Versatile Nanoparticulate Systems as a Prosperous Platform for Targeted Nose-Brain Drug Delivery.

The intranasal route has proven to be a reliable and promising route for delivering therapeutics to the central nervous system (CNS), averting the blood-brain barrier (BBB) and avoiding extensive first-pass metabolism of some drugs, with minimal systemic exposure. This is considered to be the main problem associated with other routes of drug delivery such as oral, parenteral, and transdermal, among other administration methods. The intranasal route maximizes drug bioavailability, particularly those susceptible to enzymatic degradation such as peptides and proteins. This review will stipulate an overview of the intranasal route as a channel for drug delivery, including its benefits and drawbacks, as well as different mechanisms of CNS drug targeting using nanoparticulate drug delivery systems devices; it also focuses on pharmaceutical dosage forms such as drops, sprays, or gels via the nasal route comprising different polymers, absorption promoters, CNS ligands, and permeation enhancers.

Electrospun nano-fibrous bilayer scaffold prepared from polycaprolactone/gelatin and bioactive glass for bone tissue engineering.

This work is focused on integrating nanotechnology with bone tissue engineering (BTE) to fabricate a bilayer scaffold with enhanced biological, physical and mechanical properties, using polycaprolactone (PCL) and gelatin (Gt) as the base nanofibrous layer, followed by the deposition of a bioactive glass (BG) nanofibrous layer via the electrospinning technique. Electrospun scaffolds were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy. Surface area and porosity were evaluated using the nitrogen adsorption method and mercury intrusion porosimetry. Moreover, scaffold swelling rate, degradation rate and in vitro bioactivity were examined in simulated body fluid (SBF) for up to 14 days. Mechanical properties of the prepared scaffolds were evaluated. Cell cytotoxicity was assessed using MRC-5 cells. Analyses showed successful formation of bead-free uniform fibers and the incorporation of BG nanoparticles within fibers. The bilayer scaffold showed enhanced surface area and total pore volume in comparison to the composite single layer scaffold. Moreover, a hydroxyapatite-like layer with a Ca/P molar ratio of 1.4 was formed after 14 days of immersion in SBF. Furthermore, its swelling and degradation rates were significantly higher than those of pure PCL scaffold. The bilayer's tensile strength was four times higher than that of PCL/Gt scaffold with greatly enhanced elongation. Cytotoxicity test revealed the bilayer's biocompatibility. Overall analyses showed that the incorporation of BG within a bilayer scaffold enhances the scaffold's properties in comparison to those of a composite single layer scaffold, and offers potential avenues for development in the field of BTE.

Self-assembly of a nanoscale DNA box with a controllable lid.

The unique structural motifs and self-recognition properties of DNA can be exploited to generate self-assembling DNA nanostructures of specific shapes using a 'bottom-up' approach. Several assembly strategies have been developed for building complex three-dimensional (3D) DNA nanostructures. Recently, the DNA 'origami' method was used to build two-dimensional addressable DNA structures of arbitrary shape that can be used as platforms to arrange nanomaterials with high precision and specificity. A long-term goal of this field has been to construct fully addressable 3D DNA nanostructures. Here we extend the DNA origami method into three dimensions by creating an addressable DNA box 42 x 36 x 36 nm(3) in size that can be opened in the presence of externally supplied DNA 'keys'. We thoroughly characterize the structure of this DNA box using cryogenic transmission electron microscopy, small-angle X-ray scattering and atomic force microscopy, and use fluorescence resonance energy transfer to optically monitor the opening of the lid. Controlled access to the interior compartment of this DNA nanocontainer could yield several interesting applications, for example as a logic sensor for multiple-sequence signals or for the controlled release of nanocargos.

"Review of strategic methods for encapsulating essential oils into chitosan nanosystems and their applications".

Essential oils (EOs) are hydrophobic, concentrated extracts of botanical origin containing diverse bioactive molecules that have been used for their biomedical properties. On the other hand, the volatility, toxicity, and hydrophobicity limited their use in their pure form. Therefore, nano-encapsulation of EOs in a biodegradable polymeric platform showed a solution. Chitosan (CS) is a biodegradable polymer that has been intensively used for EOs encapsulation. Various approaches such as homogenization, probe sonication, electrospinning, and 3D printing have been utilized to integrate EOs in CS polymer. Different CS-based platforms were investigated for EOs encapsulation such as nanoparticles (NPs), nanofibers, films, nanoemulsions, 3D printed composites, and hydrogels. Biological applications of encapsulating EOs in CS include antioxidant, antimicrobial, and anticancer functions. This review explores the principles for nanoencapsulation strategies, and the available technologies are also reviewed, in addition to an in-depth overview of the current research and application of nano-encapsulated EOs.

Investigating the potential of highly porous zopiclone-loaded 3D electrospun nanofibers for brain targeting via the intranasal route.

Nanofibers (NFs) have proven to be very attractive tool as drug delivery plateform among the different plethora of nanosystems, owing to their unique features. They exhibit two- and three-dimensional structures some of which mimic structural environment of the body tissues, in addition to being safe, efficacious, and biocompatible drug delivery platform. Thus, this study embarked on fabricating polyvinyl alcohol/chitosan (PVA/CS) electrospun NFs encapsulating zopiclone (ZP) drug for intranasal brain targeted drug delivery. Electrospun NFs were optimized by adopting a three factor-two level full factorial design. The independent variables were: PVA/CS ratio (X1), flow rate (X2), and applied voltage (X3). The measured responses were: fiber diameter (Y1,nm), pore size (Y2,nm) and ultimate tensile strength (UTS,Y3,MPa). The selected optimum formula had resulted in NFs diameter of 215.90 ± 15.46 nm, pore size 7.12 ± 0.27 nm, and tensile strength around 6.64 ± 0.95 MPa. In-vitro biodegradability testing confirmed proper degradation of the NFs within 8 h. Moreover, swellability and breathability assessment revealed good hydrophilicity and permeability of the prepared NFs. Ex-vivo permeability study declared boosted ex-vivo permeation with an enhancement factor of 2.73 compared to ZP suspension. In addition, optimized NFs formula significantly reduced sleep latency and prolonged sleep duration in rats compared to IV ZP drug solution. These findings demonstrate the feasibility of employing the designed NFs as an effective safe platform for intranasal delivery of ZP for insomnia management.

Synergistic antioxidant and antibacterial effects of a Zn-ascorbate metal-organic framework loaded with marjoram essential oil.

Antimicrobial resistance (AMR) has become an immense threat to public health leading to an urgent need for development of new technologies to tackle such a challenge. Plant-based drugs, specifically essential oils (EOs) and plant extracts, have shown significant potential as effective green antimicrobial agents. However, they suffer from high volatility and low thermal stability resulting in their inefficient utilization in commercial settings. Among the various nanoencapsulation technologies reported, metal-organic frameworks (MOFs) have been recently investigated as potential nanocarriers of EOs in attempt to enhance their stability. Herein, we report the utilization of Zn-ascorbate MOF for the encapsulation of marjoram essential oil (MEO) with synergistic antioxidant and antibacterial activities. The prepared composite was thoroughly characterized via a number of techniques and its antibacterial performance was investigated against various strains of Gram-negative and Gram-positive bacteria. The results demonstrated that the antioxidant activity originated from the ascorbic acid ligand (l-Asc), while the antibacterial activity originated from Zn2+ ions as well as encapsulated MEO.

The potential of carbon-based nanomaterials in hepatitis C virus treatment: a review of carbon nanotubes, dendrimers and fullerenes.

HCV, hepatitis C virus, is a virus that causes damage to the liver. Both chronic infection or lack of treatment increase morbidity except if it is an acute infection, as the body clears the virus without any intervention. Also, the virus has many genotypes, and until now, there has yet to be a single treatment capable of affecting and treating all these genotypes at once. This review will discuss the main and most used old treatments, IFN-a, PEG IFN-a, Ribavirin, Celgosvir, and sofosbuvir alone and with the combination of other drugs and their drawbacks. They should be given in combination to improve the effect on the virus compared with being administrated independently, as in the case of sofosbuvir. For these reasons, the need for new treatments and diagnostic tools arises, and the rule of nanotechnology comes here. The role of carbon nanotubes, dendrimers, and fullerenes will be discussed. CNTs, carbon nanotubes, are one-dimensional structures composed of a cylindrical sheet of graphite and are mainly used for diagnostic purposes against HCV. Dendrimers, three-dimensional highly branched structures, are macromolecules that provide better drug delivery and treatment options due to their unique structure that can be modified, producing versatile types; each has unique properties. Fullerenes which are cage like structures derived and closely related to CNTs, and composed of carbon atoms that can be substituted by other atoms which in return open unlimited usage for these carbon based materials. Fullerenes rule is unique since it has two mechanisms that prevent the virus from binding and acting on the virus-replicating enzyme. However, their charge needs to be determined; otherwise, it will lead to cytotoxicity. Lastly, no review has been done on the role of nanotechnology against HCV yet.

Cod liver oil nano-structured lipid carriers (Cod-NLCs) as a promising platform for nose to brain delivery: Preparation, in vitro optimization, ex vivo cytotoxicity & in vivo biodistribution utilizing radioiodinated zopiclone.

Nano-structured lipid carriers containing zopiclone were prepared as a targeted drug delivery system to convey zopiclone directly to brain via nasal route. Nano-structured lipid carriers were constructed adopting hot emulsification-ultrasonication method using palmitic acid in place of the solid lipid, cod liver oil as liquid lipid, and poloxamer 407 as a surfactant. A three-factor three-level central composite face-centered design was used to optimize the formulated nano-structured lipid carriers. The independent factors were lipid amount (X1), surfactant amount (X2), and sonication time (X3). The examined responses were entrapment efficiency (EE,Y1,%), particle size (PS,Y2,nm), zeta potential(mV), polydispersity index(PDI,Y3), in vitro release(Q8h,Y4,%) and dissolution efficiency (DE,Y5,%). The optimum formula showed high entrapment efficiency of 94.31% ± 2.44, in vitro drug release of 83.89% ± 1.77 with dissolution efficiency equals 88.63% ± 2.01, small particle size of 71.27 nm ± 13.57 and low polydispersity index 0.097 ± 0.15. In vivo biodistribution in mice was evaluated by a radiobiological technique using radioiodinated zopiclone([131I]iodo-ZP). Results revealed the superiority of the intranasal route to deliver zopiclone directly to brain faster and higher brain uptake (6.9 ± 1.02%ID/g at 5 min post-administration). The current study confirmed that intranasal administration of nano-structured lipid carriers had great potential as an effective tool for targeted brain zopiclone delivery for insomnia treatment.

Influence of "glow discharge plasma" as an external stimulus on the self-assembly, morphology and binding affinity of gold nanoparticle-streptavidin conjugates.

In this study, we investigate the influence of glow discharge plasma (GDP) on the self-assembly, morphology and binding affinity of streptavidin coated gold nanoparticles (Au-NP-SV) and biotinylated antibody (bAb) adsorbed on a highly oriented pyrolytic graphite (HOPG) substrate. Atomic force microscope (AFM) was used to image the pre- and post-GDP treated samples. The analysis of the AFM images showed a considerable change in the aggregation and morphology of Au-NP-conjugates after treatment with GDP. To our knowledge, this is the first report on using GDP to enhance and speed-up the aggregation (sintering) of adsorbed NP biomolecular conjugates. These results show a promising route that could be generalized for other NPs and their conjugates. It can also be considered as an alternative and cheap aggregation method for controlling the binding affinity of biomolecular species on different surfaces with interesting applications.

Antibacterial and antioxidant properties of Cichorium intybus extract embedded in chitosan nanocomposite nanofibers.

Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacteria acquired serious bacterial resistance against antibiotics. Untreated dangerous infections can cause death. We proposed nanofibers (NFs) of Polyvinyl alcohol (PVA)/Chitosan (CS) nanocomposite embedded with Chicory root extract (CRE) as a safe solution. We determined the best extraction solvent and drying method, 70 % ethanol and freeze-drying, respectively. We investigated the optimal electrospinner parameters for a smooth PVA/CS NFs. Finally, we discovered PVA/CS/CRE-50 mg (F4) to be the most effective antibacterial and antioxidant CRE concentration. Interestingly, it was found that ethanolic extract had the highest yield % at 24.7 % with Total Phenolic Contents (TPC) of 4 mg Gallic Acid Equivalent (GAE)/1 g, 80 % antioxidant activity at 25 mg with an IC50 of 4.15 mg/mL and a Minimum Bactericidal Concentration (MBC) of 100 mg against S. aureus and 25 mg against E. coli. Remarkably, F4 NFs had an IC50 33.32 mg/mL, Entrapment Efficiency 64.89 %, Loading Capacity 4.41 %, obeying Noyes-Whitney release model. F4 had an MBC of 2 mg with both bacterial strains, which proved to be potent antibacterial material that surpasses the pure extract 50 times. F4 has also shown an extraordinary antioxidant activity that exceeds PVA/CS NF activity 23 times.

Antimicrobial and Wound-Healing Activities of Graphene-Reinforced Electrospun Chitosan/Gelatin Nanofibrous Nanocomposite Scaffolds.

This study aims at preparing electrospun chitosan/gelatin nanofiber scaffolds reinforced with different amounts of graphene nanosheets to be used as antibacterial and wound-healing scaffolds. Full characterization was carried out for the different fabricated scaffolds before being assessed for their antimicrobial activity against Escherichia coli and Staphylococcus aureus, cytotoxicity, and cell migration capacity. Raman and transmission electron microscopies confirmed the successful reinforcement of nanofibers with graphene nanosheets. Scanning electron microscopy and porosity revealed that nanofibers reinforced with 0.15% graphene nanosheets produced the least diameter (106 ± 30 nm) and the highest porosity (90%), in addition to their good biodegradability and swellability. However, the excessive increase in graphene nanosheet amount produced beaded nanofibers with decreased porosity, swellability, and biodegradability. Interestingly, nanofibers reinforced with 0.15% graphene nanosheets showed E. coli and S. aureus growth inhibition percents of 50 and 80%, respectively. The cell viability assay showed no cytotoxicity on human fibroblasts when cultured with either unreinforced or reinforced nanofibers. The cell migration was higher in the case of reinforced nanofibers when compared to the unreinforced nanofibers after 24 and 48 h, which is substantially associated with the great effect of the graphene nanosheets on the cell migration capability. Unreinforced and reinforced nanofibers showed cell migration results up to 93.69 and 97%, respectively, after 48 h.

Investigating the bone regeneration activity of PVA nanofibers scaffolds loaded with simvastatin/chitosan nanoparticles in an induced bone defect rabbit model.

This study aims at preparing electrospun PVA NFs incorporating simvastatin/chitosan nanoparticles (SIM CS NPs) as a controlled drug eluting scaffold for bone regeneration. Optimization was performed by Design Expert® software through establishing two factor, three level factorial design, where the independent variables were the applied voltage, flow rate and PVA solution/SIM CS NPs ratio. Formulation variables values for the optimized formula were 18KV, 0.5 mL/h, and 3:1 respectively. NFs diameter and mesh pore size were chosen as the dependent variables. The optimized NFs were evaluated morphologically, chemically, and physically. Additionally, in-vitro SIM release from the scaffolds was investigated along 24 days. Optimum NFs possessed 136 nm diameter size and 6.5 nm porosity. Also, they showed sustained SIM release for 24 days to achieve the desired goal in bone regeneration. The optimized NFs were implanted within induced bone defects in rabbits. In-vivo assessments were performed through cone beam computed tomography 3D images, bone density measurements, histological analysis and bone morphogenetic protein 2 (BMP 2) level. The obtained results proved the high potential of the optimized NFs in promoting bone regeneration compared to untreated group, non-medicated NFs group, free SIM group and NFs loaded with SIM group after 6 weeks of implantation.

Improvement of doxorubicin radioiodination and in-vivo cancer suppression via loading in nanosilver system.

This study aimed at improving the radioiodination of doxorubicin (DOX) and its localization in cancer cell for theranostic purposes. To achieve this goal, a composite of DOX with polyvinyl pyrrolidone (PVP) and silver nanoparticles (AgNPs) was prepared. Both DOX and (DOX/PVP/AgNPs) were radiolabelled with iodine-125 [125I] and optimized using iodogen as a preferable oxidizing agent. The maximum obtained radiochemical yields for both systems were 79.9% and 96.6%, respectively. Interestingly, the biodistribution study revealed that [125I]DOX/PVP/AgNPs had an effective localization on tumors. Moreover, Target/control target (T/CT) ratio of [125I] DOX/PVP/AgNPs showed the highest value of 9.1 at 1 h post injection, suggesting that [125I]DOX/PVP/AgNPs has a great potential as a proposed tumor targeting agent.

Quercetin loaded cosm-nutraceutical electrospun composite nanofibers for acne alleviation: Preparation, characterization and experimental clinical appraisal.

In the cosmeceutical field, it is essential to develop topical delivery systems which would allow drugs to create a depot and permeate within the skin. The aim of the present study was to develop composite nanofibers of polyvinyl alcohol/quercetin/essential oils using the electrospinning technique, and assess their efficiency in acne alleviation. Quercetin was chosen due to its anti-inflammatory, anti-oxidant, and antibacterial activities. Nanofibers were characterized for their morphology, ex-vivo deposition/permeation, physical/mechanical integrity, thermal properties, and chemical characteristics. In addition, the anti-bacterial efficacy was tested on Propionibacterium acne (P. acne), and a cytotoxicity assay was carried out. Lastly, an experimental clinical trial was conducted on acne patients, where the percentage reduction of inflammatory, non-inflammatory and total acne lesions was taken as evaluation criterion. Results showed that quercetin was successfully loaded into the nanofibers which were homogenously dispersed. They showed a reasonable skin deposition percentage of 28.24% ± 0.012, a significantly higher antibacterial efficacy against Propionibacterium acne than quercetin alone, and were utterly safe on skin fibroblastic cells. Upon clinical examination on acne patients, the nanofibers showed 61.2%, 14.7%, and 52.9% reduction of inflammatory, comedonal, and total acne lesions respectively, suggesting a promising topical anti-acne delivery system.

Targeted doxorubicin delivery and release within breast cancer environment using PEGylated chitosan nanoparticles labeled with monoclonal antibodies.

Breast cancer has been one of the top chronic and life-threatening diseases worldwide. Nano-drug therapeutic systems have proved their efficacy as a selective treatment compared to the traditional ones that are associated with serious adverse effects. Here, biodegradable chitosan nanoparticles (CSNPs) were synthesized to provide selective and sustained release of doxorubicin (DOX) within the breast tumor microenvironment. CSNPs surface was modified using Polyethylene glycol (PEG) to enhance their blood circulation timing. To provide high drug selectivity, CSNPs functionalized with two different types of breast cancer-specific monoclonal antibodies (mAb); anti-human mammaglobin (Anti-hMAM) and anti-human epidermal growth factor (Anti-HER2). Anti-hMAM PEGylated DOX loaded CSNPs and Anti-HER2 PEGylated DOX loaded CSNPs nano-formulations were the most cytotoxic against MCF-7 cancer cells than L-929 normal cells compared to free DOX. Finally, we believe that dose-dependent system toxicity of freely ingested DOX can be managed with such targeted nano-formulated drug delivery platforms.

Green tea essential oil encapsulated chitosan nanoparticles-based radiopharmaceutical as a new trend for solid tumor theranosis.

The existing study is embarked on investigating the antineoplastic activity of green tea essential oil (GTO) as a natural product. In this regard, GTO was encapsulated in cationic chitosan, nitrogenous-polysaccharide derived by partial deacetylation of chitin, nanoparticles (CS NPs) with entrapment efficiency (EE%) of 81.4 ± 5.7% and a mean particle-size of 30.7 ± 1.13 nm. Moreover, the cytotoxic effect of CS/GTO NPs was evaluated versus human liver (HepG-2), breast (MCF-7) and colon (HCT-116) cancer cell-lines and exhibited a positive impact when compared to bare CS NPs by 3, 2.3 and 1.7 fold for the three cell lines, respectively. More interestingly, CS/GTO NPs were complexed with technethium-99m (99mTc) radionuclide. With a view to achieve a successful radiolabeling process, different parameters were optimized resulting in a radiolabeling efficiency (RE%) of 93.4 ± 1.2%. Radiopharmacokinetics of the radiolabeled NPs in healthy mice demonstrated a reticuloendothelial system (RES) evading and long blood circulation time up to 4 h. On the other hand, the biodistribution profile in solid tumor models showed 20.3 ± 2.1% localization and cancer cell targeting within just 30 min. On the whole, the reported results encourage the potential use of CS/GTO NPs as a side effect-free anticancer agent and its 99mTc-analogue as a novel CS/GTO NPs-based diagnostic-radiopharmaceutical for cancer.

Applying Box-Behnken Design for Formulation and Optimization of PLGA-Coffee Nanoparticles and Detecting Enhanced Antioxidant and Anticancer Activities.

In an attempt to prove biological activity enhancement upon particle size reduction to the nanoscale, coffee (Cf) was chosen to be formulated into poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) using the single emulsion-solvent evaporation (SE-SE) method via Box-Behnken Design (BBD) to study the impact of certain process and formulation parameters on the particle size and size homogeneity, surface stability and encapsulation efficiency (EE%). The coffee-loaded PLGA (PLGA-Cf) NPs were characterized by different methods to aid in selecting the optimum formulation conditions. The desirable physicochemical characteristics involved small particle sizes with an average of 318.60 ± 5.65 nm, uniformly distributed within a narrow range (PDI of 0.074 ± 0.015), with considerable stability (Zeta Potential of -20.50 ± 0.52 mV) and the highest EE% (85.92 ± 4.01%). The antioxidant and anticancer activities of plain PLGA NPs, pure Cf and the optimum PLGA-Cf NPs, were evaluated using 2,2-Diphenyl-1-picryl-hydrazyl (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. As a result of nano-encapsulation, antioxidant activity was enhanced by 26.5%. Encapsulated Cf showed higher anticancer potency than pure Cf against different cancerous cell lines with an increase of 86.78%, 78.17%, 85.84% and 84.84% against MCF-7, A-549, HeLa and HepG-2, respectively. The in vitro release followed the Weibull release model with slow and biphasic release profile in both tested pH media, 7.4 and 5.5.

In Vitro Biological Evaluation of a Fabricated Polycaprolactone/Pomegranate Electrospun Scaffold for Bone Regeneration.

Different scaffold biomaterials are being investigated as a solution for bone loss due to disease or trauma. The aim of this study is the fabrication, characterization, and in vitro biological evaluation of a novel polycaprolactone (PCL) nanoscaffold incorporating pomegranate peel extract (PG) for bone regeneration. Using electrospinning, three groups of scaffolds were prepared: the control group PCL and two groups of PCL with PG concentrations (11 and 18 weight %). The antioxidant activity and the total phenolic content (TPC) of the fabricated nanoscaffolds were evaluated, in addition to the porosity and degradation measurement. Cultured osteoblasts derived from rabbit bone marrow mesenchymal stem cells were used for the assessment of cell proliferation and attachment on the scaffold's surface. Scaffolds' characterization showed uniform nanofibers (NFs) with a fiber diameter range of 149-168 nm. Meanwhile, higher antioxidant activity and TPC of the PG groups were detected. Furthermore, total porosities of 59 and 62% were determined for the PCL-PG scaffolds. An increased degradation rate and significant improvement in cell proliferation and cell attachment were revealed for the PCL-PG fabricated scaffolds. Such incorporation of natural food waste, PG, in PCL NFs offered novel PCL-PG scaffolds as a promising candidate for bone regeneration applications.

Two-dimensional network stability of nucleobases and amino acids on graphite under ambient conditions: adenine, L-serine and L-tyrosine.

We have investigated the stability of two-dimensional self-assembled molecular networks formed upon co-adsorption of the DNA base, adenine, with each of the amino acids, L-serine and L-tyrosine, on a highly oriented pyrolytic graphite (HOPG) surface by drop-casting from a water solution. L-serine and L-tyrosine were chosen as model systems due to their different interaction with the solvent molecules and the graphite substrate, which is reflected in a high and low solubility in water, respectively, compared with adenine. Combined scanning tunneling microscopy (STM) measurements and density functional theory (DFT) calculations show that the self-assembly process is mainly driven by the formation of strong adenine-adenine hydrogen bonds. We find that pure adenine networks are energetically more stable than networks built up of either pure L-serine, pure L-tyrosine or combinations of adenine with L-serine or L-tyrosine, and that only pure adenine networks are stable enough to be observable by STM under ambient conditions.

Fabrication of Nanofibrous/Xerogel Layer-by-Layer Biocomposite Scaffolds for Skin Tissue Regeneration: In Vitro Study.

Skin burn wounds are a crucial issue that could reduce life quality. Although numerous effective skin products have invaded the biomedical market, most of them still demonstrate some limitations regarding their porosity, swelling and degradation behaviors, antibacterial properties, and cytotoxicity. Thus, the aim of this study is to fabricate novel trilayered asymmetric porous scaffolds that can mimic the natural skin layers. In particular, the fabricated scaffold constitutes an upper electrospun chitosan-poly(vinyl alcohol) layer and a lower xerogel layer, which is made of effective skin extracellular matrix components. Both layers are fixed together using fibrin glue as a middle layer. The results of this study revealed promising scaffold swelling capability suitable for absorbing wound exudates, followed by a constant degradable weight over time, which is appropriate for a burn wound environment. Scanning electron microscopy images revealed an average pore diameter in the range of 138.39-170.18 nm for the cross-linked electrospun mats and an average pore size of 2.29-30.62 µm for the fabricated xerogel layers. This further provided an optimum environment for fibroblast migration and proliferation. The electrospun nanofibrous layer was examined for its antibacterial properties and showed expressive complete bacterial inhibition against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacterial strains (log reduction = 3 and 2.70, respectively). Next, mouse embryonic fibroblast cytotoxicity and migration rate were investigated against the developed asymmetrical composite to assess its biocompatibility. Tissue culture experiments demonstrated significant cell proliferation and migration in the presence of the constructed scaffold (P < 0.0001). A complete wound closure was observed in vitro in the presence of the three scaffold asymmetrical layers against the mouse embryonic fibroblast. The results of this study proved superior biological characteristics of the innovative asymmetrical composite that could further replace the burned or damaged skin layers with promising potential for clinical applications.