Antimicrobial Composites Based on Methacrylic Acid-Methyl Methacrylate Electrospun Fibers Stabilized with Copper(II).

This study presents fibers based on methacrylic acid-methyl methacrylate (Eudragit L100) as Cu(II) adsorbents, resulting in antimicrobial complexes. Eudragit L100, an anionic copolymer synthesized by radical polymerization, was electrospun in dimethylformamide (DMF) and ethanol (EtOH). The electrospinning process was optimized through a 22-factorial design, with independent variables (copolymer concentration and EtOH/DMF volume ratio) and three repetitions at the central point. The smallest average fiber diameter (259 ± 53 nm) was obtained at 14% w/v Eudragit L100 and 80/20 EtOH/DMF volume ratio. The fibers were characterized using scanning electron microscopy (SEM), infrared spectroscopy in attenuated total reflectance mode (FTIR-ATR), and differential scanning calorimetry (DSC). The pseudo-second-order mechanism explained the kinetic adsorption toward Cu(II). The fibers exhibited a maximum adsorption capacity (qe) of 43.70 mg/g. The DSC analysis confirmed the Cu(II) absorption, indicating complexation between metallic ions and copolymer networks. The complexed fibers showed a lower degree of swelling than the non-complexed fibers. The complexed fibers exhibited bacteriostatic activity against Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. This study successfully optimized the electrospinning process to produce thin fibers based on Eudragit L100 for potential applications as adsorbents for Cu(II) ions in aqueous media and for controlling bacterial growth.

The Inclusion of Chitosan in Poly-ε-caprolactone Nanoparticles: Impact on the Delivery System Characteristics and on the Adsorbed Ovalbumin Secondary Structure.

This report extensively explores the benefits of including chitosan into poly-ε-caprolactone (PCL) nanoparticles (NPs) to obtain an improved protein/antigen delivery system. Blend NPs (PCL/chitosan NPs) showed improved protein adsorption efficacy (84%) in low shear stress and aqueous environment, suggesting that a synergistic effect between PCL hydrophobic nature and the positive charges of chitosan present at the particle surface was responsible for protein interaction. Additionally, thermal analysis suggested the blend NPs were more stable than the isolated polymers and cytotoxicity assays in a primary cell culture revealed chitosan inclusion in PCL NPs reduced the toxicity of the delivery system. A quantitative 6-month stability study showed that the inclusion of chitosan in PCL NPs did not induce a change in adsorbed ovalbumin (OVA) secondary structure characterized by the increase in the unordered conformation (random coil), as it was observed for OVA adsorbed to chitosan NPs. Additionally, the slight conformational changes occurred, are not expected to compromise ovalbumin secondary structure and activity, during a 6-month storage even at high temperatures (45°C). In simulated biological fluids, PCL/chitosan NPs showed an advantageous release profile for oral delivery. Overall, the combination of PCL and chitosan characteristics provide PCL/chitosan NPs valuable features particularly important to the development of vaccines for developing countries, where it is difficult to ensure cold chain transportation and non-parenteral formulations would be preferred.

Preparing silk fibroin nanofibers through electrospinning: further heparin immobilization toward hemocompatibility improvement.

Sodium heparin (HS) was immobilized on the surface of the silk fibroin nanofibers (FS) prepared by electrospinning with the objective of improving the hemocompatibility of the fibers for application as scaffolds in tissue engineering. The nanofiber mats of silk fibroin without (MF-FS) and with (MF-FS/HS) immobilized heparin were characterized through scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR), thermogravimetric analyses (TGA), energy dispersive spectroscopy (EDS), contact angle, chemical analysis, and biological tests. The formation of hydrogen bonds between the silk fibroin and heparin was discussed based on FTIR-ATR spectra. The amount of immobilized heparin was quantified through papain/N-acetyl-l-cysteine digestion followed by dimethylmethylene blue complexation. Furthermore, the samples with immobilized HS showed higher hydrophilic capability compared to samples without HS due to lower contact angles. It was possible to verify that the capillary end-to-collector distance of 8.5 cm and flow rate of 0.35 mL h(-1) used in the electrospinning process at 20 kV are good conditions for obtaining a small average fiber diameter maintaining the amount of immobilized heparin on MF-FS/HS in ca. 4% w/w. Biological analysis showed that no hemolysis is provoked by MF-FS and MF-FS/HS mat fragments and those such mats are not toxic to Vero cells. However, the MF-FS/HS showed higher cell growth and proliferation than MF-FS, indicating an improvement in the hemocompatibility of the material due to heparin immobilization.

Recent advances in food-packing, pharmaceutical and biomedical applications of zein and zein-based materials.

Zein is a biodegradable and biocompatible material extracted from renewable resources; it comprises almost 80% of the whole protein content in corn. This review highlights and describes some zein and zein-based materials, focusing on biomedical applications. It was demonstrated in this review that the biodegradation and biocompatibility of zein are key parameters for its uses in the food-packing, biomedical and pharmaceutical fields. Furthermore, it was pointed out that the presence of hydrophilic-hydrophobic groups in zein chains is a very important aspect for obtaining material with different hydrophobicities by mixing with other moieties (polymeric or not), but also for obtaining derivatives with different properties. The physical and chemical characteristics and special structure (at the molecular, nano and micro scales) make zein molecules inherently superior to many other polymers from natural sources and synthetic ones. The film-forming property of zein and zein-based materials is important for several applications. The good electrospinnability of zein is important for producing zein and zein-based nanofibers for applications in tissue engineering and drug delivery. The use of zein's hydrolysate peptides for reducing blood pressure is another important issue related to the application of derivatives of zein in the biomedical field. It is pointed out that the biodegradability and biocompatibility of zein and other inherent properties associated with zein's structure allow a myriad of applications of such materials with great potential in the near future.

Antimicrobial activity of chitosan derivatives containing N-quaternized moieties in its backbone: a review.

Chitosan, which is derived from a deacetylation reaction of chitin, has attractive antimicrobial activity. However, chitosan applications as a biocide are only effective in acidic medium due to its low solubility in neutral and basic conditions. Also, the positive charges carried by the protonated amine groups of chitosan (in acidic conditions) that are the driving force for its solubilization are also associated with its antimicrobial activity. Therefore, chemical modifications of chitosan are required to enhance its solubility and broaden the spectrum of its applications, including as biocide. Quaternization on the nitrogen atom of chitosan is the most used route to render water-soluble chitosan-derivatives, especially at physiological pH conditions. Recent reports in the literature demonstrate that such chitosan-derivatives present excellent antimicrobial activity due to permanent positive charge on nitrogen atoms side-bonded to the polymer backbone. This review presents some relevant work regarding the use of quaternized chitosan-derivatives obtained by different synthetic paths in applications as antimicrobial agents.

Antiadhesive and antibacterial multilayer films via layer-by-layer assembly of TMC/heparin complexes.

N-Trimethyl chitosan (TMC), an antibacterial agent, and heparin (HP), an antiadhesive biopolymer, were alternately deposited on modified polystyrene films, as substrates, to built antiadhesive and antibacterial multilayer films. The properties of the multilayer films were investigated by Fourier transform infrared spectroscopy, atomic force microscopy, scanning electron microscopy, and Kelvin force microscopy. In vitro studies of controlled release of HP were evaluated in simulated intestinal fluid and simulated gastric fluid. The initial adhesion test of E. coli on multilayer films surface showed effective antiadhesive properties. The in vitro antibacterial test indicated that the multilayer films of TMC/HP based on TMC80 can kill the E. coli bacteria. Therefore, antiadhesive and antibacterial multilayer films may have good potential for coatings and surface modification of biomedical applications.

Magnetic-responsive polysaccharide hydrogels as smart biomaterials: Synthesis, properties, and biomedical applications.

This review reports recent advances in polysaccharide-based magnetic hydrogels as smart platforms for different biomedical applications. These hydrogels have proved to be excellent, viable, eco-friendly alternative materials for the biomedical field due to their biocompatibility, biodegradability, and possibility of controlling delivery processes via modulation of the remote magnetic field. We first present their main synthesis methods and compare their advantages and disadvantages. Next, the synergic properties of hydrogels prepared with polysaccharides and magnetic nanoparticles (MNPs) are discussed. Finally, we describe the main contributions of polysaccharide-based magnetic hydrogels in the targeted drug delivery, tissue regeneration, and hyperthermia therapy fields. Overall, this review aims to motivate the synthesis of novel composite biomaterials, based on the combination of magnetic nanoparticles and natural polysaccharides, to overcome challenges that still exist in the treatment of several diseases.

Development of composite hydrogel based on hydroxyapatite mineralization over pectin reinforced with cellulose nanocrystal.

Hydrogels based on pectin and cellulose nanocrystals (CNC) were used in our study to nucleation and growth of hydroxyapatite (HAp) by the biomimetic method. In this study, we evaluated the direct impact of the different percentages of CNC on pectin hydrogel and the influence of HAp obtained through two methods. CNC were obtained from HCl hydrolysis following chemical functionalization through vinyl groups. The percentage of CNC positively induces thermal stability, mechanical properties and HAp mineralization from biomimetic using simulated body fluid (1.5 SBF). Hydrogels with 5% of CNC showed a higher amount of HAp immersed for 14 days, about 28% of HAp. The obtained hydrogels were compared with hydrogels containing 20% of HAp nanoparticles obtained by chemical precipitation. Biocompatibility of the hydrogels was evaluated by cell viability using fibroblasts (L929). In general, the hydrogels obtained through the biomimetic method show slightly larger biocompatibility compared to the hybrid hydrogels obtained from chemical precipitation.

pH-responsive hybrid hydrogels: Chondroitin sulfate/casein trapped silica nanospheres for controlled drug release.

In this study, the materials were synthesized by chemically crosslinking chondroitin sulfate (CS), casein (CAS), and silica nanospheres (SiO2), creating a highly crosslinked network. The hydrogel release profile was adaptable (that is, it could be faster or slower as needed) simply by changing the polymeric proportion. The incorporation of 5% of silica nanospheres, in mass, for all CAS/CS matrices promoted a better-controlled and sustained release of l-dopa, focusing on the matrix based on 70% of CAS, 30% of CS and 5% of silica, whose l-dopa release lasted for 87 h. Besides, hydrogels are cytocompatible. These new hydrogels can be considered highly attractive materials to be used for controlled and sustained drug release purposes, as well as scaffolds and wound dressing systems.

Nanofibrous silica microparticles/polymer hybrid aerogels for sustained delivery of poorly water-soluble camptothecin.

The surface functionalization of nanoporous silica materials with chemical agents opens up numerous possibilities, including improvement in the materials' ability to carry high payloads of drugs. In this study, KCC-1 nanofibrous silica microparticles are functionalized with methyl groups and then combined with poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) to produce hybrid aerogels that can deliver a poorly water-soluble anticancer drug. The synthetic steps involve freeze-drying a polymer solution of PVA and PAA that contains methyl-modified KCC-1 microparticles and then cross-linking the two polymers via a solid-state reaction. Benefiting from the incorporated methyl-modified KCC-1 microparticles, the hybrid aerogels can load and deliver a payload of camptothecin (CPT), an anticancer drug with antitumor activity but limited clinical application due to its hydrophobicity. The aerogels also show a sustained release of CPT for more than two weeks. The drug release profile can further be tuned by varying the relative amounts of PVA, PAA, and methyl-modified KCC-1. The aerogels are biocompatible to healthy cells, such as immortalized human epithelial (HaCaT), African green monkey kidney (Vero) and murine fibroblast (L929) cells. When loaded with CPT, they show potent antitumor activity against HeLa (HPV18-positive), SiHa (HPV16-positive) and C33A (HPV-negative) cancer cells, significantly inhibiting cell growth.

Synthesis and water absorption transport mechanism of a pH-sensitive polymer network structured on vinyl-functionalized pectin.

Polysaccharide-structured copolymer hydrogel having excellent pH-sensitivity was developed from N,N-dimethylacrylamide (DMAc) and vinyl-functionalized Pectin (Pec). The Pec was vinyl-functionalized by way of chemical reaction with glycidyl metacrylate (GMA) in water under acidic and thermal stimuli. 13C NMR, 1H NMR, and FT-IR spectra revealed that the vinyl groups coming from the GMA were attached onto backbone of the polysaccharide. The hydrogels were obtained by polymerization of the Pec-vinyl with the DMAc. 13C-CP/MAS NMR and FTIR spectra confirmed that the gelling process occurred by way of the vinyl groups attached on Pec-vinyl backbone. The values of apparent swelling rate constant (k) decreased appreciably for pH greater than 6, demonstrating the swelling process of the hydrogel becomes slower at more alkaline conditions. There was an increase of diffusional exponent (n) with increasing pH of the surrounding liquid. This means the water absorption profile becomes more dependent on the polymer relaxation in basified swelling media. In this condition, a longer water absorption half-time (t1/2) was verified, suggesting the polymer relaxation mechanism of the hydrogel would have a considerable effect on the t1/2.

Designing hybrid materials with multifunctional interfaces for wound dressing, electrocatalysis, and chemical separation.

An infinite number of possibilities can emerge from the combination of phases in hybrid systems. Interfacing phases is a strategy to obtain a set of properties in one system that are beyond the abilities of single phases. Herein, the progress in materials science exploring hybrid systems are discussed from the point of view of three important applications: wound dressing; electrocatalysis; and chemical separation. These three unrelated applications exemplify the broad impact of hybrid materials, which can be coherently designed to achieve outstanding performance. Many inspiring works have been published in the last few years, remodeling the edges of human knowledge on hybrid materials. However, the challenges in the coherent design seem to rely on the development of synthetic processes to achieve stronger integration among the phases in a hybrid material.

Two-dimensional thermoresponsive sub-microporous substrate for accelerated cell tissue growth and facile detachment.

Thermoresponsive sub-microporous films having a lower critical solution temperature (LCST), promptly obtained by using the breath figure method, were applied to tissue engineering. These sub-microporous films, sized 100-400 nm, were prepared by blending poly(N-isopropylacrylamide) (PNIPAAm) with polystyrene (PS), in addition to applying the dynamic breath figure (BF) method. The thermoresponsive blends were prepared with polyethylene terephthalate (PET) substrate by using a spin coater; the pore size was modulated according to the spin speed. The sub-microporous films, either with pure PNIPAAm or with different PNIPAAm contents were applied as substrates in order to obtain cell growth (Vero cells); moreover, the effect of PNIPAAm use was evaluated. The PNIPAAm sub-microporous films made the cellular viability to be 9-13-fold higher than the control sample commonly used in cell culture. In addition, the thermoresponsive PNIPAAm properties were even noticed at a low PNIPAAm content in the porous films. Such polymer system was successfully applied to detach the Vero cell tissue using temperature variation.

Biomimetic nanocomposite based on hydroxyapatite mineralization over chemically modified cellulose nanowhiskers: An active platform for osteoblast proliferation.

Functionalized-cellulose nanowhiskers (CNWs) were obtained and used to improve hydroxyapatite (HAp) growth by the biomimetic method. CNWs were obtained through HCl hydrolysis and then submitted to chemical functionalization with carboxylate or amine groups that can induce selective HAp mineralization efficiently. Functionalized-CNWs were tested against HAp growth through the biomimetic method using a simulated body fluid (SBF) as a medium during 14 and 28 days of mineralization. Both chemical surface nature (bearing carboxylate or amine reactive groups) and contact time with SBF influenced the nucleation and growth of HAp crystals over CNWs surface. Nanocomposites immersed for 28 days showed a higher amount of HAp crystals compared to bare CNWs or the ones immersed for 14 days. Biocompatibility of the nanomaterials immersed for 14 days in SBF was evaluated through cell viability test using pre-osteoblasts (MC3T3-E1). In general, functionalized-CNWs containing HAp crystals deposited through biomimetic method showed promising results, with CNWs bearing amine groups showing a slightly larger biocompatibility compared to the ones bearing carboxylate groups during an incubation period of 24 h.

Cellulose nanowhiskers decorated with silver nanoparticles as an additive to antibacterial polymers membranes fabricated by electrospinning.

Antimicrobial films based on distinct polymer matrices, poly (vinyl alcohol) (PVA) or poly (N-isopropylacrylamide) (PNIPAAm), and silver nanoparticles (AgNPs) immobilized onto cellulose nanowhiskers (CWs) were successfully prepared by either casting or electrospinning. CWs were first functionalized with carboxylate groups (labeled as CWSAc) and later they were immersed in a silver nitrate solution (AgNO3). After Ag+ ions anchored in the COO- groups are chemically reduced to produce AgNPs. The CWSAc/AgNPs biological activity was evaluated against Staphylococcus aureus (S. aureus), Bacillus Subtilis (B. subtilis), Escherichia coli (E. coli), and Candida albicans (C. albicans). The materials were more effective against C. albicans that showed a MIC of 15.6 µg/mL. In the process of AgNPs synthesis, the activity of the stabilizing agent (gelatin) and concentration of precursor and reducing agents were evaluated. The synthesized polymeric films displayed good antimicrobial activity against S. aureus, E. coli, and Pseudomonas aeruginosa (P. aeruginosa) bacteria. The PVA films with CWSAc/AgNPs showed diameter of the inhibition halo of up to 11 mm. The results obtained displayed that the films obtained have a potential application to be used in different fields such as packaging, membrane filtration, wound dressing, clothing and in different biomedical applications.

Antibacterial Performance of a PCL-PDMAEMA Blend Nanofiber-Based Scaffold Enhanced with Immobilized Silver Nanoparticles.

In the present study, nanofiber meshes (NFs), composed of polycaprolactone and poly[(2-dimethylamino)ethyl methacrylate] at 80/20 and 50/50 PCL/PDMAEMA blend ratios, were obtained through electrospinning. Silver nanoparticles (AgNPs) formed in situ were then immobilized on NF surfaces through adsorption processes at different pHs. It was possible to observe that the amount of NF-AgNPs can be tuned by changing the pH of AgNPs immobilization and the PCL/PDMAEMA ratio in the blend. The neat NF and NF-AgNPs were characterized with respect to their morphology and mechanical properties. The effects of AgNPs on the antibacterial activities and cytotoxicity of meshes were also evaluated. The antibacterial performance of such NF was improved by the presence of AgNPs. The NF-AgNPs presented good antibacterial effect against S. aureus and partial toxicity against E. coli and P. aeruginosa. Also, compared with neat PCL/PDMAEMA the NF-AgNPs presented lower cytotoxicity against VERO cells, showing their potential for applications in tissue engineering for different types of cell growth.

Covalently-layers of PVA and PAA and in situ formed Ag nanoparticles as versatile antimicrobial surfaces.

The in situ synthesis of silver nanoparticles (AgNPs) within covalently-modified poly(ethylene terephthalate) (PET) films possessing ultra-thin layer of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA) is successfully demonstrated. The resulting polymeric films are shown to exhibit antimicrobial activities toward Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria and fungus (Candida albicans). To make the films, first PET surfaces were subject to photo-oxidation and subsequent solid-state grafting to attach a PVA layer, followed by a PAA layer. To synthesize the AgNPs inside the films, the PVA and PAA-modified PET was soaked in AgNO3 solution and the polymeric film was modified with the Ag(+) ions via Ag(+)-carboxylate interaction, and then the Ag(+) ions-containing polymer film was subject to either photo-reduction or thermal reduction processes. The PVA and PAA thin layers attached by covalent bonds to the PET surface uniquely promoted not only the in situ synthesis but also the stabilization of AgNPs. The formation of the AgNPs was confirmed by UV-vis spectroscopy or by monitoring the surface plasmon resonance (SPR) peak associated with AgNPs. The resulting PVA and PAA ultrathin layers modified and AgNPs containing PET served as bactericide and fungicide, inhibiting the growth of bacteria and fungi on the surfaces. Given PET's versatility and common use in many commercial processes, the method can be used for producing plastic surfaces with versatile antimicrobial and antibacterial properties.

Controlling cell growth with tailorable 2D nanoholes arrays.

A facile and reproducible route that can lead to two-dimensional arrays of nanopores in thin polymer films is demonstrated. The formation of the pores in the polymer films involves breath figure phenomenon and occurs during the film deposition by spin coating. The formation of nanoporous thin films takes only few seconds, and the method does not require complex equipment or expensive chemicals. This method also constitutes a straightforward approach to control the size of the pores formed in thin films. Besides allowing control over the average pore size of the porous films, the use of dynamic deposition with the breath figure phenomenon causes the reduction in the pore size to nanometer scale. The nanoporous arrays obtained by the breath figure are applied as substrates for cell growth, and the effect of their nanopore size on cell growth was evaluated. Notably, it is found that cell viability is related to pore size, where 2D nanoporous structure is more beneficial for cell culture than 2D microporous structures. The change in the average pore size of the polymer films from 1.22 µm to 346 nm results in a threefold increase in cell viability.

Hybrid materials for bone tissue engineering from biomimetic growth of hydroxiapatite on cellulose nanowhiskers.

Cellulose nanowhiskers (CNWs) with different surface composition were used to generate the biomimetic growth hydroxyapatite (HAp). Hybrids materials primarily consist of CNWs with HAp content below 24%. CNWs were produced by different inorganic acid hydrolyses to generate cellulose particles with surface groups to induce HAp mineralization. In the present study, we evaluate the use of CNWs prepared from hydrochloric acid, sulfuric acid and phosphoric acid. HAp growth was obtained from the biomimetic method using a simulated body fluid concentration of 1.5M (SBF). The sulfonate and phosphonate groups on the CNW surface have a direct impact on the nucleation and growth of HAp. HAp/CNW were also compared with the physical mixture method using HAp nanoparticles prepared by chemical precipitation. The bioactivity and biocompatibility of the hybrid materials were assessed by cell viability studies using fibroblast cells (L929). The materials obtained from the biomimetic method have superior biocompatibility/bioactivity compared to the material synthesized by the wet chemical precipitation method with an incubation period of 24h.

Synthesis of a microhydrogel composite from cellulose nanowhiskers and starch for drug delivery.

This work describes the preparation of a microhydrogel composite from cellulose nanowhiskers (CNW) and starch in an ultrasound assisted-emulsion. CNW, which showed rod-like morphology, was obtained by acid hydrolysis of cane-based cellulose. The introduction of vinyl bonds to both CNW and starch enabled us to create the microhydrogel composite in which CNW played a role as a covalent cross-linker. Furthermore, CNW may act as an emulsifying agent for emulsion, improving both sphericity and homogeneity of the microparticles. The drug release was regulated in response to changes in the CNW amounts. The modeling of the release kinetics indicated that the drug release is driven by an anomalous mechanism and that the addition of CNW to starch microparticles led to differences in that mechanism. The release rate became ca. 2.9 times slower when CNW is added. When combined with starch, CNW played a role as a retardant factor for drug release.