Tideglusib-incorporated nanofibrous scaffolds potently induce odontogenic differentiation.

Pulp-Dentin regeneration is a key aspect of maintain tooth vitality and enabling good oral-systemic health. This study aimed to investigate a nanofibrous scaffold loaded with a small molecule i.e. Tideglusib to promote odontogenic differentiation. Tideglusib (GSK-3ß inhibitor) interaction with GSK-3ß was determined using molecular docking and stabilization of ß-catenin was examined by confocal microscopy. 3D nanofibrous scaffolds were fabricated through electrospinning and their physicochemical characterizations were performed. Scaffolds were seeded with mesenchymal stem cells or pre-odontoblast cells to determine the cells proliferation and odontogenic differentiation. Our results showed that Tideglusib (TG) binds with GSK-3ß at Cys199 residue. Stabilization and nuclear translocation of ß-catenin was increased in the odontoblast cells treated with TG. SEM analysis revealed that nanofibers exhibited controlled architectural features that effectively mimicked the natural ECM. UV-Vis spectroscopy demonstrated that TG was incorporated successfully and released in a controlled manner. Both kinds of biomimetic nanofibrous matrices (PCLF-TG100, PCLF-TG1000) significantly stimulated cells proliferation. Furthermore, these scaffolds significantly induced dentinogenic markers (ALP, and DSPP) expression and biomineralization. In contrast to current pulp capping material driving dentin repair, the sophisticated, polymeric scaffold systems with soluble and insoluble spatiotemporal cues described here can direct stem cell differentiation and dentin regeneration. Hence, bioactive small molecule-incorporated nanofibrous scaffold suggests an innovative clinical tool for dentin tissue engineering.

Drug/bioactive eluting chitosan composite foams for osteochondral tissue engineering.

Joint defects associated with a variety of etiologies often extend deep into the subchondral bone leading to functional impairment and joint immobility, and it is a very challenging task to regenerate the bone-cartilage interface offering significant opportunities for biomaterial-based interventions to improve the quality of life of patients. Herein drug-/bioactive-loaded porous tissue scaffolds incorporating nano-hydroxyapatite (nHAp), chitosan (CS) and either hydroxypropyl methylcellulose (HPMC) or Bombyx mori silk fibroin (SF) are fabricated through freeze drying method as subchondral bone substitute. A combination of spectroscopy and microscopy (Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray (EDX), and X-ray fluorescence (XRF) were used to analyze the structure of the porous biomaterials. The compressive mechanical properties of these scaffolds are biomimetic of cancellous bone tissues and capable of releasing drugs/bioactives (exemplified with triamcinolone acetonide, TA, or transforming growth factor-ß1, TGF-ß1, respectively) over a period of days. Mouse preosteoblast MC3T3-E1 cells were observed to adhere and proliferate on the tissue scaffolds as confirmed by the cell attachment, live-dead assay and alamarBlue™ assay. Interestingly, RT-qPCR analysis showed that the TA downregulated inflammatory biomarkers and upregulated the bone-specific biomarkers, suggesting such tissue scaffolds have long-term potential for clinical application.

Electrospun Antibacterial Composites for Cartilage Tissue Engineering.

Implantation of biomaterials capable of the controlled release of antibacterials during articular cartilage repair may prevent postoperative infections. Herein, biomaterials are prepared with biomimetic architectures (nonwoven mats of fibers) via electrospinning that are composed of poly(ɛ-caprolactone), poly(lactic acid), and Bombyx mori silk fibroin (with varying ratios) and, optionally, an antibiotic drug (cefixime trihydrate). The composition, morphology, and mechanical properties of the nanofibrous mats are characterized using scanning electron microscope, Fourier transform infrared spectroscopy, and tensile testing. The nonwoven mats have nanoscale fibers (typical diameters of 324-725 nm) and are capable of controlling the release profiles of the drug, with antibacterial activity against Gram +ve and Gram -ve bacteria (two common strains of human pathogenic bacteria, Staphylococcus aureus and Escherichia coli) under in vitro static conditions. The drug loaded nanofiber mats display cytocompatibility comparable to pure poly(ɛ-caprolactone) nanofibers when cultured with National Institutes of Health (NIH) NIH-3T3 fibroblast cell line and have long-term potential for clinical applications in the field of pharmaceutical sciences.

Synthesis and Biological Evaluation of Amoxicillin Loaded Hybrid Material Composite Spheres Against Methicillin-Resistant Staphylococcus aureus.

BACKGROUND: Incoherent use of antibiotics has led toward resistance in MRSA, becoming multidrug-resistant with a high rate of virulence in the community and hospital settings. OBJECTIVE: Synergistic anti-MRSA activity was investigated in this study for hybrid material composite spheres of amoxicillin, Ag nanoparticles, and chitosan, which were prepared by one-step synthesis method, and various characterizations were performed. METHODS: Antimicrobial-susceptibility assay on MRSA was achieved by disc diffusion and agar dilution techniques, while agar well diffusion was used for hybrid composite spheres. The in vitro and cytotoxicity studies were conducted on the skin abrasion mouse model and MTT assay on RD cell, respectively. RESULTS: All isolates showed resistance to the tested antibiotics except vancomycin. MIC against MRSA showed high resistance with amoxicillin from 4 to 128 mg L-1. The mean diameter of chitosan spheres and Ag nanoparticles was 02 mm and 277 nm, respectively. Morphology of spheres was uneven, varied, porous, and irregular in SEM, and Ag nanoparticles presence and formation was also seen in the micrograph. No substantial interface among drug, nanoparticles, and polymer was found in XRD, and IR showed characteristic peaks of all compounds in the formulation. The in vitro assay showed augmented anti-MRSA activity with amoxicillin loaded hybrid composite spheres (22-29 mm). A significant reduction in microbial burden (~6.5 log10 CFU mL-1) was seen in vivo with loaded hybrid composite spheres formulation. The MTT assay indicated no potential cytotoxicity with hybrid composite spheres. CONCLUSION: The synergistic effect of Amoxycillin in the current study predicts a promising hybrid formulation with enhanced anti-MRSA activity.

Bi-layered α-tocopherol acetate loaded membranes for potential wound healing and skin regeneration.

With an increase in the demand for skin regeneration products, there is a noticeable increase in developing materials that encourage, wound healing and skin regeneration. It has been reported that antioxidants play an important role in anti-inflammatory reactions, cellular proliferation and remodeling phase of wound healing. While consideration all these factors, a novel α-tocopherol acetate (vitamin E) (VE) loaded bi-layered electrospun membrane, based on lower polycaprolactone (PCL) layer and upper polylactic acid (PLA) layer, was fabricated through electrospinning. Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), in-vitro degradation studies, swelling studies and VE release studies were performed to evaluate structural, physical and in-vitro behavior of membranes. Biological properties of membranes were evaluated through cell proliferation assay, cell adhesion studies, live/dead cell assay and CAM assay. SEM images showed that the average diameter of nanofibers ranged from 1 to 6 µm, while addition of VE changed the diameter and morphology of fibers. Bi-layered membranes showed significant swelling behavior through water uptake, membranes loaded with 30% VE showed 8.7% and 6.8% degradation in lysozyme and H2O2 respectively. 20% and 30% VE loaded membranes followed Korsmeyer-Peppas and first order drug release kinetics followed by non-fickian drug release kinetics. Membranes showed non-toxic behavior and supported cell proliferation via alamar blue assay, cell adhesion via SEM, cell viability via live/dead assay and wound healing by scratch assay. CAM assay showed that membranes having VE supported angiogenesis and showed significant formation of blood vessels making it suitable for skin regeneration and wound healing. Results showed that large surface area of nanofibers, porous structure and biocompatible nature are suitable for targeted clinical applications.

Design, Formulation and In Vitro Evaluation of Sustained-release Tablet Formulations of Levosulpiride.

OBJECTIVES: Levosulpiride is a widely used gastroprokinetic agent in the treatment of various gastric disorders; however, its short half-life and increased dosage frequency leads to non-compliance and possible adverse effects. The prime objective of the current study was to develop a sustained-release formulation of Levosulpiride incorporating bioresorbable cellulose derivatives. MATERIALS AND METHODS: Sustained-release formulations of Levosulpiride were prepared through direct compression using various cellulose derivatives such as CMC sodium, HPC, and HPMC in different polymer-to-drug weight ratios as release-modifying polymers. The powder blends and compressed tablets were then subjected to pre-compressional and post-compressional evaluation, as well as FTIR analysis. In vitro release studies were performed for all formulations of the model drug in buffer solution of pH 6.8 at a wave length of 214 nm by a UV-visible light spectrophotometer. RESULTS: The FTIR results confirmed that the interaction between components was physical, and from the different kinetic models data, the release profile was best expressed by the Higuchi model because the results showed high linearity. The results also showed formulation F9 to be the ideal one among the developed formulations, exhibiting sustained- release behavior. CONCLUSION: Levosulpiride sustained-release matrices were prepared successfully using CMC sodium, HPC, and HPMC as the release-retarding polymer/carrier.