarthritis are irreversible processes with no approved medical product for complete repair of cartilage dysfunction. 1 Articular cartilage has a limited capacity of self-repair due to its low cellularity and avascular matrix. A Masoud Taghizadehjahed and Asma Sepahdar contributed equally to this work.