Project description:Two glycosaminoglycan (GAG) biopolymers, hyaluronic acid (HA) and chondroitin sulfate (CS), were chemically modified via carbodiimide chemistry to facilitate the loading and release of nitric oxide (NO) to develop a multi-action wound healing agent. The resulting NO-releasing GAGs released 0.2-0.9 μmol NO mg-1 GAG into simulated wound fluid with NO-release half-lives ranging from 20 to 110 min. GAGs containing alkylamines with terminal primary amines and displaying intermediate NO-release kinetics exhibited potent, broad spectrum bactericidal action against three strains each of Pseudomonas aeruginosa and Staphylococcus aureus ranging in antibiotic resistance profile. NO loading of the GAGs was also found to decrease murine TLR4 activation, suggesting that the therapeutic exhibits anti-inflammatory mechanisms. In vitro adhesion and proliferation assays utilizing human dermal fibroblasts and human epidermal keratinocytes displayed differences as a function of the GAG backbone, alkylamine identity, and NO-release properties. In combination with antibacterial properties, the adhesion and proliferation profiles of the GAG derivatives enabled the selection of the most promising wound healing candidates for subsequent in vivo studies. A P. aeruginosa-infected murine wound model revealed the benefits of CS over HA as a pro-wound healing NO donor scaffold, with benefits of accelerated wound closure and decreased bacterial burden attributable to both active NO release and the biopolymer backbone.
Project description:Chronic wounds are caused by bacterial infections and create major healthcare discomforts; to overcome this issue, wound dressings with antibacterial properties are to be utilized. The requirements of antibacterial wound dressings cannot be fulfilled by traditional wound dressing materials. Hence, to improve and accelerate the process of wound healing, an antibacterial wound dressing is to be designed. Electrospun nanofibers offer a promising solution to the management of wound healing, and numerous options are available to load antibacterial compounds onto the nanofiber webs. This review gives us an overview of some recent advances of electrospun antibacterial nanomaterials used in wound dressings. First, we provide a brief overview of the electrospinning process of nanofibers in wound healing and later discuss electrospun fibers that have incorporated various antimicrobial agents to be used in wound dressings. In addition, we highlight the latest research and patents related to electrospun nanofibers in wound dressing. This review also aims to concentrate on the importance of nanofibers for wound dressing applications and discuss functionalized antibacterial nanofibers in wound dressing.
Project description:The preparation of electrospun polymer microfibers with nitric oxide (NO)-release capabilities is described. Polymer solutions containing disodium 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), a low-molecular-weight NO donor, were electrospun to generate fibers ranging from 100-3000 nm in diameter capable of releasing NO upon immersion in aqueous solutions under physiological conditions (pH 7.4, 37 °C), with kinetics depending on polymer composition and fiber diameter. The NO release half-life for PROLI/NO-doped electrospun fibers was 2-200 times longer than that of PROLI/NO alone. The influence of polymer concentration, applied voltage, capillary diameter, solution conductivity, flow rate, and additives on fiber properties are reported and discussed with respect to potential applications.
Project description:Herein, we report a novel design and the antimicrobial efficacy of a flexible nitric oxide (NO) releasing patch for potential wound healing applications. The compact sized polydimethylsiloxane (PDMS) planar patch generates NO via electrochemical reduction of nitrite ions mediated by a copper(II)-ligand catalyst using a portable power system and an internal gold coated stainless steel mesh working electrode. Patches are fabricated via soft lithography and 3-D printing. The devices can continuously release NO over 4 days and exhibit potent bactericidal effects on both Escherichia coli and Staphylococcus aureus. The device may provide an effective, safe, and less costly alternative for treating chronic wounds.
Project description:The prevalence of chronic, non-healing skin wounds in the general population, most notably diabetic foot ulcers, venous leg ulcers and pressure ulcers, is approximately 2% and is expected to increase, driven mostly by the aging population and the steady rise in obesity and diabetes. Non-healing wounds often become infected, increasing the risk of life-threatening complications, which poses a significant socioeconomic burden. Aiming at the improved management of infected wounds, a variety of wound dressings that incorporate antimicrobials (AMDs), namely polyhexanide (poly(hexamethylene biguanide); PHMB), have been introduced in the wound-care market. However, many wound-care professionals agree that none of these wound dressings show comprehensive or optimal antimicrobial activity. This manuscript summarizes and discusses studies on PHMB-releasing membranes (PRMs) for wound dressings, detailing their preparation, physical properties that are relevant to the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound-healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall efficacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.
Project description:IntroductionAccording to the American Diabetes Association (ADA), 9-12 million patients suffer from chronic ulceration each year, costing the healthcare system over USD $25 billion annually. There is a significant unmet need for new and efficacious therapies to accelerate closure of non-healing wounds. Nitric Oxide (NO) levels typically increase rapidly after skin injury in the inflammatory phase and gradually diminish as wound healing progresses. The effect of increased NO concentration on promoting re-epithelization and wound closure has yet to be described in the context of diabetic wound healing.MethodsIn this study, we investigated the effects of local administration of an NO-releasing gel on excisional wound healing in diabetic mice. The excisional wounds of each mouse received either NO-releasing gel or a control phosphate-buffered saline (PBS)-releasing gel treatment twice daily until complete wound closure.ResultsTopical administration of NO-gel significantly accelerated the rate of wound healing as compared with PBS-gel-treated mice during the later stages of healing. The treatment also promoted a more regenerative ECM architecture resulting in shorter, less dense, and more randomly aligned collagen fibers within the healed scars, similar to that of unwounded skin. Wound healing promoting factors fibronectin, TGF-β1, CD31, and VEGF were significantly elevated in NO vs. PBS-gel-treated wounds.DiscussionThe results of this work may have important clinical implications for the management of patients with non-healing wounds.
Project description:Nitric oxide (NO) plays an important role in wound healing, due to its ability to contract wound surfaces, dilate blood vessels, participate in inflammation as well as promote collagen synthesis, angiogenesis and fibroblast proliferation. Herein, keratin was first nitrosated to afford S-nitrosated keratin (KSNO). As a NO donor, KSNO was then co-electrospun with polyurethane (PU). These as-spun PU/KSNO biocomposite mats could release NO sustainably for 72 h, matching the renewal time of the wound dressing. Moreover, these mats exhibited excellent cytocompatibility with good cell adhesion and cell migration. Further, the biocomposite mats exhibited antibacterial properties without inducing severe inflammatory responses. The wound repair in vivo demonstrated that these mats accelerated wound healing by promoting tissue formation, collagen deposition, cell migration, re-epithelialization and angiogenesis. Overall, PU/KSNO mats may be promising candidates for wound dressing.
Project description:Electrospun polyurethane fibers doped with nitric oxide (NO)-releasing silica particles are presented as novel macromolecular scaffolds with prolonged NO-release and high porosity. Fiber diameter (119-614 nm) and mechanical strength (1.7-34.5 MPa of modulus) were varied by altering polyurethane type and concentration, as well as the NO-releasing particle composition, size, and concentration. The resulting NO-releasing electrospun nanofibers exhibited ~83% porosity with flexible plastic or elastomeric behavior. The use of N-diazeniumdiolate- or S-nitrosothiol-modified particles yielded scaffolds exhibiting a wide range of NO release totals and durations (7.5 nmol mg(-1)-0.12 μmol mg(-1) and 7 h to 2 weeks, respectively). The application of NO-releasing porous materials as coatings for subcutaneous implants may improve tissue biocompatibility by mitigating the foreign body response and promoting cell integration.
Project description:Objective: Wound healing is a complex process that involves the interaction between different cell types and bioactive factors. Impaired wound healing is characterized by a loss in synchronization of these interactions, resulting in nonhealing chronic wounds. Chronic wounds are a socioeconomic burden, one of the most prominent clinical manifestations of diabetes, however, they lack satisfactory treatment options. The objective of this study was to develop polymeric composites that deliver ions having wound healing properties and evaluate its performance using a pressure ulcer model in diabetic mice. Approach: To develop a polymeric composite wound dressing containing ion-releasing nanoparticles for chronic wound healing. This composite was chemically and physically characterized and evaluated using a pressure ulcer wound model in diabetic (db/db) mice to explore their potential as novel wound dressing. Results: This dressing exhibits a controlled ion release and a good in vitro bioactivity. The polymeric composite dressing treatment stimulates angiogenesis, collagen synthesis, granulation tissue formation, and accelerates wound closure of ischemic wounds created in diabetic mice. In addition, the performance of the newly designed composite is remarkably better than a commercially available dressing frequently used for the treatment of low-exuding chronic wounds. Innovation: The developed nanoplatforms are cell- and growth factor free and control the host microenvironment resulting in enhanced wound healing. These nanoplatforms are available by cost-effective synthesis with a defined composition, offering an additional advantage in potential clinical application. Conclusion: Based on the obtained results, these polymeric composites offer an optimum approach for chronic wound healing without adding cells or external biological factors.
Project description:The fabrication of electrospun composite polyurethane fibers capable of dual-action antibacterial dendrimer release is reported. Generation 4 (G4) poly(amidoamine) dendrimers were functionalized with octyl alkyl chain or quaternary ammonium (QA) moieties followed by modification of the resulting secondary amines with N-diazeniumdiolate nitric oxide (NO) donors to produce dual-action antibacterial dendrimers. Control and NO-releasing dendrimers were doped into polyurethane solutions prior to electrospinning of the polymer to yield well-defined dendrimer-doped composite polyurethane fibers. The fiber mats were semi-porous (≥30% porosity) and exhibited high water uptake (>100% relative to fiber mass). Dendrimer- and NO-release characteristics (rates and totals) were dependent on the dendrimer modification and polyurethane composition, with total dendrimer- and NO-release amounts ranging from 10 - 80 μg/mg and 0.027 - 0.072 μmol NO/mg, respectively. The antibacterial action of the fibers was evaluated against Gram-negative and Gram-positive bacterial strains. Nitric oxide-releasing fibers demonstrated broad-spectrum bactericidal action at short (2 h) and long (24 h) timescales.