Search Results (28)

Negative pressure wound therapy (NPWT) is widely recognized for its efficacy in treating diabetic wounds, but the mechanisms involved in the wound healing process remain unclear. By examining changes in blood cytokine levels as molecular signaling precursors, we aim to provide a comprehensive cytokine profile to support adjunctive therapy research and clinical applications. A diabetic mouse wound model was established to compare cytokine profiles between NPWT-treated and standard dressing groups, identifying key signaling candidates that may facilitate wound healing. By integrating normal mouse data with large-scale cytokine analysis, we developed a time-stratified NPWT approach to track acute-phase cytokine fluctuations in diabetic conditions. NPWT did not significantly enhance coagulation-related cytokine expression but effectively reduced inflammation, albeit with a delayed regulatory effect compared to wild-type mice. A one-sided binomial test revealed that NPWT advanced the cytokine expression peak from 16 to 2 h, partially restoring the early healing pattern seen in normal mice and suggesting its potential role in modulating early-stage wound repair. These findings provide novel insights into early cytokine regulation during wound healing and highlight the potential of NPWT to inform therapeutic strategies. This refined monitoring approach may contribute to improved clinical decision-making and support enhanced wound management in diabetic patients. Full article

Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%. Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in metabolic syndrome, and more elective surgeries. To heal a wound, an orchestrated, evolutionarily conserved, and complex series of events involving cellular and molecular agents at the local and systemic levels are necessary. The principal factors of this important function include elements from the neurological, cardiovascular, immune, nutritional, and endocrine systems. The objectives of this review are to provide clinicians engaged in wound care and basic science researchers interested in wound healing with an updated synopsis from recent publications. We also present data from our primary investigations, testing the hypothesis that cannabidiol can alter cutaneous wound healing and documenting their effects in wild type (C57/BL6) and db/db mice (Type 2 Diabetes Mellitus, T2DM). The focus is on the potential roles of the endocannabinoid system, cannabidiol, and the important immune-regulatory wound cytokine IL-33, a member of the IL-1 family, and connective tissue growth factor, CTGF, due to their roles in both normal and abnormal wound healing. We found an initial delay in the rate of wound closure in B6 mice with CBD, but this difference disappeared with time. CBD decreased IL-33 + cells in B6 by 70% while nearly increasing CTGF + cells in db/db mice by two folds from 18.6% to 38.8% (p < 0.05) using a dorsal wound model. We review the current literature on normal and abnormal wound healing, and document effects of CBD in B6 and db/db dorsal cutaneous wounds. CBD may have some beneficial effects in diabetic wounds. We applied 6–mm circular punch to create standard size full-thickness dorsal wounds in B6 and db/db mice. The experimental group received CBD while the control group got only vehicle. The outcome measures were rate of wound closure, wound cells expressing IL-33 and CTGF, and ILC profiles. In B6, the initial rate of wound closure was slower but there was no delay in the time to final closure, and cells expressing IL-33 was significantly reduced. CTGF + cells were higher in db/bd wounds treated with CBD. These data support the potential use of CBD to improve diabetic cutaneous wound healing. Full article

The present study compares sugarcane-wax purified policosanols sourced from Cuba (Raydel^®) and China (BOC Sciences) and utilized following the synthesis of reconstituted high-density lipoproteins (rHDL). The two policosanols exhibited distinctly different ingredient ratios of long-chain aliphatic alcohols, particularly 1-octacosanol (C28) and 1-tetratriacotanol (C34). After synthesizing rHDL with apolipoprotein A-I (apoA-I), the two policosanols bound well with phospholipid and apoA-I to form the discoidal rHDL. Notably, rHDL-1, containing Cuban policosanol, displayed the largest particle diameter at approximately 78 ± 3 nm. In contrast, both control rHDL (rHDL-0) and rHDL containing Chinese policosanol (rHDL-2) exhibited smaller particles, with diameters of approximately 58 ± 3 nm and 61 ± 2 nm, respectively. Furthermore, rHDL-1 demonstrated enhanced anti-glycation activity, safeguarding apoA-I from degradation within HDL, and displayed the antioxidant ability to inhibit LDL oxidation. A microinjection of each rHDL into zebrafish embryos in the presence of carboxymethyllysine (CML) revealed rHDL-1 to have the strongest antioxidant activity with the highest embryo survivability and normal developmental morphology. Dermal application to recover the wound revealed rHDL-1 to have the highest wound-healing activity (75%) and survivability (92%) in the cutaneous wound area in the presence of CML. In adult zebrafish, injecting CML (250 μg) caused acute death and hyperinflammation, marked by heightened neutrophil infiltration and interleukin (IL)-6 production in liver. However, co-administering rHDL-1 notably increased survival (85%) and exhibited strong anti-inflammatory properties, reducing IL-6 production while improving the blood lipid profile. However, a co-injection of rHDL-2 resulted in the lowest survivability (47%) with more hepatic inflammation. In conclusion, Cuban policosanol (Raydel^®) has more desirable properties for the in vitro synthesis of rHDL with stronger anti-glycation and antioxidant activities than those of Chinese policosanol (BOC Sciences). Moreover, Raydel-policosanol-integrated rHDL demonstrates a noteworthy effect on accelerated wound healing and robust anti-inflammatory properties, leading to increased survivability in zebrafish embryos and adults by effectively suppressing CML-induced hyperinflammation. Full article

The inability of wounds to heal effectively through normal repair has become a burden that seriously affects socio-economic development and human health. The therapy of acute and chronic skin wounds still poses great clinical difficulty due to the lack of suitable functional wound dressings. It has been found that dressings made of polyurethane exhibit excellent and diverse biological properties, but lack the functionality of clinical needs, and most dressings are unable to dynamically adapt to microenvironmental changes during the healing process at different stages of chronic wounds. Therefore, the development of multifunctional polyurethane composite materials has become a hot topic of research. This review describes the changes in physicochemical and biological properties caused by the incorporation of different polymers and fillers into polyurethane dressings and describes their applications in wound repair and regeneration. We listed several polymers, mainly including natural-based polymers (e.g., collagen, chitosan, and hyaluronic acid), synthetic-based polymers (e.g., polyethylene glycol, polyvinyl alcohol, and polyacrylamide), and some other active ingredients (e.g., LL37 peptide, platelet lysate, and exosomes). In addition to an introduction to the design and application of polyurethane-related dressings, we discuss the conversion and use of advanced functional dressings for applications, as well as future directions for development, providing reference for the development and new applications of novel polyurethane dressings. Full article

Emerging evidence has shown that microRNAs play pivotal roles in wound healing. MicroRNA-21 (miR-21) was previously found to upregulate in order to fulfill an anti-inflammation role for wounds. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the role of exosomal miR-21 in wounds has yet to be well studied. In order to facilitate the early management of poorly healing wounds, we developed an easy-to-use, rapid, paper-based microfluidic-exosomal miR-21 extraction device to determine wound prognosis in a timely manner. We isolated and then quantitatively examined exosomal miR-21 in wound fluids from normal tissues and acute and chronic wounds. Eight improving wounds displayed lower levels of exosomal miR-21 expression after wound debridement. However, four instances of increased exosomal miR-21 expression levels were notably associated with patients with poor healing wounds despite aggressive wound debridement, indicating a predictive role of tissue exosomal miR-21 for wound outcome. Paper-based nucleic acid extraction device provides a rapid and user-friendly approach for evaluating exosomal miR-21 in wound fluids as a means of monitoring wounds. Our data suggest that tissue exosomal miR-21 is a reliable marker for determining current wound status. Full article

Blue light is reported to be harmful to eyes by inducing reactive oxygen species (ROS). Herein, the roles of Peucedanum japonicum Thunb. leaf extract (PJE) in corneal wound healing under blue light irradiation are investigated. Blue-light-irradiated human corneal epithelial cells (HCECs) show increased intracellular ROS levels and delayed wound healing without a change in survival, and these effects are reversed by PJE treatment. In acute toxicity tests, a single oral administration of PJE (5000 mg/kg) does not induce any signs of clinical toxicity or body weight changes for 15 days post-administration. Rats with OD (oculus dexter, right eye) corneal wounds are divided into seven treatment groups: NL (nonwounded OS (oculus sinister, left eye)), NR (wounded OD), BL (wounded OD + blue light (BL)), and PJE (BL + 25, 50, 100, 200 mg/kg). Blue-light-induced delayed wound healing is dose-dependently recovered by orally administering PJE once daily starting 5 days before wound generation. The reduced tear volume in both eyes in the BL group is also restored by PJE. Forty-eight hours after wound generation, the numbers of inflammatory and apoptotic cells and the expression levels of interleukin-6 (IL-6) largely increase in the BL group, but these values return to almost normal after PJE treatment. The key components of PJE, identified by high-performance liquid chromatography (HPLC) fractionation, are CA, neochlorogenic acid (NCA), and cryptochlorogenic acid (CCA). Each CA isomer effectively reverses the delayed wound healing and excessive ROS production, and their mixture synergistically enhances these effects. The expression of messenger RNAs (mRNAs) related to ROS, such as SOD1, CAT, GPX1, GSTM1, GSTP1, HO-1, and TRXR1, is significantly upregulated by PJE, its components, and the component mixture. Therefore, PJE protects against blue-light-induced delayed corneal wound healing via its antioxidative, anti-inflammatory, and antiapoptotic effects mechanistically related to ROS production. Full article

Hypertrophic scarring (HTS) is an aberrant form of wound healing that is associated with excessive deposition of extracellular matrix and connective tissue at the site of injury. In this review article, we provide an overview of normal (acute) wound healing phases (hemostasis, inflammation, proliferation, and remodeling). We next discuss the dysregulated and/or impaired mechanisms in wound healing phases that are associated with HTS development. We next discuss the animal models of HTS and their limitations, and review the current and emerging treatments of HTS. Full article

The human xylosyltransferase isoform XT-I catalyzes the initial step in proteoglycan biosynthesis and represents a biomarker of myofibroblast differentiation. Furthermore, XT-I overexpression is associated with fibrosis, whereby a fibrotic process initially develops from a dysregulated wound healing. In a physiologically wound healing process, extracellular matrix-producing myofibroblasts enter acute senescence to protect against fibrosis. The aim of this study was to determine the role of XT-I in acute senescent proto-myofibroblasts. Normal human dermal fibroblasts were seeded in a low cell density to promote myofibroblast differentiation and treated with H₂O₂ to induce acute senescence. Initiation of the acute senescence program in human proto-myofibroblasts resulted in a suppression of XYLT mRNA expression compared to the control, whereby the isoform XYLT1 was more affected than XYLT2. Moreover, the XT-I protein expression and enzyme activity were also reduced in H₂O₂-treated cells compared to the control. The examination of extracellular matrix remodeling revealed reduced expression of collagen I, fibronectin and decorin. In summary, acute senescent proto-myofibroblasts formed an anti-fibrotic phenotype, and suppression of XT-I during the induction process of acute senescence significantly contributed to subsequent ECM remodeling. XT-I therefore plays an important role in the switch between physiological and pathological wound healing. Full article

Traditional wound dressings often cannot treat wounds caused by bacterial infections or other wound types that are insensitive to these wound treatments. Therefore, a biodegradable, bioactive hydrogel wound dressing could be an effective alternative option. The purpose of this study was to develop a hydrogel membrane comprised of sodium alginate, polyvinyl alcohol, acrylic acid, and gallic acid for treating skin wounds. The newly developed membranes were analyzed using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), sol-gel fraction, porosity, mechanical strength, swelling, drug release and data modelling, polymeric network parameters, biodegradation, and antioxidation (DPPH and ABTS) and antimicrobial activity against Gram-positive and negative bacteria. The results revealed that hydrogel membranes were crosslinked successfully and had excellent thermal stability, high drug loading, greater mechanical strength, and exhibited excellent biodegradation. Additionally, the swelling ability and the porosity of the surface facilitated a controlled release of the encapsulated drug (gallic acid), with 70.34% release observed at pH 1.2, 70.10% at pH 5.5 (normal skin pH), and 86.24% at pH 7.4 (wounds pH) in 48 h. The gallic acid-loaded hydrogel membranes showed a greater area of inhibition against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli bacteria as well as demonstrated excellent antioxidant properties. Based on Franz cell analyses, the permeation flux of the drug from optimized formulations through mice skin was 92 (pH 5.5) and 110 (pH 7.4) μg/cm²·h⁻¹. Moreover, hydrogel membranes retained significant amounts of drug in the skin for 24 h, such as 2371 (pH 5.5) and 3300 µg/cm² (pH 7.4). Acute dermal irritation tests in rats showed that hydrogel membranes were nonirritating. Hydrogel membranes containing gallic acid could be an effective option for improving wound healing and could result in faster wound healing. Full article

Wound management remains a challenging issue around the world, although a lot of wound dressing materials have been produced for the treatment of chronic and acute wounds. Wound healing is a highly dynamic and complex regulatory process that involves four principal integrated phases, including hemostasis, inflammation, proliferation, and remodeling. Chronic non-healing wounds are wounds that heal significantly more slowly, fail to progress to all the phases of the normal wound healing process, and are usually stalled at the inflammatory phase. These wounds cause a lot of challenges to patients, such as severe emotional and physical stress and generate a considerable financial burden on patients and the general public healthcare system. It has been reported that about 1–2% of the global population suffers from chronic non-healing wounds during their lifetime in developed nations. Traditional wound dressings are dry, and therefore cannot provide moist environment for wound healing and do not possess antibacterial properties. Wound dressings that are currently used consist of bandages, films, foams, patches and hydrogels. Currently, hydrogels are gaining much attention as a result of their water-holding capacity, providing a moist wound-healing milieu. Chitosan is a biopolymer that has gained a lot of attention recently in the pharmaceutical industry due to its unique chemical and antibacterial nature. However, with its poor mechanical properties, chitosan is incorporated with other biopolymers, such as the cellulose of desirable biocompatibility, at the same time having the improved mechanical and physical properties of the hydrogels. This review focuses on the study of biopolymers, such as cellulose and chitosan hydrogels, for wound treatment. Full article

In traditional medicine, Cucurbita pepo L. is used for the treatment of rheumatism, diabetes, inflammations, and wound injuries. This study was conducted to evaluate the phytochemical constituents, safety profile, wound healing, and anti-inflammatory activities of Cucurbita pepo leaf extract in rats. The phytochemical analysis of C. pepo extract was carried out using gas chromatography-mass spectrometry (GC-MS). In acute toxicity tests, the rats orally received a single dose of 5 g/kg extract of C. pepo. In a subacute toxicity study, the rats received 200, 400, and 800 mg/kg of the C. pepo extract via daily gavage for 14 days. Bioactive compounds 1-octen-3-ol, nonanal, trans-β-ionone, phytol, trans-farnesol, and squalene were identified. There were no toxic effects detected in any of the evaluated parameters, namely liver, kidney, haematological, lipid, and antioxidant enzymes. In wound healing, C. pepo extract showed greater % wound contraction and tensile strength, as well as reduced wound healing time (12 days) and epithelialization when compared to the control (normal saline) and povidone-iodine treated groups. Rats treated with C. pepo extract elicit anti-inflammatory activity. The findings of this study revealed that the C. pepo extract has wound healing and anti-inflammatory properties with a wide margin of safety. Full article

Acute skin damage caused by burns or cuts occurs frequently in people’s daily lives. Such wounds are difficult to heal normally and have persistent inflammation. Wound dressings not only improve the speed of wound healing, but also protect and cover the wound well. Hydrogels have the characteristics of good flexibility, high water content, and good biocompatibility, and are widely used in biomedicine and other fields. Common hydrogels are mainly natural hydrogels and synthetic hydrogels. Hydrogels cross-linked using different raw materials and different methods have different performance characteristics. Natural hydrogels prepared using polysaccharides are simple to obtain and have good biocompatibility, but are inferior to synthetic hydrogels in terms of mechanical properties and stability, and a single polysaccharide hydrogel cannot meet the component requirements for wound healing. Therefore, functional composite hydrogels with high mechanical properties, high biocompatibility, and high antibacterial properties are the current research hotspots. In this review, several common polysaccharides for hydrogel synthesis and the synthesis methods of polysaccharide hydrogels are introduced, and functional composite hydrogel dressings from recent years are classified. It is hoped that this can provide useful references for relevant research in this field. Full article

Macrophage differentiation and polarization are essential players in the success of the wound-healing process. Acute simple wounds progress from inflammation to proliferation/regeneration and, finally, to remodeling. In injured skin, macrophages either reside in the epithelium or are recruited from monocytes. Their main role is supported by their plasticity, which allows them to adopt different phenotypic states, such as the M1-inflammatory state, in which they produce TNF and NO, and the M2-reparative state, in which they resolve inflammation and exhibit a reparative function. Reparative macrophages are an essential source of growth factors such as TGF-β and VEGF and are not found in nonhealing wounds. This review discusses the differences between macrophage phenotypes in vitro and in vivo, how macrophages originate, and how they cross-communicate with other cellular components in a wound. This review also highlights the dysregulation of macrophages that occurs in nonhealing versus overhealing wounds and fibrosis. Then, the therapeutic manipulation of macrophages is presented as an attractive strategy for promoting healing through the secretion of growth factors for angiogenesis, keratinocyte migration, and collagen production. Finally, Hoxa3 overexpression is discussed as an example of the therapeutic repolarization of macrophages to the normal maturation state and phenotype with better healing outcomes. Full article

Wounds with impaired healing, including delayed acute injuries and chronic injuries, generally fail to progress through normal healing stages. A deeper understanding of the biochemical processes involved in chronic wound cures is necessary to correct the microenvironmental imbalances in the wound treatment designs of products. The therapeutic benefits of honey, particularly its antimicrobial activity, make it a viable option for wound treatment in a variety of situations. Integration with nanotechnology has opened up new possibilities not only for wound healing but also for other medicinal applications. In this review, recent advances in honey-based nanoparticles for wound healing are discussed. This also covers the mechanism of the action of nanoparticles in the wound healing process and perspectives on the challenges and future trends of using honey-based nanoparticles. The underlying mechanisms of wound healing using honey are believed to be attributed to hydrogen peroxide, high osmolality, acidity, non-peroxide components, and phenols. Therefore, incorporating honey into various wound dressings has become a major trend due to the increasing demand for combination dressings in the global wound dressing market because these dressings contain two or more types of chemical and physical properties to ensure optimal functionality. At the same time, their multiple features (low cost, biocompatibility, and swelling index) and diverse fabrication methods (electrospun fibres, hydrogels, etc.) make them a popular choice among researchers. Full article

A complete redevelopment of the skin remains a challenge in the management of acute and chronic wounds. Recently, the application of extracellular vesicles (EVs) for soft tissue wound healing has received much attention. As fibroblasts are fundamental cells for soft tissues and skin, we investigate the proangiogenic factors in human normal fibroblast-derived EVs (hNF-EVs) and their effects on wound healing. Normal fibroblasts were isolated from human skin tissues and characterized by immunofluorescence (IF) and Western blotting (WB). hNF-EVs were isolated by ultracentrifugation and characterized using transmission electron microscopy and WB. The proangiogenic cargos in hNF-EVs were identified by a TaqMan assay and a protein array. Other in vitro assays, including internalization assays, cell counting kit-8 analysis, scratch wound assays, WBs, and tube formation assays were conducted to assess the effects of hNF-EVs on fibroblasts and endothelial cells. A novel scaffold-free noninvasive delivery of hNF-EVs with or without fibrin glue was applied onto full-thickness skin wounds in mice. The wound healing therapeutical effect of hNF-EVs was assessed by calculating the rate of wound closure and through histological analysis. Isolated hNF was confirmed by verifying the expression of the fibroblast markers vimentin, αSMA, Hsp70, and S100A4. Isolated hNF-EVs showed intact EVs with round morphology, enriched in CD81 and CD63, and devoid of the cell markers GM130, Calnexin, and Cytochrome C. Our TaqMan assay showed that hNF-EVs were enriched in miR130a and miR210, and protein arrays showed enriched levels of the proangiogenic proteins’ vascular endothelial growth factor (VEGF)-D and CXCL8. Next, we found that the internalization of hNF-EVs into hNF increased the proliferation and migration of hNF, in addition to increasing the expression of bFGF, MMP2, and αSMA. The internalization of hNF-EVs into the endothelial cells increased their proliferation and tube formation. A scaffold-free noninvasive delivery of hNF-EVs with or without fibrin glue accelerated the wound healing rate in full-thickness skin wounds in mice, and the treatments increased the cellular density, deposition, and maturation of collagens in the wounds. Moreover, the scaffold-free noninvasive delivery of hNF-EVs with or without fibrin glue increased the VEGF and CD31 expression in the wounds, indicating that hNF-EVs have an angiogenic ability to achieve complete skin regeneration. These findings open up for new treatment strategies to be developed for wound healing. Further, we offer a new approach to the efficient, scaffold-free noninvasive delivery of hNF-EVs to wounds. Full article