Wound Fluid Research Articles

Chronic wound dressings – Pathogenic bacteria anti-biofilm treatment with bacterial cellulose-chitosan polymer or bacterial cellulose-chitosan dots composite hydrogels

Since the pathogenic bacteria biofilms are involved in 70% of chronic infections and their resistance to antibiotics is increased, the research in this field requires new healing agents.New composite hydrogels were designed as potential chronic wound dressings composed of bacterial cellulose (BC) with chitosan polymer (Chi) – BC-Chi and chitosan nanoparticles (nChiD) – BC-nChiD. nChiD were obtained by gamma irradiation at doses: 20, 40 and 60 kGy. Physical and chemical analyses showed incorporation of Chi and encapsulation of nChiD into BC. The BC-Chi has the highest average surface roughness. BC-nChiD hydrogels show an irradiated dose-dependent increase of average surface roughness. New composite hydrogels are biocompatible with excellent anti-biofilm potential with up to 90% reduction of viable biofilm and up to 65% reduction of biofilm height. The BC-nChiD showed better dressing characteristics: higher porosity, higher wound fluid absorption and faster migration of cells (in vitro healing). All obtained results confirmed both composite hydrogels as promising chronic wound healing agents.

Enamel matrix derivative effects on palatal mucosa wound healing: Randomized clinical trial.

This study was conducted to evaluate the clinical, immunologic, and patient-centered outcomes of enamel matrix protein derivative (EMD) on excisional wounds in palatal mucosa. Forty-four patients in need of ridge preservation were randomly allocated into two groups: control group (n=22): open palatal wound after free gingival graft (FGG) harvest and EMD group (n=22): open palatal wound after FGG harvest that received 0.3ml of EMD. Clinical and patient-centered parameters were analyzed for 3months post-treatment. Wound fluid levels of inflammatory markers were assessed 3 and 7days postoperatively. No significant inter-group difference was observed in remaining wound area and re-epithelialization. EMD and control groups achieved wound closure and re-epithelialization 30days postoperatively (p<.001), without inter-group differences. Similarly, number of analgesics and Oral Health Impact Profile scores did not present significant inter-group differences (p>.05). EMD appeared to selectively modulate wound fluid levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, matrix metallopeptidase 9, and tissue inhibitor of metalloproteinases-2. Within the limits of the present study, it can be concluded that EMD application to excisional palatal wounds using the investigated protocol does not provide clinical healing benefits, despite an apparent modulation of selected inflammatory markers.

Single-Cell Analysis Reveals Major Histocompatibility Complex II‒Expressing Keratinocytes in Pressure Ulcers with Worse Healing Outcomes

Pressure ulcer (PU) is a chronic wound often seen in patients with spinal cord injury and other bed-bound individuals, particularly in the elderly population. Despite its association with high mortality, the pathophysiology of PU remains poorly understood. In this study, we compared single-cell transcriptomic profiles of human epidermal cells from PU wound edges with those from uninjured skin and acute wounds in healthy donors. We identified significant shifts in the cell composition and gene expression patterns in PU. In particular, we found that major histocompatibility complex class II‒expressing keratinocytes were enriched in patients with worse healing outcomes. Furthermore, we showed that the IFN-γ in PU-derived wound fluid could induce major histocompatibility complex II expression in keratinocytes and that these wound fluid‒treated keratinocytes inhibited autologous T-cell activation. In line with this observation, we found that T cells from PUs enriched with major histocompatibility complex II+ keratinocytes produced fewer inflammatory cytokines. Overall, our study provides a high-resolution molecular map of human PU compared with that of acute wounds and intact skin, providing insights into PU pathology and the future development of tailored wound therapy.

MiR-195-5p and miR-205-5p in extracellular vesicles isolated from diabetic foot ulcer wound fluid decrease angiogenesis by inhibiting VEGFA expression.

Diabetic foot ulcers are recalcitrant to healing, and poor angiogenesis is considered as the main contributing factor. We aimed to explore the effect of extracellular vesicles (EVs) derived from wound fluids on new vessel formation in diabetic foot ulcers. EVs were isolated from wound fluids of diabetic foot ulcers (DF-EVs). The inhibitory effect of DF-EVs on human umbilical vein endothelial cells (HUVECs) and wound healing was tested. To elucidate the potential mechanism of these effects, we screened the differentially expressed microRNAs (miRNAs) in DF-EVs via microarray analysis and verified the upregulation of miR-195-5p and miR-205-5p in DF-EVs via quantitative real-time polymerase chain reaction (qRT-PCR). Further dual-luciferase reporter assays and overexpression experiments proved these two miRNAs inhibited the expression of vascular endothelial growth factor A (VEGFA) directly to the 3′ untranslated region (UTR) of VEGFA and, in turn, promoted an inhibitory effect of DF-EVs on angiogenesis and wound healing in patients with diabetic foot ulcers. Our study shows EVs in the wound fluids of diabetic foot ulcer lesions carrying antiangiogenic miR-195-5p and miR-205-5p negatively regulated angiogenesis and wound healing in patients with diabetic foot.

This Review Recent Advances in Chitosan and Alginate‐Based Hydrogels for Wound Healing Application

Wound healing is a complicated yet necessary event that takes place in both animals and human beings for the body to repair itself due to injury. Wound healing involves various stages that ensure the restoration of the injured tissue at the end of the process. Wound dressing material acts as a protective extracellular barrier against potential damage to the injury and microbial invasion. Naturally, polysaccharides (chitosan and alginate) have inherent properties that have made them attractive for their usage in wound healing therapy. Alginate and chitosan have been used to develop novel wound healing and smart biomaterials due to various functionalities such as reducing swelling, non-toxic nature, biocompatibility, antimicrobial potential, and maintenance moist environment, ability to absorb wound fluid, and skin regeneration promotion. Functionalization of polysaccharides is one of the many approaches that have been used to modify and enhance the wound healing properties of these biomaterials. Many studies have been done to modify the polysaccharide hydrogels. Some of these are highlighted in this paper. The designing and development of smart hydrogels that react to their environment have recently sparked a significant scientific and pharmaceutical interest. Smart hydrogel development has been the primary focal area for developing highly advanced and sophisticated wound healing therapeutic technologies. This paper seeks to comprehensively shed light on the advancements of functionalized chitosan and alginate-based hydrogels and their applicability in wound healing therapeutics. In addition to this, thus identifying critical drawbacks faced in existing hydrogel systems and how prospective technologies enable digitally controlled bio-platforms coupled with biomaterials to improve wound care. This review hopes to stimulate and encourage researchers to identify future avenues worth investigation.

Medicated multi-targeted alginate-based dressings for potential treatment of mixed bacterial-fungal infections in diabetic foot ulcers

Recently developed medicated dressings target either bacterial or fungal infection only, which is not effective for the treatment of mixed infections common in diabetic foot ulcers (DFUs). This study aimed to develop advanced bioactive alginate-based dressings (films and wafers) to deliver therapeutically relevant doses of ciprofloxacin (CIP) and fluconazole (FLU) to target mixed bacterial and fungal infections in DFUs. The alginate compatibility with the drugs was confirmed by SEM, XRD, FTIR and texture analysis, while the medicated wafers showed better fluid handling properties than the films in the presence of simulated wound fluid. The dressings showed initial fast release of FLU followed by sustained release of CIP which completely eradicated E. coli, S. aureus, P. aeruginosa and reduced fungal load (C. albicans) by 10-fold within 24 h. Moreover, the medicated dressings were biocompatible (>70% cell viability over 72 h) with human primary adult keratinocytes and in-vitro scratch assay showed 65–68% wound closure within 7 days.

Effects of wound fluid on breast cancer-derived spheroids in a 3D culture system: a case series study

Surgery is the standard treatment for breast malignancies, although local and distant relapses might occur. Previous studies have shown that surgery-induced wound fluid (WF) contains tumor-initiating and progressing factors; however, these experiments have only been performed on breast cancer cell lines. Since a cancerous tumor includes various components like malignant cells, recruited non-malignant cells and extracellular matrix, those investigations that only focused on cancer cell lines themselves are not adequate to establish WF's effects. We conducted a 3D model study where we mimicked the in vivo tumor microenvironment to re-assess previous in vitro findings. We generated human-derived breast tumor spheroids from 23 patient specimens, dissociated and cultured them in microfluidic devices. The spheroids from each sample were treated with the patients’ WF or RPMI medium. The proportion of live and dead cells was assessed using live/dead assays and fluorescent imaging on day 6. In 22 samples, the percentage of live cells was significantly higher in the WF-treated group than in the RPMI-treated group. In one sample, we observed an opposite trend. The results were contrary in one of the samples, and we reported that case with more details. We compared the two groups using the 3D culture environment of human-derived tumor spheroids prepared from different microfluidic devices to mimic the tumor environment heterogeneity. Our findings showed that most patients with breast cancer benefit from surgical wound healing. However, removal of the surgical-induced serum may not be a method of inhibiting the tumor in all patients.

Method development and characterisation of the low-molecular-weight peptidome of human wound fluids.

The normal wound healing process is characterised by proteolytic events, whereas infection results in dysfunctional activations by endogenous and bacterial proteases. Peptides, downstream reporters of these proteolytic actions, could therefore serve as a promising tool for diagnosis of wounds. Using mass-spectrometry analyses, we here for the first time characterise the peptidome of human wound fluids. Sterile post-surgical wound fluids were found to contain a high degree of peptides in comparison to human plasma. Analyses of the peptidome from uninfected healing wounds and Staphylococcus aureus -infected wounds identify unique peptide patterns of various proteins, including coagulation and complement factors, proteases, and antiproteinases. Together, the work defines a workflow for analysis of peptides derived from wound fluids and demonstrates a proof-of-concept that such fluids can be used for analysis of qualitative differences of peptide patterns from larger patient cohorts, providing potential biomarkers for wound healing and infection.

266-OR: Proteomic Analysis of Diabetic Foot Ulcer Fluid to Identify Biomarkers of Wound Healing: A Prospective Study

Objective: The aim of this study is to compare markers found in wound fluid of healing and non-healing diabetic foot ulcers using tandem mass spectrometry. Methods: Wound fluid samples were collected using a microfilament, centrifugated and frozen at -80C. Clinical outcome of the ulcers was determined after 6 months follow-up. Proteomic analysis of the samples was conducted and compared between 5 healing and 3 non-healing ulcers using the Fisher’s exact test with Benjamini-Hochberg’s corrected P values. Pathway-specific analysis was done to examine the functional differences in up- and downregulated proteins. Results: Up to 2155 proteins were identified in each sample, 113 of which were differentially expressed between two groups. Proteins upregulated in non-healing wounds were mainly associated with neutrophil degranulation, inflammatory/immune response, and cell adhesion and migration. The downregulated proteins were linked to smooth muscle cell proliferation, regulation of gene expression, and Wnt signaling pathway, proteins regulated by insulin and glucose and most of the proteins involved in negative regulation of apoptosis. Conclusions: Our findings signal activation of naive inflammatory pathway and cell migration, and potential downregulation of gene transcription and expression, cytoskeleton and intracellular calcium control mechanisms in non-healing diabetic ulcers. Disclosure N. Vatankhah: None. V. Jalili: None. Y. Jahangiri: None.

Targeting Antibacterial Effect and Promoting of Skin Wound Healing After Infected with Methicillin-Resistant Staphylococcus aureus for the Novel Polyvinyl Alcohol Nanoparticles.

IntroductionTopical agents typically remain in the wound site for time duration that are too short to effectively eradicate MRSA tradition formation of BZK that can be maintained within the wound site for longer time periods, should be more effective.MethodsThe novel chitosan and poly (D,L-lactide-co-glycoside) nanoparticles loaded with benzalkonium bromide (BZK) were designed, for the promotion wound healing after MRSA infection. The physical characterization of these nanoparticles, as well as their antibacterial activity in vitro, release profile in simulated wound fluid, cell toxicity, anti-biofilm activity, and their ability to improve the skin wound healing in a mouse model were also studied.ResultsThese novel nanoparticles were found to have a significant antibacterial activity (p<0.01), both in vitro and in vivo test. The stronger anti-biofilm ability of the nanoparticles to inhibit the formation of bacterial biofilms, at a concentration of 3.33 μg/mL, and clear existing bacterial biofilms, at a concentration of 5 mg/mL, compared with its water solution. In addition, significant damage to bacterial cell walls also was found, providing insight into the mechanism of antibacterial activity.ConclusionTaken together, these results demonstrated the ability of BZK-loaded nanoparticles in the promotion of skin wound healing with MRSA infection. The current findings open a new avenue for nanomedicine development and future clinical applications in the treatment of wounds.

(Invited) Wearable Electrochemical Sensor for Detection of Multianalyte Biomarkers in Wound Healing Efficacy

The targeted diagnosis and effective treatments of chronic wounds remain a significant healthcare challenge, requiring the design of analytical sensors for real-time monitoring of wound healing activity. Herein, we describe an adaptable method for the fabrication of carbon ultramicroelectrode arrays (CUAs) on flexible substrates with the goal to utilize this sensor as a wearable device to monitor chronic wounds. As a proof-of-concept study, we demonstrate the electrochemical detection of three electroactive analytes as biomarkers for wound healing state in a wound fluid simulant on flexible CUAs. Notably, to follow pathogenic responses, we characterize the analytical figures of merit for identification and monitoring of bacterial warfare toxin pyocyanin (PYO) secreted by the opportunistic human pathogen Pseudomonas aeruginosa. We also demonstrate the detection of uric acid (UA) and nitric oxide (NO•), which are signaling biomolecules indicative of wound healing, and immune responses, respectively. The electrochemically determined limit of detection (LOD) and linear dynamic range (LDR) for PYO, UA, and NO• fall within the clinically relevant concentrations for each biomarker. In addition, we demonstrate the successful use of flexible CUAs for quantitative, electrochemical detection of PYO from P. aeruginosa strains and cellular NO• from immune cells in the wound matrix. An electrochemical examination of the interaction between PYO and NO• is also presented, providing insight into pathogen-host responses. Finally, the effects of the antimicrobial agent, silver (Ag+), on P. aeruginosa PYO production rates are investigated on flexible CUAs. Our quantitative electrochemical results show that the addition of Ag+ to P. aeruginosa cultures in wound simulant decreases PYO secretion rates.

Curdlan-Based Hydrogels for Potential Application as Dressings for Promotion of Skin Wound Healing—Preliminary In Vitro Studies

The aim of this work was to establish whether novel curdlan-based hydrogels enriched with Ca2+ ions may be considered as potential candidates for dressings, for the acceleration of skin wound healing. Firstly, biomaterials were allocated for evaluation of structural and mechanical properties. Subsequently, the ability of hydrogels to absorb simulated wound fluid and water vapor permeability, as well their capacity to release calcium ions, was evaluated. The biocompatibility of biomaterials was assessed using normal human skin fibroblasts. Importantly, the main features of the obtained curdlan-based hydrogels were compared with those of KALTOSTAT® (a commercial calcium sodium alginate wound dressing). The obtained results showed that curdlan-based biomaterials possessed a mesoporous structure (pore diameter ranged from 14–48 nm) and exhibited a good ability to absorb simulated wound fluid (swelling ratio close to 974–1229%). Moreover, in a wet state, they enabled proper water vapor transmission rate (>2000 g/m2/day), thanks to their hydrogel structure. Finally, it was found that biomaterial composed of 11 wt.% of curdlan (Cur_11%) possessed the most desirable biological properties in vitro. It released a beneficial amount of calcium ions to the aqueous environment (approximately 6.12 mM), which significantly enhanced fibroblast viability and proliferation. Taking into account the beneficial properties of Cur_11% biomaterial, it seems justified to subject it to more advanced cell culture experiments in vitro and to in vivo studies in order to determine its precise influence on skin wound healing.

Wound Fluid from Breast Cancer Patients Undergoing Intraoperative Radiotherapy Exhibits an Altered Cytokine Profile and Impairs Mesenchymal Stromal Cell Function.

Simple SummaryIntraoperative radiotherapy (IORT) is increasingly used in the therapy of early breast cancer. Besides the direct radiotoxic effects, IORT may add at inhibiting local recurrences by a modulation of the microenvironment. Our aim was to assess the impact of IORT in altering immunological responses and wound healing processes. Thus, we analyzed surgical wound fluid collected after breast conserving surgery with and without IORT concerning acute changes in immune cell populations and cytokine levels. Furthermore, their impact on functions of breast cancer cells and mammary mesenchymal stromal cells (MSC) was assessed. We found no changes in the immune cell composition, yet group-related differences in the expression levels of several cytokines. The application of the wound fluid in MSC cultures caused group-dependent differences in MSC proliferation, wound healing and migration with an alteration of the MSC secretome. Our findings help to elucidate the biological effects of IORT and to clarify the concomitant role of MSC.Intraoperative radiotherapy (IORT) displays an increasingly used treatment option for early breast cancer. It exhibits non-inferiority concerning the risk of recurrence compared to conventional external irradiation (EBRT) in suitable patients with early breast cancer. Since most relapses occur in direct proximity of the former tumor site, the reduction of the risk of local recurrence effected by radiotherapy might partially be due to an alteration of the irradiated tumor bed’s micromilieu. Our aim was to investigate if IORT affects the local micromilieu, especially immune cells with concomitant cytokine profile, and if it has an impact on growth conditions for breast cancer cells as well as mammary mesenchymal stromal cells (MSC), the latter considered as a model of the tumor bed stroma.42 breast cancer patients with breast-conserving surgery were included, of whom 21 received IORT (IORT group) and 21 underwent surgery without IORT (control group). Drainage wound fluid (WF) was collected from both groups 24 h after surgery for flow cytometric analysis of immune cell subset counts and potential apoptosis and for multiplex cytokine analyses (cytokine array and ELISA). It served further as a supplement in cultures of MDA-MB 231 breast cancer cells and mammary MSC for functional analyses, including proliferation, wound healing and migration. Furthermore, the cytokine profile within conditioned media from WF-treated MSC cultures was assessed. Flow cytometric analysis showed no group-related changes of cell count, activation state and apoptosis rates of myeloid, lymphoid leucocytes and regulatory T cells in the WF. Multiplex cytokine analysis of the WF revealed group-related differences in the expression levels of several cytokines, e.g., oncostatin-M, leptin and IL-1β. The application of WF in MDA-MB 231 cultures did not show a group-related difference in proliferation, wound healing and chemotactic migration. However, WF from IORT-treated patients significantly inhibited mammary MSC proliferation, wound healing and migration compared to WF from the control group. The conditioned media collected from WF-treated MSC-cultures also exhibited altered concentrations of VEGF, RANTES and GROα. IORT causes significant changes in the cytokine profile and MSC growth behavior. These changes in the tumor bed could potentially contribute to the beneficial oncological outcome entailed by this technique. The consideration whether this alteration also affects MSC interaction with other stroma components presents a promising gateway for future investigations.

Cultivation of Head and Neck Squamous Cell Carcinoma Cells with Wound Fluid Leads to Cisplatin Resistance via Epithelial-Mesenchymal Transition Induction.

Locoregional recurrence is a major reason for therapy failure after surgical resection of head and neck squamous cell carcinoma (HNSCC). The physiological process of postoperative wound healing could potentially support the proliferation of remaining tumor cells. The aim of this study was to evaluate the influence of wound fluid (WF) on the cell cycle distribution and a potential induction of epithelial-mesenchymal transition (EMT). To verify this hypothesis, we incubated FaDu and HLaC78 cells with postoperative WF from patients after neck dissection. Cell viability in dependence of WF concentration and cisplatin was measured by flow cytometry. Cell cycle analysis was performed by flow cytometry and EMT-marker expression by rtPCR. WF showed high concentrations of interleukin (IL)-6, IL-8, IL-10, CCL2, MCP-1, EGF, angiogenin, and leptin. The cultivation of tumor cells with WF resulted in a significant increase in cell proliferation without affecting the cell cycle. In addition, there was a significant enhancement of the mesenchymal markers Snail 2 and vimentin, while the expression of the epithelial marker E-cadherin was significantly decreased. After cisplatin treatment, tumor cells incubated with WF showed a significantly higher resistance compared with the control group. The effect of cisplatin-resistance was dependent on the WF concentration. In summary, proinflammatory cytokines are predominantly found in WF. Furthermore, the results suggest that EMT can be induced by WF, which could be a possible mechanism for cisplatin resistance.

640 Single-cell transcriptomics of human pressure ulcers reveals MHCII expressing keratinocytes in patients with a worse healing outcome

Pressure ulcer (PU) is a chronic non-healing wound caused by continuous pressure of the bodyweight to the skin, which is often seen in spinal cord injury patients and the bedridden elderly population. Despite high mortality, the pathophysiology of PU remains poorly understood. Here we compared single-cell transcriptomic profiles on human epidermal cells from PU wound-edges with uninjured skin and acute wounds (AW) from healthy donors. We identified significant shifts of cellular composition and gene expression pattern in PU wound-edges, which could stratify PU into two groups. Interestingly, our study identified a subset of keratinocytes expressing major histocompatibility complex class II (MHCII), and these cells are enriched in patients with worse healing outcomes. We showed that IFNg in PU-derived wound fluid could induce MHCII expression in keratinocytes, and these wound fluid-treated keratinocytes inhibit autologous T cell activation. In line with this, we found that T cells from PUs enriched with MHCII+ keratinocytes produced less inflammatory cytokines. Together, our study provides a high-resolution molecular map of human PU compared to AW and the skin, which sheds new insights into the understanding of PU pathology and the future development of tailored wound therapy.

Milieu matters: An in vitro wound milieu to recapitulate key features of, and probe new insights into, mixed-species bacterial biofilms

Bacterial biofilms are a major cause of delayed wound healing. Consequently, the study of wound biofilms, particularly in host-relevant conditions, has gained importance. Most in vitro studies employ refined laboratory media to study biofilms, representing conditions that are not relevant to the infection state. To mimic the wound milieu, in vitro biofilm studies often incorporate serum or plasma in growth conditions, or employ clot or matrix-based biofilm models. While incorporating serum or plasma alone is a minimalistic approach, the more complex in vitro wound models are technically demanding, and poorly compatible with standard biofilm assays. Based on previous reports of clinical wound fluid composition, we have developed an in vitro wound milieu (IVWM) that includes, in addition to serum (to recapitulate wound fluid), matrix elements and biochemical factors. With Luria-Bertani broth and Fetal Bovine Serum (FBS) for comparison, the IVWM was used to study planktonic growth, biofilm features, and interspecies interactions, of common wound pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. We demonstrate that the IVWM recapitulates widely reported in vivo biofilm features such as biomass formation, metabolic activity, increased antibiotic tolerance, 3D structure, and interspecies interactions for monospecies and mixed-species biofilms. Further, the IVWM is simple to formulate, uses laboratory-grade components, and is compatible with standard biofilm assays. Given this, it holds potential as a tractable approach to study wound biofilms under host-relevant conditions.

Prospective comparative study: metabolomics profiles of exudate and serum for patients with and without venous ulcer wound itch

Introduction: Itch is an unpleasant sensation that elicits the desire to scratch and can cause great distress, particularly in persons with venous ulcers. This pilot study explored the difference in metabolic profiles for wound exudate and serum in patients with or without venous ulcer wound itch. Methods: Patient information, wound assessment, and itch sensation ratings were recorded. Wound fluid and blood were collected for metabolomics assays. High-resolution mass spectrometry coupled with liquid chromatography and 1-dimensional proton nuclear magnetic resonance spectrometry were used to profile wound fluid and serum samples. Results: Patients (N=21) were included (ages: 32–91 y) with venous ulcers that itched (n=10) or did not itch (n=11). Metabolomic profiling discovered a previously unreported biochemical pathway for glycine, serine, and threonine metabolism in both serum and wound fluid significantly associated with itch. Using wound exudate, we developed diagnostic algorithms capable of discriminating between patients who itched and those who did not, with an area under the curve (95% confidence interval)=0.705 (0.461–0.948). Discussion: Our results demonstrate that the glycine-serine-threonine pathway is the most significantly altered metabolic pathway associated with venous ulcer itch. This pathway may serve as a biomarker for itch in patients with venous ulcers and help to identify itch before scratching further exasperates the ulcer. Studies with larger patient numbers are critically required to validate these findings. Our results may lead to novel therapeutic targets for the prophylactic treatment of itch.

Novel Negative-Pressure Wound Therapy System Provides Accurate Pressure Delivery and Exceptional Fluid Handling Capability.

Negative-pressure wound therapy (NPWT) is a widely accepted modality in the treatment of complex wounds.1 However, there are fundamental requirements2 not incorporated in all current NPWT systems that must be met in order to realize its full clinical benefits, which include (1) accurately delivering a set level of negative pressure to the wound bed, (2) creating a pressure gradient between the wound bed and the waste canister to efficiently remove fluid and prevent stagnation in the tubing, and (3) maintaining a sealed wound environment. The objective of this investigation3 was to use a simulated wound model to compare the ability of two NPWT systems (System A, Invia® Liberty™ [Medela AG] and System B, V.A.C.ULTA™ [3M+KCI]) to deliver set levels of NPWT and simultaneously manage volumes of simulated wound exudate.* TEST METHOD 1: ACCURATE PRESSURE DELIVERY TO THE WOUND BED This test assessed the ability of System A and System B to accurately deliver set pressure to the wound at three different heights with respect to the wound model and was repeated at two different pressure settings. Data were recorded three times at each height and pressure setting (Figure 1).Figure 1.: TEST METHODOLOGY FOR 1 M ABOVE, SAME LEVEL, AND 1 M BELOWResults. Both System A and System B accurately and precisely delivered the set level of negative pressure regardless of their position relative to the wound model without pressure loss. (Figure 1). TEST METHOD 2: EFFICIENT EXUDATE REMOVAL System A and System B were compared to assess their ability to efficiently remove simulated wound fluid at a pressure setting of −125 mmHg. The test was repeated three times per system. Wound models were dressed with the respective black foam dressing kits specific to each NPWT system, and the systems were set up to simulate the delivery of therapy with the wound and at the same height. After each system’s wound dressing was applied, therapy was initiated and allowed to reach a steady state (~10 minutes), and pressure sensors confirmed pressure at the wound bed of −125 mmHg. After this, 150 ml of simulated wound fluid was introduced into the wound model. Measurements of airflow cycles, pressure at the wound bed, and fluid weight in the canister were continuously recorded (Figure 2). This test method simulated a bolus fluid challenge and measured each NPWT system’s distinct ability to efficiently react and manage wound fluid. (The results shown here represent a set pressure of 125 mmHg with the device at the same level as the wound model; similar observations were made at a set pressure of −75 mmHg [data not shown].)Figure 2.: TEST METHOD AT THE SAME LEVELResults. System A removed simulated wound fluid more efficiently than System B, evacuating 89% of the fluid from the simulated wound into the canister in less than 20 minutes after introduction of the fluid. System B did not attain 89% fluid removal throughout the 125-minute duration of the experiment (Figure 3).Figure 3.: COMPARISON OF EXUDATE REMOVAL RATESIn less than 20 minutes, System A was able to reestablish a set pressure of −125 mmHg, returning patency and delivering consistent levels of therapy at the wound bed. System B fluctuated widely from the set pressure (−125 mmHg) throughout the test method. In addition, System B had frequent excursions that exceeded +/−10 mmHg of the set pressure, directly impacting its ability to maintain set pressure at the wound bed (Figure 4).Figure 4.: COMPARISON OF PRESSURE DELIVERY AT THE WOUND BEDCONCLUSIONS This study demonstrated the Intelligent Pressure Control™ and Dynamic Exudate Removal™ technologies provided by System A; it improved fluid management and helped reduce the risk of tubing blockages from simulated exudate while maintaining a set pressure at the wound bed. The results confirm the Intelligent Pressure Control™ feature illustrated by System A meets the standard of care. Further, the results of the bolus fluid challenge illustrate that the Dynamic Exudate Removal™ (unique to System A) allowed for faster and more efficient removal of fluid volumes while maintaining set pressure at the wound bed when compared with System B. Accordingly, System A innovates the standard of care.

Superabsorbent curdlan-based foam dressings with typical hydrocolloids properties for highly exuding wound management

Effective management of chronic wounds with excessive exudate may be challenging for medical doctors. Over the years, there has been an increasing interest in the engineering of biomaterials, focusing on the development of polymer-based wound dressings to accelerate the healing of exuding wounds. The aim of this study was to use curdlan, which is known to support wound healing, as a base for the production of superabsorbent hybrid biomaterials (curdlan/agarose and curdlan/chitosan) with the intended use as wound dressings for highly exuding wound management. To evaluate the biomedical potential of the fabricated curdlan-based biomaterials, they were subjected to a comprehensive assessment of their microstructural, physicochemical, and biological properties. The obtained results showed that foam-like biomaterials with highly porous structure (66–77%) transform into soft gel after contact with the wound fluid, acting as typical hydrocolloid dressings. Novel biomaterials have the superabsorbent ability (1 g of the biomaterial absorbs approx. 15 ml of exudate) with horizontal wicking direction while keeping dry edges, and show water vapor transmission rate of approx. 1700–1800 g/m2/day which is recommended for optimal wound healing. Moreover, they are stable in the presence of collagenases, but prone to biodegradation in lysozyme solution (simulated infected wound environment). Importantly, the developed biomaterials are non-toxic and their surface hinders fibroblast attachment, which is essential during dressing changes to avoid damage to newly formed tissues in the wound bed. All mentioned features make the developed biomaterials promising candidates to be used as the wound dressings for the management of chronic wounds with moderate to high exudate.

Designing moringa gum-sterculia gum-polyacrylamide hydrogel wound dressings for drug delivery applications

Herein this manuscript the potential of moringa gum and sterculia gum polysaccharides has been explored for developing the hydrogel wound dressing for better wound care. The polysaccharide gum and polyacrylamide network structure was formed through grafting and crosslinking polymerization. The cryo-SEM and AFM of the films indicated the porosity in the polymer films and roughness of the polymer surface. The polymers were also characterized by FTIR, and 13C NMR studies. The release of the antibiotic drug levofloxacin from polymer dressings occurred with non-Fickian diffusion mechanism. The blood compatibility, wound fluid absorption, antioxidant activity, mucoadhesion and mechanical properties were evaluated along with O2 and H2O permeability. The drug released fitted in Korsmeyer-Peppas kinetic model. The hydrogel films were permeable to O2 and H2O vapor and impermeable to microbes in open environment and showed high wound fluid absorption, mucoadhesion and antioxidant activity.