Biocompatible Chitosan Films Containing Acetic Acid Manifested Potent Antiviral Activity against Enveloped and Non-Enveloped Viruses.

Chitosan films were prepared by solvent casting using an acetic acid-based solution. The films that were developed contained 15.49% of acetic acid solution (10% v/v) and showed biocompatibility in vitro in human keratinocyte HaCaT cells and potent antiviral activity against both enveloped and non-enveloped viruses. The results showed up to 99.98% and 99.92% viral inactivation against the phi 6 enveloped bacteriophage and MS2 non-enveloped bacteriophage, respectively, suggesting that this chitosan/acetic acid film is a promising material for biomedical applications that require biodegradable broad-spectrum antiviral materials.

Nanomaterials and Their Impact on the Immune System.

Nanomaterials have been the focus of intensive development and research in the medical and industrial sectors over the past several decades. Some studies have found that these compounds can have a detrimental impact on living organisms, including their cellular components. Despite the obvious advantages of using nanomaterials in a wide range of applications, there is sometimes skepticism caused by the lack of substantial proof that evaluates potential toxicities. The interactions of nanoparticles (NPs) with cells of the immune system and their biomolecule pathways are an area of interest for researchers. It is possible to modify NPs so that they are not recognized by the immune system or so that they suppress or stimulate the immune system in a targeted manner. In this review, we look at the literature on nanomaterials for immunostimulation and immunosuppression and their impact on how changing the physicochemical features of the particles could alter their interactions with immune cells for the better or for the worse (immunotoxicity). We also look into whether the NPs have a unique or unexpected (but desired) effect on the immune system, and whether the surface grafting of polymers or surface coatings makes stealth nanomaterials that the immune system cannot find and get rid of.

Antiviral Characterization of Advanced Materials: Use of Bacteriophage Phi 6 as Surrogate of Enveloped Viruses Such as SARS-CoV-2.

The bacteriophage phi 6 is a virus that belongs to a different Baltimore group than SARS-CoV-2 (group III instead of IV). However, it has a round-like shape and a lipid envelope like SARS-CoV-2, which render it very useful to be used as a surrogate of this infectious pathogen for biosafety reasons. Thus, recent antiviral studies have demonstrated that antiviral materials such as calcium alginate hydrogels, polyester-based fabrics coated with benzalkonium chloride (BAK), polyethylene terephthalate (PET) coated with BAK and polyester-based fabrics coated with cranberry extracts or solidified hand soap produce similar log reductions in viral titers of both types of enveloped viruses after similar viral contact times. Therefore, researchers with no access to biosafety level 3 facilities can perform antiviral tests of a broad range of biomaterials, composites, nanomaterials, nanocomposites, coatings and compounds against the bacteriophage phi 6 as a biosafe viral model of SARS-CoV-2. In fact, this bacteriophage has been used as a surrogate of SARS-CoV-2 to test a broad range of antiviral materials and compounds of different chemical natures (polymers, metals, alloys, ceramics, composites, etc.) and forms (films, coatings, nanomaterials, extracts, porous supports produced by additive manufacturing, etc.) during the current pandemic. Furthermore, this biosafe viral model has also been used as a surrogate of SARS-CoV-2 and other highly pathogenic enveloped viruses such as Ebola and influenza in a wide range of biotechnological applications.

Alginate: Enhancement Strategies for Advanced Applications.

Alginate is an excellent biodegradable and renewable material that is already used for a broad range of industrial applications, including advanced fields, such as biomedicine and bioengineering, due to its excellent biodegradable and biocompatible properties. This biopolymer can be produced from brown algae or a microorganism culture. This review presents the principles, chemical structures, gelation properties, chemical interactions, production, sterilization, purification, types, and alginate-based hydrogels developed so far. We present all of the advanced strategies used to remarkably enhance this biopolymer's physicochemical and biological characteristics in various forms, such as injectable gels, fibers, films, hydrogels, and scaffolds. Thus, we present here all of the material engineering enhancement approaches achieved so far in this biopolymer in terms of mechanical reinforcement, thermal and electrical performance, wettability, water sorption and diffusion, antimicrobial activity, in vivo and in vitro biological behavior, including toxicity, cell adhesion, proliferation, and differentiation, immunological response, biodegradation, porosity, and its use as scaffolds for tissue engineering applications. These improvements to overcome the drawbacks of the alginate biopolymer could exponentially increase the significant number of alginate applications that go from the paper industry to the bioprinting of organs.

Recent Advances in Metal-Based Antimicrobial Coatings for High-Touch Surfaces.

International interest in metal-based antimicrobial coatings to control the spread of bacteria, fungi, and viruses via high contact human touch surfaces are growing at an exponential rate. This interest recently reached an all-time high with the outbreak of the deadly COVID-19 disease, which has already claimed the lives of more than 5 million people worldwide. This global pandemic has highlighted the major role that antimicrobial coatings can play in controlling the spread of deadly viruses such as SARS-CoV-2 and scientists and engineers are now working harder than ever to develop the next generation of antimicrobial materials. This article begins with a review of three discrete microorganism-killing phenomena of contact-killing surfaces, nanoprotrusions, and superhydrophobic surfaces. The antimicrobial properties of metals such as copper (Cu), silver (Ag), and zinc (Zn) are reviewed along with the effects of combining them with titanium dioxide (TiO2) to create a binary or ternary contact-killing surface coatings. The self-cleaning and bacterial resistance of purely structural superhydrophobic surfaces and the potential of physical surface nanoprotrusions to damage microbial cells are then considered. The article then gives a detailed discussion on recent advances in attempting to combine these individual phenomena to create super-antimicrobial metal-based coatings with binary or ternary killing potential against a broad range of microorganisms, including SARS-CoV-2, for high-touch surface applications such as hand rails, door plates, and water fittings on public transport and in healthcare, care home and leisure settings as well as personal protective equipment commonly used in hospitals and in the current COVID-19 pandemic.

3D Printed Cobalt-Chromium-Molybdenum Porous Superalloy with Superior Antiviral Activity.

COVID-19 pandemic and associated supply-chain disruptions emphasise the requirement for antimicrobial materials for on-demand manufacturing. Besides aerosol transmission, SARS-CoV-2 is also propagated through contact with virus-contaminated surfaces. As such, the development of effective biofunctional materials that can inactivate SARS-CoV-2 is critical for pandemic preparedness. Such materials will enable the rational development of antiviral devices with prolonged serviceability, reducing the environmental burden of disposable alternatives. This research reveals the novel use of Laser Powder Bed Fusion (LPBF) to 3D print porous Cobalt-Chromium-Molybdenum (Co-Cr-Mo) superalloy with potent antiviral activity (100% viral inactivation in 30 min). The porous material was rationally conceived using a multi-objective surrogate model featuring track thickness (tt) and pore diameter (ϕd) as responses. The regression analysis found the most significant parameters for Co-Cr-Mo track formation to be the interaction effects of scanning rate (Vs) and laser power (Pl) in the order PlVs>Vs>Pl. Contrastively, the pore diameter was found to be primarily driven by the hatch spacing (Sh). The study is the first to demonstrate the superior antiviral properties of 3D printed Co-Cr-Mo superalloy against an enveloped virus used as biosafe viral model of SARS-CoV-2. The material significantly outperforms the viral inactivation time of other broadly used antiviral metals such as copper and silver, as the material's viral inactivation time was from 5 h to 30 min. As such, the study goes beyond the current state-of-the-art in antiviral alloys to provide extra protection to combat the SARS-CoV-2 viral spread. The evolving nature of the COVID-19 pandemic brings new and unpredictable challenges where on-demand 3D printing of antiviral materials can achieve rapid solutions while reducing the environmental impact of disposable devices.

Antimicrobial Face Shield: Next Generation of Facial Protective Equipment against SARS-CoV-2 and Multidrug-Resistant Bacteria.

Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can become infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.

Engineering alginate hydrogel films with poly(3-hydroxybutyrate-co-3-valerate) and graphene nanoplatelets: Enhancement of antiviral activity, cell adhesion and electroactive properties.

A new biodegradable semi-interpenetrated polymer network (semi-IPN) of two US Food and Drug Administration approved materials, poly(3-hydroxybutyrate-co-3-valerate) (PHBV) and calcium alginate (CA) was engineered to provide an alternative strategy to enhance the poor adhesion properties of CA. The synthesis procedure allows the additional incorporation of 10 % w/w of graphene nanoplatelets (GNPs), which have no cytotoxic effect on human keratinocytes. This quantity of multilayer graphene provides superior antiviral activity to the novel semi-IPN against a surrogate virus of SARS-CoV-2. Adding GNPs hardly affects the water absorption or electrical conductivity of the pure components of CA and PHBV. However, the semi-IPN's electrical conductivity increases dramatically after adding GNP due to molecular rearrangements of the intertwined polymer chains that continuously distribute the GNP nanosheets, This new hydrophilic composite biomaterial film shows great promise for skin biomedical applications, especially those that require antiviral and/or biodegradable electroconductive materials.

Prosthetic meshes for hernia repair: State of art, classification, biomaterials, antimicrobial approaches, and fabrication methods.

Worldwide, hernia repair represents one of the most frequent surgical procedures encompassing a global market valued at several billion dollars. This type of surgery usually requires the implantation of a mesh that needs the appropriate chemical, physical and biological properties for the type of repair. This review thus presents a description of the types of hernias, current hernia repair methods, and the state of the art of prosthetic meshes for hernia repair providing the most important meshes used in clinical practice by surgeons working in this area classified according to their biological or chemical nature, morphology and whether bioabsorbable or not. We emphasise the importance of surgical site infection in herniatology, how to deal with this microbial problem, and we go further into the future research lines on the production of advanced antimicrobial meshes to improve hernia repair and prevent microbial infections, including multidrug-resistant strains. A great deal of progress has been made in this biomedical field in the last decade. However, we are still far from an ideal antimicrobial mesh that can also provide excellent integration to the abdominal wall, mechanical performance, low visceral adhesion and minimal inflammatory or foreign body reactions, among many other problems.

Antiviral Properties of Alginate-Based Biomaterials: Promising Antiviral Agents against SARS-CoV-2.

The COVID-19 pandemic has made it essential to explore alternative antiviral materials. Alginate is a biodegradable, renewable, biocompatible, water-soluble and antiviral biopolymer with many potential biomedical applications. In this regard, this review shows 17 types of viruses that have been tested in contact with alginate and its related biomaterials. Most of these studies show that alginate-based materials possess little or no toxicity and are able to inhibit a wide variety of viruses affecting different organisms: in humans by the human immunodeficiency virus type 1, the hepatitis A, B, and C viruses, Sindbis virus, herpes simplex virus type 1 and 2, poliovirus type 1, rabies virus, rubella virus, and the influenza virus; in mice by the murine norovirus; in bacteria by the T4 coliphage, and in plants by the tobacco mosaic virus and the potato virus X. Many of these are enveloped positive-sense single-stranded RNA viruses, like SARS-CoV-2, which render alginate-based materials highly promising in the COVID-19 pandemic.

Physical and biological properties of alginate/carbon nanofibers hydrogel films.

Alginates are renewable materials with excellent biocompatibility and cost-effectiveness in comparison with other biodegradable polymers. However, these hydrogels have poor mechanical properties that restrict their applications in biomedical fields such as skin tissue engineering. In this regard, the study follows an enhanced engineering route to produce alginate-based films reinforced with different amounts (0, 0.1, 0.5, 1 and 2% w/w) of carbon nanofibers (CNFs) and characterize their physical and biological properties. The results of this study showed that these composites possess similar biological properties to neat alginate hydrogels. Thus, none of the synthesized composite materials were cytotoxic and no cell adhesion was observed on the films. Water sorption at the body temperature did not suffer strong changes with the incorporation of CNFs into the alginate matrix. The dynamic mechanical and tensile/compressive properties of calcium alginate significantly improved with the addition of even a very low amount of CNFs. Thus, the tensile and compression modulus of the calcium alginate films in the dry and hydrated state increases up to three and six times, respectively, with the addition of 2% w/w CNFs. In addition, the composites reinforced with the lowest CNFs content have the advantage of possessing more transparency and lower production costs.

Graphene oxide nanosheets versus carbon nanofibers: Enhancement of physical and biological properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) films for biomedical applications.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a microbial biodegradable polymer with a wide range of potential industrial applications. However, its biomedical uses could increase exponentially if certain physical and biological properties were enhanced without compromising on the non-cytotoxic property of this biocompatible polymer. Graphene oxide (GO) nanosheets and carbon nanofibers (CNFs) have proven to be very promising reinforcing agents for the development of new composite materials. Therefore, PHBV films were prepared with 1% w/w of GO nanosheets or CNFs with the aim of enhancing their compression performance, thermal behaviour, wettability and cell adhesion using canine adipose-derived mesenchymal stem cells, and antibacterial activity against the model bacterium Staphylococcus aureus. The results of this study showed that both nanomaterials produced similar enhancements of the physical properties. However, PHBV/GO exhibited higher proliferative activity against time, cell adhesion and antibacterial activity than that of PHBV/CNFs. Nonetheless, both PHBV/GO and PHBV/CNFs composite films have shown considerable promise for biomedical applications.

Graphene oxide in zinc alginate films: Antibacterial activity, cytotoxicity, zinc release, water sorption/diffusion, wettability and opacity.

Alginate is considered an exceptional biomaterial due to its hydrophilicity, biocompatibility, biodegradability, nontoxicity and low-cost in comparison with other biopolymers. We have recently demonstrated that the incorporation of 1% graphene oxide (GO) into alginate films crosslinked with Ca2+ cations provides antibacterial activity against Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis, and no cytotoxicity for human keratinocyte HaCaT cells. However, many other reports in literature have shown controversial results about the toxicity of GO demanding further investigation. Furthermore, the synergic effect of GO with other divalent cations with intrinsic antibacterial and cytotoxic activity such as Zn2+ has not been explored yet. Thus, here, two commercially available sodium alginates were characterised and utilized in the synthesis of zinc alginate films with GO following the same chemical route reported for the calcium alginate/GO composites. The results of this study showed that zinc release, water sorption/diffusion and wettability depended significantly on the type of alginate utilized. Furthermore, Zn2+ and GO produced alginate films with increased water diffusion, wettability and opacity. However, neither the combination of GO with Zn2+ nor the use of different types of sodium alginates modified the antibacterial activity and cytotoxicity of the zinc alginates against these Gram-positive pathogens and human cells respectively.

Synthesis of irregular graphene oxide tubes using green chemistry and their potential use as reinforcement materials for biomedical applications.

Micrometer length tubes of graphene oxide (GO) with irregular form were synthesised following facile and green metal complexation reactions. These materials were obtained by crosslinking of GO with calcium, zinc or strontium chlorides at three different temperatures (24, 34 and 55°C) using distilled water as solvent for the compounds and following a remarkably simple and low-cost synthetic method, which employs no hazardous substances and is conducted without consumption of thermal or sonic energy. These irregular continuous GO networks showed a very particular interconnected structure by Field Emission Scanning Electron Microscopy with Energy-Disperse X-Ray Spectroscopy for elemental analysis and High-resolution Transmission Electron Microscopy with Scanning Transmission Electron Microscope Dark Field Imaging, and were analysed by Raman Spectroscopy. To demonstrate the potential use of these 3D GO networks as reinforcement materials for biomedical applications, two composites of calcium alginate with irregular tubes of GO and with single GO nanosheets were prepared with the same amount of GO and divalent atoms and analysed. Thus, the dynamic-mechanical modulus of the composites synthesised with the 3D crosslinked GO networks showed a very significant mechanical improvement due to marked microstructural changes confirmed by confocal microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy.

Three-dimensional nanocomposite scaffolds with ordered cylindrical orthogonal pores.

A silica reinforcement can improve the mechanical properties of hydrogels in the rubbery state. A method to prepare a scaffold with a well-ordered array of cylindrical pores is presented in this work, which yields a scaffold with a biphasic matrix of a hybrid nanocomposite: the hydrogel poly(2-hydroxyethyl acrylate) (PHEA) and a silica network obtained by an acid catalyzed sol-gel process of tetraethoxysilane (TEOS). As porogenic template of the scaffold stacked layers of commercial polyamide 6 fabrics were used, which were compressed and sintered. Porosity and dynamic mechanical response of the resulting scaffolds were measured and compared with the bulk properties. Removal of the organic polymer phase of the scaffold by pyrolysis revealed the overall continuity of the silica network; the residue maintained the original cylindrical pore structure of the scaffolds, though slightly shrunk. Atomic force microscopy topography measurements of these pyrolysed residues revealed a silica structure with particle aggregates having sizes around tens of nanometers. The silica distribution was assessed by X-ray microanalysis mapping, showing homogeneity at a micrometer scale.