Chronic Wounds Research Articles

Impact of Epigenetics, Diet, and Nutrition-Related Pathologies on Wound Healing.

Chronic wounds pose a significant challenge to healthcare. Stemming from impaired wound healing, the consequences can be severe, ranging from amputation to mortality. This comprehensive review explores the multifaceted impact of chronic wounds in medicine and the roles that diet and nutritional pathologies play in the wound-healing process. It has been well established that an adequate diet is crucial to proper wound healing. Nutrients such as vitamin D, zinc, and amino acids play significant roles in cellular regeneration, immune functioning, and collagen synthesis and processing. Additionally, this review discusses how patients with chronic conditions like diabetes, obesity, and nutritional deficiencies result in the formation of chronic wounds. By integrating current research findings, this review highlights the significant impact of the genetic make-up of an individual on the risk of developing chronic wounds and the necessity for adequate personalized dietary interventions. Addressing the nutritional needs of individuals, especially those with chronic conditions, is essential for improving wound outcomes and overall patient care. With new developments in the field of genomics, there are unprecedented opportunities to develop targeted interventions that can precisely address the unique metabolic needs of individuals suffering from chronic wounds, thereby enhancing treatment effectiveness and patient outcomes.

Global Trends of Exosomes Application in Clinical Trials: A Scoping Review.

Exosomes, nano-sized extracellular vesicles, have emerged as a promising tool for the diagnosis and treatment of various intractable diseases, including chronic wounds and cancers. As our understanding of exosomes continues to grow, their potential as a powerful therapeutic modality in medicine is also expanding. This systematic review aims to examine the progress of exosome-based clinical trials and provide a comprehensive overview of the therapeutic perspectives of exosomes. This systematic review strictly follows PRISMA guidelines and has been registered in PROSPERO, the International Prospective Register of Systematic Reviews. It encompasses articles from January 2000 to January 2023, sourced from bibliographic databases, with targeted search terms targeting exosome applications in clinical trials. During the screening process, strict inclusion and exclusion criteria were applied, including a focus on clinical trials utilizing different cell-derived exosomes for therapeutic purposes. Among the 522 publications initially identified, only 10 studies met the stringent eligibility criteria after meticulous screening. The selection process involved systematically excluding duplicates and irrelevant articles to provide a transparent overview. According to our systematic review, exosomes have promising applications in a variety of medical fields, including cell-free therapies and drug delivery systems for treating a variety of diseases, especially cancers and chronic wounds. To ensure safety, potency, and broader clinical applications, further optimization of exosome extraction, loading, targeting, and administration is necessary. While cell-based therapeutics are increasingly utilizing exosomes, this field is still in its infancy, and ongoing clinical trials will provide valuable insights into the clinical utility of exosomes.

Development of Halloysite Nanohybrids-Based Films: Enhancing Mechanical and Hydrophilic Properties for Wound Healing.

Most of the therapeutic systems developed for managing chronic skin wounds lack adequate mechanical and hydration properties, primarily because they rely on a single component. This study addresses this issue by combining organic and inorganic materials to obtain hybrid films with enhanced mechanical behavior, adhesion, and fluid absorption properties. To that aim, chitosan/hydrolyzed collagen blends were mixed with halloysite/antimicrobial nanohybrids at 10% and 20% (w/w) using glycerin or glycerin/polyethylene glycol-1500 as plasticizers. The films were characterized through the use of Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and electron microscopy. The mechanical properties were evaluated macroscopically using tensile tests, and at a nanoscale through atomic force microscopy (AFM) and nanoindentation. Thermodynamic studies were conducted to assess their hydrophilic or hydrophobic character. Additionally, in vitro cytocompatibility tests were performed on human keratinocytes. Results from FTIR, TGA, AFM and electron microscopy confirmed the hybrid nature of the films. Both tensile tests and nanomechanical measurements postulated that the nanohybrids improved the films' toughness and adhesion and optimized the nanoindentation properties. All nanohybrid-loaded films were hydrophilic and non-cytotoxic, showcasing their potential for skin wound applications given their enhanced performance at the macro- and nanoscale.

Assessment and Monitoring of the Wound Micro-Environment in Chronic Wounds Using Standardized Wound Swabbing for Individualized Diagnostics and Targeted Interventions.

Background/Objectives: Patient-specific diagnostic and therapeutic approaches are important in the care of people with chronic wounds. The heterogeneity of underlying disease profiles and the diversity of the wound micro-environment make generalized approaches difficult. While high-throughput molecular diagnostic methods are increasingly widespread and available, the analysis of objective biomolecular disease patterns has not found its way into everyday wound management. The aim of this study is to evaluate the use of wound swab samples for the analysis of biomarkers and disease patterns in people with chronic wounds. Methods: A sample cohort from the multicenter "Wound-BIOME" project was analyzed. The project aims to comprehensively investigate the local micro-environment of chronic wounds of various entities, healing tendencies and regeneration stages at the biomolecular level. A sample collection and handling protocol suitable for everyday use was tested and evaluated regarding feasibility for multiplex immunoassay, proteomics, small RNA sequencing (miRNA) and metagenome analyses (microbiomics). Results: It could be shown that standard wound swabs are well-suited for the analysis of the complex wound micro-environment using various high-throughput methods. Despite the sample heterogeneity, the quality was adequate to analyze biomolecular patterns. Conclusions: Initial analyses of protein signatures, microbial wound communities and miRNA patterns show promising results for future individualized diagnostics and targeted interventions.

Advanced alginate-based nanofiber aerogels: A synthetic matrix for high-efficiency lysozyme adsorption and controlled release

The development of materials with high lysozyme adsorption is critical for drug delivery and skin wound applications, as it enhances antibacterial properties, stability, and controlled release of therapeutic agents, thereby improving treatment efficacy and safety. Alginate-based nanofiber scaffolds, featuring high surface area and multiple adsorption sites, can efficiently absorb lysozyme and regulate its release through tunable pore channels, offering a promising approach to chronic wound management. In this study, we fabricated poly (vinyl alcohol-co-ethylene) (EVOH) nanofiber-based sodium alginate (ENSA) aerogels using a simple two-step crosslinking procedure. The resulting aerogels, with controllable porosity formed via high-pressure spraying techniques (aerogel film) and molding (aerogel sponge), were evaluated for their high-loading capacity and controllable release of lysozyme. The aerogel film exhibited a remarkable lysozyme adsorption capacity of 1965 ± 36 mg/g, while the aerogel sponge sustained lysozyme release over 14 days. Analysis of the drug-release mechanism through four kinetic models revealed two distinct processes: cation exchange and matrix diffusion. The aerogel's pore structure influenced the diffusion processes, enabling tailored drug release profiles. Additionally, the ENSA aerogels demonstrated good mechanical properties, non-cytotoxicity, and potent antibacterial activity, positioning them as promising materials for skin wound dressings.

Production and Characterization of Electrospun Chitosan, Nanochitosan and Hyaluronic Acid Membranes for Skin Wound Healing.

The development of new wound dressings made from biomaterials, which offer a better cost-benefit ratio and accelerate the healing process, is increasing nowadays. Various biopolymers can be electrospun to form functional membranes for wound healing. Therefore, in this study, chitosan and nanochitosan membranes with or without hyaluronic acid were prepared using the electrospinning technique, characterized and evaluated in the healing of skin wounds in rats. Chitosan and nanochitosan solutions, with or without hyaluronic acid, were prepared at concentrations of 1%-4% using PEO (polyethylene oxide) and subjected to the electrospinning process to obtain membranes characterized by scanning electron microscopy (SEM), mechanical tests, and antimicrobial activity. The healing effect of the membranes was evaluated by monitoring the area of the lesions, contraction of the wounds, histologic analysis, and induction of pro-inflammatory cytokine (IL-1 α and TNF-α) production in rats. The nanochitosan and nanochitosan membranes with hyaluronic acid achieved greater fiber diameter and uniformity, resistance, elasticity, and thermal stability, in addition to good adhesion to the wound bed and permeation capacity. Despite not presenting antimicrobial activity in vitro, they contributed to the production of pro-inflammatory interleukins in the animals tested, provided physical protection, reduced the wound area more markedly until the seventh day of the evaluation, with an acceleration of the healing process and especially when functionalized with hyaluronic acid. These results indicate that the membranes may be promising for accelerating the healing process of chronic wounds in humans.

Using Hybrid MnO2-Au Nanoflowers to Accelerate ROS Scavenging and Wound Healing in Diabetes

Objectives: Excessive reactive oxygen species (ROS) in diabetic wounds are major contributors to chronic wounds and impaired healing, posing significant challenges in regenerative medicine. Developing innovative drug delivery systems is crucial to address these issues by modifying the adverse microenvironment and promoting effective wound healing. Methods: Herein, we designed a novel drug delivery platform using manganese dioxide nanoflower hybridized gold nanoparticle composites (MnO2-Au) synthesized via a hydrothermal reaction, and investigated the potential of MnO2-Au nanoflowers to relieve the high oxidative stress microenvironment and regulate diabetic wound tissue healing. Results: This hybrid material demonstrated superior catalytic activity compared to MnO2 alone, enabling the rapid decomposition of hydrogen peroxide and a substantial reduction in ROS levels within dermal fibroblasts. The MnO2-Au nanoflowers also facilitated enhanced dermal fibroblast migration and Col-I expression, which are critical for tissue regeneration. Additionally, a hydrogel-based wound dressing incorporating MnO2-Au nanoflowers was developed, showing its potential as an intelligent drug delivery system. This dressing significantly reduced oxidative stress, accelerated wound closure, and improved the quality of neonatal epithelial tissue regeneration in a diabetic rat skin defect model. Conclusions: Our findings underscore the potential of MnO2-Au nanoflower-based drug delivery systems as a promising therapeutic approach for chronic wound healing, particularly in regenerative medicine.

Galectin-3/Gelatin Electrospun Scaffolds Modulate Collagen Synthesis in Skin Healing but Do Not Improve Wound Closure Kinetics.

Chronic wounds remain trapped in a pro-inflammatory state, with strategies targeted at inducing re-epithelialization and the proliferative phase of healing desirable. As a member of the lectin family, galectin-3 is implicated in the regulation of macrophage phenotype and epithelial migration. We investigated if local delivery of galectin-3 enhanced skin healing in a full-thickness excisional C57BL/6 mouse model. An electrospun gelatin scaffold loaded with galectin-3 was developed and compared to topical delivery of galectin-3. Electrospun gelatin/galectin-3 scaffolds had an average fiber diameter of 200 nm, with 83% scaffold porosity approximately and an average pore diameter of 1.15 μm. The developed scaffolds supported dermal fibroblast adhesion, matrix deposition, and proliferation in vitro. In vivo treatment of 6 mm full-thickness excisional wounds with gelatin/galectin-3 scaffolds did not influence wound closure, re-epithelialization, or macrophage phenotypes, but increased collagen synthesis. In comparison, topical delivery of galectin-3 [6.7 µg/mL] significantly increased arginase-I cell density at day 7 versus untreated and gelatin/galectin-3 scaffolds (p < 0.05). A preliminary assessment of increasing the concentration of topical galectin-3 demonstrated that at day 7, galectin-3 [12.5 µg/mL] significantly increased both epithelial migration and collagen content in a concentration-dependent manner. In conclusion, local delivery of galectin 3 shows potential efficacy in modulating skin healing in a concentration-dependent manner.

Preparation of photo-crosslinked microalgae-carboxymethyl chitosan composite hydrogels for enhanced wound healing

Integrating microalgae into wound dressings has proven effective in promoting chronic wound healing through photosynthesis-induced oxygen release. However, challenges such as high crosslinking temperatures and prolonged gel molding processes limit microalgae growth and reduce the overall therapeutic impact. In this work, inspired by cell-symbiotic photo-crosslinked hydrogels, we present a novel photo-crosslinked microalgae carboxymethyl chitosan composite hydrogel. This hydrogel completes crosslinking at room temperature within 30 s, enhancing chronic wound healing. The composite gel incorporates photosynthesizing unicellular microalgae (Chlamydomonas reinhardtii) and the antimicrobial agent ciprofloxacin during preparation. In light, the gel continues to photosynthesize, releasing oxygen while simultaneously acting as an antibacterial agent. This dual action results in the upregulation of CD31 and VEGFA levels and the downregulation of HIF-1α levels in diabetic wounds. The wound closure rate reached approximately 96.70 % on day 12 in the composite gel group, compared to only 78.98 % in the control group. Therefore, the composite gel promotes healing by reducing local hypoxia, encouraging angiogenesis, and lowering infection risk. These results suggest that photo-crosslinked microalgae composite gels provide an effective strategy for localized oxygen delivery to promote wound healing and offer a viable method for rapidly preparing living biomaterials under suitable conditions.

A Prospective, Interventional, Comparative Study to Evaluate the Efficacy of Using Combined Platelet-Rich Plasma and Platelet-Rich Fibrin Over Standard Cleaning and Dressing in Chronic Wounds.

Chronic wounds are defined as wounds that have failed to proceed through the orderly process that produces satisfactory anatomic and functional integrity or that have proceeded through the repair process without producing an adequate anatomic and functional result. The majority of wounds that have not healed in three months are considered chronic, although a duration as low as four weeks has been used to indicate chronicity.Our study aimed to compare the efficacy of autologous platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) versus standard cleaning and dressing as a regenerative medicine strategy to promote healing in chronic wounds. A prospective randomized controlled trial was undertaken to test the efficacy of autologous PRPand PRFin the healing of chronic wounds. A series of 60 cases was compiled from patients attending the outpatient department regularly for the management of chronic wounds. A total of 30 cases were randomly chosen for study with autologous PRP and PRF and 30 cases received conventional dressing. The average healing duration in the study was significantly shorter for the PRP & PRF group. The mean healing time for this group was 4.45 weeks (31.2 ± 3.07 days) compared to 9.61 weeks (67.27 ± 9.19 days) for the conventional dressing group. PRP and PRF belong to a new generation of platelet concentrates that help efficaciously for enhanced healing and functional recovery, safely and cost-effectively. They help by shortening the recovery period overall, improving the quality of life of patients, and altogether eliminating the additional morbidity of operative procedures.

Immunomodulatory hydrogel orchestrates pro-regenerative response of macrophages and angiogenesis for chronic wound healing

Chronic wound healing often encounters challenges characterized by prolonged inflammation and impaired angiogenesis. While the immune response plays a pivotal role in orchestrating the intricate process of wound healing, excessive inflammation can hinder tissue repair. In this study, a bilayer alginate hydrogel system encapsulating polyelectrolyte complex nanoparticles (PCNs) loaded with anti-inflammatory cytokines and angiogenic growth factors is developed to address the challenges of chronic wound healing. The alginate hydrogel is designed using two distinct crosslinking methods to achieve differential degradation, thereby enabling precise spatial and temporal controlled release of PCNs. Initially, interleukin-10 (IL-10) is released to mitigate inflammation, while unsaturated PCNs bind and remove accumulated pro-inflammatory cytokines at the wound site. Subsequently, angiogenic growth factors, including vascular endothelial growth factor and platelet-derived growth factor, are released to promote vascularization and vessel maturation. Our results demonstrate that the bilayer hydrogel exhibits distinct degradation kinetics between the two layers, facilitating the staged release of multiple signaling molecules. In vitro experiments reveal that IL-10 can activate the Jak1/STAT3 pathway, thereby suppressing pro-inflammatory cytokines and chemokines while down-regulating inflammation-related genes. In vivo studies demonstrate that application of the hydrogel in chronic wounds using diabetic murine model promotes healing by positively modulating multiple integral reparative mechanisms. These include reducing inflammation, promoting macrophage polarization towards a pro-regenerative phenotype, enhancing keratinocyte migration, stimulating angiogenesis, and expediting wound closure. In conclusion, our hydrogel system effectively mitigates inflammatory responses and provides essential physiological cues by inducing a synergistic angiogenic effect, thus offering a promising approach for the treatment of chronic wounds.

Application of self powered black phosphorus nanosheets-based hydrogel skin patch in wound healing of diabetes

Diabetes mellitus-related chronic non-healing wounds have greatly lowered the quality of life for people afflicted and placed a heavy financial burden on the healthcare system. In order to hasten the healing of diabetic wounds, a wearable hydrogel-based triboelectric nanogenerator (BP-TENG) was created as a skin patch, which combines the beneficial effects of electrical and photothermal stimulation. The triboelectric output performance of the BP-TENG was adjusted and photothermal conversion capacity was brought about by the black phosphorus nanosheets (BPNS) doped in PVA hydrogel. In just 60 seconds, BP-TENG managed to bring the temperature of the mouse wound region up to 48.6°C under the irradiation of 808 nm near-infrared light. BP-TENG also exhibited spectral antibacterial activity against E. coli, S. aureus, and P. aeruginosa. Furthermore, BP-TENG had the ability to capture the energy from mechanical movements of mice and transform it into electrical stimulation. Under 808 nm near-infrared light irradiation, BP-TENG was shown to significantly speed the healing of skin wounds in the incision mouse model of type I diabetes. According to in vitro research, these benefits may be ascribed to photothermal and electric stimulation, which can both repair the healthy microenvironment of wound area and speed up the deposition and remodeling of collagen during the healing process of diabetic wounds. As far as we are aware, this is the first report on the creation and use of hydrogel-based TENG doped with BP for wound healing. We believe that this study improves the quality of life for patients with persistent non-healing wounds and opens up new possibilities for 2D materials and TENG in the application of wearable healthcare devices.

Assessing Biofilm at the Bedside: Exploring Reliable Accessible Biofilm Detection Methods.

Biofilm is linked through a variety of mechanisms to the pathogenesis of chronic wounds. However, accurate biofilm detection is challenging, demanding highly specialized and technically complex methods rendering it unapplicable for most clinical settings. This study evaluated promising methods of bedside biofilm localization, fluorescence imaging of wound bacterial loads, and biofilm blotting by comparing their performance against validation scanning electron microscopy (SEM). In this clinical trial, 40 chronic hard-to-heal wounds underwent the following assessments: (1) clinical signs of biofilm (CSB), (2) biofilm blotting, (3) fluorescence imaging for localizing bacterial loads, wound scraping taken for (4) SEM to confirm matrix encased bacteria (biofilm), and (5) PCR (Polymerase Chain Reaction) and NGS (Next Generation Sequencing) to determine absolute bacterial load and species present. We used a combination of SEM and PCR microbiology to calculate the diagnostic accuracy measures of the CSB, biofilm blotting assay, and fluorescence imaging. Study data demonstrate that 62.5% of wounds were identified as biofilm-positive based on SEM and microbiological assessment. By employing this method to determine the gold truth, and thus calculate accuracy measures for all methods, fluorescence imaging demonstrated superior sensitivity (84%) and accuracy (63%) compared to CSB (sensitivity 44% and accuracy 43%) and biofilm blotting (sensitivity 24% and accuracy 40%). Biofilm blotting exhibited the highest specificity (64%), albeit with lower sensitivity and accuracy. Using SEM alone as the validation method slightly altered the results, but all trends held constant. This trial provides the first comparative assessment of bedside methods for wound biofilm detection. We report the diagnostic accuracy measures of these more feasibly implementable methods versus laboratory-based SEM. Fluorescence imaging showed the greatest number of true positives (highest sensitivity), which is clinically relevant and provides assurance that no pathogenic bacteria will be missed. It effectively alerted regions of biofilm at the point-of-care with greater accuracy than standard clinical assessment (CSB) or biofilm blotting paper, providing actionable information that will likely translate into enhanced therapeutic approaches and better patient outcomes.

Commercial Silver-Based Dressings: In Vitro and Clinical Studies in Treatment of Chronic and Burn Wounds.

Chronic wounds are a major health problem because of delayed healing, causing hardships for the patient. The infection present in these wounds plays a role in delayed wound healing. Silver wound dressings have been used for decades, beginning in the 1960s with silver sulfadiazine for infection prevention for burn wounds. Since that time, there has been a large number of commercial silver dressings that have obtained FDA clearance. In this review, we examine the literature involving in vitro and in vivo (both animal and human clinical) studies with commercial silver dressings and attempt to glean the important characteristics of these dressings in treating infected wounds. The primary presentation of the literature is in the form of detailed tables. The narrative part of the review focuses on the different types of silver dressings, including the supporting matrix, the release characteristics of the silver into the surroundings, and their toxicity. Though there are many clinical studies of chronic and burn wounds using silver dressings that we discuss, it is difficult to compare the performances of the dressings directly because of the differences in the study protocols. We conclude that silver dressings can assist in wound healing, although it is difficult to provide general treatment guidelines. From a wound dressing point of view, future studies will need to focus on new delivery systems for silver, as well as the type of matrix in which the silver is deposited. Clearly, adding other actives to enhance the antimicrobial activity, including the disruption of mature biofilms is of interest. From a clinical point of view, the focus needs to be on the wound healing characteristics, and thus randomized control trials will provide more confidence in the results. The application of different wound dressings for specific wounds needs to be clarified, along with the application protocols. It is most likely that no single silver-based dressing can be used for all wounds.

Essential oils: a potential alternative with promising active ingredients for pharmaceutical formulations in chronic wound management.

Chronic wound is a major clinical challenge that complicates wound healing, mainly associated with bacterial biofilms. Bacterial burden damages tissue and persists inflammation, failing to granulate, leading to morbidity and mortality. Various therapeutic strategies and approaches have been developed for chronic wound healing in clinical practice. As treating biofilm infection is crucial in chronic wounds, a potent antibiofilm agent, essential oils have been explored extensively for their therapeutic properties and as a replacement for antibiotic therapy. Currently, several studies on essential oils and their active compounds in therapeutics, such as adjunctive therapies, nanotechnology-based treatment and their drug delivery systems, help heal chronic wounds. The antimicrobial, anti-inflammatory and antioxidant properties of essential oils make them distinct and are renowned as natural remedies to improve the healing of infected chronic wounds. Consequently, it accelerates wound closure by reducing inflammation, increasing angiogenesis and tissue regeneration. This review focuses on different essential oils and their active compounds that are exploited for the treatment of biofilm infection, chronic inflammation and wound healing. Thus, an effective novel treatment can be developed to improve the current treatment strategy to overcome multidrug resistance bacteria or antibiotic resistance in various chronic wound infections that support wound healing.

Economic burden and health-related quality of life in patients with epidermolysis bullosa in Spain

Background. Epidermolysis bullosa (EB) is a rare genetic skin disorder characterized by fragility of skin with appearance of acute and chronic wounds. The aim of this study was to determine the economic burden and the health-related quality of life (HRQoL) of patients with epidermolysis bullosa (EB) in Spain from a societal perspective.Methods. We conducted a cross-sectional, retrospective study including 62 patients with EB (62% dystrophic, 9.6% junctional, 3.2% Kindler syndrome, and 26% with simplex EB). Data were collected from questionnaires completed by patients or their caregivers. The costs were estimated, including not only direct healthcare costs but also direct non-healthcare costs and productivity losses. We compared severe EB (Dystrophic, Junctional EB and Kindler syndrome) to non-severe EB (simplex EB) using as reference year 2022. HRQoL was measured by generic (EQ-5D) and specific (QoLEB) questionnaires.ResultsThe average annual cost for an EB patient was €31,352. Direct healthcare costs represented 17.2% of the total cost, direct non-healthcare costs (mainly informal care costs) 71.3% and productivity losses 11.5% of the total cost. Participants in the severe EB group had a slightly higher average cost than participants in the non-severe EB group (€31,706 vs. €30,337). Direct healthcare costs and non-healthcare costs were higher in the severe EB group (€6,205 vs. €3,024 and €23,148 vs. €20,113) while productivity losses were higher in the non-severe EB group (€7,200 vs. €2,353). The mean utility index score, where the maximum value possible is one, was 0.45 for patients with severe EB (0.76 for their caregivers) and 0.62 for those with non-severe EB (0.77 for their caregivers).Conclusions. The social economic burden of EB, resulting from the high direct non-healthcare cost of informal care, and from the loss of productivity, accentuates the importance of not restricting cost analysis to direct healthcare costs. This substantiates that EB, particularly severe EB represents a significant hidden cost that should be revealed to society and should be considered in the support programmes for people who suffer from this disease, and in the economic evaluation of new treatments.

A ROS‐Responsive Lipid Nanoparticles Release Multifunctional Hydrogel Based on Microenvironment Regulation Promotes Infected Diabetic Wound Healing

AbstractThe continuous imbalance of the diabetic wound microenvironment is an important cause of chronic nonhealing, which manifests as a vicious cycle between excessive accumulation of reactive oxygen species (ROS) and abnormal healing. Regulating the microenvironment by suppressing wound inflammation, oxidative stress, and bacterial infection is a key challenge in treating diabetic wounds. In this study, ROS‐responsive hydrogels are developed composed of silk fibroin methacrylated (SFMA), modified collagen type III (rCol3MA), and lipid nanoparticles (LNPs). The newly designed hydrogel system demonstrated stable physicochemical properties and excellent biocompatibility. Moreover, the release of antimicrobial peptide (AMP) and puerarin (PUE) demonstrated remarkable efficacy in eradicating bacteria, regulating inflammatory responses, and modulating vascular functions. This multifunctional hydrogel is a simple and efficient approach for the treatment of chronic diabetic infected wounds and holds tremendous potential for future clinical applications.

Enhanced wound healing effects of nanoscale lipid-diclofenac conjugates

Cold burn wounds have protracted and destructive effects on the body, like contracture, hypertrophic scars, and necrosis. Around 6.5 million people in the US are affected by chronic wounds every year. Different approaches have been utilized to cure this ailment, including cell-based therapy, drug based therapy, and temporary wound dressings, but no single treatment has been effective. Therefore, researchers are constantly searching for alternative therapeutic options. The present study evaluated the effects of nanoscale lipid-diclofenac conjugate (NLDCs) on cold-induced burn wounds. After NLDCs preparation and characterization, the therapeutic potential of them were evaluated. NLDCs exhibited better cell migration (in vitro), wound regeneration which in turn showed enhanced wound healing potential compared to diclofenac (positive control). Cell migration and wound closure in vitro was monitored by scratch assay. In vivo, a cold burn wound model was developed by direct exposure of the dorsal rat skin to liquid nitrogen. NLDCs were subcutaneously injected after 15 min of burn wound induction. The gross macroscopic examination of wound tissues was performed at days 1, 4, 8, and 16. Wound regeneration was observed in control (untreated) and treated groups (diclofenac and NLDCs). The wound regeneration was subsequently assessed by histological, gene expression, and immunohistochemical analyses at the early (day 8) and late (day 16) phases of wound healing. Scratch assay exhibited enhanced cell migration towards scratch area in the treated groups compared to the control. Macroscopic examination revealed early scab formations at day 8 in treated groups, while complete regeneration was only observed in the NLDCs group at day 16. Histological findings showed enhanced regeneration of skin layers along with hair follicles in the NLDCs treated group, while increased neovascularization was noted in both the treated groups. Gene expression profile of wound healing mediators showed downregulation of inflammatory (IL-1β, IL-6, and TNF-α) and Pain (COX-2, YKL-40, and Substance-7) markers and upregulation of angiogenic and remodeling (VEGF, TGFβ, FGF, PDGF, MMP-9, and EGF) markers at respective time points. In conclusion, NLDCs are potential anti-inflammatory, pain relieving, and wound healing agents. Prospects; We are optimistic that the NLDCs development and their scale-up production may pave the way towards clinical translation of nanomedicine in the management of pain, inflammation, and wound complications.

Bioactive Curcuma aromatica-stabilized silver nanoparticles embedded chitosan dressing with improved antibacterial, anti-inflammatory, and wound healing properties

Chronic wounds, particularly those infected with multidrug-resistant (MDR) pathogens, present significant challenges for effective healing. Silver nanoparticles (CAAgNPs) were synthsized using aqueous rhizome extract of Curcuma aromatica (CA), known for its wound-healing properties. CAAgNPs were incorporated in a chitosan (CS) dressing (CAAgNPs/CS) and tested for their wound healing potential, expecting synergistic action of AgNPs and phytochemicals capped on it. The porous nature of the CAAgNPs was confirmed using Field emission scanning electron microscopy. Fourier-transform infrared spectroscopy demonstrated a shift in peak intensity from 1589.06 to 1575.54 cm-1 for CAAgNPs/CS dressing confirming crosslinking with glutaraldehyde. Antibacterial activity of the dressings was cofirmed against isolates of Pseudomonas aeruginosa and Staphylococcus aureus. Wound healing studies were carried out using Wistar rats (six groups)- wound control, CS, CAAgNPs256/CS, CAAgNPs512/CS, CAAgNPs1024/CS, and commercial dressings. Histological examination and direct red-80 staining demonstrated maximum epithelization and collagen deposition (58.02%) within CAAgNPs1024/CS groups on day 10. Increased hydroxyproline levels (76.51 µg/mL) on day 7 for CAAgNPs1024/CS indicated maximum collagen formation. Reduced levels of inflammatory cytokines IL-6 (17.38 pg/mL) and TNF-α (80.38 pg/mL) on day 10 indicated quick wound healing without scar formation and damaging effects. The present study highlights the antibacterial and anti-inflammatory properties of CAAgNPs1024/CS dressings with a potential for wound healing applications.

Synthesis and characterization of a novel dual sensitive iron nanoparticles incorporated Schiff base composite hydrogel for diabetic wound healing therapy

Chronic wounds in diabetic patients deteriorate into multiple infections. A multifunctional transdermal material with high self-healing ability, remodeling capability, antibacterial and radicle scavenging activity, and an excellent multi-sensitive carrier was needed to promote wound healing. For that, Oxidized Cellulose (OC) and gelatin (GLN) are selected to construct a dual drug-loaded Schiff base hydrogel with iron nanoparticle (IONPS) incorporation for the controlled and sustained release of Insulin (INS) and Metfomin (MET), which synergistically promote wound repair. The INS/MET-IONPS-OC/GLN hydrogel drug payload was characterized using FT-IR, XRD, DLS, ZETA, TG, FE-SEM, TEM, and VSM analysis. The high drug loading and encapsulation efficiency were 93.20 % and 98.8 % for INS and 90.2 % and 95.1 % for MET, respectively. The temperature-sensitive drug release (92.0 % of INS and 90.0 % of MET) percentage is much better than the pH-sensitive drug release (83.5 % of INS and 80.2 % of MET). Above 90.0 % viability in MTT and apoptosis assay reveals the nontoxic nature of the INS/MET-IONPS-OC/GLN towards L929 normal cell lines. The zone of inhibition value of 12 and 15 mm in gram-negative bacteria reveals the anti-bacterial effect. The antioxidant activity of the carrier shields the cells against reactive oxygen species promotes healing rate ensures by DPPH assay.The cell proliferation and angiogenesis were confirmed by scratch assay on L929 cell lines in diabetic and non-diabetic conditions, showing the healing ability of the INS/MET-IONPS-OC/GLN hydrogel.