Potential Wound Healing Agent Research Articles

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.

Inhibiting miR-618 Promotes Keratinocytes Proliferation and Migration to Enhance Wound Healing in Mice.

The delay in wound healing caused by chronic wounds or pathological scars is a pressing issue in clinical practice, imposing significant economic and psychological burdens on patients. In particular, with the aging of the population and the increasing incidence of diseases such as diabetes, impaired wound healing is one of the growing health problems. MicroRNA (miRNA) plays a crucial role in wound healing and regulates various biological processes. Our results show that miR-618 was significantly upregulated during the inflammatory phase of wound healing.Subsequently, miR-618 promotes the secretion of pro-inflammatory cytokines and regulates the proliferation and migration of keratinocytes. Mechanistically, miR-618 binds to the target gene-Atp11b and inhibits the PI3K-Akt signaling pathway, inhibiting the epithelial-mesenchymal transition (EMT) of keratinocytes. In addition, the PI3K-Akt signaling pathway induces the enrichment of nuclear miR-618, and miR-618 binds to the promoter of Lin7a to regulate gene transcription. Intradermal injection of miR-618 antagomir around full-thickness wounds in peridermal mice effectively accelerates wound closure compared to control. In conclusion, miR-618 antagomir can be a potential therapeutic agent for wound healing.

Double-modified, thio and methylene ATP analogue facilitates wound healing in vitro and in vivo

Recent data indicate that extracellular ATP affects wound healing efficacy via P2Y2-dependent signaling pathway. In the current work, we propose double-modified ATP analogue—alpha-thio-beta,gamma-methylene-ATP as a potential therapeutic agent for a skin regeneration. For the better understanding of structure–activity relationship, beside tested ATP analogues, the appropriate single-modified derivatives of target compound, such as alpha-thio-ATP and beta,gamma-methylene-ATP, were also tested in the context of their involvement in the activation of ATP-dependent purinergic signaling pathway via the P2Y2 receptor. The diastereomerically pure alpha-thio-modified-ATP derivatives were obtained using the oxathiaphospholane method as separate SP and RP diastereomers. Both the single- and double- modified ATP analogues were then tested for their impact on the viability and migration of human keratinocytes. The involvement of P2Y2-dependent purinergic signaling was analyzed in silico by molecular docking of the tested compounds to the P2Y2 receptor and experimentally by studying intracellular calcium mobilization in the human keratinocytes HaCaT. The effects obtained for ATP analogues were compared with the results for ATP as a natural P2Y2 agonist. To confirm the contribution of the P2Y2 receptor to the observed effects, the tests were also performed in the presence of the selective P2Y2 antagonist—AR-C118925XX. The ability of the alpha-thio-beta,gamma-methylene-ATP to influence cell migration was analyzed in vitro on the model HaCaT and MDA-MB-231 cells by wound healing assay and transwell migration test as well as in vivo using zebrafish system. The impact on tissue regeneration was estimated based on the regrowth rate of cut zebrafish tails. The in vitro and in vivo studies have shown that the SP-alpha-thio-beta,gamma-methylene-ATP analogue promotes regeneration-related processes, making it a suitable agent for enhance wound healing. Performed studies indicated its impact on the cell migration, induction of epithelial–mesenchymal transition and intracellular calcium mobilization. The enhanced regeneration of cut zebrafish tails confirmed the pro-regenerative activity of this ATP analogue. Based on the performed studies, the SP-alpha-thio-beta,gamma-methylene-ATP is proposed as a potential therapeutic agent for wound healing and skin regeneration treatment.

Phytochemical Analysis, Antimicrobial Screening and In Vitro Pharmacological Activity of Artemisia vestita Leaf Extract.

Artemisia vestita Wall. Ex Besser is a folklore medicinal plant that belongs to Asteraceae family and a treasure trove of drugs. The aim of this research study was to investigate the phytoconstituents, antimicrobial activity, antioxidant, anti-inflammatory, cytotoxicity and wound healing potential of A. vestita leaf extract (ALE). Phytochemical analysis of the ALE was carried out by Soxhlet extraction and GCMS (gas chromatography-mass spectrometry) analysis. Antimicrobial activity was performed by the agar well diffusion method against selected bacterial and fungal strains. Free radical scavenging potential was evaluated by DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (Ferric reducing antioxidant power) assays. Anti-inflammatory activity was performed by enzyme inhibition assay-COXII. The cytotoxicity of ALE on HaCaT cells was studied via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. An in vitro scratch assay was performed for the evaluation of the wound healing property of ALE. It showed satisfactory antimicrobial activity against Staphylococcus aureus (14.2 ± 0.28 mm), Escherichia coli (17.6 ± 0.52 mm), Bacillus subtilis (13.1 ± 0.37 mm), Streptococcus pyogenes (17.3 ± 0.64 mm), Proteus mirabilis (9.4 ± 0.56 mm), Aspergillus niger (12.7 ± 0.53 mm), Aspergilus flavus (15.3 ± 0.25 mm) and Candida albicans (17.6 ± 0.11 mm). In ALE, 36 phytochemicals were detected by GCMS analysis, but 22 were dominant. Moreover, the ALE was effective in scavenging free radicals with different assays and exhibited reasonable anti-inflammatory activity. The MTT assay revealed that ALE had a cytotoxic effect on the HaCaT cells. The scratch assay showed 94.6% wound closure (after 24 h incubation) compared to the positive control Cipladine, which is remarkable wound healing activity. This is the first report on the wound healing property of A. vestita, which can serve as a potential agent for wound healing and extends knowledge on its therapeutic potential.

Stability and Safety Analysis of Statin-Loaded Nano-films for the Treatment of Diabetic Wound

Diabetes mellitus (DM) is a metabolic disease that delays the regular stages of the wound's healing process due to delayed inflammatory stages. Due to foot pressure points, chronic foot wounds are ultimately considered the primary cause of lower leg amputation. Diabetic patients have vascular dysfunction and neuropathy, leading to inadequate oxygen supply to the wound area. Statins have a crucial role in the regulation of angiogenesis that could increase vascular endothelial growth factor (VEGF) synthesis. By offering a localized treatment approach while minimizing systemic side effects associated with oral medication, this study aimed to develop statin-loaded nanofilms to determine their stability and safety among healthy individuals as a potential procedure for diabetic wound healing. Simvastatin (SIM) loaded nanofilms formulations (F1-F10) were prepared using the solvent casting method. The formulation was optimized based on tests such as physical appearance, tensile strength, microscopic photographs, morphology, and drug content uniformity. ICH guidelines were followed to determine various parameters (physical appearances, tensile strength, microscopic photographs, morphology, and drug content uniformity) for six-month stability study at three different storage conditions. Safety analysis of the nanofilms was performed on healthy human skin using the Draize skin irritation test. Results showed F7 formulation was considered an optimized formulation as well as stable through the storage period at 4 ± 2°C, 25 ± 2°C, and 40 ± 2 °C. Furthermore, Primary Irritation Index results (PII was 0 showed no irritation in case and control groups) indicate its safety and biocompatibility to skin. Thus, the optimized statin-loaded nanofilm is stable, safe, and non-toxic, which may be used as a potential diabetic wound healing agent.

КОМПОЗИЦІЇ НА ОСНОВІ КОЛАГЕНУ З ГІДРОБІОНТІВ ЯК ПОТЕНЦІЙНІ РАНОЗАГОЮВАЛЬНІ ЗАСОБИ

B a c k g r o u n d. The work was devoted to the study of compositions based on collagen extracted from hydrobionts as potential wound healing agents. The scales of Antarctic fish Champsocephalus gunnari, Nototheniidae and the biomass of jellyfish Diplulmaris antarctica were used as raw materials for obtaining collagen. M e t h o d s. To obtain collagen, the following steps were done: salting out non-collagen proteins with 10% NaCl, demineralization with 0.4 M HClO4, extraction of collagen with 0.5 M CH3COOH, reprecipitation of the obtained collagen with NaCl and CH3COOH, and lyophilization. R e s u l t s. Obtained collagen was collagen type I, which was confirmed by an electrophoretic analysis, in particular, the molecular weight of collagen chains (117 and 110 kDa) and their ratio as 2:1. The wound-healing effect of compositions based on 5% collagen was studied on a model of full-thickness wound in rats. The collagen compositions were prepared on 0.5% carbopol. Application of the compositions began on the third day after modeling the full-thickness wound; the wounds were treated every other day and until complete healing. C o n c l u s I o n s. A wound-healing effect of collagen-based compositions has been established, manifested in the acceleration of the wound-healing process. Thus, when applying compositions based on collagen from scales and collagen extracted from jellyfish to the wound surface, complete epithelialization of wounds was observed on the 18th day compared to the result in the group of animals where the wounds healed naturally and for which complete healing took place on the 22nd day.Although the composition based on fish scale collagen was more effective in the first week, an assessment of the wound area at the time of complete healing indicates a slightly better wound healing effect of the D. antarctica collagen-based composition.

Molecular docking and molecular dynamics simulations discover curcumin analogs as potential wound healing agents

Chronic non-healing wounds impose a significant economic burden on the healthcare system. Among the existing strategies in wound healing therapy, targeting specific enzymes, namely tyrosyl-tRNA synthetase, TGFBR1, IL-1β, and Pseudomonas aeruginosa MvfR, represents an important aspect of the strategy of wound healing. Our research focuses on creating new curcumin hybrids (SV01-SV20) for harnessing wound healing activities and possesses considerable therapeutic implications. The compounds were designed and evaluated through in-silico screening using Molinspiration Cheminformatics, Osiris Property Explorer, AdmetSAR, and SwissADME. The initial filtering process identified the top 19 hybrids, which were then subjected to docking using the AutoDock tool. The results of the molecular docking analysis indicate that the curcumin hybrids, specifically tyrosyl-tRNA synthetase (SV09, SV15), TGFBR1 (SV01, and SV11), IL-1β (SV07, SV08), and Pseudomonas aeruginosa MvfR (SV09, SV13), showed the most significant binding energies (-8.69, -9.01, -8.49, -8.13, -8.48, -6.14, -9.7, and -9.2 kcal/mol, respectively) among the designed compounds. The binding energies were higher than the standard curcumin, indicating a potentially more substantial interaction with the target. Extensive molecular dynamics simulations confirmed the stability of these derivatives throughout the 100 ns simulation; the ligand-protein complexes maintained structural stability. The designed compounds demonstrated favorable pharmacokinetic properties, drug-likeness scores, bioactivity assessments, adherence to Lipinski's rule of five, and low toxicity risks. Overall, results consistently demonstrated that SV01, SV07, SV08, SV09, SV11, SV13, and SV15 compounds hold significant potential as effective agents in treating chronic wounds.

Gynura divaricata (L.) DC. promotes diabetic wound healing by activating Nrf2 signaling in diabetic rats

The ethnopharmacological significanceDiabetic chronic foot ulcers pose a significant therapeutic challenge as a result of the oxidative stress caused by hyperglycemia. Which impairs angiogenesis and delays wound healing, potentially leading to amputation. Gynura divaricata (L.) DC. (GD), a traditional Chinese herbal medicine with hypoglycemic effects, has been proposed as a potential therapeutic agent for diabetic wound healing. However, the underlying mechanisms of its effects remain unclear. Aim of the studyIn this study, we aimed to reveal the effect and potential mechanisms of GD on accelerating diabetic wound healing in vitro and in vivo. Materials and methodsThe effects of GD on cell proliferation, apoptosis, reactive oxygen species (ROS) production, migration, mitochondrial membrane potential (MMP), and potential molecular mechanisms were investigated in high glucose (HG) stimulated human umbilical vein endothelial cells (HUVECs) using CCK-8, flow cytometry assay, wound healing assay, immunofluorescence, DCFH-DA staining, JC-1 staining, and Western blot. Full-thickness skin defects were created in STZ-induced diabetic rats, and wound healing rate was tracked by photographing them every day. HE staining, immunohistochemistry, and Western blot were employed to investigate the effect and molecular mechanism of GD on wound healing in diabetic rats. ResultsGD significantly improved HUVEC survival, decreased apoptosis, lowered ROS production, restored MMP, improved migration ability, and raised VEGF expression. The use of Nrf2-siRNA completely abrogated these effects. Topical application of GD promoted angiogenesis and granulation tissue growth, resulting in faster healing of diabetic wounds. The expression of VEGF, CD31, and VEGFR was elevated in the skin tissue of diabetic rats after GD treatment, which upregulated HO-1, NQO-1, and Bcl-2 expression while downregulating Bax expression via activation of the Nrf2 signaling pathway. ConclusionThe findings of this study indicate that GD has the potential to serve as a viable alternative treatment for diabetic wounds. This potential arises from its ability to mitigate the negative effects of oxidative stress on angiogenesis, which is regulated by the Nrf2 signaling pathway. The results of our study offer valuable insights into the therapeutic efficacy of GD in the treatment of diabetic wounds, emphasizing the significance of directing interventions towards the Nrf2 signaling pathway to mitigate oxidative stress and facilitate the process of angiogenesis.

Celery leaf extract cream is a potential wound healing agent

Natural ingredients have been widely used for wound care and healing because of their flavonoid, saponin, and tannin contents, which can facilitate the healing process. This study aimed to examine the efficacy of celery leaf extract cream in the treatment of cutaneous wounds on the surfaces of white Wistar rats. This study involved laboratory-based experimental research utilizing a pretest-posttest with a control group design. Twenty white rats were sampled for this study and divided into four groups, each consisting of five rats, including one control group and three treatment groups. The extract was obtained via maceration, whereas the celery leaf extract cream contained an oil-in-water emulsion. A one-way Anova test was used to test differences between groups (p < 0.05), and a Post Hoc test with LSD technique was conducted to determine the most effective treatment group. Celery leaf extract cream has been found to be more efficient in accelerating skin regeneration and stimulating fibroblast proliferation than base cream. This is evidenced by the superior performance of the celery leaf extract cream treatment group in closing the incision wound, as well as the group's higher production of fibroblasts that are essential for wound healing, compared to the base cream group. This is evidenced by the superior performance of the celery leaf extract cream treatment group in closing the incision wound, as well as the group's higher production of fibroblasts that are essential for wound healing, compared to the base cream group. The anti-inflammatory and antioxidant properties of the flavonoids found in celery leaves can potentially prevent the formation of free radicals and expedite wound healing.

A topical formulation of Anacardium occidentale L. leaves extract enhances wound healing via mediating TNF-α and TGF- β

Repeated trauma, inadequate perfusion or oxygenation, excessive inflammation, infection, oxidative stress, anddiabetes all contribute to impaired wound healing. In a clinical setting, delay in healing may result in severe complicationssuch as gangrene, leading to extended hospitalization, amputation and even death of the patient. Slow wound healing andlimitations of currently available synthetic medication, urges the need for a safe, affordable, patient-friendly, andmulti-modal herbal wound care agent. Anacardium occidentale L., commonly known as cashew and locally, Kaju, isreported to possess antidiabetic, antibacterial, antioxidant, anti-inflammatory and antiulcerogenic activities. In this study, weevaluated the wound healing activity of gel containing the extract of A. occidentale leaves in rats using incision, excisionand dead space wound models. Increased wound contraction, breaking strength, hydroxyproline and hexosamine content,TGF-β level and decreased level of TNF-α indicated that the developed gel accelerated the wound healing process.Moreover, the docking studies indicated that the aqueous alcoholic extract exerted healing activity by inhibiting GSK3-βthrough β-catenin dependent Wnt signaling pathway. Thus, it can be concluded that the Anacardium occidentale leavesextract can be a potential wound healing agent by acting on various phases of healing process.

Optimisation of Calophyllum inophyllum seed oil nanoemulsion as a potential wound healing agent

BackgroundEfficient delivery systems of Calophyllum inophyllum seed oil (CSO) in the form of nanoemulsion were optimised to enhance its stability and ensure its therapeutic efficiency as a potential agent for various biomedical applications.MethodResponse Surface Methodology (RSM) was used to determine the effects of independent variables (oil, surfactant, water percentage and homogenisation time) on physicochemical characteristics, including droplet size, polydispersity index and turbidity.ResultsThe optimised CSO nanoemulsion (CSONE) has a 46.68 nm particle size, 0.15 Polydispersity index value and 1.16 turbidity. After 4 weeks of storage at 5 ± 1 °C and 25 ± 1 °C, the CSONE was physically stable. The optimised CSO nanoemulsion showed enhancement in cell viability and wound healing in baby hamster kidney a clone BHK-21 (BSR) cells as compared to the CSO. The wound healing property of CSONE was higher than CSO.ConclusionThus, our in vitro wound healing results demonstrated that CSO in the nanoemulsion form can promote wound healing by enhancing the proliferation and migration of epidermal cells.Graphical The coarse emulsion of Calophyllum inophyllum seed oil nano emulsion was prepared using high shear homogeniser techniques. The optimised CSONE with the droplet size of 46.68 nm was prepared from a mixture of CSO, Tween 80, and high pure water (HPW), then used for the biological investigation. The in vitro cell monolayer scratch assay revealed that CSONE in the lowest concentration of CSO resulted in 100% wound closure after 48 hrs. The optimised CSO nanoemulsion was found to be a promising and effective approach in the treatment of wounds by boosting the proliferation and migration of epidermal cells.

Design, synthesis, in silico and antibacterial evaluation of curcumin derivatives loaded nanofiber as potential wound healing agents

ObjectiveDrug resistance can result in mortality and morbidity due to treatment failures. Therefore, researchers are actively involved in the urgent development of new antibacterial agents which are more effective against drug-resistant bacteria. This study is aimed to prepare curcumin derivatives (CD) nanofiber and test its antibacterial activity by disk diffusion test and evaluate their role in wound healing when potentially binds with transforming growth factor-beta type 1 kinase domain (TGF-β) and Glycogen synthase kinase-3 beta (GSK3-β). MethodMolecular docking and molecular dynamic have been used to select the most potent dual-action molecules on both TGF-β and GSK3-β, most active 2 compounds have been synthesized and characterized by 1H and 13C (NMR), IR spectroscopy, Electrospinning of CD in ethanol were studied by adding Poly vinyl alcohol (PVA) as a polymer. The properties of the CD\\PVA solutions measured, morphology of electrospun CD\\PVA was tested by Scanning Electrode Microscope (SEM), antibacterial activity of electrospun nanofiber against Staphylococcus aureus (S. aureus) was tested by disk diffusion method.Results and Conclusions: CD nanofiber were synthesized successfully. The results showed that CD were successfully synthesized with good yield (72% and 78%) for compound1 and 2 respectively, Disc diffusion antibacterial test demonstrated an increased inhibition zone from 0.5 to 5.0 mg loaded CD with the largest inhibition zone of 8.5 ± 0.71 and 9.67 ± 0.29 mm for compound1 and 2 respectively. Hence, it can be concluded that these CD\\PVA could be a new source in designing new antibacterial wound dressing for diabetic patients.

Extraction and Characterization of Bioactive Fish By-Product Collagen as Promising for Potential Wound Healing Agent in Pharmaceutical Applications: Current Trend and Future Perspective.

Collagen is a structural protein naturally found in mammals. Vertebrates and other connective tissues comprise about 30% of an animal's overall protein. Collagen is used in a variety of applications including cosmetics, biomedical, biomaterials, food, and pharmaceuticals. The use of marine-based collagen as a substitute source is rapidly increasing due to its unique properties, which include the absence of religious restrictions, a low molecular weight, no risk of disease transmission, biocompatibility, and ease of absorption by the body system. This review discusses recent research on collagen extraction from marine-based raw material, specifically fish by-products. Furthermore, pretreatment on various sources of fish materials, followed by extraction methods, was described. The extraction procedures for acid soluble collagen (ASC) and pepsin soluble collagen (PSC) for fish collagen isolation are specifically discussed and compared. As a result, the efficacy of collagen yield was also demonstrated. The recent trend of extracting fish collagen from marine biomaterials has been summarized, with the potential to be exploited as a wound healing agent in pharmaceutical applications. Furthermore, background information on collagen and characterization techniques primarily related to the composition, properties, and structure of fish collagen are discussed.

Plasma polymers from oregano secondary metabolites: Antibacterial and biocompatible plant‐based polymers

AbstractBacterial infection of chronic wounds is a major healthcare problem that affects the quality of life of millions of patients worldwide and leads to a substantial healthcare cost burden. This project focused on the manufacture of a potential wound healing agent. Plasma polymers from oregano secondary metabolites (PP‐OSMs) were fabricated by radiofrequency plasma‐enhanced chemical vapor deposition (RF‐PECVD) in continuous and pulse plasma modes at room temperature. The surface, biocompatibility, and antibacterial properties of the PP‐OSMs were investigated. Polymers fabricated by RF‐PECVD retained the functional groups of OSMs, promoted human dermal fibroblast adhesion, inhibited Staphylococcus aureus attachment, and eliminated Pseudomonas aeruginosa. The PP‐OSM coatings are potential candidates for use in medical applications where cell biocompatibility and antibacterial properties are required.

Self-Gelling Solid Lipid Nanoparticle Hydrogel Containing Simvastatin as Suitable Wound Dressing: An Investigative Study.

Hydrogels, an advanced interactive system, is finding use as wound dressings, however, they exhibit restricted mechanical properties, macroscopic nature, and may not manage high exudate wounds or incorporate lipophilic actives. In this study, we developed a self-gelling solid lipid nanoparticle (SLNs) dressing to incorporate simvastatin (SIM), a lipophilic, potential wound-healing agent, clinically limited due to poor solubility (0.03 mg/mL) and absorption. The study explores unconventional and novel application of SIM. The idea was to incorporate a significant amount of SIM in a soluble form and release it slowly over a prolonged time. Further, a suitable polymeric surfactant was selected that assigned a self-gelling property to SLNs (SLN-hydrogel) so as to be used as a novel wound dressing. SLNs assign porosity, elasticity, and occlusivity to the dressing to keep the wound area moist. It will also provide better tolerance and sensory properties to the hydrogel. SIM loaded SLN-hydrogel was prepared employing an industry amenable high-pressure homogenization technique. The unique hydrogel dressing was characterized for particle size, zeta potential, Fourier transform infra-red spectroscopy, powder X-ray diffraction, differential scanning calorimetry, rheology, and texture. Significant loading of SIM (10% w/w) was achieved in spherical nanoparticule hydrogel (0.3 nm (nanoparticles) to 2 µm (gelled-matrix)) that exhibited good spreadability and mechanical properties and slow release up to 72 h. SLN-hydrogel was safe as per the organization for economic co-operation and development (OECD-404) guidelines, with no signs of irritation. Complete healing of excision wound observed in rats within 11 days was 10 times better than marketed povidone-iodine product. The presented work is novel both in terms of classifying a per se SLN-hydrogel and employing SIM. Further, it was established to be a safe, effective, and industry amenable invention.

Recent advances in biopolymer-based formulations for wound healing applications

Since decades, the field of wound healing has gained immense attention from the researchers worldwide. The ultimate goal is to develop effective techniques that can speed up the healing process and avoid scar formation to facilitate proper wound management. This has resulted in advances and discoveries in different biopolymeric nanosystems and their combinations as wound healing agents as alternatives for conventional wound dressings. This review primarily outlines wound healing cascade by human body’s natural defence mechanism and highlights the recent developments in wound healing agents. The aim of the review is to discuss the suitability of biopolymeric nanosystems based on chitin, chitosan, collagen, alginate, fucoidan, gelatin, silk fibroin and hyaluronic acid as potential wound healing agents to provide wound healing environment for enhanced healing rate.

Investigation of Wound Healing and Anti-Inflammatory Activities of Leaf Gel of Aloe trigonantha L.C. Leach in Rats.

BackgroundTraditionally Aloe trigonantha leaf is used for the treatment of different diseases. However, there were no in vivo studies which prove its claimed use for wound healing and anti-inflammatory activity. Therefore, the present study aimed at evaluating the in vivo wound healing and anti-inflammatory effects of the leaf gel of the plant in rats.MethodsThe leaf gel powder of the Aloe trigonantha was prepared after the gel gets lyophilized. It was evaluated for wound healing activity topically by incorporating it in a simple ointment base at a concentration of 5% (w/w) and 10% (w/w). Excision and incision models were used for wound healing activity in rats. For the excision wound model, wound contraction and period of epithelialization were evaluated, while wound tensile strength was evaluated using an incision wound model. A Xylene-induced ear edema model and cotton pellet-induced granuloma model were used for anti-inflammatory study. The leaf gel powder of Aloe trigonantha was given orally at a dose of 100, 200, and 400 mg/kg in both models of anti-inflammatory studies. An anti-inflammatory effect was measured by reduction of ear edema weight and reduction of wet exudate and dry granuloma weight in both of xylene-induced ear edema and cotton pellet-induced granuloma models, respectively.ResultsTreatment of wounds with ointment containing 5% and 10% (w/w) of the gel exhibited a significantly increased wound contraction rate, shorter epithelialization time, and higher skin breaking strength (p<0.05) compared to controls. Aloe trigonantha leaf gel powder also produced dose-dependent significant reductions (p<0.05) of inflammation compared to control in both models.ConclusionData obtained from this study collectively indicated that Aloe trigonantha is a potential wound-healing and anti-inflammatory agent in rat models of wound and inflammation which provides evidence for the traditional claim.

Thromboelastometric Analysis of Anticancer Cerrena unicolor Subfractions Reveal Their Potential as Fibrin Glue Drug Carrier Enhancers

In this study, the influence of two subfractions (with previously proven anti-cancer properties) isolated from wood rot fungus Cerrena unicolor on the formation of a fibrin clot was investigated in the context of potential use as fibrin glue and sealant enhancers and potential wound healing agents. With the use of ROTEM thromboelastometry, we demonstrated that, in the presence of fibrinogen and thrombin, the S6 fraction accelerated the formation of a fibrin clot, had a positive effect on its elasticity modulus, and enhanced the degree of fibrin cross-linking. The S5 fraction alone showed no influence on the fibrin coagulation process; however, in the presence of fibrin, it exhibited a decrease in anti-proliferative properties against the HT-29 line, while it increased the proliferation of cells in general at a concentration of 100 µg/mL. Both fractions retained their proapoptotic properties to a lesser degree. In combination with the S6 fraction in the ratio of 1:1 and 1:3, the fractions contributed to increased inhibition of the activity of matrix metalloproteinases (MMPs). This may suggest anti-metastatic activity of the combined fractions. In conclusion, the potential of the fractions isolated from the C. unicolor secretome to be used as a means of improving the wound healing process was presented. The potential for delivering agents with cytostatic properties introduced far from the site of action or exerting a pro-proliferative effect at the wound site with the aid of a fibrin sealant was demonstrated.

Evaluation of the Wheat Germ Oil Topical Formulations for Wound Healing Activity in Rats.

Wheat Germ Oil (WGO), the flour-milling by-product of wheat has essential constituents for skin health care as vitamin E, B-complex, squalene and unsaturated fatty acids. Incorporate WGO into polymers of the cream and ointment bases and evaluate the wound healing potential of these WGO formulations in the rat-animal model. &lt;b&gt;Materials and Methods:&lt;/b&gt; WGO creams and ointments were prepared in two concentrations, 10 and 20% and evaluated for storage stability, homogeneity and compatibility using Fourier Transform Infrared (FT-IR) spectrometry. An amount of 0.5 g of the WGO formulations was applied daily to the injured area of the rats back. Wounds were observed for any clinical changes and healing compared to the control animal group. &lt;b&gt;Results:&lt;/b&gt; The WGO was compatible with the cream and ointment bases and physically stables over 60 days of storage. The formulations of WGO have induced dose-dependent wound healing properties however the ointment formulations were demonstrating wound healing activity significantly better than the creams at all the intervals of the treatment. Within three weeks, 20% WGO ointment has induced a 90%reduction in the wound size diameter. Also, wounds recovered by 50% in 10 and 14 days of treatment with 20% WGO ointment and cream, respectively. &lt;b&gt;Conclusion:&lt;/b&gt; The results revealed that WGO is a potential wound-healing agent from the scope that WGO is a common cosmetic ingredient and available at affordable prices.

Novel positive allosteric modulator of protease-activated receptor 1 promotes skin wound healing in hairless mice.

Protease-activated receptor 1 (PAR1) is a GPCR expressed in several skin cell types, including keratinocyte and dermal fibroblast. PAR1 activation plays a crucial role in the process of skin wound healing such as thrombosis, inflammation, proliferation and tissue repair. In the present study, we identified a novel positive allosteric modulator of PAR1, GB83, and investigated its effect on skin wound healing. The enhancement of PAR1 activity by GB83 was measured using Fluo-4 calcium assay. In silico docking analysis of GB83 in PAR1 was performed using dock ligands method (CDOCKER) with CHARMm force field. Effects of GB83 on cell viability and gene expression were observed using MTS assay and quantitative real-time PCRs, respectively. SKH-1 hairless mice were used to investigate the wound healing effect of GB83. We demonstrated that GB83 did not activate PAR1 by itself but strongly enhanced PAR1 activation by thrombin and PAR1-activating peptide (AP). In silico docking analysis revealed that GB83 can bind to the PAR1 binding site of vorapaxar. GB83 significantly promoted PAR1-mediated cell viability and migration. In addition, the enhancement of PAR1 activity by GB83 strongly increased gene expression of TGF-β, fibronectin and type I collagen in vitro and promoted skin wound healing in vivo. Our results revealed that GB83 is the first positive allosteric modulator of PAR1 and it can be a useful pharmacological tool for studying PAR1 and a potential therapeutic agent for skin wound healing.