The Influence of Novel,Biocompatible, and Bioresorbable Poly(3-hydroxyoctanoate) Dressings on Wound Healing in Mice

The human body’s natural protective barrier, the skin, is exposed daily to minor or major mechanical trauma, which can compromise its integrity. Therefore, the search for new dressing materials that can offer new functionalisation is fully justified. In this work, the development of two new types of dressings based on poly(3-hydroxyoctanoate) (P(3HO)) is presented. One of the groups was supplemented with conjugates of an anti-inflammatory substance (diclofenac) that was covalently linked to oligomers of hydroxycarboxylic acids (Oli-dicP(3HO)). The novel dressings were prepared using the solvent casting/particulate leaching technique. To our knowledge, this is the first paper in which P(3HO)-based dressings were used in mice wound treatment. The results of our research confirm that dressings based on P(3HO) are safe, do not induce an inflammatory response, reduce the expression of pro-inflammatory cytokines, provide adequate wound moisture, support angiogenesis, and, thanks to their hydrophobic characteristics, provide an ideal protective barrier. Newly designed dressings containing Oli-dicP(3HO) can promote tissue regeneration by partially reducing the inflammation at the injury site. To conclude, the presented materials might be potential candidates as excellent dressings for wound treatment.     

The Antimicrobial Effects of Bacterial Cellulose Produced by Komagataeibacter intermedius in Promoting Wound Healing in Diabetic Mice

As a conventional medical dressing, medical gauze does not adequately protect complex and hard-to-heal diabetic wounds and is likely to permit bacterial entry and infections. Therefore, it is necessary to develop novel dressings to promote wound healing in diabetic patients. Komagataeibacter intermedius was used to produce unmodified bacterial cellulose, which is rarely applied directly to diabetic wounds. The produced cellulose was evaluated for wound recovery rate, level of inflammation, epidermal histopathology, and antimicrobial activities in treated wounds. Diabetic mices’ wounds treated with bacterial cellulose healed 1.63 times faster than those treated with gauze; the values for the skin indicators in bacterial cellulose treated wounds were more significant than those treated with gauze. Bacterial cellulose was more effective than gauze in promoting tissue proliferation with more complete epidermal layers and the formation of compact collagen in the histological examination. Moreover, wounds treated with bacterial cellulose alone had less water and glucose content than those treated with gauze; this led to an increase of 6.82 times in antimicrobial protection, lower levels of TNF-α and IL-6 (39.6% and 83.2%), and higher levels of IL-10 (2.07 times) than in mice wounds treated with gauze. The results show that bacterial cellulose produced using K. intermedius beneficially affects diabetic wound healing and creates a hygienic microenvironment by preventing inflammation. We suggest that bacterial cellulose can replace medical gauze as a wound dressing for diabetic patients.     

Molecular design,synthesis strategies and recent advances of hydrogels for wound dressing applications

With the changes in the modern disease spectrum, pressure ulcers, diabetic feet, and vascular-derived diseases caused refractory wounds is increasing rapidly. The development of wound dressings has partly improved the effect of wound management. However, traditional wound dressings can only cover the wound and block bacteria, but are generally powerless to recurrent wound infection and tissue healing. There is an urgent need to develop a new type of wound dressing with comprehensive performance to achieve multiple effects such as protecting the wound site from the external environment, absorbing wound exudate, anti-inflammatory, antibacterial, and accelerating wound healing process. Hydrogel wound dressings have the aforementioned characteristics, and can keep the wound in a moist environment because of the high water content, which is an ideal choice for wound treatment. This review introduces the wound healing process and the development and performance advantages of hydrogel wound dressings. The choice of different preparation materials gives the particularities of different hydrogel wound dressings. It also systematically explains the main physical and chemical crosslinking methods for hydrogel synthesis. Besides, in-depth discussion of four typical hydrogel wound dressings including double network hydrogels, nanocomposite hydrogels, drug-loaded hydrogels and smart hydrogels fully demonstrates the feasibility of developing hydrogels as wound dressing products and their future development trends.     

PVA/PAA-Based Antibacterial Wound Dressing Material with Aloe Vera

The incorporation of drugs into the dressings make these dressings antimicrobial and help in control of infection around the wound. The wound dressing materials based on PVA/PAA, ciprofloxacin HCl, and aloe vera have been designed and developed so that the wound undergoes proper healing and scar formation is minimal. These wound dressing materials are produced using the electrospinning method. The wound dressing materials are characterized using the FT-IR, DSC, DTA, TGA, and SEM techniques. The wound dressing materials are tested for microbial activity tests and drug release experiments. Controlled ciprofloxacin HCl release is observed.     

Plasma-Functionalised Dressings for Enhanced Wound Healing

Fundamental knowledge about cell–surface interactions can be applied in the development of wound dressings and scaffolds to encourage wounds to heal. As surfaces produced with acid-functionalised monomers encourage keratinocyte adhesion, proliferation and migration, whilst amine functionalisation enhances fibroblast proliferation and migration in vitro, standard care wound dressings were plasma-coated with either acrylic acid or allylamine and applied to 6 mm excisional wounds on the backs of mice to test their effectiveness in vivo. At day 3, the rate of wound healing was increased in mice treated with dressings that were plasma-coated with allylamine compared to uncoated dressings, with a significantly reduced wound area. However, healing may be impaired following prolonged treatment with allylamine-functionalised dressings, with delayed re-epithelialisation and increased cellularisation of the wound site at later timepoints. Acrylic acid functionalisation, however, offered no early improvement in wound healing, but wounds treated with these dressings displayed increased collagen deposition at day 7 post wounding. These results suggest that plasma polymerisation may allow for the development of new dressings which can enhance wound closure by directing cell behaviour, but that the application of these dressings may require a timed approach to enhance specific phases of the wound healing response.     

Biohybrid Nanostructured Iron Oxide Nanoparticles and Satureja hortensis to Prevent Fungal Biofilm Development

Cutaneous wounds are often superinfected during the healing process and this leads to prolonged convalescence and discomfort. Usage of suitable wound dressings is very important for an appropriate wound care leading to a correct healing. The aim of this study was to demonstrate the influence of a nano-coated wound dressing (WD) on Candida albicans colonization rate and biofilm formation. The modified WD was achieved by submerging the dressing pieces into a nanofluid composed of functionalized magnetite nanoparticles and Satureja hortensis (SO) essential oil (EO). Chemical composition of the EO was established by GC-MS. The fabricated nanostructure was characterized by X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Differential Thermal Analysis (DTA) and Fourier Transform-Infrared Spectroscopy (FT-IR). The analysis of the colonized surfaces using (Scanning Electron Microscopy) SEM revealed that C. albicans adherence and subsequent biofilm development are strongly inhibited on the surface of wound dressing fibers coated with the obtained nanofluid, comparing with regular uncoated materials. The results were also confirmed by the assay of the viable fungal cells embedded in the biofilm. Our data demonstrate that the obtained phytonanocoating improve the resistance of wound dressing surface to C. albicans colonization, which is often an etiological cause of local infections, impairing the appropriate wound healing.     

Preparation of physically crosslinked PVA/HLC/SA hydrogel and exploration of its effects on full-thickness skin defects

Abstract

In this study, single factor experiments and orthogonal test were designed to fabricate a novel poly(vinyl alcohol) (PVA), human-like collagen (HLC) and sodium alginate (SA) composite hydrogel as wound dressings. The obtained hydrogel dressing was soft, elastic and breathable with uniform macro pores, and it remains soft after lyophilization which restore to the original appearance after absorbing a large amount of water. In vivo full-thickness skin defects treated with the hydrogel dressings in rabbit revealed that the hydrogel promoted wound healing through accelerating reepithelization and the growth of collagen fibers. All the results demonstrated the great potential of the hydrogel as wound dressing.     

Nanofibrous wound dressing material by electrospinning method

Abstract

Wound dressings are very useful materials for accelerating the wound healing process. In this study, nanofibrous wound dressings were produced from blending solution of Poly-lactic acid(PLA)/Chitosan(C)/Starch(S)/Zinc oxide(Z) by electrospinning method. Morphology, chemical interaction, mechanical, water uptake and weight loss tests were performed on each samples. Moreover, the biocompatibility of primary dermal fibroblast (ATCC, PCS-201-012) on prepared wound dressings was investigated with MTT assays in vitro, and the samples were found suitable for cell viability and proliferation. These results suggest that produced nanofibrous wound dressings can be promising candidate for wound dressing applications.     

Chitosan/Alginate Hydrogel Dressing Loaded FGF/VE-Cadherin to Accelerate Full-Thickness Skin Regeneration and More Normal Skin Repairs

The process of full-thickness skin regeneration is complex and has many parameters involved, which makes it difficult to use a single dressing to meet the various requirements of the complete regeneration at the same time. Therefore, developing hydrogel dressings with multifunction, including tunable rheological properties and aperture, hemostatic, antibacterial and super cytocompatibility, is a desirable candidate in wound healing. In this study, a series of complex hydrogels were developed via the hydrogen bond and covalent bond between chitosan (CS) and alginate (SA). These hydrogels exhibited suitable pore size and tunable rheological properties for cell adhesion. Chitosan endowed hemostatic, antibacterial properties and great cytocompatibility and thus solved two primary problems in the early stage of the wound healing process. Moreover, the sustained cytocompatibility of the hydrogels was further investigated after adding FGF and VE-cadherin via the co-culture of L929 and EC for 12 days. The confocal 3D fluorescent images showed that the cells were spherical and tended to form multicellular spheroids, which distributed in about 40–60 μm thick hydrogels. Furthermore, the hydrogel dressings significantly accelerate defected skin turn to normal skin with proper epithelial thickness and new blood vessels and hair follicles through the histological analysis of in vivo wound healing. The findings mentioned above demonstrated that the CS/SA hydrogels with growth factors have great potential as multifunctional hydrogel dressings for full-thickness skin regeneration incorporated with hemostatic, antibacterial, sustained cytocompatibility for 3D cell culture and normal skin repairing.     

Developing Wound Dressings Using 2-deoxy-D-Ribose to Induce Angiogenesis as a Backdoor Route for Stimulating the Production of Vascular Endothelial Growth Factor

2-deoxy-D-Ribose (2dDR) was first identified in 1930 in the structure of DNA and discovered as a degradation product of it later when the enzyme thymidine phosphorylase breaks down thymidine into thymine. In 2017, our research group explored the development of wound dressings based on the delivery of this sugar to induce angiogenesis in chronic wounds. In this review, we will survey the small volume of conflicting literature on this and related sugars, some of which are reported to be anti-angiogenic. We review the evidence of 2dDR having the ability to stimulate a range of pro-angiogenic activities in vitro and in a chick pro-angiogenic bioassay and to stimulate new blood vessel formation and wound healing in normal and diabetic rat models. The biological actions of 2dDR were found to be 80 to 100% as effective as VEGF in addition to upregulating the production of VEGF. We then demonstrated the uptake and delivery of the sugar from a range of experimental and commercial dressings. In conclusion, its pro-angiogenic properties combined with its improved stability on storage compared to VEGF, its low cost, and ease of incorporation into a range of established wound dressings make 2dDR an attractive alternative to VEGF for wound dressing development.     

Advances in wound dressing based on electrospinning nanofibers

In recent years, there has been a significant focus on bioactive dressings suitable for treating chronic and acute wounds. Electrospinning nanofibers are considered advanced dressing options due to their high porosity and permeability to air and water, effective barrier properties against external pathogens, and excellent resemblance to the extracellular matrix for wound healing and skin regeneration. This article reviews the recent advancements in the application of electrospinning nanofibers for bioactive wound healing. The review begins with an overview of the wound healing process and electrospinning methods. It then explores the advantages and disadvantages of different synthetic and natural polymers used in the preparation of electrospinning wound dressings. The natural polymers discussed in this review include collagen, gelatin, silk fibroin, chitosan, hyaluronic acid, and sodium alginate. Additionally, the review delves into commonly used synthetic polymers like polyvinyl alcohol, polyvinyl chloride, polyethylene lactone, polylactide, and polyurethane for wound dressing applications. Furthermore, the review examines the blending of natural and synthetic polymers to create high-performance wound dressings. It also explores the incorporation of functional additives, such as antimicrobial agents, growth factors, and natural extracts, into electrospinning nanofibers to expedite wound healing and tissue repair. In conclusion, electrospinning is an emerging technology that provides unique opportunities for designing more effective wound dressings and care products.     

Design of moxifloxacin encapsulated network hydrogel wound dressings: Evaluation of polymer-drug,polymer-blood,and polymer-bio membrane interactions

It is an exploration of the inherent wound-healing tendency of Azadirachta indica gum (AIG) or neem gum polysaccharides to develop the hydrogel wound dressings with enhanced potential during wound management. Herein this research work, antibiotic moxifloxacin encapsulated AIG network copolymeric hydrogels were developed by functionalizing with carbapol and poly(acrylamide) [poly(AAm)] for better wound healing. The polymer-drug, polymer-blood, and polymer-bio membrane interactions were evaluated in biomedical properties. The copolymeric network structure was confirmed by scanning electron micrographs (SEMs), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and ¹³C solid-state nuclear magnetic resonance (NMR) spectroscopy. The results confirmed sustained release of the moxifloxacin with diffusion by non-Fickian process and Korsmeyer–Peppas kinetic model in the phosphate buffer saline (PBS). These interactions inferred the blood-compatible (hemolytic index 3.41 ± 0.70%) and mucoadhesive nature (polymer-biomembrane detachment force 0.09 ± 0.01 mN) of hydrogel dressing. The per gram of hydrogel dressings absorbed 10.22 ± 0.23 g of simulated wound fluid which is very useful to maintain moist wound environment for better wound healing. All these interactions and properties indicated the suitability of the hydrogel material for wound dressing applications for better wound care.     

Resveratrol-Induced Signal Transduction in Wound Healing

Resveratrol is a well-known polyphenol that harbors various health benefits. Besides its well-known anti-oxidative potential, resveratrol exerts anti-inflammatory, pro-angiogenic, and cell-protective effects. It seems to be a promising adjuvant for various medical indications, such as cancer, vascular, and neurodegenerative diseases. Additionally, resveratrol was shown to display beneficial effects on the human skin. The polyphenol is discussed to be a feasible treatment approach to accelerate wound healing and prevent the development of chronic wounds without the drawback of systemic side effects. Despite resveratrol’s increasing popularity, its molecular mechanisms of action are still poorly understood. To take full advantage of resveratrol’s therapeutic potential, a profound knowledge of its interactions with its targets is needed. Therefore, this review highlights the resveratrol-induced molecular pathways with particular focus on the most relevant variables in wound healing, namely inflammation, oxidative stress, autophagy, collagen proliferation and angiogenesis.     

In Situ Electrospinning Wound Healing Films Composed of Zein and Clove Essential Oil

Electrospun fibrous membranes have the potential to be effective wound dressings for promoting wound healing. However, the fabrication and application of the common electrospun fibrous wound dressings are usually complicated and separated. Here, electrospun zein/clove essential oil (CEO) fibrous membranes are fabricated and applied as a potential wound dressing through in situ electrospinning process by a portable electrospinning device. The in situ electrospinning process can directly electrospin zein/CEO membranes onto a wound site to cover the wound well and improve the convenience and comfort in use. The as‐spun zein/CEO membranes show a porous structure and exhibit higher gas permeability at 168.2 ± 43.3 mm s^?1, with superhydrophilicity to absorb the wound exudate and good biocompatibility as well as antibacterial effects to protect from infection. Moreover, the mice wound model study suggests that in situ electrospun zein/CEO promotes the wound healing process.     

Wound dressings: Current advances and future directions

Wound healing is a complicated and continuous process affected by several factors, which needs an appropriate surrounding to achieve accelerated healing. Wound healing process recruits three different phases: inflammation, proliferation, and maturation. Due to the different types of wounds, as well as the advancement in medical technology, various products have been developed to repair different skin lesions. Our objective is to investigate the advancement in wound dressings from traditional to the current methods of treatment. The article presents the characteristics of an ideal wound dressing, the requirements for the appropriate selection of different types of wounds, and a detailed classification of wound dressings. Animal origin, herbal origin, and synthetic dressings are firstly introduced and reviewed. Then, nonmedicated dressings including alginate, hydrogel, and hydrocolloid dressings, as well as medicated dressings are discussed. Finally, the developmental prospectives of the new generations of wound dressings for future researches are presented. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47738.     

Development and characterization of a poly (vinyl alcohol) and sodium alginate blend foam for wound dressing loaded with propolis and all-trans retinoic acid

Propolis is a complex mixture of phytochemicals, with antibacterial, anti-inflammatory, and healing properties. All-trans retinoic acid is implicated in wound healing by stimulating angiogenesis, cell recruitment, extracellular matrix deposition, and reepithelization. The incorporation of both agents to a polymeric wound dressing composed of poly (vinyl alcohol) and sodium alginate may result in improved healing allied to controlled release, fluid uptake, and wound protection. In the present work, we have physically characterized this wound dressing and analyzed its release kinetics. The anti-inflammatory capacity was assayed. SEM images showed a highly porous structure with a diverse morphology. FTIR spectra displayed a highly cross-linked structure with both polymers connected by hydrogen bonds and acetal bridges. The wound dressings were able to retain great volumes of PBS. Propolis and vitamin A releasing behavior were maintained for 6 h. The concentrations of the biologically active substances were capable of promoting anti-inflammatory action in an erythrocyte membrane stabilization model. The wound dressings obtained here showed adequate physical properties. The fabrication process did not affect the anti-inflammatory capacity. Further tests are needed to ensure the biocompatibility and to assess other biological activities of the therapeutic agents.     

In Vitro Models in Biocompatibility Assessment for Biomedical-Grade Chitosan Derivatives in Wound Management

One of the ultimate goals of wound healing research is to find effective healing techniques that utilize the regeneration of similar tissues. This involves the modification of various wound dressing biomaterials for proper wound management. The biopolymer chitosan (β-1,4-D-glucosamine) has natural biocompatibility and biodegradability that render it suitable for wound management. By definition, a biocompatible biomaterial does not have toxic or injurious effects on biological systems. Chemical and physical modifications of chitosan influence its biocompatibility and biodegradability to an uncertain degree. Hence, the modified biomedical-grade of chitosan derivatives should be pre-examined in vitro in order to produce high-quality, biocompatible dressings. In vitro toxicity examinations are more favorable than those performed in vivo, as the results are more reproducible and predictive. In this paper, basic in vitro tools were used to evaluate cellular and molecular responses with regard to the biocompatibility of biomedical-grade chitosan. Three paramount experimental parameters of biocompatibility in vitro namely cytocompatibility, genotoxicity and skin pro-inflammatory cytokine expression, were generally reviewed for biomedical-grade chitosan as wound dressing.     

Procoagulant and Antimicrobial Effects of Chitosan in Wound Healing

Chitosan, a polysaccharide derived from chitin, has excellent wound healing properties, including intrinsic antimicrobial and hemostatic activities. This study investigated the effectiveness of chitosan dressing and compared it with that of regular gauze dressing in controlling clinically surgical bleeding wounds and profiled the community structure of the microbiota affected by these treatments. The dressings were evaluated based on biocompatibility, blood coagulation factors in rat, as well as antimicrobial and procoagulant activities, and the microbial phylogenetic profile in patients with abdominal surgical wounds. The chitosan dressing exhibited a uniformly fibrous morphology with a large surface area and good biocompatibility. Compared to regular gauze dressing, the chitosan dressing accelerated platelet aggregation, indicated by the lower ratio of prothrombin time and activated partial thromboplastin time, and had outstanding blood absorption ability. Adenosine triphosphate assay results revealed that the chitosan dressing inhibited bacterial growth up to 8 d post-surgery. Moreover, 16S rRNA-based sequencing revealed that the chitosan dressing effectively protected the wound from microbial infection and promoted the growth of probiotic microbes, thereby improving skin immunity and promoting wound healing. Our findings suggest that chitosan dressing is an effective antimicrobial and procoagulant and promotes wound repair by providing a suitable environment for beneficial microbiota.     

Manipulating drug release from tridimensional porous substrates coated by initiated chemical vapor deposition

In the recent years, modern wound dressings have attracted much interest to accelerate wound healing processes with the topical delivery of drugs directly on wounds having a significant effect on wound rehabilitation. The objective of this study was to develop a model dressing that would not only provide wound protection from the environment but might also provide the possibility to keep it moist and deliver a drug for potential speeding the healing process. Poly(ethylene terephthalate), cotton fabrics, and polycaprolactone (PCL) nanofibers were used as different tridimensional porous substrates, loaded with a model drug, clotrimazole. The results show that the chemical structure and surface area to volume ratio of the pristine substrates affect the drug release profile. Coating of such substrates by hydrogels poly(2-hydroxyethyl methacrylate) (p-HEMA) and poly(methacrylic acid) (p-MAA) was successfully achieved by initiated chemical vapor deposition. This method was chosen because it is gentle and solventless and most important it can coat free areas within the three-dimensional structures. Scanning electron microscopy results revealed that p-HEMA and p-MAA conformally coated the fibers of the substrates. Moreover, drug release experiments showed that p-HEMA and p-MAA coatings provide barriers preventing sudden drug release. In conclusion, our results indicated the possibility of fabricating dressings containing a drug with tunable drug release profile depending on several parameters even though a strong porous structure exists. © 2019 The Authors. Journal of Applied Polymer Science published by Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47858.     

Poly(L-lactide-co-caprolactone)/collagen electrospun mat: Potential for wound dressing and controlled drug delivery

Here we report a novel bioactive electrospun mat based on poly(L-lactide-co-caprolactone) (PLLC) and collagen for wound dressing and sustained drug delivery of gentamicin. PLLC/collagen electrospun mat loaded with 10% gentamicin showed bioactivity for 15 days against Gram-positive and Gram-negative bacteria. The in vitro cell culture of 3T3 fibroblasts confirmed that these electrospun mat provide an increased specific interface area and hydrophilicity to enhance cell attachment, proliferation, and migration. The modified PLLC/collagen mat provided an excellent enhancement in properties of antibacterial wound dressings with a minimum in vitro toxicity and high potency for promoting wound healing stages.