A bi-functional nanofibrous composite membrane for wound healing applications.

Various wound dressings have been developed so far for wound healing, but most of them are ineffective in properly reestablishing the skin's structure, which increases infection risks and dehydration. Electrospun membranes are particularly interesting for wound dressing applications because they mimic the extracellular matrix of healthy skin. In this study, a potential wound healing platform capable of inducing synergistic antibacterial and antioxidation activities was developed by incorporating bio-active rosmarinic acid-hydroxyapatite hybrid (HAP-RA) with different contents (0.5, 1, and 1.5 wt.%) into the electrospun polyamide 6 (PA6) nanofibers. Then, polyethylene glycol (PEG) was introduced to the nanofibrous composite to improve the biocompatibility and biodegradability of the dressing. The results indicated that the hydrophilicity, water uptake, biodegradability, and mechanical properties of the obtained PA6/PEG/HAP-RA nanofibrous composite enhanced at 1 wt.% of HAP-RA. The nanofibrous composite had excellent antibacterial activity. The antioxidation potential of the samples was assessed in vitro. The MTT assay performed on the L929 cell line confirmed the positive effects of the nanofibrous scaffold on cell viability and proliferation. According to the results, the PA6/PEG/HAP-RA nanofibrous composite showed the desirable physiochemical and biological properties besides antibacterial and antioxidative capabilities, making it a promising candidate for further studies in wound healing applications.

Growth factors and growth factor gene therapies for treating chronic wounds.

Chronic wounds are an unmet clinical need affecting millions of patients globally, and current standards of care fail to consistently promote complete wound closure and prevent recurrence. Disruptions in growth factor signaling, a hallmark of chronic wounds, have led researchers to pursue growth factor therapies as potential supplements to standards of care. Initial studies delivering growth factors in protein form showed promise, with a few formulations reaching clinical trials and one obtaining clinical approval. However, protein-form growth factors are limited by instability and off-target effects. Gene therapy offers an alternative approach to deliver growth factors to the chronic wound environment, but safety concerns surrounding gene therapy as well as efficacy challenges in the gene delivery process have prevented clinical translation. Current growth factor delivery and gene therapy approaches have primarily used single growth factor formulations, but recent efforts have aimed to develop multi-growth factor approaches that are better suited to address growth factor insufficiencies in the chronic wound environment, and these strategies have demonstrated improved efficacy in preclinical studies. This review provides an overview of chronic wound healing, emphasizing the need and potential for growth factor therapies. It includes a summary of current standards of care, recent advances in growth factor, cell-based, and gene therapy approaches, and future perspectives for multi-growth factor therapeutics.

Electrospun nylon 6/hyaluronic acid/chitosan bioactive nanofibrous composite as a potential antibacterial wound dressing.

Hyaluronic acid (HA) and chitosan (CS), as natural biomaterials, display excellent biocompatibility and stimulate the growth and proliferation of fibroblasts. Furthermore, nylon 6 (N6) is a low-cost polymer with good compatibility with human tissues and high mechanical stability. In this study, HA and CS were applied to modify N6 nanofibrous mat (N6/HA/CS) for potential wound dressing. N6/HA/CS nanofibrous composite mats were developed using a simple one-step electrospinning technique at different CS concentrations of 1, 2, and 3 wt%. The results demonstrated that incorporating HA and CS into N6 resulted in increased hydrophilicity, as well as favorable physical and mechanical properties. In addition, the minimum inhibitory concentration and (MIC) optical density techniques were used to determine the antibacterial properties of N6/HA/CS nanofibrous composite mats, and the results demonstrated that the composites could markedly inhibit the growth of Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli. Because of its superior mechanical properties, substantial antimicrobial effects, and hydrophilic surface, N6/HA/CS at 2 wt% of CS (N6/HA/CS2) was chosen as the most suitable nanofibrous mat. The swelling, porosity, gel content, and in vitro degradation studies imply that N6/HA/CS2 nanofibrous composite mat has proper moisture retention and biodegradability. Furthermore, the N6/HA/CS2 nanofibrous composite mat was discovered to be nontoxic to L929 fibroblast cells and to even improve cell proliferation. Based on the findings, this research offers a simple and rapid method for creating material that could be utilized as prospective wound dressings in clinical environments.

Point-Of-Care Ultrasonography for Identification of Skin and Soft Tissue Abscess in Adult and Pediatric Patients; a Systematic Review and Meta-Analysis.

Introduction: Differentiating the soft tissue abscess from other types of skin and soft tissue infections (SSTIs) poses a particular challenge because they have similar physical evaluation findings, but each disease has a different course, outcome, and treatment. This meta-analysis aimed to investigate the diagnostic accuracy of point-of-care ultrasonography for diagnosis of soft tissue abscess in the emergency departments. Methods: A comprehensive literature search of MEDLINE, Scopus, Web of Science, Embase, and Google Scholar, from inception to January 2023, was conducted to identify relevant studies investigating the diagnostic performance of point-of-care ultrasonography for identification of abscess. Methodological quality of the included studies was assessed using a revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). Results: The pooled estimates of diagnostic parameters of ultrasonography for diagnosis of abscess were as follows: sensitivity, 0.93 (95% CI: 0.92-0.94); specificity, 0.87 (95% CI: 0.85-0.89), and the area under the summary receiver-operating characteristic (SROC), 0.95. The pooled sensitivity, specificity, and area under the SROC of studies in adult patients were 0.98 (95% CI: 0.92-1), 0.92 (95% CI: 0.86-0.95), and 0.99, respectively. The pooled sensitivity, specificity, and area under the SROC of studies in pediatric patients were 0.9 (95% CI: 0.87-0.92), 0.78 (95% CI: 0.73-0.82), and 0.91, respectively. Conclusion: Our meta-analysis demonstrated that the point-of-care ultrasonography has excellent diagnostic value for the abscess in the emergency department. Furthermore, we found that the diagnostic performance of point-of-care ultrasonography for diagnosis of abscess was higher for adult cases than for pediatric patients.

Diagnostic Accuracy of Ottawa Knee Rule for Diagnosis of Fracture in Patients with Knee Trauma; a Systematic Review and Meta-analysis.

Introduction: In order to improve the efficacy of requesting knee radiography and reduce unnecessary radiation exposure, some clinical decision rules have been proposed for the assessment of knee injuries. Among them, the Ottawa Knee Rule (OKR) was considered as one of the best guidelines with several validation studies. Therefore, in this meta-analysis, we aimed to investigate the accuracy of OKR for diagnosis of fracture in patients presenting with knee trauma. Methods: A systematic search was conducted in PubMed, Web of Science, Scopus, Google Scholar, and EBSCO from inception to September 2022. Quality assessment of the included studies was performed using QUADAS-2 tool. Diagnostic accuracy parameters were analyzed using random-effects model. Statistical analysis was performed using Meta-Disc and Stata softwares. Results: The meta-analysis of the 18 included studies (6702 patients) showed that the pooled sensitivity and specificity of OKR for diagnosis of fractures were 0.98 (95% CI: 0.96-0.99) and 0.43 (95% CI: 0.42-0.45), respectively. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 1.56 (95% CI: 1.39-1.75) and 0.12 (95% CI: 0.05-0.26), respectively. The area under curve (AUC) of the hierarchical summary receiver operating characteristic (HSROC) curve was 0.54. Conclusion: This meta-analysis indicates that OKR has a high diagnostic performance for diagnosis of fracture, with a pooled sensitivity of 98% and a pooled specificity of 43%. These results propose potential effects of OKR on reduction of unnecessary radiography, time spent in emergency departments, and direct and indirect costs, which should be confirmed using high-quality studies in the future.

Green synthesized polyvinylpyrrolidone/titanium dioxide hydrogel nanocomposite modified with agarose macromolecules for sustained and pH-responsive release of anticancer drug.

Cancer, as one of the most challenging diseases of the last century, has a significant number of patients and deaths every year. Various strategies have been explored for the treatment of cancer. Chemotherapy is one of the methods of treating cancer. Doxorubicin is one of the compounds used in chemotherapy to kill cancer cells. Due to their unique properties and low toxicity, metal oxide nanoparticles are effective in combination therapy and increase the effectiveness of anti-cancer compounds. The limited in vivo circulatory period, poor solubility, and inadequate penetration of doxorubicin (DOX) restrict its use in cancer treatment, notwithstanding its attractive characteristics. It is possible to circumvent some of the difficulties in cancer therapy by using green synthesized pH-responsive nanocomposite consisting of polyvinylpyrrolidone (PVP), titanium dioxide (TiO2) modified with agarose (Ag) macromolecules. TiO2 incorporation into the PVP-Ag nanocomposite resulted in limited increased loading and encapsulation efficiencies from 41 % to 47 % and 84 % to 88.5 %, respectively. DOX diffusion among normal cells is prevented by the PVP-Ag-TiO2 nanocarrier at pH = 7.4, though the acidic intracellular microenvironments activate the PVP-Ag-TiO2 nanocarrier at pH = 5.4. Characterization of the nanocarrier was performed using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectrophotometry, field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), and zeta potential. The average particle size and the zeta potential of the particles showed values of 349.8 nm and +57 mV, respectively. In vitro release after 96 h showed a release rate of 92 % at pH 7.4 and a release rate of 96 % at pH 5.4. Meanwhile, the initial release after 24 h was 42 % for pH 7.4 and 76 % for pH 5.4. As shown by an MTT analysis on MCF-7 cells, the toxicity of DOX-loaded PVP-Ag-TiO2 nanocomposite was substantially greater than that of unbound DOX and PVP-Ag-TiO2. After integrating TiO2 nanomaterials into the PVP-Ag-DOX nanocarrier, flow cytometry data showed a greater stimulation of cell death. These data indicate that the DOX-loaded nanocomposite is a suitable alternative for drug delivery systems.

Diagnostic Accuracy of Ultrasonography for Detection of Intussusception in Children; a Systematic Review and Meta-Analysis.

Introduction: The diagnosis of intussusception can be challenging in children due to the fact that the findings of clinical evaluations are nonspecific and most of the patients present with unclear history. Therefore, in this systematic review and meta-analysis, we aimed to investigate the diagnostic accuracy of ultrasonography for detection of intussusception and also compare the efficacy of point-of-care ultrasound (POCUS) with radiologist-performed ultrasound (RADUS). Methods: Two independent reviewers systematically searched different online electronic databases including MEDLINE, Scopus, Web of Science, Google Scholar, Embase, and Cochrane from inception to December 1, 2022 to identify published papers reporting accuracy of ultrasonography for diagnosis of intussusception. The quality assessment of the included studies was investigated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Results: A total of 1446 records were retrieved in the initial search of databases. After screening the titles, a total of 344 studies were retrieved for the detailed assessment of full-text. Finally, 37 studies were included in qualitative and quantitative analysis. The pooled sensitivity and specificity of ultrasonography for diagnosis of intussusception were 0.96 (95% CI: 0.95-0.97) and 0.97 (95% CI: 0.97-0.98), respectively. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 24.57 (95% CI: 8.26-73.03) and 0.05 (95% CI: 0.04-0.08), respectively. The area under the hierarchical summary receiver operating characteristic (HSROC) curve was 0.989. Mete-regression showed that there is no significant difference between diagnostic performance of POCUS and RADUS (p = 0.06 and rDOR (diagnostic odds ratio) = 4.38 (95% CI: 0.92-20.89)). Conclusion: This meta-analysis shows that ultrasonography has excellent sensitivity, specificity, and accuracy for diagnosis of intussusception in pediatric patients. Moreover, we found that diagnostic performance of POCUS is similar to that of RADUS for diagnosis of intussusception.

pH-Responsive PVA-Based Nanofibers Containing GO Modified with Ag Nanoparticles: Physico-Chemical Characterization, Wound Dressing, and Drug Delivery.

Site-specific drug delivery and carrying repairing agents for wound healing purposes can be achieved using the intertwined three-dimensional structure of nanofibers. This study aimed to optimize and fabricate poly (vinyl alcohol) (PVA)-graphene oxide (GO)-silver (Ag) nanofibers containing curcumin (CUR) using the electrospinning method for potential wound healing applications. Fourier Transform Infrared (FTIR) spectrophotometry, X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), and zeta potential were used to characterize the nanostructures. The mechanical properties of the nanostructures were subsequently examined by tensile strength and elongation test. As shown by MIC analysis of E. coli and S. aureus bacteria, the fabricated nanofibers had superior inhibitory effects on the bacteria growth. Ag nanoparticles incorporation into the nanofibers resulted in increased loading and encapsulation efficiencies from 21% to 56% and from 61% to 86%, respectively. CUR release from PVA/GO-Ag-CUR nanofiber at pH 7.4 was prevented, while the acidic microenvironment (pH 5.4) increased the release of CUR from PVA/GO-Ag-CUR nanofiber, corroborating the pH-sensitivity of the nanofibers. Using the in vitro wound healing test on NIH 3T3 fibroblast cells, we observed accelerated growth and proliferation of cells cultured on PVA/GO-Ag-CUR nanofibers.

Role of Iron Oxide (Fe2O3) Nanocomposites in Advanced Biomedical Applications: A State-of-the-Art Review.

Nanomaterials have demonstrated a wide range of applications and recently, novel biomedical studies are devoted to improving the functionality and effectivity of traditional and unmodified systems, either drug carriers and common scaffolds for tissue engineering or advanced hydrogels for wound healing purposes. In this regard, metal oxide nanoparticles show great potential as versatile tools in biomedical science. In particular, iron oxide nanoparticles with different shape and sizes hold outstanding physiochemical characteristics, such as high specific area and porous structure that make them idoneous nanomaterials to be used in diverse aspects of medicine and biological systems. Moreover, due to the high thermal stability and mechanical strength of Fe2O3, they have been combined with several polymers and employed for various nano-treatments for specific human diseases. This review is focused on summarizing the applications of Fe2O3-based nanocomposites in the biomedical field, including nanocarriers for drug delivery, tissue engineering, and wound healing. Additionally, their structure, magnetic properties, biocompatibility, and toxicity will be discussed.

Curcumin Sustained Release with a Hybrid Chitosan-Silk Fibroin Nanofiber Containing Silver Nanoparticles as a Novel Highly Efficient Antibacterial Wound Dressing.

Drug loading in electrospun nanofibers has gained a lot of attention as a novel method for direct drug release in an injury site to accelerate wound healing. The present study deals with the fabrication of silk fibroin (SF)-chitosan (CS)-silver (Ag)-curcumin (CUR) nanofibers using the electrospinning method, which facilitates the pH-responsive release of CUR, accelerates wound healing, and improves mechanical properties. Response surface methodology (RSM) was used to investigate the effect of the solution parameters on the nanofiber diameter and morphology. The nanofibers were characterized via Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), zeta potential, and Dynamic Light Scattering (DLS). CS concentration plays a crucial role in the physical and mechanical properties of the nanofibers. Drug loading and entrapment efficiencies improved from 13 to 44% and 43 to 82%, respectively, after the incorporation of Ag nanoparticles. The application of CS hydrogel enabled a pH-responsive release of CUR under acid conditions. The Minimum Inhibitory Concentration (MIC) assay on E. coli and S. aureus bacteria showed that nanofibers with lower CS concentration cause stronger inhibitory effects on bacterial growth. The nanofibers do not have any toxic effect on cell culture, as revealed by in vitro wound healing test on NIH 3T3 fibroblasts.

Preparation of a pH-responsive chitosan-montmorillonite-nitrogen-doped carbon quantum dots nanocarrier for attenuating doxorubicin limitations in cancer therapy.

Despite its widespread usage as a chemotherapy drug in cancer treatment, doxorubicin (DOX) has limitations such as short in vivo circulation time, low solubility, and poor permeability. In this regard, a pH-responsive chitosan (CS)- montmorillonite (MMT)- nitrogen-doped carbon quantum dots (NCQDs) nanocomposite was first developed, loaded with DOX, and then incorporated into a double emulsion to further develop the sustained release. The incorporated NCQDs into the CS-MMT hydrogel exhibited enhanced loading and entrapment efficiencies. The presence of NCQDs nanoparticles in the CS-MMT hydrogel also resulted in an extended pH-responsive release of DOX over a period of 96 h compared to that of CS-MMT-DOX nanocarriers at pH 5.4. Based on the Korsmeyer-Peppas model, there was a controlled DOX release at pH 5.4, while no diffusion was observed at pH 7.4, indicating fewer side effects. MTT assay showed that the cytotoxicity of DOX-loaded CS-MMT-NCQDs hydrogel nanocomposite was significantly higher than those of free DOX (p < 0.001) and CS-MMT-NCQDs (p < 0.001) on MCF-7 cells. Flow cytometry results demonstrated that a higher apoptosis induction achieved after incorporating NCQDs nanoparticles into CS-MMT-DOX nanocarrier. These findings suggest that the DOX-loaded nanocomposite is a promising candidate for the targeted treatment of cancer cells.