Antiepileptic drug-loaded and multifunctional iron oxide@silica@gelatin nanoparticles for acid-triggered drug delivery.

The current study developed an innovative design for the production of smart multifunctional core-double shell superparamagnetic nanoparticles (NPs) with a focus on the development of a pH-responsive drug delivery system tailored for the controlled release of Phenytoin, accompanied by real-time monitoring capabilities. In this regard, the ultra-small superparamagnetic iron oxide@silica NPs (IO@Si MNPs) were synthesized and then coated with a layer of gelatin containing Phenytoin as an antiepileptic drug. The precise saturation magnetization value for the resultant NPs was established at 26 emu g-1. The polymeric shell showed a pH-sensitive behavior with the capacity to regulate the release of encapsulated drug under neutral pH conditions, simultaneously, releasing more amount of the drug in a simulated tumorous-epileptic acidic condition. The NPs showed an average size of 41.04 nm, which is in the desired size range facilitating entry through the blood-brain barrier. The values of drug loading and encapsulation efficiency were determined to be 2.01 and 10.05%, respectively. Moreover, kinetic studies revealed a Fickian diffusion process of Phenytoin release, and diffusional exponent values based on the Korsmeyer-Peppas equation were achieved at pH 7.4 and pH 6.3. The synthesized NPs did not show any cytotoxicity. Consequently, this new design offers a faster release of PHT at the site of a tumor in response to a change in pH, which is essential to prevent epileptic attacks.

Self-healing interpenetrating network hydrogel based on GelMA/alginate/nano-clay.

Today, tissue engineering strategies need the improvement of advanced hydrogels with biological and mechanical properties similar to natural cartilage for joint regeneration. In this study, an interpenetrating network (IPN) hydrogel composed of gelatin methacrylate (GelMA)/alginate (Algin)/nano-clay (NC) with self-healing ability was developed with particular consideration to balancing of the mechanical properties and biocompatibility of bioink material. Subsequently, the properties of the synthesized nanocomposite IPN, including the chemical structure, rheological behavior, physical properties (i.e. porosity and swelling), mechanical properties, biocompatibility, and self-healing performance were evaluated to investigate the potential application of the developed hydrogel for cartilage tissue engineering (CTE). The synthesized hydrogels showed highly porous structures with dissimilar pore sizes. The results revealed that the NC incorporation improved the properties of GelMA/Algin IPN, such as porosity, and mechanical strength (reached 170 ± 3.5 kPa), while the NC incorporation decreased the degradation (63.8 %) along with retaining biocompatibility. Therefore, the developed hydrogel showed a promising potential for the treatment of tissue defects in cartilage.

Cytocompatibility and Antibacterial Properties of Coaxial Electrospun Nanofibers Containing Ciprofloxacin and Indomethacin Drugs.

A coaxial nanofibrous scaffold of poly (ε-caprolactone) and gelatin/cellulose acetate encapsulating anti-inflammatory and antibacterial drugs was co-electrospun for skin tissue regeneration. Indomethacin and ciprofloxacin as model drugs were added to the core and the shell solutions, respectively. The effect of the drugs' presence and crosslinking on the scaffold properties was investigated. TEM images confirmed the core−shell structure of the scaffold. The fiber diameter and the pore size of the scaffold increased after crosslinking. The tensile properties of the scaffold improved after crosslinking. The crosslinked scaffold illustrated a higher rate of swelling, and a lower rate of degradation and drug release compared to the uncrosslinked one. Fitting the release data into the Peppas equation showed that Fickian diffusion was the dominant mechanism of drug release from the scaffolds. The results of biocompatibility evaluations showed no cytotoxicity and suitable adhesion and cell growth on the prepared core−shell structure. The antibacterial activity of the scaffolds was studied against one of the most common pathogens in skin wounds, where the existence of ciprofloxacin could prevent the growth of the Staphylococcus aureus bacteria around the scaffold. The obtained results suggested a new coaxial nanofibrous scaffold as a promising candidate for simultaneous tissue regeneration and controlled drug release.

Facile preparation of chitosan-dopamine-inulin aldehyde hydrogel for drug delivery application.

Chitosan-based hydrogels are a suitable and versatile system for the design of localized and controlled drug delivery systems. In the current study, a hydrogel based on chitosan (CS), Dopamine (DA), and Inulin aldehyde (IA) was fabricated without the further use of catalyst or initiators. The effect of the IA contents as a crosslinking agent on the properties of the prepared hydrogel was studied. The crosslinking reaction between CS and IA was verified by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Various characteristics of the CS/DA/IA hydrogels were further assessed utilizing swelling experiment, in vitro drug release, in vitro cytotoxicity assay. The drug-loaded hydrogels represented the sustained release of Indomethacin according to the in vitro drug release test in acidic (pH = 4), basic (pH = 10) medium as well as physiological condition (pH = 7). Finally, the CS/DA/IA hydrogels exhibited appropriate cytocompatibility against the L-929 fibroblast cell line according to the direct contact MTT assay.

Regeneration of the peripheral nerve via multifunctional electrospun scaffolds.

Over the last two decades, electrospun scaffolds have proved to be advantageous in the field of nerve tissue regeneration by connecting the cavity among the proximal and distal nerve stumps growth cones and leading to functional recovery after injury. Multifunctional nanofibrous structure of these scaffolds provides enormous potential by combining the advantages of nano-scale topography, and biological science. In these structures, selecting the appropriate materials, designing an optimized structure, modifying the surface to enhance biological functions and neurotrophic factors loading, and native cell-like stem cells should be considered as the essential factors. In this systematic review paper, the fabrication methods for the preparation of aligned nanofibrous scaffolds in yarn or conduit architecture are reviewed. Subsequently, the utilized polymeric materials, including natural, synthetic and blend are presented. Finally, their surface modification techniques, as well as, the recent advances and outcomes of the scaffolds, both in vitro and in vivo, are reviewed and discussed.

Development of a Highly Proliferated Bilayer Coating on 316L Stainless Steel Implants.

In this research, a bilayer coating has been applied on the surface of 316 L stainless steel (316LSS) to provide highly proliferated metallic implants for bone regeneration. The first layer was prepared using electrophoretic deposition of graphene oxide (GO), while the top layer was coated utilizing electrospinning of poly (ε-caprolactone) (PCL)/gelatin (Ge)/forsterite solutions. The morphology, porosity, wettability, biodegradability, bioactivity, cell attachment and cell viability of the prepared coatings were evaluated. The Field Emission Scanning Electron Microscopy (FESEM) results revealed the formation of uniform, continuous, and bead-free nanofibers. The Energy Dispersive X-ray (EDS) results confirmed well-distributed forsterite nanoparticles in the structure of the top coating. The porosity of the electrospun nanofibers was found to be above 70%. The water contact angle measurements indicated an improvement in the wettability of the coating by increasing the amount of nanoparticles. Furthermore, the electrospun nanofibers containing 1 and 3 wt.% of forsterite nanoparticles showed significant bioactivity after soaking in the simulated body fluid (SBF) solution for 21 days. In addition, to investigate the in vitro analysis, the MG-63 cells were cultured on the PCL/Ge/forsterite and GO-PCL/Ge/forsterite coatings. The results confirmed an excellent cell adhesion along with considerable cell growth and proliferation. It should be also noted that the existence of the forsterite nanoparticles and the GO layer substantially enhanced the cell proliferation of the coatings.

Nanofibrous Scaffolds with Biomimetic Composition for Skin Regeneration.

Treatments of skin injuries caused by trauma and diseases are among the most considerable medical problems. The use of scaffolds that can cover the wound area and support cellular ingrowth has shown great promise. However, mimicking the physicochemical properties of the native skin extracellular matrix (ECM) is essential for the successful integration of these scaffolds. Elastin has been known as the second main protein-based component of the native skin ECM. In this research, scaffolds containing gelatin, cellulose acetate, and elastin were fabricated using electrospinning. Subsequently, the effects of soluble elastin on the physical, mechanical, and biological properties of the prepared scaffolds were studied. The results confirmed that the presence of elastin in the composition changed the fiber morphology from straight to ribbon-like structure and decreased the swelling ratio and degradation rate of the scaffold. In vitro experiments showed that elastin-containing scaffolds supported the attachment and proliferation of fibroblast cells. Overall, the obtained results suggest the ternary blend of gelatin, cellulose acetate, and elastin as a good candidate for skin tissue engineering.

Nanofibrous scaffolds with biomimetic structure.

This research studies the effect of using a grid-like pattern as a collector on increasing the pore size of the electrospun gelatin/cellulose acetate/elastin scaffolds. The morphological study showed an enlargement in pore size and a decline in fiber diameter in comparison with the scaffold fabricated using conventional flat sheet collectors. The use of the pattern increased the swelling ratio and degradation rate of the scaffold. Investigating the tensile properties of scaffolds revealed that the patterned collector increased the elongation at break up to 145%. In vitro experiments revealed the patterned scaffold as a good substrate for attachment and proliferation of fibroblast cells. Overall, our results indicated that the patterned scaffold of gelatin/cellulose acetate/elastin could provide a better microenvironment for fibroblast cells compared to the conventional scaffolds. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 370-376, 2018.

Highly Stretchable Potentiometric pH Sensor Fabricated via Laser Carbonization and Machining of Carbon-Polyaniline Composite.

The development of stretchable sensors has recently attracted considerable attention. These sensors have been used in wearable and robotics applications, such as personalized health-monitoring, motion detection, and human-machine interfaces. Herein, we report on a highly stretchable electrochemical pH sensor for wearable point-of-care applications that consists of a pH-sensitive working electrode and a liquid-junction-free reference electrode, in which the stretchable conductive interconnections are fabricated by laser carbonizing and micromachining of a polyimide sheet bonded to an Ecoflex substrate. This method produces highly porous carbonized 2D serpentine traces that are subsequently permeated with polyaniline (PANI) as the conductive filler, binding material, and pH-sensitive membrane. The experimental and simulation results demonstrate that the stretchable serpentine PANI/C-PI interconnections with an optimal trace width of 0.3 mm can withstand elongations of up to 135% and are robust to more than 12 000 stretch-and-release cycles at 20% strain without noticeable change in the resistance. The pH sensor displays a linear sensitivity of -53 mV/pH (r2 = 0.976) with stable performance in the physiological range of pH 4-10. The sensor shows excellent stability to applied longitudinal and transverse strains up to 100% in different pH buffer solutions with a minimal deviation of less than ±4 mV. The material biocompatibility is confirmed with NIH 3T3 fibroblast cells via PrestoBlue assays.

Preparation and characterization of poly (hydroxy butyrate)/chitosan blend scaffolds for tissue engineering applications.

BACKGROUND: Poly (hydroxy butyrate) (PHB) is a biodegradable and biocompatible polymer with good mechanical properties. This polymer could be a promising material for scaffolds if some features improve. MATERIALS AND METHODS: In the present work, new PHB/chitosan blend scaffolds were prepared as a three-dimensional substrate in cartilage tissue engineering. Chitosan in different weight percent was added to PHB and solved in trifluoroacetic acid. Statistical Taguchi method was employed in the design of experiments. RESULTS: The Fourier-transform infrared spectroscopy test revealed that the crystallization of PHB in these blends is suppressed with increasing the amount of chitosan. Scanning electron microscopy images showed a thin and rough top layer with a nodular structure, supported with a porous sub-layer in the surface of the scaffolds. In vitro degradation rate of the scaffolds was higher than pure PHB scaffolds. Maximum degradation rate has been seen for the scaffold with 90% wt. NaCl and 40% wt. chitosan. CONCLUSIONS: The obtained results suggest that these newly developed PHB/chitosan blend scaffolds may serve as a three-dimensional substrate in cartilage tissue engineering.