Hydrogel Complex Containing the Antimicrobial Peptide HX-12C Accelerates Healing of Infected Wounds

Bacterial infections of the wound surface can be painful for patients, and traditional dressings do not effectively address this problem. In this study, an antimicrobial wound dressing is prepared using a novel antimicrobial peptide, HX-12C. This hydrogel system is based on the natural biomaterials sodium alginate and gelatin, utilizing calcium carbonate as a source of Ca²⁺, and ionic cross-linking is facilitated by lowering the solution pH. The resulting sodium alginate/gelatin HX-12C-loaded hydrogel (CaAGEAM) has good mechanical and adhesion properties, biocompatibility and in vitro degradability. Its extraordinary antibacterial efficacy (>98%) is verified by an antibacterial experiment. More importantly, in vivo experiments further demonstrate its healing-promotion effect, with a 95% wound healing rate by day 9. Tissue staining demonstrates that the hydrogel containing antimicrobial peptides is effective in suppressing inflammation. The dressing promotes wound healing by stimulating the deposition of skin appendages and collagen. The results of this study suggest that composite hydrogels containing antimicrobial peptides are a promising new type of dressing to promote the healing of infected wounds.     

Nature‐Inspired Bacterial Cellulose/Methylglyoxal (BC/MGO) Nanocomposite for Broad‐Spectrum Antimicrobial Wound Dressing

Bacterial cellulose (BC) is a natural material produced by Acetobacter xylinum, widely used in wound dressings due to the high water‐holding capacity and great mechanical strength. In this paper, a novel antimicrobial dressing made from BC/methylglyoxal (MGO) composite with a dip‐coating method inspired by naturally antimicrobial Manuka honey is proposed, which to our best knowledge, has not yet to be reported. Characterizations by scanning electron microscope and atomic force microscopy show the interconnected nanostructure of BC and MGO and increase surface roughness of the BC/MGO composite. Thermal analysis indicates high temperature stability of both BC and BC/MGO, while compared with BC, BC/MGO exhibits slightly weaker thermal stability possibly due to reduction of hydrogen bonding and increase of crystallinity. Mechanical test confirms the strong mechanical property of BC and BC/MGO nanocomposite. From the disk diffusion antimicrobial test, the BC/MGO nanocomposite with highest MGO concentration (4%) shows great zone inhibition diameter (around 14.3, 12.3, 17.1, and 15.5 mm against Micrococcus luteus, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli). Compared with other antimicrobial wound dressing composite materials, the proposed BC/MGO nanocomposite has among the greatest antimicrobial property against broad‐spectrum bacteria, making it a promising antimicrobial dressing in chronic wounds care.     

Dual‐Functional Dextran‐PEG Hydrogel as an Antimicrobial Biomedical Material

Microbial infections continually present a major worldwide public healthcare threat, particularly in instances of impaired wound healing and biomedical implant fouling. The development of new materials with the desired antimicrobial property to avoid and treat wound infection is urgently needed in wound care management. This study reports a novel dual‐functional biodegradable dextran‐poly(ethylene glycol) (PEG) hydrogel covalently conjugated with antibacterial Polymyxin B and Vancomycin (Vanco). The hydrogel is designed as a specialized wound dressing that eradicates existing bacteria and inhibits further bacteria growth, while, ameliorating the side effects of antibiotics and accelerating tissue repair and regeneration. The hydrogel exhibits potent antibacterial activities against both gram‐negative bacteria Escherichia coli (E. coli) and gram‐positive bacteria Staphylococcus aureus (S. aureus) with no observable toxicity to mouse fibroblast cell line NIH 3T3. These results demonstrate the immense potential of dextran‐PEG hydrogel as a wound dressing healthcare material in efficiently controlling bacteria growth in complex biological systems.     

Covalently Immobilized Battacin Lipopeptide Gels with Activity against Bacterial Biofilms

Novel antibiotic treatments are in increasing demand to tackle life-threatening infections from bacterial pathogens. In this study, we report the use of a potent battacin lipopeptide as an antimicrobial gel to inhibit planktonic and mature biofilms of S. aureus and P. aeruginosa. The antimicrobial gels were made by covalently linking the N-terminal cysteine containing lipopeptide (GZ3.163) onto the polyethylene glycol polymer matrix and initiating gelation using thiol-ene click chemistry. The gels were prepared both in methanol and in water and were characterised using rheology, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Antibacterial and antibiofilm analyses revealed that the gels prepared in methanol have better antibacterial and antibiofilm activity. Additionally, a minimum peptide content of 0.5 wt% (relative to polymer content) is required to successfully inhibit the planktonic bacterial growth and disperse mature biofilms of P. aeruginosa and S. aureus. The antibacterial activity of these lipopeptide gels is mediated by a contact kill mechanism of action. The gels are non-haemolytic against mouse red blood cells and are non-cytotoxic against human dermal fibroblasts. Findings from this study show that battacin lipopeptide gels have the potential to be developed as novel topical antibacterial agents to combat skin infections, particularly caused by S. aureus.     

Antibiotic protected silver nanoparticles for microbicidal cotton

Surface coating of metal nanoparticles is one of the major aspects to be optimized in the design of antimicrobial nanoparticles. The novelty of this work is that antimicrobial derivatives have been used as stabilizers to protect silver nanoparticles (Ag NPs). Microbicidal activity studies of fabricated cotton textiles coated with these Ag@Antibio were performed. Protective ligand layers of Ag NPs resulted to be a deterministic factor in their antimicrobial activity. The best bactericidal activity was obtained for Fabric TAM (coated with Ag NPs with triarylmethane derivates in surface, Ag@TAMSH), with a bacterial decrease of 3 log units for the S. aureus strain. Intrinsic antibiotic activity and partial positive charge of the TAMSH probably enhanced their antimicrobial effects. Fabric Eu (coated with Ag NPs with eugenol derivates in surface, Ag@EugenolSH) and Fabric FQPEG (coated with Ag NPs embedded in PEG-fluoroquinolone derivatives in surface, Ag@FQPEG) displayed antibacterial activity for both Staphylococcus aureus and Pseudomonas aeruginosa strains. These coated antimicrobial cotton fabrics can be applied in different medical textiles.     

Antimicrobial activity of collagen material with thymol addition for potential application as wound dressing

Recently, special attention has been paid to the development of active wound dressing materials based on biopolymers. Collagen is a natural polymer, which meets the requirements of modern materials for medical applications. However, despite its unique properties, collagen has no antimicrobial activity. In this work thymol was incorporated into collagen films to meet antimicrobial properties of the material. Thymol is a naturally occurring phenolic compound recognized as an antimicrobial agent. Collagen/thymol thin films were obtained through solvent evaporation using collagen solutions containing different amounts of thymol. The structure of the obtained materials was studied using FTIR-ATR spectroscopy. The inhibition ability on the growth of several strains of microorganisms was tested. The standard ISO 22196:2007 was used to define the bactericidal properties of the material. The growth of the following bacteria on the collagen/thymol films was studied: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Enterobacter aerogenes, Candida albicans. The results showed that the growth of Staphylococcus aureus was the most inhibited compared to the other tested strains. Collagen/thymol material is more efficient against pathogens through direct contact compared to the diffusion of thymol from the material. In general, the thymol addition inhibits biofilm formation on the collagen surface.     

Antiviral and Antibacterial Polyurethanes of Various Modalities

We have prepared and characterized a new polyurethane-based antimicrobial material, N,N-dodecyl,methyl-polyurethane (Quat-12-PU). It exhibits strong antiviral and antibacterial activities when coated (as an organic solution or an aqueous nanosuspension) onto surfaces and antibacterial activity when electrospun into nanofibers. Quat-12-PU surfaces are able to kill airborne Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria, as well as inactivate the enveloped influenza virus (but not the non-enveloped poliovirus).     

Hyaluronic Acid (HA)‐Based Silk Fibroin/Zinc Oxide Core–Shell Electrospun Dressing for Burn Wound Management

Burn injuries represent a major life‐threatening event that impacts the quality of life of patients, and places enormous demands on the global healthcare systems. This study introduces the fabrication and characterization of a novel wound dressing made of core–shell hyaluronic acid–silk fibroin/zinc oxide (ZO) nanofibers for treatment of burn injuries. The core–shell configuration enables loading ZO—an antibacterial agent—in the core of nanofibers, which in return improves the sustained release of the drug and maintains its bioactivity. Successful formation of core–shell nanofibers and loading of zinc oxide are confirmed by transmission electron microscopy, Fourier‐transform infrared spectroscopy, and energy dispersive X‐ray. The antibacterial activity of the dressings are examined against Escherichia coli and Staphylococcus aureus and it is shown that addition of ZO improves the antibacterial property of the dressing in a dose‐dependent fashion. However, in vitro cytotoxicity studies show that high concentration of ZO (>3 wt%) is toxic to the cells. In vivo studies indicate that the wound dressings loaded with ZO (3 wt%) substantially improves the wound healing procedure and significantly reduces the inflammatory response at the wound site. Overall, the dressing introduced herein holds great promise for the management of burn injuries.     

Enhancing the Activity of Surface Immobilized Antimicrobial Peptides Using Thiol-Mediated Tethering to Poly(ethylene glycol)

Considering the need for versatile surface coatings that can display multiple bioactive signals and chemistries, the use of more novel surface modification methods is starting to emerge. Thiol-mediated conjugation of biomolecules is shown to be quite advantageous for such purposes due to the reactivity and chemoselectivity of thiol functional groups. Herein, the immobilization of poly(ethylene glycol) (PEG) and antimicrobial peptides (AMPs) to silica colloidal particles based on thiol-mediated conjugation techniques, along with an assessment of the antimicrobial potential of the functionalized particles against Pseudomonas aeruginosa and Staphylococcus aureus is investigated. Immobilization of PEG to thiolated Si particles is performed by either a two-step thiol–ene “photo-click” reaction or a “one-pot” thiol–maleimide type conjugation using terminal acrylate or maleimide functional groups, respectively. It is demonstrated that both immobilization methods result in a significant reduction in the number of viable bacterial cells compared to unmodified samples after the designated incubation periods with the PEG-AMP-modified colloidal suspensions. These findings provide a promising outlook for the fabrication of multifunctional surfaces based upon the tethering of PEG and AMPs to colloidal particles through thiol-mediated biocompatible chemistry, which has potential for use as implant coatings or as antibacterial formulations that can be incorporated into wound dressings to prevent or control bacterial infections.     

Recent Advances on Antimicrobial and Anti-Inflammatory Cotton Fabrics Containing Nanostructures

Hydrophilic cotton textiles, used in hospitals and sportswear, are prone to the growth of microorganisms (bacteria, fungi) resulting in hygiene and health risks. Thus, healthcare concerns have motivated the interest for the development of multifunctional antimicrobial cotton fabrics. Moreover, cotton textiles are also used in medical applications such as wound dressings. Their functionalization with anti-inflammatory agents is desirable in order to accelerate cicatrisation in the treatment of chronic wounds. This review summarizes recent advances (from January 2016 to January 2021) on the modification and coating of cotton fabrics with nanostructures (mainly metal and metal oxide nanoparticles, functionalized silica nanoparticles) to provide them antimicrobial (antibacterial and antifungal) and anti-inflammatory properties.     

Hyaluronic acid-methacrylic anhydride/polyhexamethylene biguanide hybrid hydrogel with antibacterial and proangiogenic functions for diabetic wound repair

Diabetic wounds lead to a decrease in quality of life and an increase in mortality. Current treatment strategies include preventing bacterial adhesion while improving microcirculation. As a new type of wound dressing that imitates natural skin, hydrogel has gradually emerged with its excellent properties. However, existing hydrogels rarely achieve satisfactory results in promoting wound repair and antibacterial simultaneously. In this case, we prepared methacrylic anhydride chemically modified hyaluronic acid as a hydrogel matrix, added polyhexamethylene biguanide as an antibacterial component, and loaded sodium alginate/salidroside composite microspheres which could sustainably release salidroside and thus promote angiogenesis. Hybrid hydrogel (HAMA/PHMB-Ms) was synthesized via photocrosslinking, and its chemical structure, particle size distribution and microstructure were characterized. The satisfactory antibacterial properties of the HAMA/PHMB(15%)-Ms hydrogel were studied in vitro, and its antibacterial rates against E. coli and S. aureus were 97.85% and 98.56%, respectively. In addition, after demonstrating its good biocompatibility, we verified that the HAMA/PHMB-Ms hydrogel has increased granulation tissue formation, more collagen deposition, more subcutaneous capillary formation, and better wound healing than blank control, HAMA and HAMA/PHMB hydrogel on the back wound model of diabetic mice. The results confirmed that HAMA/PHMB-Ms hydrogel was a promising material for the treatment of the diabetic wounds.     

Electrospun cellulose acetate wound dressings loaded with Pramipexole for diabetic wound healing: an in vitro and in vivo study

In the current study, a Pramipexole-loaded wound dressing was produced via electrospinning of cellulose acetate solution. Pramipexole was added to cellulose acetate solution at 3, 5, and 10% w/w concentrations and then electrospun. The produced wound dressings were studied regarding their physicochemical and biological properties. Results of cell viability assay and cytoprotection studies showed that cellulose acetate wound dressings containing 3% w/w Pramipexole had significantly higher cell viability compared with other concentrations. The wound healing potential of dressings incorporated with 3% drug was studied in a rat model of diabetic wound. Study showed that the cellulose acetate/3% Pramipexole scaffolds had significantly higher percentage of wound closure, epithelial thickness, and collagen deposition compared with drug-free dressings and control group. Gene expression study showed that the drug-loaded wound dressings could reduce oxidative stress and alleviate inflammation at significantly higher extent compared with other groups.

     

Engineering quaternized chitosan in the 3D bacterial cellulose structure for antibacterial wound dressings

Balancing antibacterial properties with biocompatibility is of paramount importance for wound dressings loaded with antibacterial agents. In this work, a water soluble antibacterial agent, quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) with an appropriate degree of substitution was introduced into the bacterial cellulose (BC) network by adding it into the BC culture medium. Results indicated that the addition of HACC could affect the yield of BC, porous structure, thermal stability, water absorption and antibacterial properties. HBC-1 with a low content of HACC (13.65 ± 0.30%) cannot inhibit the biofilm formation of bacteria, while HBC-3 with a high content of HACC (62.05 ± 0.90%) has a low yield of BC and confused structure. HBC-2 with an optimum concentration of HACC (37.33 ± 0.80%) possessed a typical porous structure, acceptable thermal stability, good water absorption and favorable antibacterial properties against Staphylococcus aureus (S. aureus, ATCC 25923) and methicillin-resistant S. aureus (ATCC 43300). Most importantly, none of the HACC/BC films exhibited cytotoxicity to NIH3T3 cells. We believe that obtained HACC/BC films with favorable bactericidal properties and biocompatibility could be potential candidates for wound dressings in clinical applications.     

Propolis-Based Nanofiber Patches to Repair Corneal Microbial Keratitis

In this research, polyvinyl-alcohol (PVA)/gelatin (GEL)/propolis (Ps) biocompatible nanofiber patches were fabricated via electrospinning technique. The controlled release of Propolis, surface wettability behaviors, antimicrobial activities against the S. aureus and P. aeruginosa, and biocompatibility properties with the mesenchymal stem cells (MSCs) were investigated in detail. By adding 0.5, 1, and 3 wt.% GEL into the 13 wt.% PVA, the morphological and mechanical results suggested that 13 wt.% PVA/0.5 wt.% GEL patch can be an ideal matrix for 3 and 5 wt.% propolis addition. Morphological results revealed that the diameters of the electrospun nanofiber patches were increased with GEL (from 290 nm to 400 nm) and Ps addition and crosslinking process cause the formation of thicker nanofibers. The tensile strength and elongation at break enhancement were also determined for 13 wt.% PVA/0.5 wt.% GEL/3 wt.% Ps patch. Propolis was released quickly in the first hour and arrived at a plateau. Cell culture and contact angle results confirmed that the 3 wt.% addition of propolis reinforced mesenchymal stem cell proliferation and wettability properties of the patches. The antimicrobial activity demonstrated that propolis loaded patches had antibacterial activity against the S. aureus, but for P. aeruginosa, more studies should be performed.     

Biodegradable Sodium Alginate/Carrageenan/Cellulose Composite Hydrogel Wound Dressings Containing Herbal Extracts for Promoting Blood Coagulation and Wound Healing

Accelerating the coagulation process and preventing wound infection are major challenges in the wound care process. Therefore, new multifunctional wound dressings with procoagulant, antibacterial, and antioxidant properties have enormous potential for clinical application. In this work, biodegradable hydrogels containing herbal extracts are prepared for wound dressings. First, the active ingredients are extracted from Amaranthus spinosus (A. spinosus) and Rubia cordifolia (R. cordifolia) and added to the hydrogels prepared from microcrystalline cellulose (MCC), carrageenan, and sodium alginate. Then the composite hydrogels are air-dried to obtain the wound dressings. The wound dressings prepared in this work have good biocompatibility and moisture retention. The mechanical properties of the wound dressings are further improved with the addition of MCC. Besides, the wound dressings have excellent procoagulant, antibacterial, and antioxidant properties due to the presence of R. cordifolia extract. Overall, the most effective group of wound dressings with different ingredient formulations reduces clotting time by 75% and largely inhibits bacterial growth. The wound dressings perform well in the animal wound models to promote wound healing. These results indicate that the hydrogel wound dressings prepared in this work have great potential for medical applications.     

One Step Fabrication and Application of Antibacterial Electrospun Zein/Cinnamon Oil Membrane Wound Dressing via In situ Electrospinning Process

Antibacterial wound dressing can benefit the wound healing by preventing bacterial infection, especially for the electrospun ones due to their porous structures and easily loading antibacterial drugs. However, it is challenging to apply the antibacterial electrospun wound dressing to covering the wound conveniently and safely. Here, we presented one step fabrication and application of antibacterial electrospun zein/cinnamon oil wound dressing via a handheld electrospinning setup. The prepared zein/cinnamon oil wound dressing showed gas permeability of (76.1±5.45) mm/s, hydrophilicity with zero body fluid contact angle, swelling stability after 24 h as well as antibacterial zones over 5 cm against both E. coli and S. aureus bacteria. Moreover, in situ electrospinning process can deposit the electrospun zein/cinnamon oil fibers directly onto the wound, meantime forming a wound dressing. The mice cut-wound model experiment demonstrated that the one step in situ fabrication and application of zein/cinnamon oil wound dressing could nearly heal the wound within 11 d.     

Antibacterial and wound healing properties of cellulose acetate electrospun nanofibers loaded with bioactive glass nanoparticles; in-vivo study

Bioactive glasses (BGs) have gained great attention owing to their versatile biological properties. Combining BG nanoparticles (BGNPs) with polymeric nanofibers produced nanocomposites of great performance in various biomedical applications especially in regenerative medicine. In this study, a novel nanocomposite nanofibrous system was developed and optimized from cellulose acetate (CA) electrospun nanofibers containing different concentrations of BGNPs. Morphology, IR and elemental analysis of the prepared electrospun nanofibers were determined using SEM, FT-IR and EDX respectively. Electrical conductivity and viscosity were also studied. Antibacterial properties were then investigated using agar well diffusion method. Moreover, biological wound healing capabilities for the prepared nanofiber dressing were assessed using in-vivo diabetic rat model with induced wounds. The fully characterized CA electrospun uniform nanofiber (100–200 nm) with incorporated BGNPs exhibited broad range of antimicrobial activity against gram negative and positive bacteria. The BGNP loaded CA nanofiber accelerated wound closure efficiently by the 10th day. The remaining wound areas for treated rats were 95.7?±?1.8, 36.4?±?3.2, 6.3?±?1.5 and 0.8?±?0.9 on 1st, 5th, 10th and 15th days respectively. Therefore, the newly prepared BGNP CA nanocomposite nanofiber could be used as a promising antibacterial and wound healing dressing for rapid and efficient recovery.

     

Construction of Antibacterial N‐Halamine Polymer Nanomaterials Capable of Bacterial Membrane Disruption for Efficient Anti‐Infective Wound Therapy

The increasing occurrence of bacterial infection at the wound sites is a serious global problem, demanding the rapid development of new antibacterial materials for wound dressing to avoid the abuse of antibiotics and thereby antibiotic resistance. In this work, the authors first report on antibacterial N‐halamine polymer nanomaterials based on a strategic copolymerization of 3‐allyl‐5,5‐dimethylhydantoin (ADMH) and methyl methacrylate (MMA), which exhibits in vitro and in vivo antimicrobial efficacy against pathogenic bacteria including Staphylococcus aureus and Escherichia coli. Particularly, when a biological evaluation is run for wound therapy, the N‐halamine polymer nanomaterials exhibit a powerful antibacterial efficiency and wound healing ability after a series of histological examination of mouse wound. After the evaluation of biological and chemical surroundings, the proposed four‐stage mechanism suggests that, with unique antibacterial N? Cl bonds, the N‐halamine polymer nanomaterials can disrupt the bacterial membrane, as a result causing intracellular content leaked out and thereby cell death. Based on the synergistic action of antibacterial and wound therapy, the N‐halamine polymer nanomaterials are expected to be promising as wound dressing materials in medical healing and biomaterials.     

Synthesis and characterization of zinc chloride containing poly(acrylic acid) hydrogel by gamma irradiation

In this study, the characterization of zinc chloride incorporated into a poly(acrylic acid) (PAAc) hydrogel prepared by gamma-ray irradiation was investigated. Zinc chloride powder with different concentrations was dissolved in the PAAc solution, and it was crosslinked with gamma-ray irradiation. The effects of various parameters such as zinc ion concentration and irradiation doses on characteristics of the hydrogel formed were investigated in detail for obtaining an antibacterial wound dressing.In addition, the gel content, pH-sensitive (pH 4 or 7) swelling ratio, and UV–vis absorption spectra of the zinc particles in the hydrogels were characterized. Moreover, antibacterial properties of these new materials against Staphylococcus aureus and Escherichia coli strains were observed on solid growth media. The antibacterial tests indicated that the zinc chloride containing PAAc hydrogels have good antibacterial activity.     

Active antibacterial coating of cotton fabrics with antimicrobial proteins

The prevention of bacteria colonization by immobilizing proteins with antimicrobial activity onto cotton fabrics was investigated. Such coatings have potential applications in medical dressing materials used in wound care and healing. Two antimicrobial proteins lysozyme and hydramacin-1 (HM-1) were surface immobilized through two linkers (3-aminopropyl) triethoxysilane (APTES) and citric acid in the presence of the water soluble carbodiimide coupling reagent 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate. Surface composition analysis by attenuated total reflection-Fourier transform infrared and X-ray photoelectron spectroscopies confirmed formation of the protein-cellulose conjugates. Antimicrobial activities of the different functionalized surfaces were found to vary between APTES and citric acid directed coatings. Citric acid immobilized lysozyme treated samples demonstrated superior activity against Gram-positive Bacillus subtilis, whereas APTES immobilized HM-1 treated samples demonstrated an advantage in inhibiting the growth of Gram-negative Escherichia coli. The antibacterial activity and stability of citric acid immobilized protein fabrics following sonication, boiling and chemical treatment were noticeably higher than that of the corresponding APTES immobilized protein fabrics. The dual coating of fibers with both antimicrobial proteins afforded efficient antimicrobial activities against both bacterial species. The results suggest that coating cotton fibers with antimicrobial proteins and peptides represents a feasible approach for developing active surfaces that prohibit growth and colonization of bacterial strains and can be potentially used in medical cotton-based fabrics.