Current procedures for the assessment of chronic wound infection are time-consuming and require complex instruments and trained personnel. The incidence of chronic wounds worldwide, and the ...associated economic burden, urge for simple and cheap point-of-care testing (PoCT) devices for fast on-site diagnosis to enable appropriate early treatment. The enzyme myeloperoxidase (MPO), whose activity in infected wounds is about ten times higher than in non-infected wounds, appears to be a suitable biomarker for wound infection diagnosis. Herein, we develop a single-component foldable paper-based device for the detection of MPO in wound fluids. The analyte detection is achieved in two steps: (i) selective immunocapture of MPO, and (ii) reaction of a specific dye with the captured MPO, yielding a purple color with increasing intensity as a function of the MPO activity in infected wounds in the range of 20–85 U/mL. Ex vivo experiments with wound fluids validated the analytic efficiency of the paper-based device, and the results strongly correlate with a spectrophotometric assay.
Chronic wounds represent a major health burden and drain on medical system. Efficient wound repair is only possible if the dressing materials target simultaneously multiple factors involved in wound ...chronicity, such as deleterious proteolytic and oxidative enzymes and high bacterial load. Here we develop multifunctional hydrogels for chronic wound management through self-assembling of thiolated hyaluronic acid (HA-SH) and bioactive silver-lignin nanoparticles (Ag@Lig NPs). Dynamic and reversible interactions between the polymer and Ag@Lig NPs yield hybrid nanocomposite hydrogels with shear-thinning and self-healing properties, coupled to zero-order kinetics release of antimicrobial silver in response to infection-related hyalurodinase. The hydrogels inhibit the major enzymes myeloperoxidase and matrix metalloproteinases responsible for wound chronicity in a patient's wound exudate. Furthermore, the lignin-capped AgNPs provide the hydrogel with antioxidant properties and strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The nanocomposite hydrogels are not toxic to human keratinocytes after 7 days of direct contact. Complete tissue remodeling and restoration of skin integrity is demonstrated in vivo in a diabetic mouse model. Hematological analysis reveals lack of wound inflammation due to bacterial infection or toxicity, confirming the potential of HA-SH/Ag@Lig NPs hydrogels for chronic wound management.
Multifunctional hydrogels are promising materials to promote healing of complex wounds. Herein, we report simple and versatile route to prepare biocompatible and multifunctional self-assembled hydrogels for efficient chronic wound treatment utilizing polymer-nanoparticle interactions. Hybrid silver-lignin nanoparticles (Ag@Lig NPs) played both: i) structural role, acting as crosslinking nodes in the hydrogel and endowing it with shear-thinning (ability to flow under applied shear stress) and self-healing properties, and ii) functional role, imparting strong antibacterial and antioxidant activity. Remarkably, the in situ self-assembling of thiolated hyaluronic acid and Ag@Lig NPs yields nanocomposite hydrogels able to simultaneously inhibits the major factors involved in wound chronicity, namely the overexpressed deleterious proteolytic and oxidative enzymes, and high bacterial load.
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•Antimicrobial and antibiofilm Co(II)-epigallocatechin gallate nanoparticles.•Nanoparticles-triggered gelation of thiolated hyaluronic acid.•Injectable, self-healing, and ...stimuli-responsive hydrogels.•Control over main factors of wound chronicity.•Comparable to commercial products efficiency for wound treatment in-vivo.
Chronic wounds are persistent non-healing lesions whose complex management is due to the interplay of multiple factors promoting chronicity, such as oxidative stress, overexpressed enzyme activities impeding the tissue repair and bacterial contamination. Currently marketed chronic wound dressings are designed mainly to absorb wound exudate, and at most to release antimicrobial agents, usually ionic silver. However, an effective wound repair requires addressing the multifactorial nature of the wound in a holistic approach. This study explores the potential of metal phenolic network (MPN) nanoparticles (NPs), comprised of epigallocatechin gallate (EGCG) and cobalt, as active agents and structural elements in wound dressings. The MPN NPs were able to generate reactive oxygen species (ROS), disturb bacterial membrane, and inhibit the biofilm of both gram-positive Staphylococcus aureus and gram-negative Pseudomonas aeruginosa. Owing to the high interfacial activity of their phenolic shells, the NPs drove the self-assembly of thiolated hyaluronic acid (THA) hydrogels featuring injectability, self-healing, stimuli-responsive NPs delivery in wound microenvironment, and control over deleterious enzyme activities, oxidative stress and bacterial colonisation. Specifically, the hydrogels inhibited matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) by 60 and 80 %, respectively, and achieved 4-log reduction of S. aureus and 2-log reduction of P. aeruginosa concentrations. Finally, the hydrogels were in-vivo validated in a mouse animal model, showing lack of toxicity and similar wound healing efficiency as an antibiotic-containing commercial product.
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•pH and salt-responsivity in the range of pH and salt concentration of chronic wounds exudate.•High ability to absorb the wound exudate which makes them very appropriate dressings ...materials for highly exuding wounds.•Ability to control the enzymes concentration in the chronic wounds through absorption without significantly inhibiting their activity.•Antibiofilm activity against S. aureus - bacteria, which is common for chronic wounds.•Non-cytotoxic and with very good tolerance by the surrounding tissues as revealed by in vivo experiments.
The current study demonstrates the benefits of poly(carboxybetaine methacrylate) hydrogels in chronic wound healing. These hydrogels demonstrate high absorbing capacity upon swelling in salt solutions thus revealing great potential as dressings for highly exuding chronic wounds. Moreover, upon swelling they expand, increasing their volume by 25%, which makes them patient friendly ensuring also the proper wound healing. Poly(carboxybetaine methacrylate) hydrogels were also shown to absorb collagenase and myeloperoxidase, two enzymes that are specific for chronic wounds, reducing in this way their amount by 30–45% in the wound bed without entirely inhibiting their activity, as the latter is necessary for the wound healing process. The hydrogels were also shown to be non-cytotoxic as well as to prevent the biofilm formation of S. aureus. The in vivo implantation in rats showed no immune response to moderate immune reaction for both studied PCB hydrogels. Thus, the properties of the PCB networks revealed in the study demonstrate their potential as chronic wounds dressing materials.
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•Temperature and salt-responsive polymeric materials.•Able to absorb wound exudate which makes them very appropriate for highly exuding wounds treatment.•Able to control the enzymes ...concentration in the chronic wounds through absorption without inhibiting their activity.•Exhibiting antibiofilm activity against S. aureus - bacteria, which is common for chronic wounds.•Non-cytotoxic and with very good tolerance by the surrounding tissues as revealed by in vivo experiments.
Polyzwitterions (PZI) recently emerged as biomaterials with excellent bio- and haemo-compatibility, demonstrating lower protein adsorption on their surfaces even compared to the golden standard in the field – poly(ethylene glycol) (PEG). Although PZI combine many beneficial for chronic wound treatment properties as nonfouling ability and high capacity to absorb wound exudate, their potential for such demanding application is still unrevealed. In this work, polysulfobetaine (PSB) networks were synthesized using PEG-based crosslinking agent, thus combining in one material two polymers with inherent antifouling properties. The obtained PSB hydrogels demonstrate linear temperature dependence of their swelling capacity in water between 20 and 70 °C. Moreover, they all exhibit strong antipolyelelctrolyte behavior, increasing their swelling ratio between 10 and 22 times depending on their crosslinking degree as the NaCl concentration increased. The study also demonstrates the PSB high ability to bind water - ∼40% bound water was determined for almost all PSB hydrogels, which is considered as the main reason for their ultra-low non-specific protein binding ability. Moreover, PZI networks effectively absorb and retain the major enzymes causing chronicity of the wounds as 30–40% myeloperoxidase (MPO) was loaded into the PSB hydrogels depending on their crosslinking degree. At the same time, PZI hydrogels do not inhibit neither MPO nor the collagenase activity, thus ensuring a decrease in their excessive amount in the chronic wounds but at the same not hampering the enzyme activity necessary for the proper wound healing. All PSB hydrogels demonstrated antibiofilm activity against S. aureus, a common bacterial representative in chronic wounds. The non-cytotoxicity and biocompatibility of the hydrogels were proved in vitro and in vivo. Thus, the study demonstrated the PSB hydrogels’ advantages as dressing materials for chronic wound healing, namely: (i) high ability to absorb wound exudate; (ii) high ability to bind water; (iii) good control on the enzymes concentration in the chronic wounds through absorption (iv) without inhibiting their activity; (v) antibiofilm activity against common for the chronic wounds bacteria; (vi) non-cytotoxicity and (vii) in vivo proved very good tolerance by the surrounding tissues.
The healing of chronic wounds requires intensive medical intervention at huge healthcare costs. Dressing materials should consider the multifactorial nature of these wounds comprising deleterious ...proteolytic and oxidative enzymes and high bacterial load. In this work, multifunctional hydrogels for chronic wound application were produced by enzymatic cross-linking of thiolated chitosan and gallic acid. The hydrogels combine several beneficial to wound healing properties, controlling the matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) activities, oxidative stress, and bacterial contamination. In vitro studies revealed above 90% antioxidant activity, and MPO and collagenase inhibition by up to 98 and 23%, respectively. Ex vivo studies with venous leg ulcer exudates confirmed the inhibitory capacity of the dressings against MPO and MMPs. Additionally, the hydrogels reduced the population of the most frequently encountered in nonhealing wounds bacterial strains. The stable at physiological conditions and resistant to lysozyme degradation hydrogels showed high biocompatibility with human skin fibroblasts.
The severity and cost of wound infections strongly demands for simple and fast methods for wound infection determination. Point-of-care testing devices play a crucial role in order to achieve a fast ...diagnosis and early treatment. Myeloperoxidase (MPO) enzyme, detected in fluids of infected wounds has been postulated as a suitable biomarker for wound diagnostics. Here we present a new system for MPO detection, based on enzyme-catalysed oxidative synthesis of a dye that can be incorporated into paper-based point of care devices. Visual MPO detection has been achieved through the use of phenylenediamine, a common colourless hair dye precursor. MPO oxidation of these compounds yielded bright coloured products distinguishable from the colour of the wound environment. Immobilisation of the MPO substrates on paper strips was achieved through in situ interaction of the oxidised coloured product with branched polyethyleneimine. The colour reaction of the immobilized substrates, detectable by naked eye, responds to the MPO levels present in infected wound fluids revealing an easy system for incorporation of MPO detection in paper based diagnostic devices.
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•A new sensitive MPO detection method for wound infection diagnose.•Fast visual detection of MPO levels corresponding to infected wounds avoiding haemoglobin cross-reaction.•A new detection method easily transferable to paper-based point of care diagnostic devices.
Integrative care model in complex wounds Hinojosa-Caballero, Dolores; Álvarez Rodríguez, Lorenzo Ramon; Torres Subires, Antonia ...
International journal of integrated care,
12/2016, Letnik:
16, Številka:
6
Journal Article
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