Biomaterials Based on Chitosan and Polyvinyl Alcohol as a Drug Delivery System with Wound-Healing Effects.

The excellent biological properties of chitosan (CS) together with the increased oxygen permeability of polyvinyl alcohol (PVA) were the prerequisites for the creation of a wound healing dressing that would also function as a system for L-arginine (L-arg) and caffeine (Caff) delivery. Using the freezing/thawing method, 12 hydrogels were obtained in PVA:CS polymer ratios of 90:10, 75:25, and 60:40, and all were loaded with L-arg, Caff, and the mixture of L-arg and Caff, respectively. Afterwards, an inorganic material (zeolite-Z) was added to the best polymeric ratio (75:25) and loaded with active substances. The interactions between the constituents of the hydrogels were analyzed by FTIR spectroscopy, the uniformity of the network was highlighted by the SEM technique, and the dynamic water vapor sorption capacity was evaluated. In the presence of the inorganic material, the release profile of the active substances is delayed, and in vitro permeation kinetics proves that the equilibrium state is not reached even after four hours. The synergy of the constituents in the polymer network recommends that they be used in medical applications, such as wound healing dressings.

Poly(Vinyl Alcohol)/Bovine Serum Albumin Hybrid Hydrogels with Tunable Mechanical Properties.

In this study, a new strategy was adopted for obtaining polymer/protein hybrid hydrogels with shape stability and tunable mechanical or rheological characteristics by using non-toxic procedures. A chemical network was created using a poly(vinyl alcohol)(PVA)/bovine serum albumin (BSA) mixture in aqueous solution in the presence of genipin and reduced glutathione (GSH). Then, a second physical network was formed through PVA after applying freezing/thawing cycles. In addition, the protein macromolecules formed intermolecular disulfide bridges in the presence of GSH. In these conditions, multiple crosslinked networks were obtained, determining the strengthening and stiffening into relatively tough porous hydrogels with tunable viscoelasticity and a self-healing ability. A SEM analysis evidenced the formation of networks with interconnected pores of sizes between 20 µm and 50 µm. The mechanical or rheological investigations showed that the hydrogels' strength and response in different conditions of deformation were influenced by the composition and crosslinking procedure. Thus, the dynamics of the hybrid hydrogels can be adjusted to mimic the viscoelastic properties of the native tissues. The dynamic water vapor-sorption ability, swelling behavior in an aqueous environment, and bioadhesive properties were also investigated and are discussed in this paper. The hybrid hydrogels with tunable viscoelasticity can be designed on request, and they are promising candidates for tissue engineering, bioinks, and wound dressing applications.

All-Polymer Piezo-Composites for Scalable Energy Harvesting and Sensing Devices.

Silicone elastomer composites with piezoelectric properties, conferred by incorporated polyimide copolymers, with pressure sensors similar to human skin and kinetic energy harvester capabilities, were developed as thin film (<100 micron thick) layered architecture. They are based on polymer materials which can be produced in industrial amounts and are scalable for large areas (m2). The piezoelectric properties of the tested materials were determined using a dynamic mode of piezoelectric force microscopy. These composite materials bring together polydimethylsiloxane polymers with customized poly(siloxane-imide) copolymers (2−20 wt% relative to siloxanes), with siloxane segments inserted into the structure to ensure the compatibility of the components. The morphology of the materials as free-standing films was studied by SEM and AFM, revealing separated phases for higher polyimide concentration (10, 20 wt%). The composites show dielectric behavior with a low loss (<10−1) and a relative permittivity superior (3−4) to pure siloxane within a 0.1−106 Hz range. The composite in the form of a thin film can generate up to 750 mV under contact with a 30 g steel ball dropped from 10 cm high. This capability to convert a pressure signal into a direct current for the tested device has potential for applications in self-powered sensors and kinetic energy-harvesting applications. Furthermore, the materials preserve the known electromechanical properties of pure polysiloxane, with lateral strain actuation values of up to 6.2% at 28.9 V/µm.

Amphiphilic Chitosan Porous Membranes as Potential Therapeutic Systems with Analgesic Effect for Burn Care.

Eliminating or at least lessening the pain is a crucial aspect of burns management, as pain can negatively affect mental health and quality of life, and it can also induce a delay on wound healing. In this context, new amphiphilic chitosan 3D porous membranes were developed and investigated as burns therapeutic systems with analgesic effect for delivery of lidocaine as local anesthetic. The highly porous morphology of the membranes and the structural modifications were evidenced by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis and infrared spectroscopy (FTIR). Improved compression mechanical properties, long-term hydrolytic degradation (28 days) evaluation and high swelling capacities (ranging from 8 to 22.6 g/g) indicate an increased capacity of the prepared membranes to absorb physiological fluids (burns exudate). Lidocaine in vitro release efficiency was favored by the decreased content of cross-linking agent (reaching maximum value of 95.24%) and the kinetic data modeling, indicating that lidocaine release occurs by quasi-Fickian diffusion. In addition to the in vitro evaluation of analgesic effect, lidocaine-loaded chitosan membranes were successfully investigated and proved antibacterial activity against most common pathogens in burns infections: Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus.

Evaluation of Physically and/or Chemically Modified Chitosan Hydrogels for Proficient Release of Insoluble Nystatin in Simulated Fluids.

To avoid fungal spreading in the bloodstream and internal organs, many research efforts concentrate on finding appropriate candidiasis treatment from the initial stage. This paper proposes chitosan-based physically or chemically cross-linked hydrogels aimed to provide sustained release of micronized nystatin (NYSm) antifungal drug, known for its large activity spectrum. Nystatin was demonstrated itself to provide hydrodynamic/mechanic stability to the chitosan hydrogel through hydrophobic interactions and H-bonds. For chemical cross-linking of the succinylated chitosan, a non-toxic diepoxy-functionalized siloxane compound was used. The chemical structure and composition of the hydrogels, also their morphology, were evidenced by infrared spectroscopy (FTIR), by energy dispersive X-ray (EDX) analysis and by scanning electron microscopy (SEM), respectively. The hydrogels presented mechanical properties which mimic those of the soft tissues (elastic moduli < 1 MPa), necessary to ensure matrix accommodation and bioadhesion. Maximum swelling capacities were reached by the hydrogels with higher succinic anhydride content at both pH 7.4 (429%) and pH 4.2 (471%), while higher amounts of nystatin released in the simulative immersion media (57% in acidic pH and 51% in pH 7.4) occurred from the physical cross-linked hydrogel. The release mechanism by non-swellable matrix diffusion and the susceptibility of three Candida strains make all the hydrogel formulations effective for NYSm local delivery and for combating fungal infections.

Mucoadhesive and Antimicrobial Allantoin/ß Cyclodextrins-Loaded Carbopol Gels as Scaffolds for Regenerative Medicine.

Allantoin and its ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin inclusion complexes 1:1 have been used to prepare carbopol-based mucoadhesive gels. The gelation process occurred by adjustment with glycerol 10% in the presence of triethanolamine. The structural features induced by the presence of allantoin and the corresponding ß-cyclodextrins inclusion complexes have been first investigated by infrared spectroscopy highlighting strong interactions within the gels network and ideal crosslinks for the self-healing behavior. The hydrophilicity of the gels was investigated by the determination of the surface tension parameters and the free energy of hydration. The interfacial free energy values indicated prolonged biocompatibility with blood. The gels-water molecule interactions in terms of sorption, permeability, and diffusion coefficients were evaluated by dynamic vapor sorption analysis. The self-assembly process through intermolecular H-bonding, the high hydrophilicity, the mechanical performance, the hydrolytic stability in simulated biological media, the biocompatibility with normal human dermal fibroblast (NHDF) cells, the mucoadhesivity and antimicrobial activity on selected microorganism species (S. Aureus and C. albicans) of the allantoin-based gels recommend them as promising scaffold alternatives in regenerative medicine.

Emulsion Gels as Precursors for Porous Silicones and All-Polymer Composites-A Proof of Concept Based on Siloxane Stabilizers.

In spite of its versatility, the emulsion templating method is rather uncommon for the preparation of porous silicones. In this contribution, two siloxane-containing stabilizers, designed to be soluble in polar (water) and non-polar (toluene) solvents, respectively, were used in low concentrations to produce stable emulsions, wherein polysiloxane gels were obtained by UV-photoinitiated thiol-ene click cross-linking. The stabilizers exhibited negative interfacial tension, as measured by Wilhelmy plate tensiometry. The emulsion gels evolved into porous silicones (xerogels), with tunable morphology and properties. According to TEM and SEM investigations, the emulsion template was preserved in the final materials. Several parameters (e.g., the structure of the polysiloxane precursors, composition of the emulsion gels, nature of the continuous phase, cross-linking conditions, or additives) can be varied in order to obtain porous elastic materials with desired properties, such as Janus membranes, absorbent monoliths, all-polymer porous composites, or silicone-swollen gels. The feasibility of these types of materials was tested, and exemplary porous silicones were briefly characterized by contact angle measurements, mechanical testing, and absorption tests. The proposed method is simple, fast, and economic, uses very little amounts of stabilizers, and can be adjusted as a green technique. In this contribution, all the silicon-based materials with a convenient design were prepared in house.

Imination of Microporous Chitosan Fibers-A Route to Biomaterials with "On Demand" Antimicrobial Activity and Biodegradation for Wound Dressings.

Microporous chitosan nanofibers functionalized with different amounts of an antimicrobial agent via imine linkage were prepared by a three-step procedure including the electrospinning of a chitosan/PEO blend, PEO removal and acid condensation reaction in a heterogeneous system with 2-formylphenylboronic acid. The fibers' characterization was undertaken keeping in mind their application to wound healing. Thus, by FTIR and 1H-NMR spectroscopy, it was confirmed the successful imination of the fibers and the conversion degree of the amine groups of chitosan into imine units. The fiber morphology in terms of fiber diameter, crystallinity, inter- and intra-fiber porosity and strength of intermolecular forces was investigated using scanning electron microscopy, polarized light microscopy, water vapor sorption and thermogravimetric analysis. The swelling ability was estimated in water and phosphate buffer by calculating the mass equilibrium swelling. The fiber biodegradation was explored in five media of different pH, corresponding to different stages of wound healing and the antimicrobial activity against the opportunistic pathogens inflicting wound infection was investigated according to standard tests. The biocompatibility and bioadhesivity were studied on normal human dermal fibroblast cells by direct contact procedure. The dynamic character of the imine linkage of the functionalized fibers was monitored by UV-vis spectroscopy. The results showed that the functionalization of the chitosan microporous nanofibers with antimicrobial agents via imine linkage is a great route towards bio-absorbable wound dressings with "on demand" antimicrobial properties and biodegradation rate matching the healing stages.

Binary Silicone Elastomeric Systems with Stepwise Crosslinking as a Tool for Tuning Electromechanical Behavior.

Interpenetrating polymer networks (IPNs) represent an interesting approach for tuning the properties of silicone elastomers due to the possible synergism that may occur between the networks. A new approach is presented, which consists of mixing two silicone-based networks with different crosslinking pathways; the first network being cured by condensation route and the second network by UV curing. The networks were mixed in different ratios and the resulted samples yield good mechanical properties (improved elongations, up to 720%, and Young's modulus, 1 MPa), thermal properties (one glass transition temperature, ~-123 °C), good dielectric strength (~50 V/µm), and toughness (63 kJ/m3).

Dielectric, Thermal and Water Absorption Properties of Some EPDM/Flax Fiber Composites.

This paper deals with the dielectric and sorption properties of some flax fiber-reinforced ethylene-propylene-diene monomer (EPDM) composites containing different fiber loadings as well as their behavior after exposure to different doses of electron beam irradiation. Three relaxation processes were evinced, a weak relaxation ß at sub-Tg temperatures and two α-type relaxations above the Tg. The EPDM/flax composites exhibited higher values of dielectric constant, dielectric loss and conductivity as compared to a pristine EPDM sample. Using thermogravimetric analysis (TG) coupled with Fourier transform infrared spectroscopy (FTIR) and mass spectrometry (MS) (TG/FTIR/MS system), the degradation products can be identified. The water uptake increased as the flax fiber level increased in composites. The water uptake tests of irradiated composites showed that the highest water content was obtained for a flax fiber level of 20 phr.

Comparative Investigation of Collagen-Based Hybrid 3D Structures for Potential Biomedical Applications.

Collagen is a key component for devices envisaging biomedical applications; however, current increasing requirements impose the use of multicomponent materials. Here, a series of hybrid collagen-based 3D materials, comprising also poly(ε-caprolactone) (PCL) and different concentrations of hyaluronic acid (HA)-in dense, porous or macroporous form-were characterized in comparison with a commercially available collagen sponge, used as control. Properties, such as water uptake ability, water vapour sorption, drug loading and delivery, were investigated in correlation with the material structural characteristics (composition and morphology). Methylene blue (MB) and curcumin (CU) were used as model drugs. For spongeous matrices, it was evidenced that, in contrast to the control sample, the multicomponent materials favor improved sustained release, the kinetics being controlled by composition and cross-linking degree. The other characteristics were within an acceptable range for the intended purpose of use. The obtained results demonstrate that such materials are promising for future biomedical applications (wound dressings and lab models).

From Amorphous Silicones to Si-Containing Highly Ordered Polymers: Some Romanian Contributions in the Field.

Polydimethylsiloxane (PDMS), in spite of its well-defined helical structure, is an amorphous fluid even at extremely high molecular weights. The cause of this behavior is the high flexibility of the siloxane backbone and the lack of intermolecular interactions attributed to the presence of methyl groups. These make PDMS incompatible with almost any organic or inorganic component leading to phase separation in siloxane-siloxane copolymers containing blocks with polar organic groups and in siloxane-organic copolymers, where dimethylsiloxane segments co-exist with organic ones. Self-assembly at the micro- or nanometric scale is common in certain mixed structures, including micelles, vesicles, et cetera, manifesting reversibly in response to an external stimulus. Polymers with a very high degree of ordering in the form of high-quality crystals were obtained when siloxane/silane segments co-exist with coordinated metal blocks in the polymer chain. While in the case of coordination of secondary building units (SBUs) with siloxane ligands 1D chains are formed; when coordination is achieved in the presence of a mixture of ligands, siloxane and organic, 2D structures are formed in most cases. The Romanian research group's results regarding these aspects are reviewed: from the synthesis of classic, amorphous silicone products, to their adaptation for use in emerging fields and to new self-assembled or highly ordered structures with properties that create perspectives for the use of silicones in hitherto unexpected areas.

Radiation Processing and Characterization of Some Ethylene-propylene-diene Terpolymer/Butyl (Halobutyl) Rubber/Nanosilica Composites.

Composites based on ethylene-propylene-diene terpolymer (EPDM), butyl/halobutyl rubber and nanosilica were prepared by melt mixing and subjected to different doses of electron beam irradiation. The effect of irradiation dose on the mechanical properties, morphology, glass transition temperature, thermal stability and water uptake was investigated. The efficiency of the crosslinking by electron beam irradiation was analyzed by Charlesby-Pinner parameter evaluation and crosslink density measurements. The scanning electron microscopy data showed a good dispersion of nanosilica in the rubber matrix. An improvement in hardness and 100% modulus was revealed by increasing irradiation dose up to 150 kGy. The interaction between polymer matrix and nanosilica was analyzed using the Kraus equation. Additionally, these results indicated that the mechanical properties, surface characteristics, and water uptake were dependent on crosslink characteristics.

Chitosan-Sulfated Titania Composite Membranes with Potential Applications in Fuel Cell: Influence of Cross-Linker Nature.

Chitosan-sulfated titania composite membranes were prepared, characterized, and evaluated for potential application as polymer electrolyte membranes. To improve the chemical stability, the membranes were cross-linked using sulfuric acid, pentasodium triphosphate, and epoxy-terminated polydimethylsiloxane. Differences in membranes' structure, thickness, morphology, mechanical, and thermal properties prior and after cross-linking reactions were evaluated. Membranes' water uptake capacities and their chemical stability in Fenton reagent were also studied. As proved by dielectric spectroscopy, the conductivity strongly depends on cross-linker nature and on hydration state of membranes. The most encouraging results were obtained for the chitosan-sulfated titania membrane cross-linked with sulfuric acid. This hydrated membrane attained values of proton conductivity of 1.1 × 10-3 S/cm and 6.2 × 10-3 S/cm, as determined at 60 °C by dielectric spectroscopy and the four-probes method, respectively.

Development and Performance of Bioactive Compounds-Loaded Cellulose/Collagen/Polyurethane Materials.

Here we present a new biomaterial based on cellulose, collagen and polyurethane, obtained by dissolving in butyl imidazole chloride. This material served as a matrix for the incorporation of tannin and lipoic acid, as well as bioactive substances with antioxidant properties. The introduction of these bioactive principles into the base matrix led to an increase of the compressive strength in the range 105-139 kPa. An increase of 29.85% of the mucoadhesiveness of the film containing tannin, as compared to the reference, prolongs the bioavailability of the active substance; a fact also demonstrated by the controlled release studies. The presence of bioactive principles, as well as tannins and lipoic acid, gives biomaterials an antioxidant capacity on average 40%-50% higher compared to the base matrix. The results of the tests of the mechanical resistance, mucoadhesiveness, bioadhesiveness, water absorption and antioxidant capacity of active principles recommend these biomaterials for the manufacture of cosmetic masks or patches.

Assessment of chemicals released in the marine environment by dielectric elastomers useful as active elements in wave energy harvesters.

A series of elastomers, either natural or synthetic (some of them commercial, while others prepared in the laboratory), suitable for use as active elements in devices for wave energy harvesting, were evaluated concerning their behavior and effects on the marine environment. In this aim, the elastomer films, initially evaluated regarding their aspect, structure, surface wettability, and tolerance of microorganisms growth, were immersed in synthetic seawater (SSW) within six months for assessing compounds released. There were analyzed the changes occurred both in the elastomers and salt water in which they were immersed. For this, water samples taken at set time intervals were analyzed by using a sequence of sensitive spectral techniques: UV-vis, IR, and in relevant cases 1H NMR and electrospray ionization mass spectrometry (ESI-MS), able to detect and identify organic compounds, while after six months, they were also investigated from the point of view of aspect, presence of metal traces, pH, and biological activity. The changes in aspect, structure and morphology of the dielectric films at the end of the dipping period were also evaluated by visual inspection, IR spectroscopy by using spectral subtraction method, and SEM-EDX technique.

Complex calcium carbonate/polymer microparticles as carriers for aminoglycoside antibiotics.

Composite microparticles of CaCO3 and two pectin samples (which differ by the functional group ratio) or corresponding nonstoichiometric polyelectrolyte complexes with different molar ratios (0.5, 0.9 and 1.2) are obtained, characterized and tested for loading and release of streptomycin and kanamycin sulphate. The synthesized carriers were characterized before and after drug loading in terms of morphology (by SEM using secondary electron and energy selective backscattered electron detectors), porosity (by water sorption isotherms) and elemental composition (by elemental mapping using energy dispersive X-ray and FTIR spectroscopy). The kinetics of the release mechanism from the microparticles was investigated using Higuchi and Korsmeyer-Peppas mathematical models.

From iron coordination compounds to metal oxide nanoparticles.

Various types, shapes and sizes of iron oxide nanoparticles were obtained depending on the nature of the precursor, preparation method and reaction conditions. The mixed valence trinuclear iron acetate, [Fe2IIIFeIIO(CH3COO)6(H2O)3]·2H2O (FeAc1), µ3-oxo trinuclear iron(III) acetate, [Fe3O(CH3COO)6(H2O)3]NO3∙4H2O (FeAc2), iron furoate, [Fe3O(C4H3OCOO)6(CH3OH)3]NO3∙2CH3OH (FeF), iron chromium furoate, FeCr2O(C4H3OCOO)6(CH3OH)3]NO3∙2CH3OH (FeCrF), and an iron complex with an original macromolecular ligand (FePAZ) were used as precursors for the corresponding oxide nanoparticles. Five series of nanoparticle samples were prepared employing either a classical thermal pathway (i.e., thermal decomposition in solution, solvothermal method, dry thermal decomposition/calcination) or using a nonconventional energy source (i.e., microwave or ultrasonic treatment) to convert precursors into iron oxides. The resulting materials were structurally characterized by wide-angle X-ray diffraction and Fourier transform infrared, Raman, energy-dispersive X-ray, and X-ray fluorescence spectroscopies, as well as thermogravimetric analysis. The morphology was characterized by transmission electron microscopy, atomic force microscopy and dynamic light scattering. The parameters were varied within each route to fine tune the size and shape of the formed nanoparticles.

Preparation of electromechanically active silicone composites and some evaluations of their suitability for biomedical applications.

Some films based on electromechanically active polymer composites have been prepared. Polydimethylsiloxane-α,ω-diols (PDMSs) having different molecular masses (Mv=60 700 and Mv=44 200) were used as matrix in which two different active fillers were incorporated: titanium dioxide in situ generated from its titanium isopropoxide precursor and silica particles functionalized with polar aminopropyl groups on surface. A reference sample based on simple crosslinked PDMS was also prepared. The composites processed as films were investigated to evaluate their ability to act as efficient electromechanical actuators for potential biomedical application. Thus, the surface morphology of interest for electrodes compliance was analysed by atomic force microscopy. Mechanical and dielectric characteristics were evaluated by tensile tests and dielectric spectroscopy, respectively. Electromechanical actuation responses were measured by interferometry. The biocompatibility of the obtained materials has been verified through tests in vitro and, for valuable films, in vivo. The experimental, clinical and anatomopathological evaluation of the in vivo tested samples did not reveal significant pathological modifications.

Experimental testing on free vibration behaviour for silicone rubbers proposed within lumbar disc prosthesis.

This research was focused on the damping capacity study of two types of silicone rubbers proposed as layers within total lumbar disc prostheses of ball-and-socket model. In order to investigate the damping capacity, the two silicone rubber types mainly differing by the molecular mass of polymeric matrix and the filler content, as was emphasized by scanning electron microscopy and differential scanning calorimetry, were subjected to free vibration testing. Using an adapted experimental installation, three kinds of damping testing were realised: tests without samples and tests with three samples of each type of silicone rubber (69 ShA and 99 ShA). The free vibration tests were performed at a frequency of about 6 Hz using a weight of 11.8 kg. The relative damping coefficient was determined by measuring of two successive amplitudes on the vibrogram and calculating of the logarithmic decrement. The test results with silicone rubber samples showed a relative damping coefficient of 0.058 and respectively 0.077, whilst test results without samples showed a relative damping coefficient of 0.042. These silicone rubbers were found to have acceptable damping properties to be used as layers placed inside the prosthetic components.