Injectable and self-healing hydrogels with tissue adhesiveness and antibacterial activity as wound dressings for infected wound healing

The design of wound dressings with excellent self-healing ability, adequate adhesion, good biocompatibility, and potential antibacterial ability is of great significance for the healing of infected wounds arising from human activities. Herein, a series of multi-functional hydrogel dressings, poly(ionized isocyanoethyl methacrylate-glutamine)/poly(hexamethylene guanidine) (iG_x/PHMG_y) hydrogels, were obtained through homopolymerization of fully ionized isocyanoethyl methacrylate-glutamine (iIEM-Gln) in the presence of poly(hexamethylene guanidine) (PHMG), in which strong hydrogen bonds were formed among urea groups in the P (iIEM-Gln) chain to form a stable hydrogel network. The prepared iG_x/PHMG_y hydrogels exhibited adequate self-healing ability and tissue adhesion, which could be firmly adhered to the wound surface and remained intact during application. In addition, the presence of PHMG imparted good antibacterial activity to the hydrogels for the effective promotion of the wound healing in S. aureus infected skin wound on mice. Overall, this multi-functional hydrogel provides a facile and effective strategy for the design of infected wound dressings, and may show great potential in clinical applications.     

Fabrication and characterization of electrospun silk fibroin/TiO2 nanofibrous mats for wound dressings

Silk fibroin (SF) nanofibrous mats were fabricated via electrospinning process. These fibers were blended with TiO₂ nanoparticles (TiO₂ NPs). The influence of TiO₂ NPs on the nanofibrous matrices was investigated by scanning electron microscopy (SEM), transmission electron microscopy, energy‐dispersive X‐ray, and thermogravimetric analysis. The SEM images revealed that the average diameter of the SF/TiO₂ fibers was 385 ± 63 nm when the concentration of SF was up to 10% (w/v). Infrared spectra showed that the β‐sheet structure of the silk fibroin increased after acetone treatment. These SF/TiO₂ nanofibrous mats exhibited higher equilibrium water content and water vapor transmission rate than hydrocolloid dressing. The hemocompatibility and cytocompatibility of SF/TiO₂ nanofibrous mats were evaluated by complete blood count, cell attachment, and the spreading of L929 fibroblasts. These SF/TiO₂ nanofibrous mats exhibited antibacterial activity against Escherichia coli under UV irradiation. Thus, these novel nanocomposite mats may be used for biomedical applications such as wound dressing. Copyright © 2011 John Wiley & Sons, Ltd.     

Dehydration kinetics of polyvinyl alcohol hydrogel wound dressings during wound healing process

<正>The hydrogel wound dressing based on polyvinyl alcohol(PVA) was prepared by the freezing-thawing cyclic method.The dehydration kinetics of prepared hydrogels was determined using the experimental method and mathematical modeling based on diffusion mechanism.The results show that the dehydration rate of PVA hydrogel wound dressing inversely depends on the hydrogel thickness as well as water content of the wound.On the other hand,the initial water content of hydrogel and the atmospheric humidity have little direct effect on the dehydration rate.The good agreement between experimental and mathematical modeling results in early stages of dehydration process shows that the predominate factor determining the dehydration of these wound dressings is diffusion.     

Preparation of chitosan–polyethylene glycol coated cotton membranes for wound dressings: preparation and characterization

Cotton fabric was coated with chitosan (CS) and polyethylene glycol (PEG) followed by freeze‐drying. The influence of PEG on the physical characteristics and the surface morphology was investigated. The scanning electron microscopy of the coated fabric revealed a porous structure. The porosity of the material was 54–70% and the pore size was in the range of 75–120µm. The increase in the PEG content in the blend composition led to an enhanced destabilization of pores, leading to an increase in the pore size with elongated morphology. There seems to be phase separation between the two components which is an important factor for the observed behavior of the porous structure. The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) showed that the CS and PEG have limited interaction. DSC suggested that addition of PEG to CS does not interfere with the crystallization behavior due to limited interaction with CS. The thermogravimetric analysis (TGA) showed that the membranes are thermally stable and PEG enhances the thermal stability of the CS coated membranes. The air and water permeability of the membranes tended to decrease with the increase in the PEG content. Copyright © 2008 John Wiley & Sons, Ltd.     

Slow release of wound healing drug from hydrogel wound dressing prepared by radiation crosslinking method

The hydrogel wound dressing was prepared by radiation crosslinking. It was used of on patients in the Navy 411 Hospital and some other hospitals. From sixty case studies of the clinical effects, the results showed that: 1. drug releasing slowly releives the pain effectively for prolonged period of application; 2. The dressing can reduce the oozing liquid from the wound and make the wound heal faster; 3. The number of the dressing change is greatly reduced. All the data indicates that the dressing is superior to the conventional kinds.     

Cotton‐hydrogel composite for improved wound healing: Antimicrobial activity and anti‐inflammatory evaluation—Part 2

Infection is one of the major risk factors for the development of chronic wounds. Antimicrobial wound dressing has been pointed out as a viable option for the prevention and treatment of wound infections. Thus, we developed a composite material based on cotton textile substrates functionalized with cyclodextrin‐hydroxypropyl methyl cellulose‐based hydrogel. The composites' ability to encapsulate and release gallic acid (antimicrobial phenolic acid) was evaluated, as well as their mechanical properties and antimicrobial and anti‐inflammatory capacity. All composites were able to retain gallic acid in their structure, with similar loading profile. The presence of gallic acid on composites was confirmed by FTIR and TGA. Composites storage moduli was reduced by the presence of gallic acid. The results suggest a straight relation between the swelling ability and gallic acid drug delivery profile. The drug delivery mechanism, of the developed composites, was mainly controlled by Fickian diffusion, based on the experimental data fitting to the Peppas‐Sahlin model. Gallic acid antimicrobial and anti‐inflammatory properties were transferred to the composite materials. According to the results, the developed composites can be applied on the prevention or treatment of chronic wounds.     

Chitosan-Based Hydrogels for Infected Wound Treatment

Wound infections slow down the healing process and lead to complications such as septicemia, osteomyelitis, and even death. Although traditional methods relying on antibiotics are effective in controlling infection, they have led to the emergence of antibiotic-resistant bacteria. Hydrogels with antimicrobial function become a viable option for reducing bacterial colonization and infection while also accelerating healing processes. Chitosan is extensively developed as antibacterial wound dressings due to its unique biochemical properties and inherent antibacterial activity. In this review, the recent research progress of chitosan-based hydrogels for infected wound treatment, including the fabrication methods, antibacterial mechanisms, antibacterial performance, wound healing efficacy, etc., is summarized. A concise assessment of current limitations and future trends is presented.     

Adapting resistive sensors for monitoring moisture in smart wound dressings

Moisture plays a critical role in the wound healing process and, given the multitude of electrochemical sensors aimed at measuring humidity, it is somewhat surprising that there are few systems dedicated to this particular application. The issues relating to wound moisture and the practical challenges facing the adaptation of generic resistive moisture sensors to this area are considered along with the potential impact such systems could have on nursing practice.     

Development of sterculia gum based wound dressings for use in drug delivery

The present study deals with the modification of sterculia gum to develop the novel wounds dressing for the delivery of antimicrobial agent (tetracycline hydrochloride). The sterculia crosslinked PVA (sterculia-cl-PVA) hydrogels were characterized by FTIR and swelling studies. For the evaluation of swelling and drug release mechanism, the swelling kinetics and in vitro release dynamics of model drug from this matrix were studied in solution of different pH and simulated wounds fluid. Per gram of polymer has taken (8.3 ± 0.1) g of simulated wounds fluid and has released (0.820 ± 0.6) mg of drug in the simulated fluid. The value of the ‘n’ (0.84) indicates the non-Fickian diffusion mechanism for the release of drug in simulated fluids.     

Bioactive polymeric formulations for wound healing

Ricinoleic acid (RA) has potential to promote wound healing because of its analgesic and anti‐inflammatory properties. This study investigates the synthesis and characterization of RA liposomes infused in a hydrogel for topical application. Lecithin liposomes containing RA were prepared and incorporated into a chitosan solution and were subsequently cross‐linked with di‐aldehyde β‐cyclodextrin (Di‐β‐CD). Chitosan/Di‐β‐CD concentrations and reaction temperatures were varied to alter gelation time, water content, and mechanical properties of the hydrogel in an effort to obtain a wide range of RA release profiles. Hydrogel cross‐linking was confirmed by spectroscopy, and liposome and carrier hydrogel morphology via microscopy. Chitosan, Di‐β‐CD, and liposome concentrations within the formulation affected the extent of matrix swelling, mechanical strength, and pore and overall morphology. Higher cross‐linking density of the hydrogel led to lower water uptake and slower release rate of RA. Optimized formulations resulted in a burst release of RA followed by a steady release pattern accounting for 80% of the encapsulated RA over a period of 48 hours. However, RA concentrations above 0.1 mg/mL were found to be cytotoxic to fibroblast cultures in vitro because of the oily nature of RA. These formulations promoted wound healing when used to treat full thickness skin wounds (2 cm²) in Wister male rats. The wound contraction rates were significantly higher compared to a commercially available topical cream after a time period of 21 days. Histopathological analysis of the RA‐liposomal chitosan hydrogel group showed that the epidermis, dermis, and subcutaneous skin layers displayed an accelerated yet normal healing compared to control group.     

Microfluidic fabrication of calcium alginate helical microfibers for highly stretchable wound dressing

Due to suitable biocompatibility and biodegradability, natural polymers have a wide range of applications in the biomedical field, but the defects of mechanical properties limit their performance in some practical scenarios. Here, the microfluidic method was used to spin alginate into helical fibers, and then the gaps of packed microfibers were filled with polyacrylamide (PAM) to obtain a calcium alginate/PAM composite polymer membrane. Compared with pure calcium alginate, this composite film greatly improved the flexibility and stretchability, and could be stretched up to 14 times of its original length, and not deform significantly under 300% strain for 8 cycles. It also had good transparency and skin adhesion, further guaranteeing the application potential in the field of wound dressings. The loading and release experiments showed that the calcium alginate fibers maintained a dense morphology, and could achieve higher loading efficiency and more controllable release than pure PAM. Above all, this film has great application potential in joint wound dressings, especially when loading with antibacterial substances or healing-promoting drugs is needed. In addition, our research of achieving substantial optimization of elasticity and stretchability through the introduction of helical shape also has certain reference significance for other natural polymers limited by mechanical properties.     

Emerging Effects of Resveratrol on Wound Healing: A Comprehensive Review

Resveratrol (RSV) is a natural extract that has been extensively studied for its significant anti-inflammatory and antioxidant effects, which are closely associated with a variety of injurious diseases and even cosmetic medicine. In this review, we have researched and summarized the role of resveratrol and its different forms of action in wound healing, exploring its role and mechanisms in promoting wound healing through different modes of action such as hydrogels, fibrous scaffolds and parallel ratio medical devices with their anti-inflammatory, antioxidant, antibacterial and anti-ageing properties and functions in various cells that may play a role in wound healing. This will provide a direction for further understanding of the mechanism of action of resveratrol in wound healing for future research.     

A review on wound dressings with an emphasis on electrospun nanofibrous polymeric bandages

Wound dressings have experienced continuous and significant changes since the ancient times. The development starts with the use of natural materials to simply cover the wounds to the materials of the present time that could be specially made to exhibit various extraordinary functions. The modern bandage materials made of electrospun biopolymers contain various active compounds that are beneficial to the healing of wounds. These materials are fibrous in nature, with the size of fibers segments ranging from tens of nanometers to micrometers. With the right choices of biopolymers used for these fibrous materials, they could enhance the healing of wounds significantly compared with the conventional fibrous dressing materials, such as gauze. These bandages could be made such that they contain bioactive ingredients, such as antimicrobial, antibacterial, and anti‐inflammatory agents, which could be released to the wounds enhancing their healing. In an active wound dressing (AWD), the main purpose is to control the biochemical states of a wound in order to aid its healing process. This review provides an overview of different types of wounds, effective parameters in wound healing and different types of wound dressing materials with a special emphasis paid to those prepared by electrospinning. Copyright © 2009 John Wiley & Sons, Ltd.     

Alginate hydrogels incorporating neomycin or propolis as potential dressings for diabetic ulcers: Structure,swelling, and antimicrobial barrier properties

Alginate hydrogels have many attractive characteristics for potential use as wound dressing materials. However, they are not considered to possess any intrinsic activity against microbial infection, often present in neuropathic wounds. To overcome this, the effect of incorporating neomycin or propolis in alginate hydrogels was investigated, both by direct blending alone and also by further addition of loaded alginate microparticles prepared by the extrusion dripping method. The morphological, microstructural, thermal, mechanical, and swelling properties of each film were evaluated, as well as particle size distribution and antimicrobial penetration analysis. Microparticle size was considered suitable for drug delivery applications and incorporation in hydrogel films. The presence of neomycin and propolis, in both blended and microparticle form, interfered with film properties leading to hydrogels with different characteristics. All samples showed swelling degrees up to 100% and mechanical and thermal properties suitable for application as wound dressings. In addition, all samples acted as barriers to microbial penetration.     

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.     

Novel Poly(vinyl alcohol)/Chitosan/Modified Graphene Oxide Biocomposite for Wound Dressing Application

Rapid absorption of wound exudate and prevention of wound infection are prerequisites for wound dressing to accelerate wound healing. In this study, a novel kind of promising wound dressing is developed by incorporating polyhexamethylene guanidine (PHMG)‐modified graphene oxide (mGO) into the poly(vinyl alcohol)/chitosan (PVA/CS) matrix, conferring the dressing the required mechanical properties, higher water vapor transmission rate (WVTR), less swelling time, improved antibacterial activity, and more cell proliferation compared to the PVA/CS film crosslinked by genipin. In vivo experiments indicate that the PVA/CS/mGO composite film can accelerate wound healing via enhancement of the re‐epithelialization. PVA/CS/mGO composite film with 0.5 wt% mGO sheets displays the best wound healing properties, as manifested by the 50% higher antibacterial rate compared to GO and the wound healing rate of the mouse using this dressing is about 41% faster than the control group and 31% faster than the pure PVA/CS dressing. The underlying mechanism of the accelerated wound healing properties may be a result of the improved antibacterial ability to eradicate pathogenic bacteria on the wound area and maintain an appropriate moist aseptic wound healing environment to accelerate re‐epithelialization. These findings suggest that this novel composite PVA/CS/mGO film may have promising applications in wound dressing.     

Drug carrying hydrogel base wound dressing

A special drug carrying hydrogel base wound dressing by radiation preparation is developed for hospital uses. The dressing possesses high water absorption property. Radiation preparation is carried out using a Van de Graaff Accelerator as an electron radiation source. The effect of absorbed dose and cmount of crosslinking agent on the gel fraction and swelling ratio of the hydrogel were determined respectively. As a bio-medical material, standard tests were made. Results showed properties conforming with requirements for clinical applications. Results obtained from clinical tests were good.     

Evaluation of a non-woven fabric coated with a chitosan bi-layer composite for wound dressing

This study presents a novel design of an easily stripped bi-layer composite that consists of an upper layer of a soybean protein non-woven fabric coated with a lower layer, a genipin-crosslinked chitosan film, as a wound dressing material. This study examines the in vitro properties of the genipin-crosslinked chitosan film and the bi-layer composite. Furthermore, in vivo experiments are conducted to study wounds treated with the composite in a rat model. Experimental results show that the degree of crosslinking and the in vitro degradation rate of the genipin-crosslinked chitosan films can be controlled by varying the genipin contents. In addition, the genipin contents should exceed 0.025 wt.-% of the chitosan-based material if complete crosslinking reactions between genipin and chitosan molecules are required. Water contact angle analysis shows that the genipin-crosslinked chitosan film is not highly hydrophilic; therefore, the genipin-crosslinked chitosan layer is not entangled with the soybean protein non-woven fabric, which forms an easily stripped interface layer between them. Furthermore, this new wound dressing material provides adequate moisture, thereby minimizing the risk of wound dehydration, and exhibits good mechanical properties. The in vivo histological assessment results reveal that epithelialization and reconstruction of the wound are achieved by covering the wound with the composite, and the composite is easily stripped from the wound surface without damaging newly regenerated tissue.     

Activating the Antibacterial Effect of 4,6-Diamino-2-pyrimidinethiol-Modified Gold Nanoparticles by Reducing their Sizes

Adequately decorated gold nanoparticles (GNPs) have excellent antibiotic activities against multidrug-resistant (MDR) bacteria. Nanoparticles exhibiting Gram selective antibacterial actions are beneficial to precise therapy. Here, we present a strategy to tune the antibacterial spectrum of a small molecule (4,6-diamino-2-pyrimidinethiol, DAPT)-modified GNPs (DAPT-GNPs, DGNPs) by adjusting their sizes. Compared to large (ca. 14 nm diameter) DGNPs (lDGNPs) and medium-sized (3–4 nm diameter) DGNPs (mDGNPs), which have no antibacterial effect or only target Gram-negative (G−) bacteria, ultrasmall DGNPs (uDGNPs, <2 nm) have a broad antibacterial spectrum, especially showing an over 60-fold increase in antibacterial efficacy against Gram-positive (G+) bacteria. Moreover, the uDGNPs-functionalized scaffolds (agarose gel) can serve as general wound dressings for healing burnt infections. Our strategy is insightful for exploring properties of the nanomaterials and their applications.