Development of Antioxidant and Antimicrobial Membranes Based on Functionalized and Crosslinked Chitosan for Tissue Regeneration.

Tissue engineering is an interdisciplinary field that develops new methods to enhance the regeneration of damaged tissues, including those of wounds. Polymer systems containing bioactive molecules can play an important role in accelerating tissue regeneration, mitigating inflammation process, and fighting bacterial infection. Chitosan (CS) has attracted much attention regarding its use in wound healing system fabrication thanks to its biocompatibility, biodegradability, and the presence of functional groups in its structure. In this work, bioactive chitosan-based membranes were obtained by both chemical and physical modifications of the polymer with glycidyl methacrylate and glycerol (GLY), respectively. The most suitable GLY concentration to obtain wound healing systems with good elongation at break, a good water vapor transmission rate (WVTR), and good wettability values was 20% (w/w). Afterwards, the membranes were crosslinked with different concentrations of ethylene glycol dimethacrylate (EGDMA). By using a concentration of 0.05 mM EGDMA, membranes with a contact angle and WVTR values suitable for the application were obtained. To make the system bioactive, 3,4-dihydrocinnamic acid (HCAF) was introduced into the membranes, either by imbibition or chemical reaction, using laccase as a catalyst. Thermal and mechanical analyses confirmed the formation of a cohesive network, which limited the plasticizing effect of GLY, particularly when HCAF was chemically bound. The HCAF-imbibed membrane showed a good antioxidant and antimicrobial activity, highlighting the potential of this system for the treatment of wound healing.

Polymeric Wet-Strength Agents in the Paper Industry: An Overview of Mechanisms and Current Challenges.

Polymeric wet-strength agents are important additives used in the paper industry to improve the mechanical properties of paper products, especially when they come into contact with water. These agents play a crucial role in enhancing the durability, strength, and dimensional stability of paper products. The aim of this review is to provide an overview of the different types of wet-strength agents available and their mechanisms of action. We will also discuss the challenges associated with the use of wet-strength agents and the recent advances in the development of more sustainable and environmentally friendly agents. As the demand for more sustainable and durable paper products continues to grow, the use of wet-strength agents is expected to increase in the coming years.

Polyglycerol Adipate-Grafted Polycaprolactone Nanoparticles as Carriers for the Antimicrobial Compound Usnic Acid.

Nanoparticle (NP) drug delivery systems are known to potentially enhance the efficacy of therapeutic agents. As for antimicrobial drugs, therapeutic solutions against drug-resistant microbes are urgently needed due to the worldwide antimicrobial resistance issue. Usnic acid is a widely investigated antimicrobial agent suffering from poor water solubility. In this study, polymer nanoparticles based on polyglycerol adipate (PGA) grafted with polycaprolactone (PCL) were developed as carriers for usnic acid. We demonstrated the potential of the developed systems in ensuring prolonged bactericidal activity against a model bacterial species, Staphylococcus epidermidis. The macromolecular architecture changes produced by PCL grafted from PGA significantly influenced the drug release profile and mechanism. Specifically, by varying the length of PCL arms linked to the PGA backbone, it was possible to tune the drug release from a burst anomalous drug release (high PCL chain length) to a slow diffusion-controlled release (low PCL chain length). The developed nanosystems showed a prolonged antimicrobial activity (up to at least 7 days) which could be used in preventing/treating infections occurring at different body sites, including medical device-related infection and mucosal/skin surface, where Gram-positive bacteria are commonly involved.

Molecularly Imprinted Polymers Based on Chitosan for 2,4-Dichlorophenoxyacetic Acid Removal.

The development of low-cost and eco-friendly materials for the removal of pollutants from water is one of the main modern challenges. For this purpose, molecularly imprinted polymers were prepared under optimized conditions starting from chitosan (CS), chemically or ionically modified with glycidyl methacrylate (GMA) or itaconic acid (ITA), respectively. 2,4-Dichlorophenoxyacetic acid (2,4-D) was used as a template, obtaining the CS_GMA and CS_ITA series. The influence of the template concentration on the MIPs' (molecularly imprinted polymers) morphology, thermal behaviour and swelling ability, as well as on the 2,4-D removal capacity, were analyzed. The amount of the template used for the imprinting, together with the different permeability of the matrices, were the key factors driving the analyte uptake process. Despite the good performance shown by the non-imprinted CS_GMA sample, the best results were obtained when CS_GMA was imprinted with the highest amount (5%) of template (CS_GMA_5). This system was also more efficient when consecutive adsorption experiments were carried out. In addition, CS_GMA_5 had a desorption efficiency of 90-100% when a low pesticide concentration was used. These findings suggest that the presence of imprinted cavities could be useful in improving the performance of sorbent materials making CS_GMA_5 a possible candidate for 2,4-D removal.

Mechanical Properties and Diffusion Studies in Wax-Cellulose Nanocomposite Packaging Material.

This article focuses on the study related to the estimation of packaging material properties of cellulose-wax nanocomposite using molecular dynamics simulation (MDS). Cellulose based packaging material is gaining lot of importance due to its good material properties and low cost. Cellulose with small amount of plant-derived wax (nonacosane-10-ol and nonacosane-5,10-diol) offers higher mechanical strength and modulus of elasticity compared to the conventional synthetic polymer materials. In this article, in addition to the estimation of mechanical properties, the thermal stability of the proposed ecofriendly cellulose-wax composite is evaluated by estimating the glass transition temperature which essentially provides critical information on the glassy state and rubbery state of this biopolymer. The glass transition temperature of this composite changes significantly compared to that of pure cellulose (which also suffers from poor mechanical strength). Transport properties such as diffusion volume and diffusion coefficient of oxygen, nitrogen, and water are estimated using the results obtained from MDS. The diffusion coefficients of these species within the cellulose-wax composite are analyzed using the diffusion volume and interaction energies of these constituents with the wax and cellulose.

Sustainable Bioactive Packaging Based on Thermoplastic Starch and Microalgae.

This study combines the use of corn starch and Tetradesmus obliquus microalgae for the production of antioxidant starch films as flexible packaging material. Starch was plasticized with glycerol and blended with 1 w% polyallylamine chosen as an agent to modify the film physical properties. The addition of polyallylamine improved film water stability and water vapor transmission rate as well as mechanical stiffness and tenacity. The dried Tetradesmus obliquus microalgae, which showed an EC50 value of 2.8 mg/mg DPPH (2.2-Diphenyl-1-picrylhydrazyl radical), was then used as antioxidant filler. The addition of microalgae provided the films with good antioxidant activity, which increased with microalgae content increasing. To our knowledge, this is the first study reporting the development of sustainable bioactive packaging films composed of almost 100% starch, and follows the European union's goals on plastics strategy concerning the promotion of bio-based, compostable plastics and the setting up of approaches to prevent food waste with a simple plastic packaging.

Silver- and Zinc-Decorated Polyurethane Ionomers with Tunable Hard/Soft Phase Segregation.

Segmented polyurethane ionomers find prominent applications in the biomedical field since they can combine the good mechanical and biostability properties of polyurethanes (PUs) with the strong hydrophilicity features of ionomers. In this work, PU ionomers were prepared from a carboxylated diol, poly(tetrahydrofuran) (soft phase) and a small library of diisocyanates (hard phase), either aliphatic or aromatic. The synthesized PUs were characterized to investigate the effect of ionic groups and the nature of diisocyanate upon the structure-property relationship. Results showed how the polymer hard/soft phase segregation was affected by both the concentration of ionic groups and the type of diisocyanate. Specifically, PUs obtained with aliphatic diisocyanates possessed a hard/soft phase segregation stronger than PUs with aromatic diisocyanates, as well as greater bulk and surface hydrophilicity. In contrast, a higher content of ionic groups per polymer repeat unit promoted phase mixing. The neutralization of polymer ionic groups with silver or zinc further increased the hard/soft phase segregation and provided polymers with antimicrobial properties. In particular, the Zinc/PU hybrid systems possessed activity only against the Gram-positive Staphylococcus epidermidis while Silver/PU systems were active also against the Gram-negative Pseudomonas aeruginosa. The herein-obtained polyurethanes could find promising applications as antimicrobial coatings for different kinds of surfaces including medical devices, fabric for wound dressings and other textiles.

Chitosan-Graphene Oxide Composite Membranes for Solid-Phase Extraction of Pesticides.

Solid-phase extraction (SPE) coupled to LC/MS/MS analysis is a valid approach for the determination of organic micropollutants (OMPs) in liquid samples. To remove the greatest number of OMPs from environmental matrices, the development of innovative sorbent materials is crucial. Recently, much attention has been paid to inorganic nanosystems such as graphite-derived materials. Graphene oxide has been employed in water-purification processes, including the removal of several micropollutants such as dyes, flame retardants, or pharmaceutical products. Polysaccharides have also been widely used as convenient media for the dispersion of sorbent materials, thanks to their unique properties such as biodegradability, biocompatibility, nontoxicity, and low cost. In this work, chitosan-graphene oxide (CS_GO) composite membranes containing different amounts of GO were prepared and used as sorbents for the SPE of pesticides. To improve their dimensional stability in aqueous medium, the CS_GO membranes were surface crosslinked with glutaraldehyde. The composite systems were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, swelling degree, contact angle, and mechanical measurements. As the GO content increased, a decrease in surface homogeneity, an improvement of mechanical properties, and a reduction of thermal stability of the CS-based membranes were observed. The increased dimensional stability in water, together with the presence of high GO amounts, made the prepared composite membranes more efficacious than the ones based just on CS in isolating and preconcentrating different hydrophilic/hydrophobic pollutants.

Hyaluronic Acid Reduces Bacterial Fouling and Promotes Fibroblasts' Adhesion onto Chitosan 2D-Wound Dressings.

Wound healing is a dynamic process that can be seriously delayed by many factors including infectious complications. The development of dressings with intrinsic wound healing activity and/or releasing bioactive compounds may help with addressing such an issue. In this study, hyaluronic acid (HA) at different percentages (1-35%) was used to modify chitosan (CS) biological and physico-chemical properties in order to obtain 2D-matrices able to promote healing and protect from infection. HA incorporation in the CS matrix decreased film transparency and homogeneity, but improved film water uptake and surface wettability. The water vapor transmission rate (WVTR) increased up to a 5% HA content, where it reached the highest value (672 g/m2 day), and decreased for higher HA contents. At all of the tested HA concentrations, HA affected mechanical properties providing matrices more flexible than pure CS with benefit for wound care. Pure CS films permitted S. epidermidis adhesion and biofilm formation. That was not true for CS/HA matrices, where HA at concentrations equal to or greater than 5% was able to avoid S. epidermidis adhesion. Fibroblasts adhesion also took benefit from the HA presence in the film, especially at 5% content, where the best adhesion and proliferation was found.

Usnic Acid: Potential Role in Management of Wound Infections.

Usnic acid (UA) is a secondary lichen metabolite extensively studied for the broad variety of biological features. The most interesting property of UA is its antimicrobial activity against Gram-positive bacteria growing either in planktonic or in biofilm mode. In this chapter, the most relevant studies assessing usnic acid activity against microbial biofilms have been summarized and the potential role of UA in the management of biofilm-based wound infections has been critically discussed. Additionally, an overview of the main strategies adopted so far to reduce drug toxicity and increase bioavailability is given in the perspective of a safe use of UA in the clinical management of infected wounds.

Polymeric Systems as Antimicrobial or Antifouling Agents.

The rapid increase in the emergence of antibiotic-resistant bacterial strains combined with a dwindling rate of discovery of novel antibiotic molecules has lately created an alarming issue worldwide [...].

Synthesis, Characterization, and Bacterial Fouling-Resistance Properties of Polyethylene Glycol-Grafted Polyurethane Elastomers.

Despite advances in material sciences and clinical procedures for surgical hygiene, medical device implantation still exposes patients to the risk of developing local or systemic infections. The development of efficacious antimicrobial/antifouling materials may help with addressing such an issue. In this framework, polyethylene glycol (PEG)-grafted segmented polyurethanes were synthesized, physico-chemically characterized, and evaluated with respect to their bacterial fouling-resistance properties. PEG grafting significantly altered the polymer bulk and surface properties. Specifically, the PEG-grafted polyurethanes possessed a more pronounced hard/soft phase segregated microstructure, which contributed to improving the mechanical resistance of the polymers. The better flexibility of the soft phase in the PEG-functionalized polyurethanes compared to the pristine polyurethane (PU) was presumably also responsible for the higher ability of the polymer to uptake water. Additionally, dynamic contact angle measurements evidenced phenomena of surface reorganization of the PEG-functionalized polyurethanes, presumably involving the exposition of the polar PEG chains towards water. As a consequence, Staphylococcus epidermidis initial adhesion onto the surface of the PEG-functionalized PU was essentially inhibited. That was not true for the pristine PU. Biofilm formation was also strongly reduced.

Antioxidant Hydroxytyrosol-Based Polyacrylate with Antimicrobial and Antiadhesive Activity Versus Staphylococcus Epidermidis.

The accumulation of reactive oxygen species (ROS) in microbial biofilms has been recently recognized to play a role in promoting antibiotic resistance in biofilm-growing bacteria. ROS are also over-produced when a medical device is implanted and they can promote device susceptibility to infection or aseptic loosening. High levels of ROS seem also to be responsible for the establishment of chronic wounds.In this study, a novel antioxidant polyacrylate was synthesized and investigated in terms of antimicrobial and antibiofilm activity. The polymer possesses in side-chain hydroxytyrosol (HTy), that is a polyphenolic compound extracted from olive oil wastewaters.The obtained 60 nm in size polymer nanoparticles showed good scavenging and antibacterial activity versus a strain of Staphylococcus epidermidis. Microbial adherence assays evidenced that the hydroxytyrosol-containing polymer was able to significantly reduce bacterial adhesion compared to the control. These findings open novel perspective for a successful use of this antioxidant polymer for the prevention or treatment of biofilm-based infections as those related to medical devices or chronic wounds.

Design of bioactive and biomimetic scaffolds based on chitosan-alginate polyelectrolyte complexes for tissue engineering.

The replacement and regeneration of biological tissues by fabricating three-dimensional functionalized constructs that can improve material interaction with cells is an important challenge of tissue engineering. In this study, bioactive and biomimetic scaffolds based on chitosan-alginate polyelectrolyte complexes (PECs) were fabricated by freeze-drying method and then crosslinked with CaCl2. Various chitosan-alginate (CS-AL) molar ratios were used to obtain PECs with different structural and mechanical properties. The CS1-AL2.3 scaffold showed to possess the best mechanical properties (8 MPa) and good pore morphology with an average size of 100-150 µm. After the crosslinking process, a less porous structure but with higher elastic modulus (30 MPa) was obtained. To make matrix bioactive and biomimetic, the CS1-AL2.3 system was first functionalized with 3,4-dihydroxyhydrocinnamic acid (HCAF) and then with PySO3 or Heparin to introduce groups/molecules mimicking the extracellular matrix. While the antioxidant properties of the scaffolds containing HCAF improved by 3 orders of magnitude, compared to the non-functionalized matrix, the introduction of sulfonic groups into the bioactive scaffold made the structure more porous and hydrophilic with respect to the heparinized one also favoring the penetration and proliferation of fibroblasts into the scaffold. These results indicate the potential of these novel systems for tissue engineering.

Recovery of cellulose acetate bioplastic from cigarette butts: realization of a sustainable sorbent for water remediation.

Cigarette butts, one of the most common forms of litter in the world, represent a source of chemical and plastic pollution releasing thousands of toxic compounds and microfibers of cellulose acetate (CA). Besides the correct waste management, the recovery of CA from cigarette filters is a way to cushion their negative effects on the environment. Thus far, recycling strategies have been limited to industrial applications, while not many solutions have designed for water remediation. This work describes a strategy to valorize this harmful waste and to reverse its environmental impact, proposing a simple and effective procedure of reclamation of CA and its reuse to prepare a composite sorbent for the treatment of polluted water. The first step entails the washing of filters with hot water (T = 90 °C) and hot ethanol (T = 58-68 °C) to remove the impurities produced during cigarette burning, as verified by means of UV and attenuated total reflection-Fourier-transform infrared (ATR-FTIR) spectroscopy, thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC). The second step involves the use of the regenerated CA to prepare porous cylinder-shaped cryogels (15 mm × 10 mm) whose sorption properties are enhanced by the combination with AC (15 % w/w). The synthesis takes advantage of the sol-gel transition of the polymer dispersion (5 % w/V) in a solution acetone/water 5 mM in NH3 (60/40, v/v). After characterization by dynamic mechanical analysis (DMA), TGA, FT-IR, and scanning electron microscopy (SEM), the adsorption capability of the physical cryogel was studied in terms of treated environmental water volume, contact time and concentration of the selected pollutants. The results have shown that the proposed strategy is a low-cost way to recycle CA from cigarette butts and that the designed sorbent is a promising material for water treatment, allowing quick removal times and yields >79.6 %.

Nanostructured Poly-l-lactide and Polyglycerol Adipate Carriers for the Encapsulation of Usnic Acid: A Promising Approach for Hepatoprotection.

The present study investigates the utilization of nanoparticles based on poly-l-lactide (PLLA) and polyglycerol adipate (PGA), alone and blended, for the encapsulation of usnic acid (UA), a potent natural compound with various therapeutic properties including antimicrobial and anticancer activities. The development of these carriers offers an innovative approach to overcome the challenges associated with usnic acid's limited aqueous solubility, bioavailability, and hepatotoxicity. The nanosystems were characterized according to their physicochemical properties (among others, size, zeta potential, thermal properties), apparent aqueous solubility, and in vitro cytotoxicity. Interestingly, the nanocarrier obtained with the PLLA-PGA 50/50 weight ratio blend showed both the lowest size and the highest UA apparent solubility as well as the ability to decrease UA cytotoxicity towards human hepatocytes (HepG2 cells). This research opens new avenues for the effective utilization of these highly degradable and biocompatible PLLA-PGA blends as nanocarriers for reducing the cytotoxicity of usnic acid.

Glycerol- and diglycerol-based polyesters: Evaluation of backbone alterations upon nano-formulation performance.

Despite the success of polyethylene glycol-based (PEGylated) polyesters in the drug delivery and biomedical fields, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited chemical handles as well as highly hydrophobic nature, can restrict their effectiveness in physiological conditions of the polyester counterpart. To address these matters, an increasing amount of research has been focused towards identifying alternatives to PEG. One promising strategy involves the use of bio-derived polyols, such as glycerol. In particular, glycerol is a hydrophilic, non-toxic, untapped waste resource and as other polyols, can be incorporated into polyesters via enzymatic catalysis routes. In the present study, a systematic screening is conducted focusing on the incorporation of 1,6-hexanediol (Hex) (hydrophobic diol) into both poly(glycerol adipate) (PGA) and poly(diglycerol adipate) (PDGA) at different (di)glycerol:hex ratios (30:70; 50:50 and 70:30 mol/mol) and its effect on purification upon NPs formation. By varying the amphiphilicity of the backbone, we demonstrated that minor adjustments influence the NPs formation, NPs stability, drug encapsulation, and degradation of these polymers, despite the high chemical similarity. Moreover, the best performing materials have shown good biocompatibility in both in vitro and in vivo (whole organism) tests. As preliminary result, the sample containing diglycerol and Hex in a 70:30 ratio, named as PDGA-Hex 30%, has shown to be the most promising candidate in this small library analysed. It demonstrated comparable stability to the glycerol-based samples in various media but exhibited superior encapsulation efficiency of a model hydrophobic dye. This in-depth investigation provides new insights into the design and modification of biodegradable (di)glycerol-based polyesters, potentially paving the way for more effective and sustainable PEG-free drug delivery nano-systems in the pharmaceutical and biomedical fields.

Glycerol-based sustainably sourced resin for volumetric printing.

Volumetric Additive Manufacturing (VAM) represents a revolutionary advancement in the field of Additive Manufacturing, as it allows for the creation of objects in a single, cohesive process, rather than in a layer-by-layer approach. This innovative technique offers unparalleled design freedom and significantly reduces printing times. A current limitation of VAM is the availability of suitable resins with the required photoreactive chemistry and from sustainable sources. To support the application of this technology, we have developed a sustainable resin based on polyglycerol, a bioderived (e.g., vegetable origin), colourless, and easily functionisable oligomer produced from glycerol. To transform polyglycerol-6 into an acrylate photo-printable resin we adopted a simple, one-step, and scalable synthesis route. Polyglycerol-6-acrylate fulfils all the necessary criteria for volumetric printing (transparency, photo-reactivity, viscosity) and was successfully used to print a variety of models with intricate geometries and good resolution. The waste resin was found to be reusable with minimal performance issues, improving resin utilisation and minimising waste material. Furthermore, by incorporating dopants such as poly(glycerol) adipate acrylate (PGA-A) and 10,12-pentacosadyinoic acid (PCDA), we demonstrated the ability to print objects with a diverse range of functionalities, including temperature sensing probes and a polyester excipient, highlighting the potential applications of these new resins.

Editorial of the special issue antimicrobial polymers.

The special issue "Antimicrobial Polymers" includes research and review papers concerning the recent advances on preparation of antimicrobial polymers and their relevance to industrial settings and biomedical field. Antimicrobial polymers have recently emerged as promising candidates to fight microbial contamination onto surfaces thanks to their interesting properties. In this special issue, the main strategies pursued for developing antimicrobial polymers, including polymer impregnation with antimicrobial agents or synthesis of polymers bearing antimicrobial moieties, were discussed. The future application of these polymers either in industrial or healthcare settings could result in an extremely positive impact not only at the economic level but also for the improvement of quality of life.

Water soluble usnic acid-polyacrylamide complexes with enhanced antimicrobial activity against Staphylococcus epidermidis.

Usnic acid, a potent antimicrobial and anticancer agent, poorly soluble in water, was complexed to novel antimicrobial polyacrylamides by establishment of strong acidic-base interactions. Thermal and spectroscopic analysis evidenced a molecular dispersion of the drug in the polymers and a complete drug/polymer miscibility for all the tested compositions. The polymer/drug complexes promptly dissolved in water and possessed a greater antimicrobial activity against Staphylococcus epidermidis than both the free drug and the polymer alone. The best results were obtained with the complex based on the lowest molecular weight polymer and containing a low drug content. Such a complex showed a larger inhibition zone of bacterial growth and a lower minimum inhibitory concentration (MIC) with respect to usnic acid alone. This improved killing effect is presumably due to the reduced size of the complexes that allows an efficient cellular uptake of the antimicrobial complexes. The killing effect extent seems to be not significantly dependent on usnic acid content in the samples.