Cold atmospheric plasma modification and electrical conductivity induction in gelatin/polyvinylidene fluoride nanofibers for neural tissue engineering.

BACKGROUND: This research follows some investigations through neural tissue engineering, including fabrication, surface treatment, and evaluation of novel self-stimuli conductive biocompatible and degradable nanocomposite scaffolds. METHODS: Gelatin as a biobased material and polyvinylidene fluoride (PVDF) as a mechanical, electrical, and piezoelectric improvement agent were co-electrospun. In addition, polyaniline/graphene (PAG) nanoparticles were synthesized and added to gelatin solutions in different percentages to induce electrical conductivity. After obtaining optimum PAG percentage, cold atmospheric plasma (CAP) treatment was applied over the best samples by different plasma variable parameters. Finally, the biocompatibility of the scaffolds was analyzed and approved by in vitro tests using two different PC12 and C6 cell lines. In the present study the morphology, FTIR, dynamic light scattering, mechanical properties, wettability, contact angle tests, differential scanning calorimetric, rate of degradation, conductivity, biocompatibility, gene expression, DAPI staining, and cell proliferation were investigated. RESULTS: The PAG percentage optimization results revealed fiber diameter reduction, conductivity enhancement, young's modulus improvement, hydrophilicity devaluation, water uptake decrement, and degradability reduction in electrospun nanofibers by increasing the PAG concentration. Furthermore, ATR-FTIR, FE-SEM, AFM, and contact angle tests revealed that helium CAP treatment improves scaffold characterizations for 90 s in duration time. Furthermore, the results of the MTT assay, FE-SEM, DAPI staining, and RT-PCR revealed that samples containing 2.5% w/w of PAG are the most biocompatible, and CAP treatment increases cell proliferation and improves neural gene expression in the differentiation medium. CONCLUSIONS: According to the results, the samples with the 2.5% w/w of PAG could provide a suitable matrix for neural tissue engineering in terms of physicochemical and biological.

Conductive nerve conduit with piezoelectric properties for enhanced PC12 differentiation.

Restoration of nerve tissue remains highly challenging, mainly due to the limited regeneration capacity of the nervous system and the development of fibrosis. This limitation necessitates designing new nerve guidance channel to promote nerve repairing. In this study, we developed a novel core/shell conduit to induce PC12 differentiation. Co-electrospinning method was utilized to produce a fibrous shell containing polycaprolactone/polyvinylidene fluoride PCL/PVDF, gelatin and polyaniline/graphene (PAG) nanocomposite. The core section of the conduit was filled with chitosan-gelatin hydrogel containing PAG and ZnO nanoparticles. Such conduit shows antibacterial activity, electrical conductivity and piezoelectric property. The effect of such engineered conduit on PC12 differentiation was investigated by analyzing differentiation markers Nestin and microtubule-associated protein 2 (MAP2) through immunocytochemistry and PCR-RT techniques. The result revealed that such conduit could significantly induce Nestin and MAP2 gene expression in the PC12 cells and, thus, it is a viable option for effective cell differentiation and nerve regeneration.

Piezoelectric conductive electrospun nanocomposite PCL/Polyaniline/Barium Titanate scaffold for tissue engineering applications.

Recent trends in tissue engineering technology have switched to electrical potentials generated through bioactive scaffolds regarding their appropriate effects on cell behaviors. Preparing a piezo-electrical stimuli scaffold with high electrical conductivity for bone and cartilage tissue regeneration is the ultimate goal of the present study. Here, Barium Titanate nanoparticles (BaTiO3 NPs) were used as piezoelectric material and highly conductive binary doped Polyaniline nanoparticles (PANI NPs) were synthesized by oxidative polymerization. Polycaprolactone (PCL) was applied as carrier substrate polymer and conductive spun nanofibrous scaffolds of PCL/PANI composites were prepared in two different amounts of PANI (3 and 5 wt.%). The conductivity of PCL/PANI nanofibers has been analyzed by standard four probes test. Based on the obtained results, the PCL/PANI5 (with 5 wt.% PANI) was selected due to the superior electrical conductivity of 8.06 × 10-4 s cm - 1. Moreover, the piezoelectric nanofibrous scaffolds of PCL/BT composite were electrospun in three different amounts of BT (20, 30, and 40 wt.%). To investigate the synergic effect of conductive PANI and piezoelectric BT, ternary nanocomposite scaffolds of PCL/PANI/BT were prepared using the dual jet electrospinning technique. The piezoelectric properties have been analyzed by determining the produced voltage. The morphological assessment, contact angle, mechanical test, and MTT assay have been conducted to evaluate other properties including biocompatibility of nanofibrous scaffolds. The PCL/PANI5/BT40 composite resulted in an unprecedented voltage of 1.9 Volt. SEM results confirm that BT NPs have been distributed and embedded inside PCL fibers quite appropriately. Also, the chosen scaffolds were homogeneously intertwined and possessed an average fiber diameter of 288 ± 180 nm, and a contact angle of 92 ± 7°, making it a desirable surface for cell attachment and protein interactions. Moreover, Young's modulus, ultimate tensile stress, and elongation were obtained as 11 ± 1 MPa, 5 ± 0.6 MPa, and 109 ± 15% respectively. Obtained results assert the novel potential of piezo-electrical stimuli conductive nanocomposite scaffold for tissue engineering applications.

Investigation on penetration of saffron components through lipid bilayer bound to spike protein of SARS-CoV-2 using steered molecular dynamics simulation.

A coronavirus identified as COVID-19 is the reason for an infection outbreak which is started in December 2019. NO completely effective drugs and treatments are not recognized for this virus. Recently, saffron and its compounds were used to treat different viral diseases. Saffron extract and its major ingredients have shown antiviral effects. In this study, the steered molecular dynamics simulation was used for investigating the effect of four main components of saffron that include: crocin, crocetin, safranal, and picrocrocin as candidate for drug molecules, on COVID-19. The binding energies between drug molecules and spike protein and the main protease of the virus were evaluated. The obtained results based on Lennard-Jones and electrostatic potentials demonstrated that crocetin has a high affinity towards spike protein and also the main protease of the virus. Also, the quantum mechanics calculations elucidated that the crocetin could overcome energy barrier of lipid bilayer with strong dipole moment and polarizability. The pharmacokinetic and ADMET properties proved that crocetin could be a suitable drug candidate. So, crocetin could be a promising drug for treatment of COVID-19.