Mostafa Mabrouk

A composite chitosan-gelatin bi-layered, biomimetic macroporous scaffold for blood vessel tissue engineering

A composite chitosan-gelatin macroporous hydrogel-based scaffold with bi-layered tubular architecture was engineered by solvent casting-co-particulate leaching. The scaffold constituted an inner macroporous layer concealed by a non-porous outer layer mimicking the 3D matrix of blood vessels with cellular adhesion and proliferation. The scaffold was evaluated for its morphological, physicochemical, physicomechanical and biodurability properties employing SEM, FTIR, DSC, XRD, porositometry, rheology and texture analysis. The fluid uptake and biodegradation in the presence of lysozymes was also investigated. Cellular attachment and proliferation was analysed using human dermal fibroblasts (HDF-a) seeded onto the scaffold and evaluated by MTT assay, SEM, and confocal microscopy. Results demonstrated that the scaffold had a desirable tensile strength=95.81±11kPa, elongation at break 112.5±13%, porosity 82% and pores between 100 and 230μm, 50% in vitro biodegradation at day 16 and proliferated fibroblasts over 20 days. These results demonstrate that scaffold may be an excellent tubular archetype for blood vessel tissue engineering.

Design of a novel crosslinked HEC-PAA porous hydrogel composite for dissolution rate and solubility enhancement of efavirenz.

The purpose of this research was to synthesize, characterize and evaluate a Crosslinked Hydrogel Composite (CHC) as a new carrier for improving the solubility of the anti-HIV drug, efavirenz. The CHC was prepared by physical blending of hydroxyethylcellulose (HEC) with poly(acrylic acid) (PAA) (1:1) in the presence of poly(vinyl alcohol) (PVA) (as a crosslinker) (1:5) under lyophilization. Efavirenz was loaded in situ into the CHC in varying proportions (200-600 mg). The CHC demonstrated impressive rheological properties (dynamic viscosity=6053 mPa; 500 s(-1)) and tensile strength (2.5 mPa) compared with the native polymers (HEC and PAA). The physicochemical and thermal behavior also confirmed that the CHC was compatible with efavirenz. The incorporation of efavirenz in the CHC increased the surface area (4.4489-8.4948 m(2)/g) and pore volume (469.547-776.916Å) of the hydrogel system which was confirmed by SEM imagery and BET surface area measurements. The solubility of efavirenz was significantly enhanced (150 times) in a sustained release manner over 24h as affirmed by the in vitro drug release studies. The hydration medium provided by the CHC network played a pivotal role in improving the efavirenz solubility via increasing hydrogen bonding as proved by the zeta potential measurements (-18.0 to +0.10). The CHC may be a promising alternative as an oral formulation for the delivery of efavirenz with enhanced solubility.

A Review of Thermo- and Ultrasound-Responsive Polymeric Systems for Delivery of Chemotherapeutic Agents

There has been an exponential increase in research into the development of thermal- and ultrasound-activated delivery systems for cancer therapy. The majority of researchers employ polymer technology that responds to environmental stimuli some of which are physiologically induced such as temperature, pH, as well as electrical impulses, which are considered as internal stimuli. External stimuli include ultrasound, light, laser, and magnetic induction. Biodegradable polymers may possess thermoresponsive and/or ultrasound-responsive properties that can complement cancer therapy through sonoporation and hyperthermia by means of High Intensity Focused Ultrasound (HIFU). Thermoresponsive and other stimuli-responsive polymers employed in drug delivery systems can be activated via ultrasound stimulation. Polyethylene oxide/polypropylene oxide co-block or triblock polymers and polymethacrylates are thermal- and pH-responsive polymer groups, respectively but both have proven to have successful activity and contribution in chemotherapy when exposed to ultrasound stimulation. This review focused on collating thermal- and ultrasound-responsive delivery systems, and combined thermo-ultrasonic responsive systems; and elaborating on the advantages, as well as shortcomings, of these systems in cancer chemotherapy. The mechanisms of these systems are explicated through their physical alteration when exposed to the corresponding stimuli. The properties they possess and the modifications that enhance the mechanism of chemotherapeutic drug delivery from systems are discussed, and the concept of pseudo-ultrasound responsive systems is introduced.

Ca3(PO4)2 precipitated layering of an in situ hybridized PVA/Ca2O4Si nanofibrous antibacterial wound dressing.

The aim of this study was to develop an in situ hybridized poly(vinyl alcohol)/calcium silicate (PVA/Ca2OSi) nanofibrous antibacterial wound dressing with calcium phosphate [Ca3(PO4)2] surface precipitation for enhanced bioactivity. This was achieved by hybridizing the antibacterial ions Zn(2+) and/or Ag(+) in a Ca2O4Si composite. The hybridization effect on the thermal behavior, physicochemical, morphological, and physicomechanical properties of the nanofibers was studied using Differential Scanning calorimetric (DSC), X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and Textural Analysis, respectively. In vitro bioactivity, biodegradation and pH variations of the nanofiber composite were evaluated in Simulated Body Fluid (SBF). The antibacterial activity was assessed against Staphylococcus aureus and Pseudomonas aeruginosa. Hybridization of Zn(2+) and/or Ag(+) into the PVA/Ca2O4Si nanofiber composite was confirmed by DSC, XRD and FTIR. The thickness of the nanofibers was dependent on the presence of Zn(2+) and Ag(+) as confirmed by SEM. The nanofibers displayed enhanced tensile strength (19-115.73MPa) compared to native PVA. Zn(2+) and/or Ag(+) hybridized nanofibers showed relatively enhanced in vitro bioactivity, biodegradation (90%) and antibacterial activity compared with the native PVA/Ca2O4Si nanofiber composite. Results of this study has shown that the PVA/Ca2O4Si composite hybridized with both Zn(2+) and Ag(+) may be promising as an antibacterial wound dressing with a nanofibrous archetype with enhanced bioactivity.

The Influence of Lyophilized EmuGel Silica Microspheres on the Physicomechanical Properties, In Vitro Bioactivity and Biodegradation of a Novel Ciprofloxacin-Loaded PCL/PAA Scaffold

A new composite poly(caprolactone) (PCL) and poly(acrylic acid) (PAA) (PCL:PAA 1:5) scaffold was synthesized via dispersion of PCL particles into a PAA network. Silica microspheres (Si) (2–12 μm) were then prepared by a lyophilized micro-emulsion/sol-gel (Emugel) system using varying weight ratios. The model drug ciprofloxacin (CFX) was used for in situ incorporation into the scaffold. The physicochemical and thermal integrity, morphology and porosity of the system was analyzed by X-Ray Diffraction (XRD), Attenuated Total Refelctance Fourier Transform Infrared (ATR-FTIR), Differential Scanning Calorimetry (DSC), SEM, surface area analysis and liquid displacement, respectively. The mechanical properties of the scaffold were measured by textural analysis and in vitro bioactivity, biodegradation and pH variations were evaluated by XRD, FTIR and SEM after immersion in Simulated Body Fluid (SBF). The in vitro and in vivo studies of the prepared scaffold were considered as future aspects for this study. CFX release was determined in phosphate buffer saline (PBS) (pH 7.4; 37 °C). The incorporation of the Si microspheres and CFX into the scaffold was confirmed by XRD, FTIR, DSC and SEM, and the scaffold microstructure was dependent on the concentration of Si microspheres and the presence of CFX. The system displayed enhanced mechanical properties (4.5–14.73 MPa), in vitro bioactivity, biodegradation and controlled CFX release. Therefore, the PCL/PAA scaffolds loaded with Si microspheres and CFX with a porosity of up to 87% may be promising for bone tissue engineering.

Customized Peptide Biomaterial Synthesis via an Environment-Reliant Auto-Programmer Stigmergic Approach

Stigmergy, a form of self-organization, was employed here to engineer a self-organizing peptide capable of forming a nano- or micro-structure and that can potentially be used in various drug delivery and biomedical applications. These self-assembling peptides exhibit several desirable qualities for drug delivery, tissue engineering, cosmetics, antibiotics, food science, and biomedical surface engineering. In this study, peptide biomaterial synthesis was carried out using an environment-reliant auto-programmer stigmergic approach. A model protein, α-gliadin (31, 36, and 38 kD), was forced to attain a primary structure with free –SH groups and broken down enzymatically into smaller fragments using chymotrypsin. This breakdown was carried out at different environment conditions (37 and 50 °C), and the fragments were allowed to self-organize at these temperatures. The new peptides so formed diverged according to the environmental conditions. Interestingly, two peptides (with molecular weights of 13.8 and 11.8 kD) were isolated when the reaction temperature was maintained at 50 °C, while four peptides with molecular weights of 54, 51, 13.8, and 12.8 kD were obtained when the reaction was conducted at 37 °C. Thus, at a higher temperature (50 °C), the peptides formed, compared to the original protein, had lower molecular weights, whereas, at a lower temperature (37 °C), two peptides had higher molecular weights and two had lower molecular weights.

Synthesis and Evaluation of a Sodium Alginate-4-Aminosalicylic Acid Based Microporous Hydrogel for Potential Viscosupplementation for Joint Injuries and Arthritis-Induced Conditions

A microporous hydrogel was developed using sodium alginate (alg) and 4-aminosalicylic acid (4-ASA). The synthesized hydrogel was characterized using various analytical techniques such as Fourier transform infrared spectroscopy (FTIR), Carbon-13 nuclear magnetic resonance (13C-NMR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Additonal carboxyl and hydroxyl functional groups of 4-ASA provided significant lubrication and stress-triggered sol-gel transition to the conjugated hydrogel. In addition, cytotoxicity analysis was undertaken on the conjugated hydrogel using human dermal fibroblast-adult (HDFa) cells, displaying non-toxic characteristics. Drug release profiles displaying 49.6% in the first 8 h and 97.5% within 72 h, similar to the native polymer (42.8% in first 8 h and 90.1% within 72 h). Under applied external stimuli, the modified hydrogel displayed significant gelling properties and structure deformation/recovery behaviour, confirmed using rheological evaluation (viscosity and thixotropic area of 8095.3 mPas and 26.23%, respectively). The modified hydrogel, thus, offers great possibility for designing smart synovial fluids as a biomimetic aqueous lubricant for joint-related injuries and arthritis-induced conditions. In addtion, the combination of thixotropy, non-toxicity, and drug release capabilities enables potential viscosupplementation for clinical application.