Wound Healing Effect Research Articles

(+)4-cholesten-3-one/sodium alginate/gelatin hydrogel for full-thickness wound repair and skin regeneration

(+)4-cholesten-3-one has been proved to have potential wound healing effect in the process of wound regeneration. This study aimed to evaluate the effect of (+)4-cholesten-3-one/sodium alginate/gelatin on skin injury and reveal its potential molecular mechanism. First, we prepared sodium alginate/gelatin hydrogel (SA/Gel hydrogel) with different ratios and tested their characteristics. Based on these results, different concentrations of (+)4-cholesten-3-one were added into SA/Gel hydrogel. A full-thickness skin injury model was successfully established to evaluate wound healing activityin vivo. HE staining and Masson staining were used to evaluate the thickness of granulation tissue and collagen deposition level. Immunohistochemical staining and immunofluorescence staining were applied to detect the level of revascularization and proliferation in each group of wounds. Western blot, quantitative-PCR and immunofluorescence staining were used to detect the expression of proteins related to Wnt/β-catenin signaling pathway in each group of wounds.In vitroresults showed that the hydrogel not only created a 3D structure for cell adhesion and growth, but also exhibited good swelling ability, excellent degradability and favorable bio-compatibility. Most importantly,in vivoexperiments further indicated that (+)4-cholesten-3-one/SA/Gel hydrogel effectively enhanced wound healing. The effectiveness is due to its superior abilities in accelerating healing process, granulation tissue regeneration, collagen deposition, promoting angiogenesis, tissue proliferation, as well as fibroblast activation and differentiation. The underlying mechanism was related to the Wnt/β-catenin signaling pathway. This study highlighted that (+)4-cholesten-3-one/SA/Gel hydrogel holds promise as a wound healing dressing in future clinical applications.

In Vitro and In Vivo Evaluation of Electrospun PVA Nanofiber Containing ZnO/Curcumin for Wound Healing Application.

The development of biocompatible wound dressings containing therapeutic agents to accelerate wound healing is an interesting field of study in biomedical sciences. Polyvinyl alcohol (PVA) nanofibers were loaded with zinc oxide nanoparticles (ZnO NPs) and curcumin (Cur) through electrospinning. Thedressings were characterized by SEM and XRD and FTIR. The antioxidant, antibacterial, and cytotoxic activities Cur/ZnO/PVA nanodressing were evaluated using DPPH radical scavenging assay, disc diffusion method, and MTT assay, respectively. Cur/ZnO/PVA nanodressing showed sustained Cur release about 19.7% and 61.1% after 8h and 168h, respectively. Cur/ZnO NPs/PVA mixture had higher antioxidant potential than PVA, ZnO NPs, and Cur. The dressing showed a good antibacterial effect. The in vivo wound healing effect of different types of prepared dressings, includingPVA, Cur/PVA,Cur/ZnO/PVA, and ZnO/PVAnanofibers, was also investigated. PVA dressing containing Cur/ZnO NPs resulted in the highestincrease of wound contraction in rats. The assembly of Cur and ZnO NPs on PVA nanofibers could propose as an effective delivery method toimprovethe wound healing process. The investigated wound dressing could be commercialized and used on a large scale after proper further studies, including clinical trials.

Chitosan/agarose hydrogel dressing: pH response real-time monitoring and chemo-/photodynamic therapy synergistic treatment of infected wounds

The early diagnosis and real-time monitoring of bacterial infections are of great significance for the establishment of integrated diagnosis and treatment systems. In this study, a pH-responsive smart hydrogel patch system, named CABP, was developed to monitor and treat wound infections. CABP has a sandwich structure, with non-woven fabric/chitosan (NF/CS) as the intermediate skeleton layer, Agarose/chitosan/Bromothymol Blue (AG/CS/BTB) hydrogel as the detection layer, and Agarose/chitosan/phthalocyanine (AG/CS/Pc) hydrogel as the treatment layer. When Staphylococcus aureus (S. aureus) infection occurs, the pH of the environment decreases, which triggers the CABP to change from its original blue color to yellow, achieving an intuitive visual transformation. Moreover, the hydrogel patch showed a significant inhibition rate of up to 99.99971 % against S. aureus under 660 nm light radiation, showing a good photodynamic therapy (PDT)/ chemotherapy (CT) synergistic effect. In addition, CABP showed excellent antibacterial and wound healing effects on S. aureus infection in a full-layer skin defect experiment. In short, the patch system is simple to prepare and easy to use, and can provide important research value for the integrated diagnosis and treatment system in biomedical applications.

Development of pectin/chitosan-based electrospun biomimetic nanofiber membranes loaded with dihydromyricetin inclusion complexes for wound healing application

Accidents and surgical procedures inevitably lead to wounds, presenting clinical challenges such as inflammation and microbial infections that impede the wound-healing process. This study aimed to address these challenges by developing a series of novel wound dressings known as electrospun biomimetic nanofiber membranes. These membranes were prepared using electrostatic spinning technique, incorporating hydroxypropyl-β-cyclodextrin/dihydromyricetin inclusion complexes. The prepared electrospun biomimetic nanofiber membranes exhibited randomly arranged fiber morphology with average fiber diameters ranging from 200 to 400 nm, resembling the collagen fibers in the native skin. These membranes demonstrated excellent biocompatibility, hemocompatibility, surface hydrophilicity, and wettability, while also releasing dihydromyricetin in a sustained manner. In vitro testing revealed that these membranes, loaded with hydroxypropyl-β-cyclodextrin/dihydromyricetin inclusion complexes, displayed higher antioxidant potential and inhibitory effects against Staphylococcus aureus and Escherichia coli. Furthermore, these membranes significantly reduced the M1 phenotypic transition in RAW264.7 cells, even when stimulated by lipopolysaccharides, effectively restoring M2 polarization, thereby shortening the inflammatory period. Additionally, the in vivo wound healing effects of these membranes were validated. In conclusion, this study introduces a promising nanofiber membrane with diverse biological properties that holds promise for addressing various crucial aspects of the wound-healing process.

Tunicate cellulose nanocrystal reinforced multifunctional hydrogel with super flexible, fatigue resistant, antifouling and self-adhesive capability for effective wound healing

Hydrogels as skin wound dressings have been extensively studied owing to their good flexibility and biocompatibility. Nevertheless, the mechanical performance, adhesive capability, antifouling and antibacterial properties of conventional hydrogels are still unsatisfactory, which hinder the application of hydrogel for cutaneous healing. Here, we developed a novel biocompatible multifunctional hydrogel with super flexible, fatigue resistant, antifouling and self-adhesive capability for effective wound healing, where naturally rigid polymers including quaternized chitosan (QCS) and Tunicate cellulose nanocrystals (TCNCs) are used as bioactive cross-linkers and reinforcers to endow the hydrogel with excellent mechanical and antibacterial property, and the synergistic contributions from the poly(acrylic acid/methacrylate anhydride dopamine/sulfobetaine methacrylate) (poly(AA/DMA/SBMA)) chains and QCS endow the hydrogel with excellent adhesive property, antioxidant, antifouling and pH-responsive sustained drug release capabilities. The optimized hydrogel exhibited high tensile strength (77.69 KPa), large tensile strain (889.9 %), large toughness (307.51KJ.m−3), high adhesive strength (35.57 KPa) and ideal compressive property. The in vivo infected full-thickness skin model demonstrated that the hydrogel with vanvomycin sustained release ability efficiently improved the granulation tissue formation, facilitating collagen deposition and reducing inflammatory expression, thus effectively accelerating wound healing. This superiorly skin-adhesive antibacterial biocompatible hydrogel appears to be a promising candidate for wound therapy.

Portulaca grandiflora phytochemicals as a potential source for wound healing activity: in vitro and in vivo studies

The management of chronic wounds presents considerable challenges and has a substantial influence on the quality of life among afflicted persons and their families. The discovery of naturally produced bioactive chemicals having good effects on the regeneration of tissue has been driven by the need for safe, effective, and cost-effective wound healing therapies. Portulaca grandiflora is an annual succulent that comes under the family of Portulacaceae. The purpose of this study was to evaluate the phytochemicals of n-hexane extracts and their effects on in vitro and in vivo wound healing models. In vitro study, Wound Scratch Assay shows that n-hexane extract of 100 ug/ml concentration significantly promotes wound healing through increased cell migration and wound closure compared to MEBO ointment-treated groups and negative control groups. The in vivo study shows that the formula of the extract ointment promotes wound healing without any complication and the percentage of wound surface area reduction was (5.39 ± 0.391) better than MEBO-treated groups (10.06 ± 0.536), and negative control groups (14.04 ± 0.304) through its ability to stimulate epidermal closure, re-epithelization, and granulation that appears in histological examination. As a result, Iraqi Portulaca grandiflora can be considered a potential resource of chemical substances, especially terpenoids, and steroids, which are helpful in healing wounds.

Nanofibrous dressing with drug/electroactivity synergistic effect for wound healing

Although electrical stimulation (ES) and drugs are desirable for wound healing, dressings that combine ES and drugs are scarce. In this study, an electroactive drug-loaded nanofibrous dressing (PUE-Zn/AB@CA) was prepared by loading zinc/acetylene black nanoparticle particles (Zn/AB) in Puerarin/cellulose acetate (PUE/CA) nanofibres, respectively. Due to the different potentials, many galvanic couples can be formed between Zn and AB, generating electrical stimulation that promotes cell migration and proliferation. Benefiting from the synergistic effect of Zn/AB electrical stimulation and PUE, PUE-Zn/AB@CA exhibits excellent antioxidant, antibacterial, and anti-inflammatory properties. The whole-layer wound defect model experiment showed that PUE-Zn/AB@CA can significantly accelerate wound closure and promote granulation tissue formation, collagen deposition, and angiogenesis at the wound. Moreover, PUE-Zn/AB@CA could inhibit the inflammatory infiltration of M1-type macrophages in damaged wounds. In addition, flow cytometry and Western blot (WB) revealed that PUE-Zn/AB@CA could effectively down-regulate the lipopolysaccharide (LPS)-induced macrophage polarisation towards M1-type and reduce the protein level of pro-inflammatory cytokines (iNOS) in the cells. This work provided an effective wound healing strategy based on drug/electroactivity synergistic effects.

A Novel Potential Treatment for Diabetic Foot Ulcers and Non-Healing Ulcers - Case Series.

<p>Introduction: Appropriate care and treatment of a wound is the need of the hour whether it is an infected or a non-infected wound. If wound healing is delayed for some reason, it leads to serious complications and further increases the hospital stay and cost of treatment. Herein, we describe a novel antimicrobial wound dressing formulation (VG111), with an objective to generate the preliminary data showing the distinct advantages in various types of wounds. <p> Method: This case series involved the treatment of acute cases of wounds or chronic wounds that did not respond well to conventional wound healing treatments with VG111 in patients with different etiologies. Thirteen cases of patients that included patients with diabetes, pressure ulcers, burns, trauma, and others treated with VG111 showed rapid wound healing in all the cases, even obviating the need for a graft when complete skin regeneration occurred. <p> Result: This was illustrated by clearing of the wound infections, reduction/disappearance of the exudate, appearance of intense granulation, epithelialization, and anti-biofilm activity followed by complete wound closure. This VG111 precludes the need for systemic antimicrobial agents in localized infections and therefore, this single agent is an attempt to address the limitations and the drawbacks of the available products. <p> Conclusion: Despite patients belonging to the old age group and having comorbidities like diabetes, still VG111 showed effective rapid wound healing, and that too without any scar formation in hardto- heal, infected, and non-infected wounds.</p>.

Polydopamine-assisted smart bacteria-responsive hydrogel: Switchable antimicrobial and antifouling capabilities for accelerated wound healing

IntroductionWound infections and formation of biofilms caused by multidrug-resistant bacteria have constituted a series of wound deteriorated and life-threatening problems. The in situ resisting bacterial adhesion, killing multidrug-resistance bacteria, and releasing dead bacteria is strongly required to supply a gap of existing sterilization strategies. ObjectivesThis study aims to present a facile approach to construct a bacteria-responsive hydrogel with switchable antimicrobial-antifouling properties through a “resisting-killing-releasing” method. MethodsThe smart bacteria-responsive hydrogel was constructed by two-step immersion strategy: a simple immersion-coating process to construct Polydopamine (pDA) coatings on the surface of a gelatin-chitosan composite hydrogel and followed by grafting of bactericidal quaternary ammonium chitosan (QCS) as well as pH-responsive PMAA to this pDA coating. The in vitro antimicrobial activity, biocompatibility and the in vivo wound healing effects in a mouse MRSA-infected full-thickness defect model of the hydrogel were further evaluated. ResultsAssisted by polydopamine coating, the pH-responsive PMAA and bactericidal QCS are successfully grafted onto a gelatin-chitosan composite hydrogel surface and hydrogels maintain the adequate mechanical properties. At physiological conditions, the PMAA hydration layer endows the hydrogel with resistance to initial bacterial attachment. Once bacteria colonize and acidize local environment, the swelling PMAA chains tend to collapse then expose the bactericidal QCS, realizing the on-demand kill bacteria. Moreover, the dead bacteria can be released and the hydrogel will resume the resistance due to hydrophilicity of PMAA at increased pH, endowing the surface renewable ability. In vitro and in vivo studies demonstrate the favorable biocompatibility and wound healing capacity of hydrogels that can inhibit infection and further facilitate granulation tissue, angiogenesis, and collagen synthesis. ConclusionThis strategy provides a novel methodology for the development and design of smart wound dressing to combat multidrug-resistant bacteria infections.

The composite biomatrix SC/CM improved the therapeutic effects of xenogeneic MSC on wound healing in immune-competent mice via immune niche reprogramming

Allogenic mesenchymal stem cell (allo-MSC) transplantation has shown great potential in the field of tissue repair. Increasing evidence has shown that allo-MSC are not completely immune-privileged; the immunogenic response after transplantation is involved in the poor survival and limited therapeutic effects of allo-MSC therapy. Here, we developed a composite biomatrix of a chondroitin sulfate/collagen scaffold (SC) loaded with conditioned medium (CM) derived from adipose mesenchymal cells and showed that SC/CM could significantly promote the survival of xenogeneic human MSC after engraftment in an immune-competent mouse wound model. The local immune niche, including the release of inflammatory cytokines and macrophage polarization, is also improved in engrafted wounds. Accordingly, the wound healing effects of MSC, including myofibroblast activation and collagen production, were most remarkable when they were coengrafted with the composite biomatrix SC/CM. Overall, the composite biomatrix SC/CM offered a novel strategy for the application of allo- or even xeno-MSC therapy in wound healing, and the exploration of the mechanism will further expand our understanding of the immunogenicity of MSC.Graphical

A bitter flavonoid gum from Dorema aucheri accelerate wound healing in rats: Involvement of Bax/HSP 70 and hydroxyprolin mechanisms.

Dorema aucherigum (DAG) is a bitter flavonoid gum widely used for numerous medicinal purposes including wound recovery. The present work investigates the acute toxicity and wound-healing effects of DAG in excisional skin injury in rats. Sprague Dawley rats (24) were clustered into four groups, each rat had a full-thickness excisional dorsal neck injury (2.00cm) and addressed with 0.2mL of the following treatments for 15 days: Group A (vehicle), rats addressed with normal saline; Group B, rats received intrasite gel; C and D, rats addressed with 250 and 500mg/kg of DAG, respectively. The results revealed the absence of any toxic signs in rats who received oral dosages of 2 and 5g/kg of DAG. Wound healing was significantly accelerated following DAG treatments indicated by smaller open areas and higher wound contraction percentages compared to vehicle rats. Histological evaluation revealed higher fibroblast formation, collagen deposition, and noticeably lower inflammatory cell infiltration in granulated skin tissues of DAG-addressed rats compared to vehicle rats. DAG treatment caused significant modulation of immunohistochemical proteins (decreased Bax and increased HSP 70) and inflammatory mediators (reduced TNF-α, IL-6, and magnified IL-10), which were significantly varied compared to vehicle rats. Moreover, topical DAG treatment led to significant upregulation of the hydroxyproline (HDX) (collagen) and antioxidant content. At the same time, decreased the lipid peroxidation (MDA) levels in healed tissues obtained from DAG-treated rats. The present wound contraction by DAG might be linked with the modulatory effect of its phytochemicals (polysaccharides, flavonoids, and phenolic) on the cellular mechanisms, which justify their folkloric use and provokes further investigation as therapeutic drug additives for wound contraction.

Kaempferia galanga L. alleviates the expression of COX-2 and NF-kappaB-p65 in the oral mucosa ulcer of Wistar rats and exhibits no irritation toward the vascular membrane of chicken eggs and the skin of albino rabbits

The global incidence of recurrent aphthous stomatitis in 2018 reached 5–66 % of the population, while in Indonesia 8 %. Moreover, the prevalence of oral mucosal fibrosis and recurrent aphthous stomatitis among male doctors and nurses in China was 21.24 % and 24.27 %, respectively. Our previous study has shown that the ethanol extract of Kaempferia galanga L. rhizome (EKGR) revealed an accelerated wound-healing effect in the oral mucosa ulcer of Wistar rats. This study aims to explore the effects of EKGR on the expression of NF-kappaB-p65 and COX-2 in the tongue tissue of male Wistar rats by Western blot analysis and immunohistochemistry technique, its safety towards the vascular membrane of the egg chorioallantoic membrane, and its single-dose application on the skin of male rabbits. The rats were randomly assigned into 7 groups: the normal control; the negative control; the positive control (treated with triamcinolone acetonide); and 4 treatment groups of EKGR (0.5 %; 1 %; 2 %; 4 %). Western blot and immunohistochemistry methods were used to measure the expression of NF-kappaB-p65 and COX-2. The hen's egg test-chorioallantoic membrane assay was employed to predict the safety of EKGR towards the vascular membrane. Moreover, the effect of 200 mg/kg BW EKGR application on the dorsal skin of male albino rabbits was also evaluated. EKGR inhibits the expression of NF-kappaB-p65 and COX-2 as proven by WB and IHC results. In the HET-CAM assay, all concentrations of EKGR do not induce irritation responses, which elicits the safety of EKGR. The administration of EKGR causes mild irritation to the dorsal skin of male rabbits but does not induce erythema and edema, no significant changes in BW, no toxic effects on organ macroscopic examination or histopathology, and does not induce abnormalities in the hematological profile of male albino rabbits. EKGR has confirmed its anti-inflammatory activity by suppressing the expression of COX-2 and NF-kappaB-p65 in the oral mucosa ulcer of Wistar rats. EKGR is safe as it does not exhibit irritating potential and harmful effects.

Comparison of proteomic profiles and biological properties for corneal wound healing of canine amniotic membrane and its extracts.

The application of canine amniotic membrane (cAM) for corneal reconstruction is widely used in the veterinary field. However, the information on biological properties and alternative forms of cAM for corneal wound healing is limited. This study aimed to investigate the proteomic profiles and corneal wound healing properties of cAM, cAM extract (cAME), and lyophilized cAM extract (cAMX). A total number of 14 cAMs were sterilely harvested from healthy full-term puppies and randomly divided into three different forms: cAM (n = 14), cAME (n = 14), and cAMX (n = 14). Each form of cAMs was subjected to proteomic analysis using label-free liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), followed by bioinformatic analysis. The proteins were classified into properties by comparing them with the literature search on human amniotic membrane (hAM) properties and the effect on corneal wound healing when given topically. The analyses identified 8136 proteins in cAM, 8211 proteins in cAME, and 7093 proteins in cAMX. A total number of 100 proteins were matched with proteins in hAM properties and were classified into anti-inflammatory, anti-fibrotic, anti-microbial, anti-angiogenic, promotion of epithelialization, analgesic, and support cell adhesion and growth properties. Furthermore, proteins with corneal wound healing effects were identified in cAME and cAMX. cAM and its extracts contain numerous proteins, including proteins related to corneal wound healing properties. Additionally, cAME and cAMX showed proteins involved in corneal wound healing and their potential benefits for topical use in ophthalmology.

A novel transdermal drug delivery system: drug-loaded ROS-responsive ferrocene fibers for effective photoprotective and wound healing activity

The present study proposes an innovative transdermal drug delivery system using ferrocene-incorporated fibers to enhance the bioavailability and therapeutic efficacy of ascorbyl tetraisopalmitate. Using electrospinning technology, the authors created ferrocene polymer fibers capable of highly efficient drug encapsulation and controlled release in response to reactive oxygen species commonly found in wound sites. The approach improves upon previous methods significantly by offering higher drug loading capacities and sustained release, directly targeting diseased cells. The results confirm the potential of ferrocene fibers for localized drug delivery, potentially reducing side effects and increasing patient convenience. The method could facilitate the application of bioactive compounds in medical textiles and targeted therapy.

Antioxidant and Immunomodulatory Polymer Vesicles for Effective Diabetic Wound Treatment through ROS Scavenging and Immune Modulating.

Chronic diabetic wound patients usually show high glucose levels and systemic immune disorder, resulting in high reactive oxygen species (ROS) levels and immune cell dysfunction, prolonged inflammation, and delayed wound healing. Herein, we prepared an antioxidant and immunomodulatory polymer vesicle for diabetic wound treatment. This vesicle is self-assembled from poly(ε-caprolactone)36-block-poly[lysine4-stat-(lysine-mannose)22-stat-tyrosine)16] ([PCL36-b-P[Lys4-stat-(Lys-Man)22-stat-Tyr16]). Polytyrosine is an antioxidant polypeptide that can scavenge ROS. d-Mannose was introduced to afford immunomodulatory functions by promoting macrophage transformation and Treg cell activation through inhibitory cytokines. The mice treated with polymer vesicles showed 23.7% higher Treg cell levels and a 91.3% higher M2/M1 ratio than those treated with PBS. Animal tests confirmed this vesicle accelerated healing and achieved complete healing of S. aureus-infected diabetic wounds within 8 days. Overall, this is the first antioxidant and immunomodulatory vesicle for diabetic wound healing by scavenging ROS and regulating immune homeostasis, opening new avenues for effective diabetic wound healing.

Nitric oxide-based treatments improve wound healing associated with diabetes mellitus.

Non-healing wounds are long-term complications of diabetes mellitus (DM) that increase mortality risk and amputation-related disability and decrease the quality of life. Nitric oxide (NO·)-based treatments (i.e., use of both systemic and topical NO· donors, NO· precursors, and NO· inducers) have received more attention as complementary approaches in treatments of DM wounds. Here, we aimed to highlight the potential benefits of NO·-based treatments on DM wounds through a literature review of experimental and clinical evidence. Various topical NO·-based treatments have been used. In rodents, topical NO·-based therapy facilitates wound healing, manifested as an increased healing rate and a decreased half-closure time. The wound healing effect of NO·-based treatments is attributed to increasing local blood flow, angiogenesis induction, collagen synthesis and deposition, re-epithelization, anti-inflammatory and anti-oxidative properties, and potent broad-spectrum antibacterial effects. The existing literature lacks human clinical evidence on the safety and efficacy of NO·-based treatments for DM wounds. Translating experimental favors of NO·-based treatments of DM wounds into human clinical practice needs conducting clinical trials with well-predefined effect sizes, i.e., wound reduction area, rate of wound healing, and hospital length of stay.

Skin anti-aging and wound healing effects of a passion fruit seed extract rich in piceatannol

BACKGROUND: UVB radiation triggers skin photoaging by inducing excess cellular oxidants, contributing to senescence, and overproducing matrix metalloproteinase-1 (MMP-1), causing skin wrinkles. Senescence also impedes skin wound closure. Passion fruit seeds (PFS) boast abundant piceatannol (PCT), recognized for its antioxidant and anti-aging properties. OBJECTIVE: To study potential of PFS extract in diminishing photoaging, accelerating wound healing, and enhancing SIRT1 production in human keratinocytes (HaCaT cells). METHODS: The PFS extract was assessed for PCT using HPLC analysis. The antioxidant effects, reduced senescence-associated β-galactosidase (SA-β-gal) activity, and MMP-1 production were measured in HaCaT cells exposed to UVB using a DCFA-DA assay, SA-β-gal activity, and flow cytometry/immunofluorescent including MMP-1 mRNA expression, respectively. The effect of wound healing acceleration was evaluated, including EGFR mRNA expression. Additionally, SIRT1 enhancement was investigated using flow cytometry and immunofluorescent techniques, which also included the assessment of SIRT1 mRNA expression. RESULTS: The PFS extract, which is rich in PCT, effectively diminished cellular oxidants and aging. It decreased UVB-induced cellular oxidants, senescence, and MMP-1 production at both protein and mRNA levels. Moreover, the extract enhanced wound closure by boosting cell migration and increasing EGFR mRNA expression. Additionally, SIRT1 production and expression, associated with cellular rejuvenation, increased in extract-treated cells. CONCLUSIONS: PFS extract exhibits potential for skincare and wound healing applications, offering a natural strategy to combat skin aging effects and support tissue repair.

Comprehensive developmental investigation on simvastatin enriched bioactive film forming spray using the quality by design paradigm: a prospective strategy for improved wound healing

The use of topical antimicrobials in wound healing presents challenges like risk of drug resistance and toxicity to local tissue. Simvastatin (SIM), a lipid-lowering agent which reduces the risk of cardiovascular events, is repurposed for its pleiotropic effect in wound healing. A bioactive bioadhesive polymer-based film forming spray (FFS) formulation of SIM was designed using chitosan, collagen, hyaluronic acid and optimised by employing the DoE approach. Optimised formulation demonstrated moderate viscosity (12.5 ± 0.3 cP), rapid film formation (231 ± 5.6 s), flexibility, tensile strength and sustained drug release (T80 – time for 80% drug release − 9.05 ± 0.7 h). Scanning electron microscopy (SEM) verified uniformly dispersed drug within the composite polymer matrix. SIM FFS demonstrated antimicrobial activity against gram positive and gram negative bacteria. In vivo excision wound model studies in mice affirmed the beneficent role of bioactive polymers and the efficacy of SIM FFS in wound contraction and closure, tissue remodelling and re-epithelization in comparison to standard antimicrobial preparation. Cytokines TNF- alpha, IL-6 were downregulated and IL-10 was upregulated. Biochemical markers; hydroxyproline, hexosamine and histopathology were consistent with wound contraction observed. This is an exploratory effort in repurposing SIM for wound healing in a novel dosage form, underscoring its potential as an alternative to conventional topical antimicrobials.

Bringing back Galium aparine L. from forgotten corners of traditional wound treatment procedures: an antimicrobial, antioxidant, and in-vitro wound healing assay along with HPTLC fingerprinting study

BackgroundThe wound healing process, restoring the functionality of the damaged tissue, can be accelerated by various compounds. The recent experimental analysis highlights the beneficial effects of phytochemicals in improving skin regeneration and wound healing. In traditional medicine, one of the widespread plants used for treating different injuries or skin afflictions is Galium aparine L. (GA). Besides, previously reported chemical compounds of GA suggested its therapeutic effects for the wound healing process, yet its regulatory effects on the cellular and molecular stages of the wound healing process have not been investigated.MethodsIn the present study, the phytochemical profile of the GA extract was analyzed using HPTLC fingerprinting, and further scientific evaluation of its phytochemicals was done. The wound-healing effects of GA extract were explored at the cellular and molecular levels while accounting for cell toxicity. The wound closure enhancing effect, antibacterial activity, and antioxidant activity were assessed.ResultsThe HPTLC fingerprinting of the GA extract proved its previously reported phytochemical profile including phenols, flavonoids, tannins, plant acids, ergot alkaloids, flavonoids, anthraquinones, terpenoids, sterols, salicin, lipophilic compounds, saponins, iridoids, and heterocyclic nitrogen compounds. Antimicrobial assessment, of the extract, indicated the more susceptibility of S. aureus to the inhibitory effects of GA rather than E. coli and S. epidermidis. DPPH test results revealed the antioxidant property of GA extract, which was comparable to ascorbic acid. The results of the viability assay showed no cytotoxicity effects on human umbilical endothelial cell (HUVEC) and normal human dermal fibroblast (NHDF) cell lines treated with different concentrations of whole plant extract and cell viability increased in a dose-dependent manner. The results of the scratch assay showed improved cell migration and wound closure.ConclusionsThis study shows the anti-oxidant, anti-microbial, and in vitro wound healing wound-healing effects of GA hydroalcoholic extract, which aligns with its use in traditional medicine. No cytotoxicity effects were shown. The results from this study can be the basis for further investigations such as animal models and phytochemical studies. Further evaluation of its effects on mechanisms and signaling pathways involved in the wound healing processes such as angiogenesis and cell proliferation can provide novel insights into the potential therapeutic effects of the GA extract.

Influence of gel matrix on the wound healing activity of adhesive dressings filled with silver nanoparticles and humic acid applied on a rat burn model

BACKGROUND: Thermal injuries to the skin (burns) are common household and man-made traumatic injuries in humans. In wartime, thermal injuries are additional damaging factors in combined skin lesions caused by the damaging elements of modern weapons. AIM: This study aimed to evaluate the effectiveness of gels based on silver nanoparticles in combination with humic acid on the healing of thermal skin injuries (burn wounds) in rats. MATERIALS AND METHODS: In the experiments on 57 white nonlinear male rats weighing 218–260 g, the wound healing effects of gels with 10% humic acid modified with nanosilver on various bases, prepared in a pharmacopoeial manner, on a grade IIIB thermal skin burn model were examined. The gel bases used in three experimental groups were as follows: sodium carboxymethylcellulose (group Ia, n = 12), polyacrylamide (group Ib, n = 12), and polyethylene glycol (group Ic, n = 12). The comparison group (group II, n = 12) received Levomekol ointment, whereas the control group (group III, n = 8) did not receive treatment. A grade III thermal burn was made on the proximal part of the back under general anesthesia using a thermal applicator with a circular-shaped flat working part with a diameter of 20 mm. Seventy-two hours after the burn, the wound was freed from scab by complete excision along the border of the intact skin, a splinting ring was applied, and the study drugs were administered. The dynamics of the changes in the burn wound were assessed on days 10, 14, 17, 21, 24, and 28 using the Universal Desktop Ruler program. RESULTS: The average times (median) to reach 75% epithelialization of wounds in groups Ia, Ic, and II were 29.4 ± 0.2, 34 (33–34), and 33.3 ± 0.45 days, respectively, whereas in groups Ib and III, the median time to 75% epithelization was not achieved. The 28-day healing index (%/day) values were 8.6, 4.8, 6.5, 6.1, and 4.4 in groups Ia, Ib, Ic, II, and III, respectively. The dynamics of epithelialization of thermal burns were most pronounced in group Ia, where the sodium carboxymethylcellulose acted as a gel base for humic substances modified with nanosilver. CONCLUSIONS: The results indicated that the gel added with nanosilver-modified humic substances based on sodium carboxymethylcellulose has a wound healing effect on thermal skin injuries, superior to the effect of the reference drug Levomekol in terms of the healing time of burn wounds.