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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.

DFT calculations were performed on nine flavones and flavonols to explain their high antioxidant activity and variations in their activity. Conformational analysis showed that only flavonols with 3-OH directed toward the B-ring are nonplanar; however, flavones and resulted radicals are planar. Hydroxyl group eligible for dissociation is the one with ortho OH directed toward it; otherwise, one of B-ring (in 2′ or 4′-position) hydroxyl group. There are two main factors responsible for stabilizing the resulted radicals and lowering the bond dissociation energy and hence there were found well correlated with the experimental activity. First, driving force resulted from the conversion of nonplanar flavonols to planar radicals accompanied by resonance toward the carbonyl group and H-bond formation with 3-OH and second, radical stabilization by H-bond with ortho hydroxyl group with resonance toward carbonyl or pyrone oxygen. All resonance and H-bonds were confirmed by spin density, bond length, and molecular orbital calculations.

Ferrocenylamine complexes have found increasing applications in the fields of catalysis in various organic reactions, industry, medical treatments and enzyme–activity determinations. Therefore, information related to the thermal and thermo-oxidative stability of these compounds is important for such applications; however, this information is currently limited. Twenty previously prepared palladium and platinum ferrocenylamine complexes with systematic structural variations are examined for their thermal (under nitrogen) and thermo-oxidation stability (under atmospheric air) using thermogravimetry (TG), differential thermal analysis (DTG), and differential scanning calorimetry (DSC) techniques. Degradation products are identified by comparing thermogravimetric analysis and theoretical calculations. Structure–stability studies are also discussed. The results show that all the compounds have high thermal and thermo-oxidative stabilities of up to 265 and 173 °C, respectively. Electron–donating substituents enhance the thermal and thermo-oxidative stabilities of the palladium complexes ( t-Bu, selenide electrophiles and dielectrophiles), while those with destabilizing effects are aromatic substituents (Ph and tolyl). Most platinum ferrocenylamine sulfides and selenides show higher thermal and thermo-oxidative stabilities than their corresponding palladium analogs. All the prepared compounds show high thermal and thermo-oxidative stability which reinforces their catalytic and industrial applications. However, their thermal stability is higher than their thermo-oxidative stability.

Antioxidant activity of anthocyanidins is greatly affected by the 3-hydroxyl group and/or a catecholic moiety. The two-hydrogen atom donation process is frequently used to explain the high antioxidant activity of polyphenolic compounds leading to the formation of stable diketones e.g. 1,2-quinones. Thermodynamic parameters, HOMO and spin density were computed to identify the favoured path, either through the 3-hydroxyl group or through the catecholic moiety in a series of catecholic and non-catecholic 3-oxy- (and deoxy)-anthocyanidins. DFT calculations showed that the donation process in non-catecholic anthocyanidins depended on the substituents on ring B. Anthocyanidins with 3′,5′-diOMe groups showed donation through 3,4′-OH or, otherwise, through 3,5-OH groups. Catecholic 3-oxyanthocyanidins, on the other hand, showed donation through the 3,4′-OH path rather than the catecholic path (4′,3′-path). The 3,4′-path was favoured by the formation of planar 3-radicals in the first step and the stabilization of 4′-radicals in the second step by H-bonding with the 3′-OH group.

Density function theory study was conducted to examine the structure, planarity, and charge and unpaired electron delocalization of some anthocyanidins and monohydroxy flavylium ions as well as all their possible phenoxyl radicals. Bond dissociation energy of O–H bond was in the order of 3

Smart materials are those materials that are responsive to chemical (organic molecules, chemical agents or specific agents), biochemical (protein, enzymes, growth factors, substrates or ligands), physical (electric field, magnetic field, temperature, pH, ionic strength or radiation) or mechanical (pressure or mechanical stress) signals. These responsive materials interact with the stimuli by changing their properties or conformational structures in a predictable manner. Recently, smart polymers have been utilized in various biomedical applications. Particularly, they have been used as a platform to synthesize stimuli-responsive systems that could deliver therapeutics to a specific site for a specific period with minimal adverse effects. For instance, stimuli-responsive polymers-based systems have been recently reported to deliver different bioactive molecules such as carbohydrates (heparin), chemotherapeutic agents (doxorubicin), small organic molecules (anti-coagulants), nucleic acids (siRNA), and proteins (growth factors and hormones). Protein therapeutics played a fundamental role in treatment of various chronic and some autoimmune diseases. For instance insulin has been used in treatment of diabetes. However, being a protein in nature, insulin delivery is limited by its instability, short half-life, and easy denaturation when administered orally. To overcome these challenges, and as highlighted in this review article, much research efforts have been recently devoted to design and develop convenient smart controlled nanosystems for protein therapeutics delivery.

Autologous and synthetic bone grafts showed some limitations during their usage in bone tissue regeneration. This is attributed to several drawbacks such as difficulty of finding a donor in addition to the autoimmune rejection. This study aims to fabricate a well-designed biocompatible double-layered structure of highly porous poly(lactic acid)-based electrospun nanofibers (NFs) as scaffolds for bone tissue regeneration. Poly(lactic acid) was chosen to fabricate the main matrix of the NFs scaffold as it is one of the FDA approved and highly recommended biopolymers for biomedical applications owing to its high biodegradability and biocompatibility Each layer is loaded with a different drug (Phenytoin and Sildenafil) to stimulate bone healing process. The solvents and the parameters of electrospinning were manipulated to produce highly porous structures in order to enhance the in-situ biodegradability of the NFs mats as well as the drug release rate. The produced NFs mats were fully characterized morphologically (SEM), chemically (FTIR), physically (DSC) and physicochemically (biodegradability, swellability, porosity and water vapor permeability) as well as studying the drug release profiles of both drugs. Cytotoxicity of the fabricated NFs was tested using fibroblast cells to detect their biocompatibility. Cell adhesion and proliferation were examined using SEM before using the NFs as scaffolds in mice animal model. The efficiency of the developed NFs scaffolds in healing bone fractures was assessed after 14 and 28 days through visual inspection, SEM investigation and bone mineral density assessment. Finally, sections from the bone fracture sites were isolated for histopathological examination. The study revealed the efficiency of the drugs-loaded NFs in enhancing cell adherence, cell proliferation, angiogenesis formation and finally tissue restoration of bone fractures.

Skin is an essential protective organ in the body, and damage inflicted on its tissues can lead to serious problems if no proper care is given. Chronic skin wounds are the more serious type of wounds since they cannot heal normally on their own. Nanofibers are one of the promising solutions for better treatment of wounds, due to their availability, ability to mimic the skin extracellular matrix (ECM), and inability to transmit diseases unlike common skin grafts. Nanofibrous scaffolds are fabricated via different techniques including electrospinning, self-assembly, phase separation, and template synthesis. In this review article, we discuss the different ways of tailoring nanofibers, in order to produce an efficient wound healing scaffold for skin tissues. Parameters of nanofibers can be manipulated more easily and effectively with electrospinning than with other techniques. Electrospun nanofibers pass through different processing stages, and in each stage different techniques and manipulations can be conducted to improve the product. Pre-electrospinning treatment depends on the composition of the polymer solution that will be added to the electrospinner, and the electropinner setup itself can affect the produced fibers. Post-electrospinning treatment, which is the final modification that can be carried out in the fabrication process can also affect the properties of the produced nanofibers. Finally, the type of bioactive substance incorporated in the scaffold can help improve the bioactivity and efficiency of the scaffold. Therefore, this review provides an overview on the parameters affecting the electrospinning process of nanofibers, with emphasis on the most popular bioactive molecules incorporated within nanofibers for skin regeneration purposes.

Phenytoin (Ph), an antiepileptic drug, was reported to exhibit high wound healing activity. However, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop new single-dose electrospun nanoparticles-in-nanofibers (NPs-in-NFs) wound dressings that allow a well-controlled release of Ph. These NPs-in-NFs systems are based on enhanced chitosan (CS)/poly(ethylene oxide) (PEO) electrospun nanofibers (NFs) incorporating optimized Ph-loaded nanocarriers. First, a study was conducted to investigate Ph loading efficiency into polymeric nanocarriers of different types; pluronic nanomicelles and poly(lactic-co-glycolic) acids nanoparticles (PLGA NPs). The drug release profile from the nanocarriers was further optimized via lecithin coating. Second, different electrospinning parameters were manipulated to fabricate beads-free homogeneous NFs with optimized polymer ratios. Plain and Ph-loaded nanocarriers were characterized using Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic light scattering (DLS), and scanning electron microscopy (SEM). Both entrapment efficiency of Ph (EE%) and its release profile in phosphate buffer saline (PBS; pH 5.5), simulating the wound environment, were studied. Biodegradability, swelling, vapor permeability, and porosity of the developed Ph-loaded NPs-in-NFs wound dressings were investigated. Morphology of the NPs-in-NFs was also studied using SEM and confocal laser microscopy (CLSM). Besides, the release profiles of Ph from the optimized NPs-in-NFs were assessed. The newly developed wound dressings were evaluated in vitro for their cytotoxicity using human fibroblasts and in vivo using a wound healing mice model. Nanocarriers with particle size ranging from 100 to 180 nm were successfully prepared. All nanocarriers attained a high drug entrapment efficiency exceeding 94% and showed promising sustained release profiles compared to free Ph. Results also demonstrated that NFs incorporating the optimized lecithin-coated Ph-loaded PLGA NPs could be the most promising candidate for efficient wound healing. These NPs-in-NFs systems conferred a well-controlled and sustained release of Ph over 9 days. Moreover, they showed the best re-epithelization and healing quality during the in vivo study with minimal inflammatory and necrotic cells formation.

Aim: This study involves, for the first time, the development of mucoadhesive biodegradable polymeric-multilayered nanoparticles-in-nanofibers (NPs-in-NFs) matrix as an innovative single-dose noninvasive ocular-insert that could substitute conventional ocular dosage-forms. Materials & methods: Azithromycin-loaded poly(lactic-co-glycolic acid) copolymer/pluronic NPs were developed then incorporated into electrospun polyvinylpyrrolidone NFs, and tested for their efficient treatment of ocular bacterial infection. Results: Release and permeation studies proved the ability of the insert to control drug release over 10 days. Conclusion: The incorporation of NPs into NFs achieved several other benefits like increasing ocular residence and contact time with conjunctival tissue, accurate dose delivery, sustaining drug release with constant rate, reducing frequency of administration, improving bioavailability along with decreasing incidence of visual and systemic side effects.

Stimuli-responsive polymers (SRPs) are a type of smart materials which can demonstrate noticeable changes in their characteristics as a response to their exposure to some environmental stimuli variations. The environmental stimuli could be physical (e.g., electric field, ionic strength, magnetic field, mechanical stress, pressure, radiation, and temperature), chemical (e.g., specific ions and chemical agents), or biochemical (e.g., enzyme substrates and ligands). Recently, SRPs were used in numerous applications including diagnostics, drug delivery systems, biosensors, regenerative medicine, and stem cells. This chapter illustrates the different categories of SRPs and highlights some of their synthesis approaches, unique features, major development, their different structures, and classifications.

QSAR study was performed on the DPPH radical scavenging activity of a wide range (51 compounds) phenolic and anilinic compounds; many of them are widely distributed in biological systems. The structural diversity includes phenols (1-3 OH groups) and anilines (1-2 NH2 groups) with many electron donating and withdrawing groups, aminophenols (o, m, p), phenolic acids (o, m, p) or esters, enols, and phenolic terpenoids. Independents used were electronic Brown parameter and the structural parameters i.e., the indicator variable Q for forming a stable quinone-like product and the number of alkoxy (RO) and alkyl (R) groups as well as the thermodynamic parameters, bond dissociation energy (BDE), proton dissociation energy of O–H or N–H bond and HOMO of the parent compounds, and the resulted radicals or radical cations. Radical scavenging activity gave fair correlation with electronic Brown and the structural Q parameters, while it gave strong correlation with the structural parameters (R, RO, and Q) and BDE (R 2 = 0.979, N = 49, SE = 5.94, p

Recently, nanofibers have been investigated with remarkable increased applicability in different fields due to their numerous advantages such as large surface area and controlled morphology. Nanofibers can be prepared using three main techniques, namely electrospinning, phase separation, and self-assembly. Of these, electrospinning is the most commonly used technique and also seems to exhibit the most desirable results. This chapter provides an overview of the electrospinning of eco-friendly polymers and polymeric nanocomposites for biomedical applications with an emphasis on their applications in wound healing and tissue regenration. Controlling the characteristics of the developed electrospun nanocomposites via tailoring the collectors used during electrospinning as well as carefully changing their surface chemistry for the proper design of wound healing nanofibrous dressings and tissue engineering nanofibrous scaffolds will be explored. Also, the challenges associated with the use of electrospun polymeric nanofibers-based nanocomposites for wound healing and tissue engineering will be described.