Wound Healing Products Research Articles

Rifampicin-Loaded PLGA/Alginate-Grafted pNVCL-Based Nanoparticles for Wound Healing

The topical therapy with rifampicin (RF)-based formulations is beneficial for treating postoperative wound infections and to accelerate healing. Despite recent research highlighting the antibiotic’s significant anti-inflammatory properties, limited topical wound healing products are currently available. The present study aimed to prove that the newly synthesized nanoparticles based on grafted alginate and poly(N-vinylcaprolactam) (pNVCL) and poly-lactic-co-glycolic acid (PLGA) contribute to the healing process of a wound. The methods used were at first the synthesis of the copolymer of alginate and pNVCL via grafting from technique and radical polymerization followed by water-in-oil-in water (W/O/W) emulsification; as oil phase PLGA dissolved in dichloromethane (DCM) was used. The formed nanoparticles were than characterized. The loaded RF was determined to be 160 µg/mL for a 20 mg formulation and within a four-hour time frame approximately 10% of the total loaded amount was released. The inhibitory concentrations (IC50) were 192.1 µg/mL for the nanoparticle, 208.8 µg/mL for pure rifampicin, and 718.1 µg/mL for the rifampicin-loaded nanoparticles. Considering the double role rifampicin was used for, the result was considered satisfactory in the way that these formulations could be used predominantly for postoperative wound irrigation in order to avoid infections and to improve healing.

Enhancing Wound Healing With Sprayable Hydrogel Releasing Multi Metallic Ions: Inspired by the Body's Endogenous Healing Mechanism.

In the pursuit of new wound care products, researchers are exploring methods to improve wound healing through exogenous wound healing products. However, diverging from this conventional approach, this work has developed an endogenous support system for wound healing, drawing inspiration from the body's innate healing mechanisms governed by the sequential release of metal ions by body at wound site to promote different stages of wound healing. This work engineers a multi-ion-releasing sprayable hydrogel system, to mimic this intricate process, representing the next evolutionary step in wound care products. It comprises Alginate (Alg) and Fibrin (Fib) hydrogel infused with Polylactic acid (PLA) polymeric microcarriers encapsulating multi (calcium, copper, and zinc) nanoparticles (Alg-Fib-PLA-nCMB). Developed sprayable Alg-Fib-PLA-nCMB hydrogel show sustained release of beneficial multi metallic ions at wound site, offering a range of advantages including enhanced cellular function, antibacterial properties, and promotion of crucial wound healing processes like cell migration, ROS mitigation, macrophage polarization, collagen deposition, and vascular regeneration. In a comparative study with a commercial product (Midstress spray), developed Alg-Fib-PLA-nCMB hydrogel demonstrates superior wound healing outcomes in a rat model, indicating its potential for next generation wound care product, addressing critical challenges and offering a promising avenue for future advancements in the wound management.

COMPARATIVE STUDY BETWEEN THE EFFECTIVENESS OF AMNION-CollaGee [COLLAGEN–GELATIN–ELASTIN] AS A BIOLOGICAL PRODUCT WOUND DRESSING AND CONVENTIONAL DRESSING ON THE DONOR SITE OF THE SPLIT THICKNESS SKIN GRAFT IN ANIMALS MODEL (RATS)

Abstract Background The clinical application of amniotic membrane wound healing products is limited partially due to handling challenges. Amnion-CollaGee sponge dressing (ACS) provides better alternatives to traditional therapy in facilitating wound healing. Objective To optimize the effectiveness of ACS as a healing agent in donor-site split-thickness skin graft (STSG) based on in vitro outcomes. Followed by comparing wound healing rates, pain sensitivity, and risks of infection between investigator ACS dressing with currently conventional Duoderm dressing (DD) via in vivo analysis. Materials and methods Seven male Sprague-Dawley rats underwent STSG harvesting, with 1x1cm grafts taken from both the right and left sides of the animals' backs. The wounds on the right side (Group 1) were dressed with ACS, while the wounds on the left side (Group 2) were dressed with DD. The donor site wounds were assessed on the seventh, fourteenth, and twenty-first days of the experiment. Primary outcomes measured were rate of healing, pain sensitivity, potential risks of infection. Secondary outcomes were lesion vascularity, pigmentation and histopathological features. Results The size of the wounds treated with ACS was statistically smaller compared to that treated with DD. On day 21st, both types of dressings showed complete healing, thus, contributing to better aesthetic value. Additionally, superior pain suppression was witnessed at ACS-treated graft sites compared to DD. Histopathological reports displayed better post-traumatic wound site inflammatory control, less tissue scarring, and abundant collagen growth in the ACS wing compared to the DD counterpart. Conclusion The biological ACS dressing appeared to facilitate rapid wound healing rates, reduce the risk of exposed wound infections, and enhance pain suppression in rodent models. ACS based dressing agents are future interventional breakthroughs in graft donor site wound management.

Recombinant human epidermal growth factor-loaded liposomes and transferosomes for dermal delivery: Development, characterization, and cytotoxicity evaluation.

Recombinant human epidermal growth factor (rhEGF) is widely utilized as an antiaging compound in wound-healing therapies and cosmetic purposes. However, topical administration of rhEGF has limited treatment outcomes because of its poor percutaneous penetration and rapid proteinase degradation. To overcome these obstacles, this study aims to develop and characterize rhEGF-containing conventional liposomes (rhEGF-CLs) and transferosomes (rhEGF-TFs) as efficient dermal carriers. Physicochemical characterization such as particle size, zeta potential (ZP), morphology, encapsulation efficiency (EE%), and release properties of nanocarriers as well as in vitro cytotoxicity in human dermal fibroblast (HDF) and human embryonic kidney (HEK293) cell lines were investigated. rhEGF-TFs at the rhEGF concentration ranging from 0.05 to 1.0 μg/mL were chosen as the optimum formulation due to the desired release profile, acceptable EE%, optimal cell proliferation, and minimal cytotoxicity compared to the control and free rhEGF. However, higher concentrations caused a decrease in cell viability. The ratio 20:80 of Tween 80 to lipid was optimal for rhEGF-TFs-2, which had an average diameter of 233.23 ± 2.64 nm, polydispersity index of 0.33 ± 0.05, ZP of -15.46 ± 0.29 mV, and EE% of 60.50 ± 1.91. The formulations remained stable at 5°C for at least 1 month. TEM and SEM microscopy revealed that rhEGF-TFs-2 had a regular shape and unilamellar structure. In vitro drug release studies confirmed the superiority of rhEGF-TFs-2 in terms of optimal cumulative release of rhEGF approximately 82% within 24 h. Franz diffusion cell study showed higher rhEGF-TFs-2 skin permeation compared to free rhEGF solution. Taken together, we concluded that rhEGF-TFs can be used as a promising formulation for wound healing and skin regeneration products.

Wound Healing Potential of a Novel Sedum Species: S. album Murales.

Natural wound healing products are in increased demand. The potential for unexplored Sedum species in wound healing was discovered based on benefits of the genus reported in traditional medicine. The objectives were to screen ten Sedum species for wound healing, to ascertain the optimal harvest period using the five best, and finally to investigate effects of extraction protocols on wound healing using the most promising species. Different protocols were used to extract leaf polyphenol and mucilage content. Wound healing was assessed from L929 fibroblast migration. April was the optimal harvest month for wound healing efficacy, whereas the highest polyphenol content and antioxidant activity were evident in September and November. S. album Murales (ALBU), the best candidate, was then compared with S. telephium (TELE), which is well recognized in skin care. The mucilage-containing aqueous extract of ALBU was shown for the first time to induce the highest fibroblast migration after 24 h, not evident in TELE. Moreover, functional constituents contained within the absolute acetone- and isopropanol-containing polyphenol pools from ALBU induced significantly higher migration compared to TELE. A prototype cream, containing the water- and solvent-extracted bioactive compounds was effective at inducing fibroblast migration at 24 h in ALBU. The potential of ALBU in wound healing was evidenced and warrants further investigation.

PLANT RAW MATERIAL AS A SOURCE OF METABOLITES FOR WOUND HEALING AND ANTI-SCARRING PRODUCT

Cosmeceutical products based on plant raw materials have a complex effect, are available, and low-toxic. The creation of new natural products for wound healing without tissue scarring is topical. For this, the secondary metabolites of the plant must demonstrate antibacterial, anti-inflammatory, and antioxidant effects, and have low cytotoxicity. Aim. To conduct an analysis of literary sources in electronic databases, regarding products on the market with a wound healing effect and plant raw materials that would have a therapeutic effect on wound healing without the formation of scars. Results. The characteristics of four types of scars are described. Plants and secondary metabolites are listed according to their action: antibacterial, antioxidant, anti-inflammatory, collagenstimulating, and anti-scarring. Lupeol, allicin, and cinnamaldehyde show antibacterial effect; quercetin, resveratrol, luteolin, naringenin, gallic acid, and curcumin show antioxidant effect; asiatic acid, pinocembrin, and myricetin show anti-inflammatory effect. Cryptotanshinone, bexarotene, taspine, sesamol, and astragaloside IV contribute to the deposition of fresh collagen in the wound. On the Ukrainian market, there are natural wound healing products in the form of a balm, cream, and gel. They include vegetable oils, essential oils, extracts of Thymus L., Arnica montana, Inula helenium, Aloe vera, Matricaria chamomilla, etc. Wound healing medicinal products of a chemical nature occupy a large part of the Ukrainian market, among them the products with dexapentanol predominate. The use of the cell culture method as an alternative source of plant raw materials for wound and scar treatment is perspective. The biotechnological method helps preserve biodiversity and obtain chemically pure plant raw materials regardless of environmental conditions. Conclusions. The study demonstrates the possibilities of using plant raw materials to create new cosmeceuticals with wound healing and anti-scaring effects for use in combined therapy.

Cerium Dioxide-Dextran Nanocomposites in the Development of a Medical Product for Wound Healing: Physical, Chemical and Biomedical Characteristics.

the creation of a dextran coating on cerium oxide crystals using different ratios of cerium and dextran to synthesize nanocomposites, and the selection of the best nanocomposite to develop a nanodrug that accelerates quality wound healing with a new type of antimicrobial effect. Nanocomposites were synthesized using cerium nitrate and dextran polysaccharide (6000 Da) at four different initial ratios of Ce(NO3)3x6H2O to dextran (by weight)-1:0.5 (Ce0.5D); 1:1 (Ce1D); 1:2 (Ce2D); and 1:3 (Ce3D). A series of physicochemical experiments were performed to characterize the created nanocomposites: UV-spectroscopy; X-ray phase analysis; transmission electron microscopy; dynamic light scattering and IR-spectroscopy. The biomedical effects of nanocomposites were studied on human fibroblast cell culture with an evaluation of their effect on the metabolic and proliferative activity of cells using an MTT test and direct cell counting. Antimicrobial activity was studied by mass spectrometry using gas chromatography-mass spectrometry against E. coli after 24 h and 48 h of co-incubation. According to the physicochemical studies, nanocrystals less than 5 nm in size with diffraction peaks characteristic of cerium dioxide were identified in all synthesized nanocomposites. With increasing polysaccharide concentration, the particle size of cerium dioxide decreased, and the smallest nanoparticles (<2 nm) were in Ce2D and Ce3D composites. The results of cell experiments showed a high level of safety of dextran nanoceria, while the absence of cytotoxicity (100% cell survival rate) was established for Ce2D and C3D sols. At a nanoceria concentration of 10-2 M, the proliferative activity of fibroblasts was statistically significantly enhanced only when co-cultured with Ce2D, but decreased with Ce3D. The metabolic activity of fibroblasts after 72 h of co-cultivation with nano composites increased with increasing dextran concentration, and the highest level was registered in Ce3D; from the dextran group, differences were registered in Ce2D and Ce3D sols. As a result of the microbiological study, the best antimicrobial activity (bacteriostatic effect) was found for Ce0.5D and Ce2D, which significantly inhibited the multiplication of E. coli after 24 h by an average of 22-27%, and after 48 h, all nanocomposites suppressed the multiplication of E. coli by 58-77%, which was the most pronounced for Ce0.5D, Ce1D, and Ce2D. The necessary physical characteristics of nanoceria-dextran nanocomposites that provide the best wound healing biological effects were determined. Ce2D at a concentration of 10-3 M, which stimulates cell proliferation and metabolism up to 2.5 times and allows a reduction in the rate of microorganism multiplication by three to four times, was selected for subsequent nanodrug creation.

Repurposing of Nano-Engineered Piroxicam as an Approach for Cutaneous Wound Healing

Drug repurposing is a potential strategy to overcome the huge economic expenses of wound healing products. This work aims to develop a topical gel of piroxicam encapsulated into a nanospanlastics vesicular system as an effective, dermal wound dressing. Firstly, piroxicam was entrapped into nanospanlastics formulations and optimized utilizing 23 full factorial experimental designs. The scrutinized factors were Span 60: Edge activator ratio, edge activator type, and permeation enhancer type. The measured responses were vesicle size (VS), polydispersity index (PDI), and% entrapment efficiency (EE). The optimized formula was further adopted into an alginate-pectin gel matrix to maximize adherence to the skin. The rheology and in-vitro release were studied for the developed nanospanlastics gel. Cytotoxicity and wound healing potential using scratch assay were assessed on human adult dermal fibroblast cells. The optimal piroxicam nanospanlastics formula demonstrated a VS of 124.1 ± 1.3 nm, PDI of 0.21 ± 0.01, and EE% of 97.27±0.21%. About 70.0 ± 0.9% and 57.4 ± 0.1% of piroxicam were released from nanospanlastics dispersion and gel within 24 h, respectively. Nanospanlastics gel of piroxicam flowed in a non-Newtonian pseudoplastic shear thinning pattern. It was also biocompatible with the human dermal fibroblast cells and significantly promoted their migration rate which suggests an auspicious cutaneous wound healing aptitude.

Progress in Wound-Healing Products Based on Natural Compounds, Stem Cells, and MicroRNA-Based Biopolymers in the European, USA, and Asian Markets: Opportunities, Barriers, and Regulatory Issues.

Wounds are breaks in the continuity of the skin and underlying tissues, resulting from external causes such as cuts, blows, impacts, or surgical interventions. Countless individuals suffer minor to severe injuries, with unfortunate cases even leading to death. In today's scenario, several commercial products are available to facilitate the healing process of wounds, although chronic wounds still present more challenges than acute wounds. Nevertheless, the huge demand for wound-care products within the healthcare sector has given rise to a rapidly growing market, fostering continuous research and development endeavors for innovative wound-healing solutions. Today, there are many commercially available products including those based on natural biopolymers, stem cells, and microRNAs that promote healing from wounds. This article explores the recent breakthroughs in wound-healing products that harness the potential of natural biopolymers, stem cells, and microRNAs. A comprehensive exploration is undertaken, covering not only commercially available products but also those still in the research phase. Additionally, we provide a thorough examination of the opportunities, obstacles, and regulatory considerations influencing the potential commercialization of wound-healing products across the diverse markets of Europe, America, and Asia.

Effects of Medicinal Plants Extracts in Healing Split-Thickness Skin Graft Donor Site Wounds: A Systematic Review of Randomized Clinical Trials

The literature on Split-Thickness Skin Graft (STSG) donor site dressings has not yet identified an ideal dressing, and most products tested by researchers for wound dressing are prohibitively expensive in Low- and Middle-income settings. Clinical trials using biological dressings have offered an alternative option for managing STSG donor sites wound. The aim of this systematic review is to find evidences regarding the effectiveness of medicinal plants on STSG donor site wound healing. A total of 249 papers were identified in the initial search. After removing duplicates and applying the inclusion and exclusion criteria, 6 Randomized Clinical Trials were deemed relevant and included in the final review. Over twenty years four medicinal plants have entered clinical trial to enhance STSG donor site wound healing. The medicinal plants reviewed have large effect size regarding time to complete wound healing and wound score. However, the effect size of Aloe vera regarding time to complete wound healing and pain control vary from study to study. No patient quality of life was assessed neither cost-effectiveness of these products. Medicinal plants are potential cost effective antimicrobial and wound healing products for STSG donor site wound dressing. However, more clinical researches including patient quality of life among outcome measures are needed.

Antimicrobial Activity of Citrate-Coated Cerium Oxide Nanoparticles.

The purpose of this study was to investigate the antimicrobial activity of citrate-stabilized sols of cerium oxide nanoparticles at different concentrations via different microbiological methods and to compare the effect with the peroxidase activity of nanoceria for the subsequent development of a regeneration-stimulating medical and/or veterinary wound-healing product providing new types of antimicrobial action. The object of this study was cerium oxide nanoparticles synthesized from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid (the size of the nanoparticles was 3-5 nm, and their aggregates were 60-130 nm). Nanoceria oxide sols with a wide range of concentrations (10-1-10-6 M) as well as powder (the dry substance) were used. Both bacterial and fungal strains (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Proteus vulgaris, Candida albicans, Aspergillus brasielensis) were used for the microbiological studies. The antimicrobial activity of nanoceria was investigated across a wide range of concentrations using three methods sequentially; the antimicrobial activity was studied by examining diffusion into agar, the serial dilution method was used to detect the minimum inhibitory and bactericidal concentrations, and, finally, gas chromatography with mass-selective detection was performed to study the inhibition of E. coli's growth. To study the redox activity of different concentrations of nanocerium, we studied the intensity of chemiluminescence in the oxidation reaction of luminol in the presence of hydrogen peroxide. As a result of this study's use of the agar diffusion and serial dilution methods followed by sowing, no significant evidence of antimicrobial activity was found. At the same time, in the current study of antimicrobial activity against E. coli strains using gas chromatography with mass spectrometry, the ability of nanoceria to significantly inhibit the growth and reproduction of microorganisms after 24 h and, in particular, after 48 h of incubation at a wide range of concentrations, 10-2-10-5 M (48-95% reduction in the number of microbes with a significant dose-dependent effect) was determined as the optimum concentration. A reliable redox activity of nanoceria coated with citrate was established, increasing in proportion to the concentration, confirming the oxidative mechanism of the action of nanoceria. Thus, nanoceria have a dose-dependent bacteriostatic effect, which is most pronounced at concentrations of 10-2-10-3 M. Unlike the effects of classical antiseptics, the effect was manifested from 2 days and increased during the observation. To study the antimicrobial activity of nanomaterials, it is advisable not to use classical qualitative and semi-quantitative methods; rather, the employment of more accurate quantitative methods is advised, in particular, gas chromatography-mass spectrometry, during several days of incubation.

Unique combination of hyaluronic acid and amino acids in the management of patients with a range of moderate-to-severe chronic wounds: Evidence from international clinical trials.

Chronic wounds present a prolonged burden to patients, their families and healthcare systems. There is evidence that the unique combination of hyaluronic acid (HA) and amino acids (Vulnamin®) promotes re-epithelialization of wounds and stimulates activation and proliferation of fibroblasts with a significant increase in the regeneration of epithelial cells. Tissue regeneration and tissue repair are considered to be the fundamental activities of this unique combination of HA and amino acids that distinguishes it from other wound healing products. A review of trials over the last 15 years indicates distinct advantages of the unique combination of HA and amino acids, in terms of healing rate and induction of granulation tissue production compared with HA alone.

Polysaccharide Composite Alginate-Pectin Hydrogels as a Basis for Developing Wound Healing Materials.

This article presents materials that highlight the bioengineering potential of polymeric systems of natural origin based on biodegradable polysaccharides, with applications in creating modern products for localized wound healing. Exploring the unique biological and physicochemical properties of polysaccharides offers a promising avenue for the atraumatic, controlled restoration of damaged tissues in extensive wounds. The study focused on alginate, pectin, and a hydrogel composed of their mixture in a 1:1 ratio. Atomic force microscopy data revealed that the two-component gel exhibits greater cohesion and is characterized by the presence of filament-like elements. The dynamic light scattering method indicated that this structural change results in a reduction in the damping of acoustic modes in the gel mixture compared to the component gels. Raman spectroscopy research on these gels revealed the emergence of new bonds between the components' molecules, contributing to the observed effects. The biocompatibility of the gels was evaluated using dental pulp stem cells, demonstrating that all the gels exhibit biocompatibility.

Current Biological Knowledge, Applications, and Potential Use of the Desert Shaggy Mane Mushroom Podaxis pistillaris (Agaricomycetes): A Review.

Podaxis pistillaris, an abundant gasteroid mushroom, has become an important biological element in arid and semiarid communities worldwide. This mushroom possesses cosmetic, edible, and medicinal attributes, playing a crucial role in communities in countries such as Australia, India, Saudi Arabia, Yemen, and Mexico. Proximate studies highlight the nutritional richness of P. pistillaris, characterized by high protein content and essential bioelements such as K, P, and Mg. Furthermore, P. pistillaris is integral to the traditional medicine of indigenous communities in America, Asia, and Africa, where it is revered for its purported wound-healing, anti-inflammatory, and coagulant properties. In the case of Mexico, the Seri community uses and markets P. pistillaris in various forms, including ointments and, within the region, its spores. Chemical analysis of this species reveals notable compounds, including epicorazines A-C exhibiting antimicrobial properties, along with polysaccharides such as β-glucans, and a recently identified ergosterol derivative named podaxisterol. Despite its importance, the chemical characterization and assessment of the biological activity of its compounds have been largely understudied. Consequently, there are currently no wound-healing products on the market derived from fungi, as the majority originate from plant sources. This work aims to present the essential aspects of P. pistillaris's ethnobiological use, medicinal properties, bioactive compounds, and biotechnological applications. In addition, it underscores the overlooked status of P. pistillaris among fungi inhabiting arid areas, emphasizing its potential as a valuable subject for further research.

Formulation And Evaluation Of Herbal Cream For The Treatment Of Wound Healing

This study was to formulate and evaluate an herbal cream for wound healing using natural plant extracts known for their therapeutic properties. The selected herbs included Centella asiatica, which was chosen based on their well-documented efficacy in promoting skin repair and regeneration. Herbal extracts were prepared using ethanol and water as solvents, followed by standardization to ensure consistent active compound concentrations. The cream base was developed as an oil-in-water emulsion, optimized for pH, viscosity, and Spreadability to ensure suitability for topical application. Comprehensive stability studies were conducted to assess the formulation's physical, chemical, and microbial stability. The wound healing efficacy was evaluated through in vitro scratch assays and in vivo studies using a rat model, demonstrating significant improvements in wound contraction and re-epithelialization compared to controls. Additionally, dermal irritation tests confirmed the formulation’s safety for skin application. This research highlights the potential of combining traditional herbal medicine with modern formulation techniques to create effective and safe wound-healing products. The findings suggest that the developed herbal cream is a promising alternative to conventional treatments, offering natural and accessible solutions for wound care.

Tailoring polyethylene oxide-modified cross-linked chitosan/PVA nanofibrous membranes: Burn dressing scaffold developed for mupirocin release

In emergency treatment research, the focus on chitosan-based products for wound healing has been consistent. This study specifically explores a dressing made by mixing chitosan (CS) and poly (vinyl alcohol) PVA. Using electrospinning technology, nanofiber membranes of CS and PVA are created with the assistance of non-toxic and hydrophilic polyethylene oxide (PEO). The outcome is a new nanofibrous membrane loaded with mupirocin, designed for healing burn wounds.The study delves into the influence of PVA, CS, and PEO concentrations on the structural and chemical characteristics of the mats. This comprehensive exploration involves techniques such as Scanning Electron Microscope (SEM), Atomic Force Microscopy (AFM) imaging, Fourier Transform Infrared Spectrometry (FTIR analysis), and Contact angle measurements. Additionally, the research evaluates the antibacterial performance and biomedical behavior of the developed scaffolds.PEO proves beneficial in the electrospinning process, contributing to smoother fibers. Meanwhile, the addition of CS and mupirocin leads to formation of the thinner nanofibers (251 ± 5 μm and 263 ± 4 μm, respectively) and scaffolds with higher swelling (up to ∼3.5 times at 90 min). Notably, the (MTT) assay confirms the non-cytotoxicity of the fabricated nanofibers, with proliferations exceeding ∼85% for all samples.The crosslinked samples released the drug more slowly than the non-crosslinked dressings, with 80% of the scaffolds releasing the drug within 24 h. The in-vivo investigations suggested that the drug-containing scaffolds performed reliably and showed promise as a medical dressing for treating burn wounds.

In Situ Sodium Chloride Cross-Linked Fish Skin Collagen Scaffolds for Functional Hemostasis Materials.

Current fish collagen hemostasis for wound healing products is commonly obtained by electrospinning or artificial cross-linking fish collagen fibers which lacks mechanical properties, and biofunctions. Here, a new bio-active fish skin scaffold (FSS) is shown using in situ cross-linked scaleless freshwater fish skin adding adipose-derived stem cells (ASCs)-produced exosomes for hemostasis and wound healing. The structure, pore size, and the thickness of FSS is studied by swelling test, Fourier-transform infrared (FT-IR) spectra, scanning electron microscope (SEM) images, and histological analysis. The biofunctions of the FSS are also tested in vitro and in vivo. FSS keeps two functional layers: The dermis layer collagen forms a sponge like structure after swelling and in situ cross-linking treatments. The pore size of the FSS is ≈152 ± 23.54 µm, which is suitable for cells growing, angiogenesis and ASCs exosomes accelerate wound healing. The fat-rich epidermis layer can keep the wound moisty and clean before completely healed. In vitro and in vivo experimental results indicate that FSS+Exosomes enhances rat skin cavity wound healing. In situ sodium chloride cross-linked FSS+Exosomes provides a new strategy as functional hemostatic dressing scaffold for wound healing.

Carvacrol-Loaded Phytosomes for Enhanced Wound Healing: Molecular Docking, Formulation, DoE-Aided Optimization, and in vitro/in vivo Evaluation.

Despite recent advances in wound healing products, phytochemicals have been considered promising and attractive alternatives. Carvacrol (CAR), a natural phenolic compound, has been reported to be effective in wound healing. This work endeavored to develop novel CAR-loaded phytosomes for the enhancement of the wound healing process. Molecular docking was performed to compare the affinities of the different types of phospholipids to CAR. Phytosomes were prepared by three methods (thin-film hydration, cosolvency, and salting out) using Lipoid S100 and Phospholipon 90H with three levels of saturation percent (0%, 50%, and 100%), and three levels of phospholipid molar percent (66.67%, 75%, and 80%). The optimization was performed using Design Expert where particle size, polydispersity index, and zeta potential were chosen as dependent variables. The optimized formula (F1) was further investigated regarding entrapment efficiency, TEM, 1H-NMR, FT-IR, DSC, X-RD, in vitro release, ex vivo permeation, and stability. Furthermore, it was incorporated into a hydrogel formulation, and an in vivo study was conducted to investigate the wound-healing properties of F1. F1 was chosen as the optimized formula prepared via the thin-film hydration method with a saturation percent and a phospholipid molar percent of zero and 66.67, respectively. TEM revealed the spherical shape of phytosomal vesicles with uniform size, while the results of 1H-NMR, FT-IR, DSC, and X-RD confirmed the formation of the phytosomal complex. F1 demonstrated a higher in vitro release and a slower permeation than free CAR. The wound area of F1-treated animals showed a marked reduction associated with a high degree of collagen fiber deposition and enhanced cellular proliferation. F1 can be considered as a promising remedy for the enhancement of wound healing and hence it would be hoped to undergo further investigation.

Development and characterization of polydeoxyribonucleotide (PDRN) loaded chitosan polyplex: In vitro and in vivo evaluation of wound healing activity

Polydeoxyribonucleotide (PDRN) is an accelerated diabetic wound healing therapy with promising abilities to promote cell growth, angiogenesis, collagen synthesis, and reduce inflammation where its sustainable delivery and release behavior is critical to ensure effective wound healing properties. Therefore, a nanopolyplex was developed here, by encapsulating PDRN with chitosan to affirm its delivery systematically. The physicochemical characterization revealed its successful encapsulation which facilitates the gradual release of PDRN. In vitro studies of the polyplex demonstrated no cytotoxicity and enhanced cell proliferation and migration properties with high antimicrobial activities. In vivo, wound healing studies in Wistar rats dorsal skin defect model induced with diabetes mellitus affirm the highest wound healing activity and wound closure rate by chitosan/PDRN polyplex treatment. Considerably high histopathological changes such as epithelialization, collagen deposition, blood vessels, and hair follicle formation were observed under the polyplex treatment. The immunohistochemical analysis for platelet endothelial cell adhesion molecule (CD31) and cluster of differentiation (CD68) revealed the ability of polyplex to increase CD31 expression and decrease CD68 expression thereby promoting the wound healing process. Collectively, these results suggest that significantly accelerated, high-quality wound healing effects could be obtained by the developed chitosan/PDRN polyplex and thus it could be introduced as a potential therapeutic product for diabetic wound healing.

Nigella sativa L. seed extracts promote wound healing progress by activating VEGF and PDGF signaling pathways: An in vitro and in silico study

Background: A significant area of clinical research is the development of natural wound healing products and the management of chronic wounds. Healing wounds with medicinal plants has been a practice of ancient civilizations for centuries. Nigella sativa L (N. sativa) is a medicinal plant that has several pharmacological properties. Methods: The present study evaluated the wound healing properties of Nigella sativa L. (N. sativa) seed extracts using normal cell lines such as normal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs). The expression levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were analyzed through western blot analysis. Furthermore, computational analyses were carried out to screen the potential bioactive compounds for wound healing applications. Results: The results of the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay revealed that, all the tested solvent extracts of N. sativa seeds (including ethanol, ethyl acetate, chloroform, and petroleum ether) did not exert any cytotoxic effects at the tested concentrations. Furthermore, the western blot analysis showed elevated levels of VEGF and PDGF upon treatment with N. sativa seed extracts. Gas chromatography-mass spectrometry (GC-MS) analysis of N. sativa extracts identified 268 phytocompounds. Molecular docking studies revealed that three phytocompounds of N. sativa extracts, including tricyclo[20.8.0.0(7,16)]triacontane, 1(22),7(16)-diepoxy-, adaphostin and obeticholic acid had strong binding affinity with wound healing-related target proteins, showing docking scores ranging from -5.5 to -10.9 Kcal/mol. These compounds had acceptable Absorption, Distribution, Metabolism, and Excretion (ADME) properties. Conclusions: Based on these results, N. sativa seed extracts might possess potential wound healing properties owing to the presence of a wide range of bioactive components.