Therapeutic Effects In Wound Healing Research Articles

Polyphenols in wound healing: unlocking prospects with clinical applications.

Wound healing is a multifaceted, complex process that factors like aging, metabolic diseases, and infections may influence. The potentiality of polyphenols, natural compounds, has shown anti-inflammatory and antimicrobial properties in promoting wound healing and their potential applications in wound management. The studies reviewed indicate that polyphenols have multiple mechanisms that promote wound healing. This involves enhancing antioxidant defenses, reducing oxidative stress, modulating inflammatory responses, improving healing times, reducing infection rates, and enhancing tissue regeneration in clinical trials and in vivo and in vitro studies. Polyphenols have been proven to be effective in managing hard-to-heal wounds, especially in diabetic and elderly populations. Polyphenols have shown significant benefits in promoting angiogenesis and stimulating collagen synthesis. Polyphenol treatment has been demonstrated to have therapeutic effects in wound healing and chronic wound management. Their ability to regulate key healing processes makes them suitable for new wound care products and treatments. Future research should enhance formulations and delivery methods to optimize polyphenols' bioavailability and therapeutic efficacy in wound management approaches.

Photothermal Fish Gelatin-Graphene Microneedle Patches for Chronic Wound Treatment.

Microneedles are demonstrated as an effective strategy for chronic wound treatment. Great endeavors are devoted to developing microneedles with natural compositions and potent functions to promote therapeutic effects for wound healing. Herein, a novel graphene oxide-integrated methacrylated fish gelatin (GO-FGelMA) microneedle patch encapsulated with bacitracin and vascular endothelial growth factor (VEGF) is developed for chronic wound management. As the natural components and porous structures of FGelMA, the fabricated microneedle patches display satisfactory biocompatibility and drug-loading ability. Owing to the integration of graphene oxide, the microneedle patches can realize promoted drug release via near-infrared (NIR) irradiation. Besides, the encapsulated bacitracin and VEGF endow the microneedle patches with the ability to inhibit bacterial growth and promote angiogenesis. It is demonstrated that the GO-FGelMA microneedle patches with efficient drug release exert a positive influence on the wound healing process through reduced inflammation, enhanced wound closure, and improved tissue regeneration. Thus, it is believed that the proposed drugs-loaded GO-FGelMA microneedle patches will hold great potential in future chronic wound treatment.

In vitro and In vivo Effects of Ethanolic Extract of Fumaria parviflora Lam. Embedded in Chitosan Nanoparticles Against Leishmania major.

Fumaria has been traditionally used to treat skin damages due to anti-inflammatory properties. In the present study, we evaluated the effect of the ethanolic extract of Fumaria parviflora Lam. (F. parviflora) against Leishmania major (L. major) using chitosan biopolymer drug delivery system both In vitro and In vivo models. The ethanolic extract of F. parviflora was analyzed by HPLC to determine its active ingredients content. The extract was then loaded on chitosan nanoparticles (CNPs). The parasite was treated with various concentrations of the ethanolic extract, CNPs and CNPs loaded with F. parviflora extract (CNPs@ F. parviflora). The size of lesions of treated mice were measured on a weekly basis. The parasite burden was evaluated 8 weeks after treatment. The HPLC analysis showed the presence of Fumaric acid at a high concentration. The percentage of the drug released from CNPs@ F. parviflora within 24 and 72 h were 65% and 90% respectively. The results showed that F. parviflora extract and CNPs@ F. parviflora caused 84% and 96% growth inhibition of L. major promastigotes as revealed by Neubauer chamber counting and MTT test respectively. The IC50 values of F. parviflora extract and CNPs@ F. parviflora were 450 and 68.4 µg/ml respectively. In amastigote assay, the best results showed in CNPs@ F. parviflora that only 2% of macrophages were infected with amastigotes. In vivo experiments for mice treated with F. parviflora and CNPs @ F. parviflora in comparison to control group showed a significant reduction (P < 0.05) in the mean diameter of the lesions (2.3 and 1.72 mm and 9.91 mm respectively). The ethanolic extract of F. parviflora both as standalone and loaded in CNPs showed promising inhibitory effects against L. major both upon In vitro and In vivo experimentation as well as therapeutic effects for wound healing in infected mice.

A Photocurable Polysaccharide-Based Hydrogel Delivery of Polydeoxyribonucleotide-Loaded Vectors for Wound Treatment.

The wounds caused by war, accidents, and diseases require timely and effective treatment. Polysaccharides, as natural macromolecules, have good biocompatibility and unique functions, and are excellent substrates for constructing new wound dressings. Short-chain chitosan (SCS) has good water solubility and, importantly, retains a large number of active amino groups. We first introduce double bonds to SCS. This chitosan derivative can be entangled with sodium alginate (SA) through electrostatic interaction. The flowing sol can be applied to a wound with an irregular shape. Under the initiation of a photoinitiator, the internal double bonds are broken and cross-linked to form a gel. The prepared hydrogel wound dressing exhibited good antibacterial properties and can provide a microenvironment conducive to wound repair. A polydeoxyribonucleotide (PDRN) has been proven to have encouraging therapeutic effects for wound healing. PDRN can be condensed by branched polyethylenimine (PEI) to form a nucleic acid delivery system, which can be efficiently uptaken by cells. The cooperation of hydrogel and nucleic-acid-based therapy presented good results in a mouse full-thickness skin wound model.

Acellular fish skin for wound healing.

Fish skin grafting as a new skin substitute is currently being used in clinical applications. Acceleration of the wound healing, lack of disease transmission, and low cost of the production process can introduce fish skin as a potential alternative to other grafts. An appropriate decellularization process allows the design of 3D acellular scaffolds for skin regeneration without damaging the morphology and extracellular matrix content. Therefore, the role of decellularization processes is very important to maintain the properties of fish skin. In this review article, recent studies on various decellularization processes as well as biological, physical, and mechanical properties of fish skin and its applications with therapeutic effects in wound healing were investigated.

Combination treatment of dendrosomal nanocurcumin and low-level laser therapy develops proliferation and migration of mouse embryonic fibroblasts and alter TGF-β, VEGF, TNF-α and IL-6 expressions involved in wound healing process.

Pressure ulcer (PU) is known as the third most costly disorder usually caused by prolonged pressure and stagnation in various parts of the body. Although several therapeutic approaches are employing, obstacles in appropriate healing for skin lesions still exist which necessitates new practical alternative or adjunctive treatments. Low level laser therapy (LLLT) as one of the mentioned new strategies have gained attention. Besides, curcumin is an herbal medicine extracted from turmeric with anti-inflammatory and antioxidative properties with promising beneficial therapeutic effects in wound healing. Employing dendrosomal nanoparticles, we overcome the hydrophobicity of curcumin in the present study. We hypothesized that combination treatment of DNC+LLLT (450 nm) simultaneously may promote the wound healing process. MTT assay, PI staining followed by flowcytometry, scratch assay and intracellular ROS measurement were used to investigate the effects caused by DNC and LLLT (450 nm) alone and in combination, on proliferation, cell cycle, migration and oxidative stress mouse embryonic fibroblast cells, respectively. The levels of growth factors and pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. Our results indicated that combination exposure with DNC and LLLT leads to increased proliferation and migration of MEFs as well as being more efficient in significantly upregulating growth factors (TGF-β, VEGF) and decline in inflammatory cytokines (TNF-α, IL-6). Moreover, findings of this research provide persuasive support for the notion that DNC could reduce the LLLT-induced enhancement in intracellular ROS in mouse embryonic fibroblasts. Concurrent exposure to anti-oxidant concentrations of DNC and LLLT enriched S phase entry and therefor increased proliferation as well as migration on MEFs through regulating the expression levels growth factors and shortening the inflammatory phase by modulating of cytokines. It should be noted that DNC were able to reduce the laser-induced oxidative stress, during wound healing, representing an informative accompaniment with LLLT.

Extracellular vesicles derived from fibroblasts promote wound healing by optimizing fibroblast and endothelial cellular functions.

Extracellular vesicles (EVs) have been exhibited as promising candidates for delivering endogenous therapeutic cargos for regenerative therapies. Fibroblasts could be candidate source cells for EVs, to investigate their therapeutic effects in wound healing. Here we demonstrated the isolation and characterization of fibroblast-derived (L929 cell line) EVs (L929-EVs). Furthermore, L929-EVs treatment showed pro-wound healing effects in vitro by enhancing proliferation, migration, and scarless wound healing related genes in fibroblast cells. L929-EVs treatment also enhanced the migration and tube formation of endothelial cells. The combination of L929-EVs with fibrin glue accelerated wound healing in the mouse skin wound model by enhancing collagen formation, collagen maturation, and blood vessels in the wounded skin. The role of fibroblast-derived EVs in wound healing could be an important phenomenon, and fibroblast-derived EVs could be harnessed for wound healing therapies.

Adipose stem cells from type 2 diabetic mice exhibit therapeutic potential in wound healing

BackgroundDiabetic patients suffer from impaired wound healing. Mesenchymal stem cell (MSC) therapy represents a promising approach toward improving skin wound healing through the release of soluble growth factors and cytokines that stimulate new vessel formation and modulate inflammation. Whether adipose tissue-derived MSCs (ASCs) from type 2 diabetes (T2D) donors are suitable for skin damage repair remains largely unknown.MethodsIn this study, we compared the phenotype and functionality of ASCs harvested from high-fat diet (HFD) and streptozotocin (STZ)-induced T2D or control mice, and assessed their abilities to promote wound healing in an excisional wound splinting mouse model with T2D.ResultsT2D ASCs expressed similar cellular markers as control ASCs but secreted less hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β). T2D ASCs were somewhat less effective in promoting healing of the wound, as manifested by slightly reduced re-epithelialization, cutaneous appendage regeneration, and collagen III deposition in wound tissues. In vitro, T2D ASCs promoted proliferation and migration of skin fibroblasts to a comparable extent as control ASCs via suppression of inflammation and macrophage infiltration.ConclusionsFrom these findings, we conclude that, although ASCs from T2D mice are marginally inferior to control ASCs, they possess comparable therapeutic effects in wound healing.

Improved surface adhesion and wound healing effect of madecassoside liposomes modified by temperature-responsive PEG-PCL-PEG copolymers

Madecassoside (MA) exhibits excellent therapeutic effects in wound healing and scar management. However, its high hydrophilic nature and low permeability through skin tissue limits its topical application. Liposomes are widely used to deliver drugs due to their high structural similarity and biocompatibility with cell membranes. However, normal liposome formulations are too fluid to maintain sufficient adhesion to the wound surface. In this study, in order to make an MA formulation conducive to topical administration, poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE), a biodegradable and temperature-responsive copolymer material, was synthesized and applied to improve the adhesion properties of MA liposomes. The mean particle size of the PECE-modified MA liposomes was 213.43±4.68 nm, and the zeta potential was −23.80±15.37 mV under the optimal conditions of EPC (egg yolk lecithin) to PECE at a mass ratio of 1:1. Additionally, PECE-modified MA liposomes maintained a hydrogel state for better adhesion until the temperature reached 43°C. Furthermore, the PECE-modified MA liposomes showed superior wound contraction effects relative to the MA liposomes in second-degree burn experiments using a rat model. These results indicated that PECE-modified MA liposomes have better surface adhesion performance and healing effects than unmodified MA liposomes.

Effects of Thyroid Hormone Therapy on Cut-Surface Healing of the Remnant Stomach with Short-Term Weight Loss Alterations after Sleeve Gastrectomy

ABSTRACTBackground: The hypothalamic–pituitary–tyhroid axis is directly affected by drastic changes in energy stores. The aim of the present study was to determine the effects of triiodothyronine (T3) treatment on cut-surface healing of remnant stomach with weight loss alterations after sleeve gastrectomy (SG). Methods: Thirty male Wistar Albino rats were divided into three groups: sham (n = 6), control (n = 12), and experimental (n = 12). Control and experimental group rats underwent sleeve gastrectomy. Experimental group rats received a single dose of T3 (400 mg/100 g) on the first postoperative day whereas control group rats received 0.9% NaCl. All rats were sacrificed on the seventh postoperative day. Results: In the group of rats receiving T3, levels of FT3 were significantly higher and that of FT4 were significantly lower compared with both the control and sham group rats (p <.05). No significant difference was found between control and T3 group rats in terms of weight loss (p >.05). Microscopic examination of the cut surface of remnant stomach in the control group rats revealed significantly more severe tissue necrosis, edema, and disruption of mucosal epithelium than in the T3 group rats (p <.05). On the other hand, bridging of the submucosal and muscular layers, tissue granulation, fibroblast accumulation, neoangiogenesis, and collagen deposition in the T3 group rats were significantly higher than in the control group rats (p <.05). Conclusions: Sleeve gastrectomy did not significantly alter thyroid hormone levels in short term. T3 hormone therapy seems to deliver constructive therapeutic effects for wound healing while causing no adverse effect on weight reduction.

Curcumin and its protective and therapeutic uses

Curcumin is a yellow orange powder, which is extracted from the turmeric plant (Curcuma longa). Curcumin is the principal curcuminoid of the turmeric (C. longa). Curcumin was first isolated in 1815 and its chemical structure was determined by Roughley and Whiting in 1973. It has been identified as 1,6-heptadiene-3,5-dione-1,7-bis (4-hydroxy-3-methoxyphenyl)-(1e,6e) or diferuloylmethane. Turmeric has been listed as “generally recognized as safe” (GRAS) as a coloring and flavoring agent in food by the US Food and Drug Administration (FDA). As per WHO, as an additive the daily acceptable dose of curcumin for humans has been defined as 0–3 mg/kg body weight. Curcumin can be administered by different routes as topical, oral, and inhalational. Curcumin inserts deep into the cell membrane in a manner similar to cholesterol. Curcumin has a high lipophilic character, and body fat has a high percentage of bound curcumin. The systemic bioavailability of orally administered curcumin is low in humans and only traces of it have been found in the liver and portal circulation. Piperine has been reported to increase the bioavailability of curcumin. Recently, it has been reported that newly developed nanoparticulate curcumin has better bioavailability. There is a growing list of disease conditions that can be treated by curcumin. Curcumin has been found to have therapeutic effects in wound healing and in various types of arthritis, cardiovascular diseases, diabetes, pulmonary diseases, Parkinson’s disease, and in Alzheimer’s disease. Curcumin has been reported to have potential role in the treatment of atherosclerosis, arthritis, chronic anterior uveitis, colon cancer, familial adenomatous polyposis, hypercholesteremia, inflammatory bowel disease, pancreatic cancer, pancreatitis, psoriasis, ulcerative colitis, and even HIV.

Carbonate ion-enriched hot spring water promotes skin wound healing in nude rats.

Hot spring or hot spa bathing (Onsen) is a traditional therapy for the treatment of certain ailments. There is a common belief that hot spring bathing has therapeutic effects for wound healing, yet the underlying molecular mechanisms remain unclear. To examine this hypothesis, we investigated the effects of Nagano hot spring water (rich in carbonate ion, 42°C) on the healing process of the skin using a nude rat skin wound model. We found that hot spring bathing led to an enhanced healing speed compared to both the unbathed and hot-water (42°C) control groups. Histologically, the hot spring water group showed increased vessel density and reduced inflammatory cells in the granulation tissue of the wound area. Real-time RT-PCR analysis along with zymography revealed that the wound area of the hot spring water group exhibited a higher expression of matrix metalloproteinases-2 and -9 compared to the two other control groups. Furthermore, we found that the enhanced wound healing process induced by the carbonate ion-enriched hot spring water was mediated by thermal insulation and moisture maintenance. Our results provide the evidence that carbonate ion-enriched hot spring water is beneficial for the treatment of skin wounds.

Reactive fluxes delivered by dielectric barrier discharge filaments to slightly wounded skin

The application of atmospheric-pressure plasmas to human tissue has been shown to have therapeutic effects for wound healing and in treatment of skin diseases. In this paper, we report on a computational study of the intersection of plasma filaments in a dielectric barrier discharge (DBD) with a small wound in human skin in the context of plasma medicine. The wound is represented as a small cut in the epidermal layer of cells. Intracellular structures and their electrical properties were incorporated into the two-dimensional computational mesh in order to self-consistently couple gas phase plasma transport with the charging of the surface of the wound. We quantify the fluxes of reactive oxygen and nitrogen species, ions and photons produced in or diffusing into the wound as might occur during the first few discharge pulses of treatment. Comparison is made to fluxes predicted by global modelling. We show that the relative location of the plasma filament with respect to the wound is important on plasma time scales (ns) for ions and photons, and for radicals directly produced by electron impact processes. On the longer-term diffusion time scales (ms) the position of the plasma filament relative to the wound is not so critical. For typical DBD conditions, the magnitude of these fluxes to the cellular surfaces corresponds to fluences of radicals nearly equal to the surface site density. These results imply that the biological reactivity is limited by reaction probabilities and not the availability of radical fluxes.

Active ingredient-containing chitosan/polycaprolactone nonwoven mats: Characterizations and their functional assays

This study demonstrates a facile method developed to generate a chitosan/polycaprolactone (CS/PCL) nonwoven mat. All nonwoven mats are composed of microfibers with an average diameter of 2.51±0.69μm. The X-ray photoelectron spectroscopy data indicate that positively charged nitrogen was generated on the surface of the mats after undergoing CS coating. By using a non-contacting electrostatic voltmeter, we determined that the nonwoven mats exhibited a positive potential and the charge density of the CS/PCL nonwoven mat was in proportion to the thickness of the CS overlayer. Moreover, platelet aggregation and anti-bacterial ability were enhanced by the CS/PCL nonwoven mat as compared to that of PCL nonwoven mat alone. The enhancements of the CS/PCL nonwoven mat on platelet aggregation are further promoted by incorporating a 1mM calcium ion in its CS overlayer. We also find that the addition of tea tree oil in the CS overlayer significantly inhibited LPS-induced nitrite formation in Raw 264.7 macrophages. In conclusion, our CS/PCL nonwoven mat possesses pharmacological effects including an increase of platelet aggregation, anti-bacterial, anti-adhesive, and anti-inflammatory activities. The performance of this CS/PCL nonwoven mat can be further promoted by incorporating active compounds to exert therapeutic effects in wound healing.

Ion activation energy delivered to wounds by atmospheric pressure dielectric-barrier discharges: sputtering of lipid-like surfaces

The application of atmospheric pressure plasmas to human tissue has been shown to have therapeutic effects for wound healing and in treatment of skin diseases. These effects are attributed to production of UV photon fluxes, electric fields and beneficial radicals which intersect with biological reaction chains, and to energetic ions bombarding the surface. In this paper we report on results from a computational investigation of the ion energy and angular distributions (IEADs) in a dielectric-barrier discharge sustained in air incident directly on cell membranes for small dry and wet wounds in human skin. We found that ion energies in excess of 20–30 eV can be delivered onto cell membranes of dry wounds, and up to 60 eV onto the liquid interface of the wet wound. The details of the IEADs depend on the orientation of the cell membrane and on the relative location of the plasma streamer to the wound. Using results from a molecular dynamics simulation of ion sputter probabilities of typical lipid-like material, we show that prolonged exposure of the cell membrane to such IEADs can produce significant carbon removal.

Intracellular electric fields produced by dielectric barrier discharge treatment of skin

The application of atmospheric pressure plasmas to human tissue has been shown to have therapeutic effects for wound healing and in treatment of skin diseases. These effects are attributed to both production of beneficial radicals which intersect with biological reaction chains and to the surface and intracellular generation of electric fields. In this paper, we report on computational studies of the intersection of plasma streamers in atmospheric pressure dielectric barrier discharges (DBDs) sustained in air with human skin tissue, with emphasis on the intracellular generation of electric fields. Intracellular structures and their electrical properties were incorporated into the computational mesh in order to self-consistently couple gas phase plasma transport with the charging of the surface of the skin and the intracellular production of electrical currents. The short duration of a single plasma filament in DBDs and its intersection with skin enables the intracellular penetration of electric fields. The magnitude of these electric fields can reach 100 kV cm−1 which may exceed the threshold for electroporation.

Extremely low frequency electromagnetic fields modulate expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and cyclooxygenase-2 in the human keratinocyte cell line HaCat: potential therapeutic effects in wound healing

Extremely low frequency (ELF) electromagnetic fields (EMF) are known to produce a variety of biological effects. Clinical studies are ongoing using EMF in healing of bone fractures and skin wounds. However, little is known about the mechanisms of action of ELF-EMF. Several studies have demonstrated that expression and regulation of nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) are vital for wound healing; however, no reports have demonstrated a direct action of ELF-EMF in the modulation of these inflammatory molecules in human keratinocytes. The present study analysed the effect of ELF-EMF on the human keratinocyte cell line HaCaT in order to assess the mechanisms of action of ELF-EMF and to provide further support for their therapeutic use in wound healing. Exposed HaCaT cells were compared with unexposed control cells. At different exposure times, expression of inducible NOS (iNOS), endothelial NOS (eNOS) and COX-2 was evaluated by Western blot analysis. Modulation of iNOS and eNOS was monitored by evaluation of NOS activities, production of nitric oxide (NO) and O(2)(-) and expression of activator protein 1 (AP-1). In addition, catalase activity and prostaglandin (PG) E(2) production were determined. Effects of ELF-EMF on cell growth and viability were monitored. The exposure of HaCaT cells to ELF-EMF increased iNOS and eNOS expression levels. These ELF-EMF-dependent increased expression levels were paralled by increased NOS activities, and increased NO production. In addition, higher levels of AP-1 expression as well as a higher cell proliferation rate were associated with ELF-EMF exposure. In contrast, ELF-EMF decreased COX-2 expression, PGE(2) production, catalase activity and O(2)(-) production. Mediators of inflammation, such as reactive nitrogen and PGE(2), and keratinocyte proliferation are critical for the tissue regenerative processes. The ability of ELF-EMF to upmodulate NOS activities, thus nitrogen intermediates, as well as cell proliferation, and to downregulate COX-2 expression and the downstream intermediate PGE(2), highlights the potential therapeutic role of ELF-EMF in wound healing processes.

The effect of 880 nm low level laser energy on human fibroblast cell numbers: a possible role in hypertrophic wound healing

Low level lasers (LLLs) have been shown to induce therapeutic effects in wound healing. However, there have been few LLL studies on burn wounds which may become unsightly, hypertrophic and impair function. Inhibitory effects on the healing of fibrotic wounds, prone to hypertrophy may be expected to reasonably reduce the problems accompanying hypertrophic scarring. The effects of LLL wavelengths and treatment parameters on wound healing cells in vitro often demonstrate meaningful results and without concurrent ethical difficulties of clinical trials. This experiment investigated the effect of an 880 nm, 16 mW GaAlAs diode at 2.4 and 4 J/cm 2 on cell numbers of two human fibroblast cell lines, derived from hypertrophic scar (HF) and normal dermal explants (NF), respectively. After irradiation by 880 nm LLL, cell numbers were measured utilising methylene blue bioassay and read by the spectrophotometer in the same microculture plates. HF and NF exhibited decreased cell numbers as compared to sham-irradiated controls. HF cell number, after 2.4 J/cm 2, was significantly lower on day 5 ( P<0.05). The NF cell numbers were significantly lower on day 4 and/or day 5 ( P<0.05). The results have implications on hypertrophic wound healing and further studies are required.