Rat Skin Research Articles

Transcutaneous Delivery of Dexamethasone Sodium Phosphate Via Microneedle-Assisted Iontophoretic Enhancement - A Potential Therapeutic Option for Inflammatory Disorders.

This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.

Preparation of recombinant mussel mucin Mfp-3P and its promotion of wound healing

To investigate the role of recombinant mussel mucin in wound healing, we aimed to prepare this mucin using Pichia pastoris as the host microbe. Our method involved constructing a genetically engineered strain of P. pastoris that expressed a fusion protein consisting of Mfp-3 and preCol-P peptide segments of mussel. After fermentation and purification, we obtained a pure recombinant mussel mucin product. We then conducted experiments to evaluate its effect at both the cellular and animal levels. At the cellular level, we examined its impact on the proliferation and migration of mouse fibroblast L929. At the animal level, we assessed its ability to promote wound healing after full-layer skin resection in rats. Our results showed that the recombinant mussel mucin protein has a content of 90.28% and a purity of 96.49%. The content of 3,4-dihydroxyphenylalanine (DOPA) was 0.73 wt%, and the endotoxin content was less than 0.5 EU/mg. Importantly, the recombinant mussel mucin protein significantly promoted both the migration and proliferation of mouse fibroblast, as well as the wound healing in rat skin. In conclusion, our findings demonstrate that recombinant mussel mucin has the potential to promote wound healing and can be considered a promising medical biomaterial.

Resveratrol-coated chitosan mats promote angiogenesis for enhanced wound healing in animal model.

Growing incidences of chronic wounds recommend the development of optimal therapeutic wound dressings. Electrospun nanofibers have been considered to show potential wound healing properties when accompanied by other wound dressing materials. This study aimed to explore the potential role of Chitosan (CS) nanofibrous mats coated with resveratrol (RS) as an antioxidant and pro-angiogenic agent in rat models of skin wound healing. Electrospun chitosan/polyethylene oxide (PEO) nanofibers were prepared using electrospinning technology and coated by 0.05 and 0.1 mg.ml resveratrol named as (CS/RS 0.05) and (CS/RS 0.1), respectively. The scaffolds were characterized physiochemically such as invitro release study, TGA, FTIR spectroscopy analysis, biodegradability, and human dermal fibroblast seeding assay. The scaffold was subsequently used invivo as a skin substitute on a rat skin wound model. In vitro tests revealed that all scaffolds promoted cell adhesion and proliferation. However, more cell viability was observed in CS/RS 0.1 scaffold. The biocompatibility of the scaffolds was validated by MTT assay, and the results did not show any toxic effects on human dermal fibroblasts. It was observed that RS-coated scaffolds had the ability to release RS in a controlled manner. In invivo tests CS/RS 0.1 scaffold had the greatest impact on the healing process by improving the neodermis formation and modulated inflammation in wound granulation tissue. Histological analysis revealed enhanced vascular endothelial growth factor expression, epithelialization and increased depth of wound granulation tissue. The RS-coated CS/PEO nanofibrous scaffold accelerates wound healing and may be useful as a dressing for cell transfer and clinical skin regeneration.

Intradermal Lactate Monitoring Based on a Microneedle Sensor Patch for Enhanced In Vivo Accuracy.

Lactate is an important diagnostic and prognostic biomarker of several human pathological conditions, such as sepsis, malaria, and dengue fever. Unfortunately, due to the lack of reliable analytical decentralized platforms, the determination of lactate yet relies on discrete blood-based assays, which are invasive and inefficient and may cause tension and pain in the patient. Herein, we demonstrate the potential of a fully integrated microneedle (MN) sensing system for the minimally invasive transdermal detection of lactate in an interstitial fluid (ISF). The originality of this analytical technology relies on: (i) a strategy to provide a uniform coating of a doped polymer-based membrane as a diffusion-limiting layer on the MN structure, optimized to perform full-range lactate detection in the ISF (linear range of response: 0.25-35 mM, 30 s assay time, 8 h operation), (ii) double validation of ex vivo and in vivo results based on ISF and blood measurements in rats, (iii) monitoring of lactate level fluctuations under the administration of anesthesia to mimic bedside clinical scenarios, and (iv) in-house design and fabrication of a fully integrated and portable sensing device in the form of a wearable patch including a custom application and user-friendly interface in a smartphone for the rapid, routine, continuous, and real-time lactate monitoring. The main analytical merits of the lactate MN sensor include appropriate selectivity, reversibility, stability, and durability by using a two-electrode amperometric readout. The ex-vivo testing of the MN patch of preconditioned rat skin pieces and euthanized rats successfully demonstrated the accuracy in measuring lactate levels. The in vivo measurements suggested the existence of a positive correlation between ISF and blood lactate when a lag time of 10 min is considered (Pearson's coefficient = 0.85, mean difference = 0.08 mM). The developed MN-based platform offers distinct advantages over noncontinuous blood sampling in a wide range of contexts, especially where access to laboratory services is limited or blood sampling is not suitable. Implementation of the wearable patch in healthcare could envision personalized medicine in a variety of clinical settings.

Biofriendly resveratrol loaded glycerosomal nanovesicles improve wound healing in chronic diabetic foot ulcers: In-vitro &in-vivo efficacy evaluation

Chronic diabetic foot ulcers (CDFUs) are complex pathological processes involving persistent inflammation, significantly impacting a patient's quality of life. Resveratrol (RES), recognized for its potent antioxidant and anti-inflammatory properties, faces challenges regarding its permeability. This study aimed to develop Resveratrol glycerosomal nanovesicles (RES-GLY-NVs) for topical application to enhance skin permeation. The optimized formulation was integrated into a 2 % HPMC gel and subjected to comprehensive physicochemical characterization, skin deposition, in vitro release, microbiological, antioxidant, and in vivo assessments. Results revealed RES-GLY-NVs with particle size ranging from 82.19 ± 6.51 nm to 145.70 ± 1.39 nm with PDI less than 0.5, encapsulation efficacy ranging from 89.14 ± 1.39 % to 96.09 ± 2.13 % and a zeta potential ranging from −27.93 ± 6.47 mV to −49.33 ± 1.89 mV. The release profile of RES was obviously ranging from % 54.40 ± 1.71 to 77.47 ± 0.54 % after 8 h. In vitro cell assessment revealed that RES-GLY-NVs have no cytotoxicity on normal cells. The optimized RES-GLY-NVs-HPMC gel displayed pseudoplastic rheological behavior and significantly enhanced RES flux and permeability through excised rat skin compared to plain gel. The In vivo study and histological evaluation of diabetic rats ensured that RES-GLY-NVs-HPMC gel acts as a more effective healing adjunct compared to free RES and conventional therapy. These findings encourage the utilization of RES-GLY-NVs-HPMC gel as a wound-healing drug delivery system in chronic diabetes-related wounds and ulcers.

Tissue Regeneration and Remodeling in Rat Models after Application of Hypericum perforatum L. Extract-Loaded Bigels.

The wound-healing effect of St. John's Wort (SJW) is mainly attributed to hyperforin (HP), but its low stability restricts its topical administration. This study investigates how "free" HP-rich SJW extract (incorporated into a bigel; B/SJW) and extract "protected" by nanostructured lipid carriers (also included in a biphasic semisolid; B/NLC-SJW) affect tissue regeneration in a rat skin excision wound model. Wound diameter, histological changes, and tissue gene expression levels of fibronectin (Fn), matrix metalloproteinase 8 (MMP8), and tumor necrosis factor-alpha (TNF-α) were employed to quantify the healing progress. A significant wound size reduction was achieved after applying both extract-containing semisolids, but after a 21-day application period, the smallest wound size was observed in the B/NLC-SJW-treated animals. However, the inflammatory response was affected more favorably by the bigel containing the "free" SJW extract, as evidenced by histological studies. Moreover, after the application of B/SJW, the expression of Fn, MMP8, and TNF-α was significantly higher than in the positive control. In conclusion, both bigel formulations exhibited beneficial effects on wound healing in rat skin, but B/SJW affected skin restoration processes in a comprehensive and more efficient way.

Decontamination of Actinide-contaminated Injured Skin with Ca-DTPA Products Using an Ex Vivo Rat Skin Model.

Skin contamination by α-emitting actinides such as plutonium and americium is a risk for workers during nuclear fuel production and reactor decommissioning. Decontamination of skin is an important medical countermeasure to limit potential internal contamination, particularly in the case of injured skin. Current recommendations include undressing of the victim followed by skin washing using soap or chelating agents, such as diethylene triamine pentaacetic acid (DTPA). The goal of the present work is to assess the efficacy of a novel Ca-DTPA loaded gel to decontaminate injured skin exposed to plutonium or americium as compared to recommended treatments. For decontaminant testing on injured skin, whole body skin was obtained from euthanized rats and lesions created using a metallic brush. Delimited test areas were contaminated with plutonium or americium solutions of known properties. Various protocols were tested including time before contamination, duration of gel application, washing steps, as well as the concomitant addition or not of dressings. Activity was measured in each decontamination product and in skin. Data indicate that healthy skin was easier to decontaminate than damaged skin. On injured skin, we demonstrated an increased decontamination efficacy of the Ca-DTPA gel formulation as compared to the solution. Importantly, gel application alone was effective, and further gel applications could be used for residual activity.

Bio-friendly oleic acid-based ufasomal topical gel of rosuvastatin for diabetic wound healing: In-vitro, ex-Vivo, and in-Vivo evaluation

This study aimed to develop bio-friendly and biodegradable oleic acid-based ufasomes coated with chitosan for topical delivery of rosuvastatin for diabetic wound healing. Rosuvastatin was chosen as a suitable candidate due to its wound healing properties. Thin film hydration technique was implemented for the preparation of ufasomes at various concentrations of oleic acid. The most promising formulation (UF 5) was coated with chitosan. The effect of oleic acid and chitosan concentrations on vesicle Size, zeta-potential, polydispersity index, entrapment efficiency, and in-vitro drug release study was assessed. Optimum chitosan-coated ufasomal dispersion (CUF 3) was subjected to further characterizations, such as FT-IR, TEM, in-vitro release, broth microdilution susceptibility test, the effect of storage, ex-vivo skin permeability study, and wound healing efficiency in rats. Finally, CUF 3 was incorporated into chitosan gel base and examined for wound healing efficiency in rats. Uncoated ufasomal dispersion (UF 5) possessed the smallest vesicle Size (149.6 nm), the highest entrapment efficiency (79.48 %), an optimum zeta-potential (−35.78 mv), with polydispersity index of 0.18. FT-IR of coated ufasomes (CUF 3) reflected the effective coating of chitosan on the surface of ufasomes which coincided with the TEM image. Similar release profiles of UF 5 and CUF 3 were observed after 4 h of dissolution due to chitosan coating surrounding ufasomes. The cumulative percent of drug permeated across rat skin after 24 h for CUF 3 dispersion, and CUF 3 in chitosan gel were 11.21 % and 10.48 %, respectively, in comparison to 2.97 % in case of control gel. This was confirmed from the results of flux and permeability coefficient. A maximum skin retention and a controlled release effect with a reduced risk of systemic absorption of rosuvastatin were attained by CUF 3 in chitosan gel. Rosuvastatin encapsulated in ufasomal vesicles augmented the antimicrobial activity against Gram-negative and Gram-positive bacteria. A remarkable wound healing of CUF 3 in chitosan gel was confirmed by morphological and histopathological studies. Oleic acid-based ufasomes coated with chitosan could be a promising bio-friendly carrier for rosuvastatin to obtain a triple effect formulation for diabetic wound healing.

Propellant Free Pressurized Spray System of Etodolac to Manage Acute Pain Conditions: In Vitro and In Vivo Evaluation.

This study aimed to develop a propellant-free topical spray formulation of Etodolac (BCS-II), a potent NSAID, which could be beneficial in the medical field for the effective treatment of pain and inflammation conditions. The developed novel propellant-free spray formulation is user-friendly, cost-effective, propellant-free, eco-friendly, enhances the penetration of Etodolac through the skin, and has a quick onset of action.Various formulations were developed by adjusting the concentrations of different components, including lecithin, buffering agents, film-forming agents, plasticizers, and permeation enhancers. The prepared propellant-free spray formulations were then extensively characterized and evaluated through various in vitro, ex vivo, and in vivo parameters. The optimized formulation exhibits an average shot weight of 0.24 ± 0.30ml and an average drug content or content uniformity of 87.3 ± 1.01% per spray. Additionally, the optimized formulation exhibits an evaporation time of 3 ± 0.24min. The skin permeation study demonstrated that the permeability coefficients of the optimized spray formulation were 21.42cm/h for rat skin, 13.64cm/h for mice skin, and 18.97cm/h for the Strat-M membrane. When assessing its potential for drug deposition using rat skin, mice skin, and the Strat-M membrane, the enhancement ratios for the optimized formulation were 1.88, 2.46, and 1.92, respectively against pure drug solution. The findings from our study suggest that the propellant-free Etodolac spray is a reliable and safe topical formulation. It demonstrates enhanced skin deposition, and improved effectiveness, and is free from any skin irritation concerns.

Facile Solvent-Free Fabrication of All-Small-Molecule Supramolecular Photothermal Bioadhesive for Sutureless Wound Closure.

Achieving underwater adhesion possesses a significant challenge, primarily due to the presence of interfacial water, which restricts the potential applications of adhesives. In this study, we present a straightforward and environmentally friendly one-pot approach for synthesizing a solvent-free supramolecular TPFe bioadhesive composed of thioctic acid, proanthocyanidins, and FeCl3. The bioadhesive exhibits excellent biocompatibility and photothermal antibacterial properties and demonstrates effective adhesion on various substrates in both wet and dry environments. Importantly, the adhesive strength of this bioadhesive on steel exceeds 1.2 MPa and that on porcine skin exceeds 100 kPa, which is greater than the adhesive strength of most reported bioadhesives. In addition, the bioadhesive exhibits the ability to effectively halt bleeding, close wounds promptly, and promote wound healing in the rat skin wound model. Therefore, the TPFe bioadhesive has potential as a medical bioadhesive for halting bleeding quickly and promoting wound healing in the biomedical field. This study provides a new idea for the development of bioadhesives with firm wet adhesion.

Spatiotemporal modulation of immune microenvironment via composite hydrogel brakes for diabetic wound healing

Uncontrolled programmed polarization of macrophages plays an important role in chronic diabetic wound healing. Therefore, correcting programmed macrophage polarization while inducing new tissue remodelling through materials and preventing scar formation is desirable. Herein, a composite hydrogel brake that enables spatiotemporal regulation of the immune microenvironment was constructed to promote skin tissue regeneration. The system was based on thiolated hyaluronic acid to reshape the programmed polarization of macrophages, methacrylate gelatin as a mechanical support, and poly (L-lactic acid) nanoparticles loaded with TGF-β receptor antagonists to inhibit scar formation. Notably, the composite hydrogel acts as a double brake: in the early stage, self-induced M2-type polarization is achieved with the help of thiols; the TNF and NLRP signalling pathways are downregulated; and the immune microenvironment is regulated. During tissue remodeling, the long-term biological effect of TGF-β secretion by M2-type macrophages is interrupted by the slow release of antagonists, which inhibits excessive collagen deposition and prevents scar formation. The dual effect of restraint on reprogramming macrophage polarization and inhibiting scar formation was further confirmed in a diabetic rat skin defect model. Therefore, based on the immunological mechanism, a composite hydrogel brake was specifically designed to regulate the immune microenvironment, induce new tissue remodelling, and provide a promising clinical strategy for treating chronic diabetic wounds.

Nanoemulsion‐laden poly(vinyl) alcohol hydrogel films for transdermal delivery of carbamazepine

AbstractThere is an unmet demand for transdermal devices that can deliver large dose of medications through the skin. Herein, nanoemulsion‐based poly(vinyl alcohol) (PVA) transdermal hydrogel films were developed for the high‐dose anti‐epileptic drug carbamazepine. A stable nanoemulsion was created with almond oil, Tween 60, and amphiphilic locust bean gum. The nanoemulsion had a hydrodynamic diameter of 251 nm, a polydispersity of 10.3%, and a zeta potential of −51.2 mV. Carbamazepine‐loaded nanoemulsion was blended with carbamazepine‐free PVA dispersion and casted into films. To accommodate a high dose, carbamazepine‐loaded nanoemulsion was trapped in a PVA dispersion containing carbamazepine to create transdermal films. The physicochemical characteristics and drug penetration characteristics of the produced films were compared. Both films had the uniform thickness, weight, and drug content. The folding endurance was found to be greater than 700 in both cases. Water vapor permeability decreased when carbamazepine was added to almond oil as well as polymer dispersion. FESEM pictures revealed a waxy paper‐like appearance for the PVA hydrogel film with dual drug‐reservoirs. FTIR spectra assessment revealed a hydrogen bonding interaction between PVA and carbamazepine. X‐ray diffraction examination revealed that the film contained an amorphous dispersion of carbamazepine. Dual carbamazepine reservoir‐based films outperformed single nanoemulsion drug reservoir‐based films in terms of drug flux through excised rat skin by 3.2 times. The in vitro skin permeation findings corresponded well to zero order kinetic models. Overall, this study showed that a high‐dose drug could be placed on nanoemulsion‐based transdermal PVA hydrogel films, resulting in improved skin permeability.Highlights Nanoemulsion was stable at almond oil:Tween 60/modified gum ratio of 5:5. Loading of high dose carbamazepine in nanoemulsion‐PVA transdermal films. Film of dual carbamazepine reservoir showed low water vapor permeation, moisture retention. Flux of carbamazepine from films improved three times through excised rat skin.

Біофізичні властивості шкіри щурів із метаболічним синдромом

It is known that metabolic syndrome (MS) prolongs the healing time of the wound surface of various genesis. We hypothesized that this may be related to changes in the biophysical properties of the skin. The aim of the work was to investigate the biophysical properties of skin (content of moisture, collagen, fused gelatin in the skin, and skin thermal fusion temperature) in rats with MS. Materials and methods. Research was conducted on 40 white non-linear rats (20 – males, 20 – females). After birth, males and females were divided into 2 groups. The first group served as a control for the second groups, in which MS was simulated by administering monosodium glutamate at a dose of 4.0 mg/kg on the 2nd, 4th, 6th, 8th, and 10th postnatal days. At the age of 4 months, the animals were decapitated under ether anesthesia. Biochemical studies were conducted to confirm the development of MS. The percentage of moisture, collagen content, destructive changes in collagen fibers and resistance of skin collagen to thermal factors were determined in native skin. The results. 4-month-old rats injected with monosodium glutamate in the early neonatal period developed MS as evidenced by abdominal obesity, insulin resistance, and dyslipidemia. In comparison with animals of the control group, in the skin of male and female rats with MS, the moisture content decreased, and the collagen content did not change. At the same time, the percentage of melted gelatin doubled, which indicates the depth of destructive changes in collagen fibers. Thermal welding of skin samples of male and female rats with signs of MS occurred at rather low temperatures compared to rats of the control group. Conclusion. Changes in the biophysical properties of the skin, which are registered in rats with MS, may be the reason for the later closure of the wound surface.

MORPHOLOGICAL CHANGES IN RAT SKIN AFTER THERMAL BURNS

Every day around the world, children and adults suffer from burn injuries. Burn injury is one of the global health problems due to its high prevalence and mortality. The skin is the largest multifunctional human organ. The area of the entire skin is on average 1.7-1.9 square meters. The skin has a wide variety of functions from protective to energy-saving and tactile. Burns have a long history, but new methods of study are needed, this is due to the increase in the frequency of burns in everyday life, production, as well as the complexity of the pathogenesis and treatment of burn disease. Pathological changes that occur in the body of burned animals lead to the fact that in the first hours with extensive burn injury, circulatory disorders occur in parenchymal organs, especially in the liver, lungs and adrenal glands. In the future, with severe intoxication, severe dystrophic processes occur in the muscles of the heart and other internal organs. Recently, the main areas of research into the pathogenesis of inflammation have become immunological, at the morphological level it has not been sufficiently studied. The article shows the morphological features of the study in thermal burns of the skin of rats during treatment with a different mechanism of action. Rats in the amount of 15 pieces were divided into 3 groups: the first control group with a burn without treatment, the second group with a thermal burn, to which levomekol gel was applied to the burn area, the third group was treated with powder from the medicinal plant yarrow Achillea millefolium L. On the 3rd, 7th, 14th, and 21st days, the rats were taken out of the experiment, after which the skin pieces were fixed in 10% formalin for further histological examination.

Evaluation of hemostatic, anti-inflammatory, wound healing, skin irritation and allergy, and antimicrobial properties of active fraction from the ethanol extract of Chromolaena odorata (L.) R.M. King & H. Rob

Ethnopharmacological relevanceChromolaenaodorata (L.) R.M. King & H. Rob, a perennial herb, has been traditionally utilized as a herbal remedy for treating leech bites, soft tissue wounds, burn wounds, skin infections, and dento-alveolitis in tropical and subtropical regions. Aim of the studyThe present study was to analyze the active fraction of C. odorata ethanol extract and investigate its hemostatic, anti-inflammatory, wound healing, and antimicrobial properties. Additionally, the safety of the active fraction as an external preparation was assessed through skin irritation and allergy tests. Materials and methodsThe leaves and stems of C. odorata were initially extracted with ethanol, followed by purification through AB-8 macroporous adsorption resin column chromatography to yield different fractions. These fractions were then screened for hemostatic activity in mice and rabbits to identify the active fraction. Subsequently, the hemostatic effect of the active fraction was assessed through the bleeding time of the rabbit ear artery in vivo and the coagulant time of rabbit blood in vitro. The anti-inflammatory activity of the active fraction was tested on mice ear edema induced by xylene and rat paw edema induced by carrageenin. Furthermore, the active fraction's promotion effect on wound healing was evaluated using a rat skin injury model, and skin safety tests were conducted on rabbits and guinea pigs. Lastly, antimicrobial activities against two Gram-positive bacteria (G+, Staphylococcus aureus and S. epidermidis) and three Gram-negative bacteria (G−, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were determined using the plate dilution method. ResultsThe ethanol extract of C. odorata leaves and stems was fractionated into 30%, 60%, and 90% ethanol eluate fractions. These fractions demonstrated hemostatic activity, with the 30% ethanol eluate fraction (30% EEF) showing the strongest effect, significantly reducing bleeding time (P < 0.05). A concentration of 1.0 g/mL of the 30% EEF accelerated cutaneous wound healing in rats on the 3rd, 6th, and 9th day post-operation, with the healing effect increasing over time. No irritation or allergy reactions were observed in rabbits and guinea pigs exposed to the 30% EEF. Additionally, the 30% EEF exhibited mild inhibitory effect on mice ear and rat paw edema, as well as antimicrobial activity against tested bacteria, with varying minimal inhibitory concentration (MIC) values. ConclusionsThe 30% EEF demonstrated a clear hemostatic effect on rabbit bleeding time, a slight inhibitory effect on mice ear edema and rat paw edema, significant wound healing activity in rats, and no observed irritation or allergic reactions. Antibacterial activity was observed against certain clinically isolated bacteria, particularly the G− bacteria. This study lays the groundwork for the potential development and application of C. odorata in wound treatment.

An in vitro and in vivo study of electrospun polyvinyl alcohol/chitosan/sildenafil citrate mat on 3D-printed polycaprolactone membrane as a double layer wound dressing

Double-layer dermal substitutes (DS) generally provide more effective therapeutic outcomes than single-layer substitutes. The architectural design of DS incorporates an outer layer to protect against bacterial invasions and maintain wound hydration, thereby reducing the risk of infection and the frequency of dressing changes. Moreover, the outer layer is a mechanical support for the wound, preventing undue tension in the affected area. A 3D-printed polycaprolactone (PCL) membrane was utilized as the outer layer to fabricate DS wound dressing. Simultaneously, a polyvinyl alcohol/chitosan/sildenafil citrate (PVA/CS/SC) scaffold was electrospun onto the PCL membrane to facilitate cellular adhesion and proliferation. Scanning electron microscopy (SEM) analysis of the PCL filaments revealed a consistent cross-sectional surface and structure, with an average diameter of 562.72 ± 29.15 μm. SEM results also demonstrated uniform morphology and beadless structure for the PVA/CS/SC scaffold, with an average fiber diameter of 366.77 ± 1.81 nm for PVA/CS. The addition of SC led to an increase in fiber diameter while resulting in a reduction in tensile strength. However, drug release analysis indicated that the SC release from the sample can last up to 72 h. Animal experimentation confirmed that DS wound dressing positively accelerated wound closure and collagen deposition in the Wistar rat skin wound model.

Usefulness of percutaneous estradiol-loaded PLGA-PEG-PLGA nanoparticles for the treatment of osteoporosis

Compared with poly (dl-lactide-co-glycolide) (PLGA) nanoparticles, triblock copolymer (PLGA-PEG-PLGA) nanoparticles composed of PLGA and polyethylene glycol (PEG) may improve the skin permeability of drugs. In this study, the usefulness of estradiol-loaded (E2-loaded) PLGA-PEG-PLGA nanoparticles in the treatment of osteoporosis was investigated by comparison with E2-loaded PLGA nanoparticles. The cumulative E2 permeation of each nanoparticle through rat skin was quantified using a Franz cell. The results showed that PLGA-PEG-PLGA nanoparticles had significantly higher permeation than PLGA nanoparticles. Next, in vivo treatment experiments were conducted using an ovariectomized rat model of osteoporosis. Nanoparticles were administered once per week in combination with iontophoresis. At 6 weeks after the initiation of treatment, significant improvement in bone density was observed in the treated group compared with the untreated group. The improvement in bone density tended to be greater in the PLGA-PEG-PLGA nanoparticle group versus the PLGA nanoparticle group. This may be attributed to the higher hydrophilicity of the particle surface of PLGA-PEG-PLGA nanoparticles compared with PLGA nanoparticles and the improved skin permeability of the particles through the trans-adnexal pathway.

High-frequency photoacoustic and ultrasound imaging for skin evaluation: Pilot study for the assessment of a chemical burn.

Skin architecture and its underlying vascular structure could be used to assess the health status of skin. A non-invasive, high resolution and deep imaging modality able to visualize skin subcutaneous layers and vasculature structures could be useful for determining and characterizing skin disease and trauma. In this study, a multispectral high-frequency, linear array-based photoacoustic/ultrasound (PAUS) probe is developed and implemented for the imaging of rat skin in vivo. The study seeks to demonstrate the probe capabilities for visualizing the skin and its underlying structures, and for monitoring changes in skin structure and composition during a 5-day course of a chemical burn. We analayze composition of lipids, water, oxy-hemoglobin, and deoxy-hemoglobin (for determination of oxygen saturation) in the skin tissue. The study successfully demonstrated the high-frequency PAUS imaging probe was able to provide 3D images of the rat skin architecture, underlying vasculature structures, and oxygen saturation, water, lipids and total hemoglobin.

Gelatin-Based Hydrogel Functionalized with Dopamine and Layered Double Hydroxide for Wound Healing.

Hydrogels with adhesion properties and a wetted structure are promising alternatives to traditional wound dressing materials. The insufficiency of gelatin hydrogels in terms of their adhesive and mechanical strength limits their application in wound dressings. This work presents the design and preparation of a gelatin-based hydrogel functionalized with dopamine (DA) and layered double hydroxide (LDH). The combination of DA and LDH improves the hydrogel's adhesion properties in terms of interfacial adhesion and inner cohesion. Hydrogels with 8% DA and 4% LDH attained the highest adhesion strength of 266.5 kPa, which increased to 295.5 and 343.3 kPa after hydrophobically modifying the gelatin with octanoyl and decanoyl aldehydes, respectively. The gelatin-based hydrogels also demonstrated a macroporous structure, excellent biocompatibility, and a good anti-inflammatory effect. The developed hydrogels accelerated wound healing in Sprague Dawley rat skin full-thickness wound models.

Janus Nanofibrous Patch with In Situ Grown Superlubricated Skin for Soft Tissue Repair with Inhibited Postoperative Adhesion.

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.