Effective Wound Treatment Research Articles

Natural Polymer-Based Antimicrobial Hydrogels without Synthetic Antibiotics as Wound Dressings.

Wound healing is usually accompanied by bacterial infection. The excessive use of synthetic antibiotics leads to drug resistance, posing a significant threat to human health. Hydrogel-based wound dressings aimed at mitigating bacterial infections have emerged as an effective wound treatment. The review presented herein particularly focuses on the hydrogels originating from natural polymers. To further enhance the performance of wound dressings, various strategies and approaches have been developed to endow the hydrogels with excellent broad-spectrum antibacterial activity. Those that are summarized in the current review are the hydrogels with intrinsic or stimuli-triggered bactericidal properties and others that serve as vehicles for loading antibacterial agents without synthetic antibiotics. Specific attention is paid to antimicrobial mechanisms and the antibacterial performance of hydrogels. Practical antibacterial applications to accelerate the wound healing employing these antibiotic-free hydrogels are also introduced along with the discussion on the current challenges and perspectives leading to new technologies.

Circular RNA hsa_circ_0084443 Is Upregulated in Diabetic Foot Ulcer and Modulates Keratinocyte Migration and Proliferation.

Objective: Insufficient knowledge about the molecular pathology of diabetic foot ulcer (DFU) impedes the development of effective wound treatment. Circular RNAs (circRNAs) are a novel class of RNA recently discovered to be widely expressed and have important biological functions; however, their role in skin wound healing remains largely unexplored. In this study, we investigated the role of circRNAs in DFU. Approach: CircRNA expression was profiled in normal wounds (NWs) and DFUs by microarray analysis, and hsa_circ_0084443 was identified as differentially expressed. The circularity and subcellular localization of hsa_circ_0084443 were characterized by northern blotting, real-time PCR, and fluorescence in situ hybridization. Cell migration, cell growth, and the transcriptome of human primary keratinocytes were analyzed after overexpression or RNA interference of hsa_circ_0084443. Results: hsa_circ_0084443 is downregulated in NWs compared with intact skin, and its level is higher in DFUs than NWs. We confirmed its circularity and presence in the cytoplasm of human epidermal keratinocytes. We showed that hsa_circ_0084443 reduced motility while enhancing the growth of keratinocytes. Furthermore, we identified a gene network with the potential to mediate the biological effect of hsa_circ_0084443. Innovation: CircRNAs have a functional role and a potential clinical significance in skin wound healing. Conclusions: We identified hsa_circ_0084443, a circRNA downregulated during NW healing, as a negative regulator of keratinocyte migration. Higher levels of hsa_circ_0084443 were detected in DFU samples, suggesting that it plays a role in pathology. These findings pave the way to understanding the functional role of circRNAs in human skin wound healing.

Poly (vinylpyrrolidone)‑iodine engineered poly (ε-caprolactone) nanofibers as potential wound dressing materials.

Facilitating the process of wound healing and effective treatment of wounds remains a serious challenge in healthcare. Wound dressing materials play a major role in the protection of wounds and in accelerating the natural healing process. In the present study, novel core/shell (c/s) nanofibrous mats of poly(vinyl pyrrolidone)‑iodine (PVPI) and polycaprolactone (PCL) were fabricated using a co-axial electrospinning process followed by their surface modification with poly-l-lysine. The developed nanofibrous mats were extensively characterized for their physicochemical properties using various analytical techniques. The core/shell structure of the PVP-I/PCL nanofibers was confirmed using TEM analysis. The PVP-I release studies showed an initial burst phase followed by a sustained release pattern of PVP-I over a period of 30days. The developed nanofibers exhibited higher BSA and fibrinogen adsorption as compared to pristine PCL. Cytotoxicity studies using MTT assay demonstrated that the PVP-I/PCL (c/s) nanofibers were cytocompatible at optimized PVP-I concentration (3wt%). The PCL-poly-l-lysine and PVP-I/PCL-poly-l-lysine nanofibers exhibited higher cell viability (24.2% and 21.4% higher at day 7) when compared to uncoated PCL and PVP-I/PCL nanofibers. The PVP-I/PCL nanofibers showed excellent antimicrobial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria. The inflammatory response of Mouse RAW 264.7 macrophage cells towards the nanofibers was studied using RT-PCR. It revealed that the pro-inflammatory cytokines (TNF-α and IL-1β) were significantly upregulated on PCL nanofibers, while their expression was comparatively lower on poly-l-lysine coated PCL or PVP-I/PCL(c/s) nanofibers. Overall, the study highlights the ability of poly-l-lysine coated PVP-I/PCL (c/s) nanofibers as potential wound dressing materials effectively facilitating the early stage wound healing and repair process by virtue of their selective modulation of inflammation, cell adhesion and antimicrobial properties.

Glycosaminoglycan-based biomaterials for growth factor and cytokine delivery: Making the right choices

Controlled, localized drug delivery is a long-standing goal of medical research, realization of which could reduce the harmful side-effects of drugs and allow more effective treatment of wounds, cancers, organ damage and other diseases. This is particularly the case for protein “drugs” and other therapeutic biological cargoes, which can be challenging to deliver effectively by conventional systemic administration. However, developing biocompatible materials that can sequester large quantities of protein and release them in a sustained and controlled manner has proven challenging. Glycosaminoglycans (GAGs) represent a promising class of bio-derived materials that possess these key properties and can additionally potentially enhance the biological effects of the delivered protein. They are a diverse group of linear polysaccharides with varied functionalities and suitabilities for different cargoes. However, most investigations so far have focused on a relatively small subset of GAGs – particularly heparin, a readily available, promiscuously-binding GAG. There is emerging evidence that for many applications other GAGs are in fact more suitable for regulated and sustained delivery. In this review, we aim to illuminate the beneficial properties of various GAGs with reference to specific protein cargoes, and to provide guidelines for informed choice of GAGs for therapeutic applications.

Insulin Promotes Wound Healing by Inactivating NFkβP50/P65 and Activating Protein and Lipid Biosynthesis and alternating Pro/Anti-inflammatory Cytokines Dynamics.

Four hundred and twenty-two million people have diabetes due to excess free body glucose in their body fluids. Diabetes leads to various problems including retinopathy, neuropathy, arthritis, damage blood vessels etc; it also causes a delay in wound healing. Insufficiency of insulin is the main reason for diabetes-I and systemic insulin treatment is a remedy. The perspective of the potential use of insulin/insulin based drugs to treat chronic wounds in diabetic conditions is focused on in this review. At the site of the wound, TNF-ɑ, IFN-ϒ, IL-1β and IL-6 pro-inflammatory cytokines cause the generation of free radicals, leading to inflammation which becomes persistent in diabetes. Insulin induces expression of IL-4/IL-13, IL-10 anti-inflammatory cytokines etc which further down-regulates NFkβP50/P65 assembly. Insulin shifts the equilibrium towards NFkβP50/P50 which leads to down-regulation of inflammatory cytokines such as IL-6, IL-10 etc through STAT6, STAT3 and c-Maf activation causing nullification of an inflammatory condition. Insulin also promotes protein and lipid biosynthesis which indeed promotes wound recovery. Here, in this article, the contributions of insulin in controlling wound tissue microenvironments and remodulation of tissue have been summarised, which may be helpful to develop novel insulin-based formulation(s) for effective treatment of wounds in diabetic conditions.

Latest Progress in Electrospun Nanofibers for Wound Healing Applications.

Electrospinning is a versatile technique used to create native tissue-like fibrous scaffolds. Recently, it has gained a large amount of attention for generation of bioactive dressing materials suitable for treatment of both chronic and acute wounds. In this Review, we focus on the latest advances made in the application of electrospun scaffolds for bioactive wound healing. We first provide a brief overview of the wound healing process and electrospinning approaches. We then discuss fabrication of scaffolds made from natural and synthetic polymers via electrospinning for effective wound treatment and management. Natural polymers used for wound healing included in our Review cover protein based polymers such as collagen, gelatin, and silk and polysaccharide based polymers such as chitosan, hyaluronic acid, and alginate. In addition, we discuss aliphatic polyesters, super hydrophilic polymers, and polyurethanes as some of the most commonly used synthetic polymers for wound healing and wound dressing applications. Next, we review multifunctional and "smart" scaffolds developed by electrospinning based approaches. We place an emphasis on how flexibility of the electrospinning process enables production of advanced scaffolds such as core-shell fibrous scaffolds, multilayer scaffolds, and surface modified scaffolds. Taken together, it is clear that electrospinning is an emerging technology that provides a unique opportunity for engineering more effective wound dressing, management, and care products.

A review on Nano-therapeutic drug delivery carriers for effective wound treatment strategies

A review on Nano-therapeutic drug delivery carriers for effective wound treatment strategies

MODERN ASSORTMENT, PROPERTIES AND PERSPECTIVES OF MEDICAL DRESSINGS IMPROVEMENT OF WOUND TREATMENT

The effectiveness of reparation is now characterized not only in terms of wound healing. The aesthetic result is also of great significance. Besides, it is important to ensure the comfort of medication, in order to combine the optimal therapy and the quality of life of the patient. The aim of the study was the literature review on the effective wound treatment with the help of modern dressings, including their assortment and prospects for improvement. Materials and methods. The materials of the study were reliable literary sources containing information about wounds, pathogenesis, the stages of the wound process and its possible violations; the assortment of modern wound coverings and the composition of biologically active substances that have a pharmacological effect; the results of preclinical and clinical trials and their prospects of use in aesthetic medicine. The research was carried out using the information retrieval and library databases (eLIBRARY, Cyberleninka), technical information. The research methods used in the work are: informational, analytical, descriptive. Results and discussion. As a result of generalization and analysis of modern publications devoted to the effective wound treatment, modern views on the wound process, wound coverings, their assortment and compositions are described. The results of pharmacological tests as well as the properties of biologically active substances and carrier polymers used are also presented. It is noted that the prospective compounds for including with the wound coverings and external drugs affecting the repair process at different stages of the wound process are tizol, bischofite, peptides (1-β-interleukin), ectoin. Conclusion. Thus, it has been established that modern wound dressings and dressings containing the substances of different pharmacological groups are offered for effective therapy: antiseptics, anesthetics, repair stimulators, antioxidants that affect different stages and elements of the wound process. Their use can be required in cosmetology. Improving the composition of wound coverings is relevant. The wound coverings based on biopolymers containing interleukins-1, ectoin, hyaluronic acid, bischofite and tizol are of great interest.

Nanocrystal cellulose as drug excipient in transdermal patch for wound healing: an overview

Wound must be carefully treated to avoid serious infection that needs costly treatment. Method to enhance the recovery of the wound is crucial to have effective wound treatment. One of the technologies in wound treatment is transdermal patch that has the benefits of being non-invasive, easy to handle and permits constant drug dosage. In order to obtain a good controlled drug release, drug excipient needs to be investigated. Recently, natural Nanocrystal Cellulose (NCC) which can be synthesized from animal, algae, microorganism or plant has been actively used in drug delivery system as excipient. The application of NCC is advantageous due to its large surface area, biodegradable, non-toxic and abundance source.

Solubilized Amnion Membrane Hyaluronic Acid Hydrogel Accelerates Full-Thickness Wound Healing.

The early and effective treatment of wounds is vital to ensure proper wound closure and healing with appropriate functional and cosmetic outcomes. The use of human amnion membranes for wound care has been shown to be safe and effective. However, the difficulty in handling and placing thin sheets of membrane, and the high costs associated with the use of living cellularized tissue has limited the clinical application of amniotic membrane wound healing products. Here, we describe a novel amnion membrane‐derived product, processed to result in a cell‐free solution, while maintaining high concentrations of cell‐derived cytokines and growth factors. The solubilized amnion membrane (SAM) combined with the carrier hyaluronic acid (HA) hydrogel (HA‐SAM) is easy to produce, store, and apply to wounds. We demonstrated the efficacy of HA‐SAM as a wound treatment using a full‐thickness murine wound model. HA‐SAM significantly accelerated wound closure through re‐epithelialization and prevented wound contraction. HA‐SAM‐treated wounds had thicker regenerated skin, increased total number of blood vessels, and greater numbers of proliferating keratinocytes within the epidermis. Overall, this study confirms the efficacy of the amnion membrane as a wound treatment/dressing, and overcomes many of the limitations associated with using fresh, cryopreserved, or dehydrated tissue by providing a hydrogel delivery system for SAM. Stem Cells Translational Medicine 2017;6:2020–2032

Co-delivery of a growth factor and a tissue-protective molecule using elastin biopolymers accelerates wound healing in diabetic mice.

Growth factor therapy is a promising approach for chronic diabetic wounds, but strategies to efficiently and cost-effectively deliver active molecules to the highly proteolytic wound environment remain as major obstacles. Here, we re-engineered keratinocyte growth factor (KGF) and the cellular protective peptide ARA290 into a protein polymer suspension with the purpose of increasing their proteolytic resistance, thus their activity invivo. KGF and ARA290 were fused with elastin-like peptide (ELP), a protein polymer derived from tropoelastin, that confers the ability to separate into a colloidal suspension of liquid-like coacervates. ELP fusion did not diminish peptides activities as demonstrated by ability of KGF-ELP to accelerate keratinocyte proliferation and migration, and ARA290-ELP to protect cells from apoptosis. We examined the healing effect of ARA290-ELP and KGF-ELP alone or in combination, in a full-thickness diabetic wound model. In this model, ARA290-ELP was found to accelerate healing, notably by increasing angiogenesis in the wound bed. We further showed that co-delivery of ARA290 and KGF, with the 1:4 KGF-ELP to ARA290-ELP ratio, was the most effective wound treatment with the fastest healing rate, the thicker granulation tissue and regenerated epidermis after 28 days. Overall, this study shows that ARA290-ELP and KGF-ELP constitute promising new therapeutics for treatment of chronic wounds.

Wound healing applications of sericin/chitosan-capped silver nanoparticles incorporated hydrogel.

Microbial contamination in wounds leading to severe sepsis can be treated by silver-based antiseptics. However, frequent application of silver-based antiseptics, staining of skin, burning, and irritation at application site resulted to poor patient compliances. Thus, we formulated sericin- and chitosan-capped silver nanoparticle (S/C-SNP)-loaded hydrogel for accelerated wound healing and antimicrobial properties. The wound healing property of sericin, antibacterial nature of chitosan and silver, and mucoadhesive property of carbopol were utilized in development of novel wound dressing hydrogel to investigate the combined effect of these materials for effective treatment of wounds. The chemical reduction method was successfully employed for the synthesis of SNPs using sericin and chitosan as a capping/reducing agent. The SNPs were characterized by ultraviolet-spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The optimized SNPs were further used for preparation of carbopol hydrogel (0.5, 0.75, and 1.0% w/v). The prepared hydrogels were characterized for pH, viscosity, and texture analysis. The antimicrobial activity and wound healing activity of the optimized hydrogel (S/C-SNPs G-1) demonstrated higher bactericidal activity and wound closure, as supported by results of histopathology. Hydrogel containing capped SNPs has application in wound healing treatment.

Comparing the Efficacy of Viable Cryopreserved Placental Membrane for the Treatment of Wounds of Diverse Etiologies

INTRODUCTION AND OBJECTIVES: The benefits of using amniotic tissue in skin regeneration are well documented. Today, cryopreservation technology allows for better availability and maintenance of mesenchymal stem cells. This is of particular interest in treating the diabetic foot ulcer as this population has fewer mesenchymal stem cells. The objective of this case series investigation was to compare the efficacy of cryopreserved human amniotic stem cells in treating foot wounds of different etiologies. We will present data and case photos for a diabetic foot ulcer, venous leg ulcer, arterial ankle ulcer, and a pyoderma gangrenosum ulcer METHODS: Cryopreserved human amniotic stem cell grafts were applied to patients with chronic ulcers of different etiologies that had been subjected to at least 4 weeks of standard wound care and did not show adequate clinical progress. Wound area was recorded and photographed on weekly basis. Area reduction was charted over time and the results of each individual case were compared to one another. RESULTS: All ulcers displayed results that well exceeded the established parameters of weekly healing rates for effective wound treatment modalities. • Pyoderma gangrenosum displayed the poorest response to treatment. However, it is worth noting that the patient was not compliant in the prescribed adjunctive treatment regimen but managed to achieve 64% wound reduction. • All ulcers showed the largest appreciable amount of healing in both total area reduction and week-to- week closure percentage after the first application. CONCLUSIONS: Cryopreserved human amniotic stem cell grafts can aid in the decreasing the time to closure of various types of lower extremity ulcerations. The therapy is a clinically viable option for physicians to consider when formulating a treatment plan for a patient with an ulcer.

Highly efficient gold nanorods assisted laser phototherapy for rapid treatment on mice wound infected by pathogenic bacteria

Treatment of wound infection is one of the most challenging problems to be addressed in infectiously microbiological world. This is mainly due to the pathogen's ability for fast mutation and generating severely antibiotic resistance to antimicrobial treatment. Pathogens causing wound infection treated by photothermal methods can avoid drug resistance problem. Beside, rapid and highly effective wound treatment method in modern medical technology is extremely required. Therefore, we have proposed a novel method by using gold nanorods (Au NRs) to assist the Nd-YAG laser (1064nm) for photothermal killing pathogenic bacteria (Pseudomonas aeruginosa) for directly healing the wound infection on the (albino) mice. In all experiments, the bacteria numbers were calculated by the plate count method and we also used MALDI-MS to evaluate the effectiveness of the treatment and the physiological condition of wound infection. The current approach can be used to control severe skin infections from antibiotic resistant pathogens in wounds.

Alocasia denudata Engler treatment enhance open wound healing activities in Wistar rat’s skin

Ethnopharmacological relevanceA. denudata is traditionally used to treat various skin disorders, including wounds. It is widely used by the traditional healers as an effective wound treatment. Aim of studyThis study was done to determine A. denudata treatment effects on open wound healing activities in Wistar rat’s skin. Materials and methods120 Wistar rats (250–300g) were divided into four main groups, 1.5% and 3% A. denudata stem juice treated group, 10% Solcoseryl® gel treated group as positive control and phosphate buffer saline (PBS) treated group as negative control. Six full thicknesses wounds (6mm) were induced bilaterally on the dorsal of the rat’s skin. Rats were sacrificed on day 1, 3, 6, 10 and 14. The percentage of wound contraction, biochemical estimations, macroscopic observation and histological examinations were done to evaluate the wound healing activities. ResultsResults showed wounds treated with A. denudata stem juice possess a significant higher rate of wound contraction (p<0.001), total protein concentration (p<0.05), hexosamine concentration (p<0.001) and uronic acid concentration (p<0.001). Moreover, cathepsin B (p<0.05) and hydroxyproline (p<0.05) level showed lower concentration in wounds treated with A. denudata stem juice. Histological observation of wounds treated with A. denudata stem juice displayed organized epithelial layer with dense and compact collagen fibers. ConclusionBoth doses of A. denudata stem juice were found to enhance wound healing process. However, wounds treated with 3% A. denudata stem juice were reported to be more effective as a wound healing agent thus support its traditional usage.

Negative pressure wound therapy: improving the patient experience Part 3 of 3

Negative pressure wound therapy (NPWT) is considered to be an effective wound treatment, yet research has highlighted a clear need for its improvement, particularly in reducing pain. This is important not only for patient well-being and treatment satisfaction but also for the healing process. In parts 1 and 2, wound care clinicians were invited to share their views on patients' experiences of NPWT. Part 3, presented here, explores the views of patients who have had NPWT, through use of a questionnaire survey and interview (n = 50). Findings show that the majority of patients felt that NPWT had a positive impact on their wound (94%) and that their overall experience was positive (88%). However, respondents identified a number of challenges associated with NPWT, such as reduced mobility, noise issues, and sleep disturbance. Respondents also identified a number of areas for improvement with NPWT, including greater training for nurses, practical alterations to the equipment, and methods of minimising pain and skin damage during NPWT. Taken together with the findings from part one and two, this study highlights several key considerations for future research and clinical practice with NPWT.

Pain and trauma in negative pressure wound therapy: a review

Negative pressure wound therapy (NPWT) is considered an effective wound treatment, but there are a number of issues that need to be addressed for improvements to be made. This review aimed to explore the literature relating to the pain and skin trauma that may be experienced during NPWT. A literature search was carried out using the following databases: Academic Search Complete, CINAHL, PsychINFO, MEDLINE and PsyARTICLES. A total of 30 articles were reviewed. Studies reported varying levels of pain in patients undergoing NPWT, with certain treatment factors affecting the level of pain, such as the NPWT system and the dressing/filler used. Similarly, although there is much less research exploring NPWT-related trauma, findings suggest that dressing and filler type may impact on whether trauma occurs. However, further research needs to consider the different stages of NPWT and how pain and trauma can be minimised during the whole procedure. As both pain and skin trauma impact on the patient's well-being and on wound healing, it is essential that research further explores the factors that may affect the experience of pain and trauma, so as to inform developments in wound care.

Development of Nanostructured Silver Hydrogel Composites for Effective Treatment of Wounds

Development of Nanostructured Silver Hydrogel Composites for Effective Treatment of Wounds

Concurrent in vitro release of silver sulfadiazine and bupivacaine from semi-interpenetrating networks for wound management.

In situ photopolymerized semi-interpenetrating networks (sIPNs) composed of poly(ethylene glycol) and gelatin are promising multifunctional matrices for a regenerative medicine approach to dermal wound treatment. In addition to previously demonstrated efficacy in critical defects, sIPNs also function as drug delivery matrices for compounds loaded as either soluble or covalently linked components. Simultaneous release of silver sulfadiazine and bupivacaine from the sIPN would provide multiple-hit management of dermal wounds that minimizes infection, and manages pain along with sIPN absorption of exudates and facilitation of epidermal regrowth. We characterized the release of soluble silver sulfadiazine and bupivacaine and compared it with an established release model. Efficacy of released silver sulfadiazine was confirmed in vitro on Staphylococcus aureus, methicillin resistant S. aureus, and Pseudomonas aeruginosa. Bupivacaine loaded without silver sulfadiazine showed incomplete release, whereas simultaneous loading with silver sulfadiazine facilitated 100% bupivacaine release. Silver sulfadiazine released at 98% without bupivacaine and 96% with bupivacaine. Silver sulfadiazine released onto bacterial cultures inhibited all three strains dose dependently. sIPNs effectively release bupivacaine and silver sulfadiazine while maintaining the antimicrobial activity of silver sulfadiazine. Drug loaded sIPNs have potential to improve wound management by providing multi-drug delivery along with an effective wound treatment.

Einsatz der Madentherapie in der Gynäkologie

Ancient societies recognised beneficial effects of certain fly larvae on wound healing. Nowadays, biosurgery with living maggots has proven very useful in the therapy of infected, necrotic, acute and chronic wounds. The larvae cause a rapid and selective wound debridement, a disinfective effect and rapid formation of granulation tissue and epithelium. In our hospital, we gathered experience in wounds caused by gynecological surgery. Here, maggot therapy has been used in locations--e. g. perineal--which are difficult to provide with hydrocolloid wound dressings. Maggots can clear wounds of staphylococci and streptococci populations, are successful in wounds caused by radiation therapy and can be used after chemotherapy. Patient acceptance is very high and psychological stress has been rare. Maggot therapy is a cheap, safe and highly effective treatment of wounds. Therefore, we want to encourage the use of biosurgery in suitable wounds.