We studied the efficacy of mesenchymal stem cells (MSC), either alone or associated with dapsone (DAP) in the treatment of dermonecrotic wounds caused by Loxosceles laeta spider venom. Twenty-five male adult rabbits were distributed into five groups, of which four groups received an intradermal injection of 20 μg of L. laeta venom and only one received ultrapure water (negative control). After 4 hours, each group that received venom, was treated with MSC, DAP, MSC + DAP and Phosphate-buffered saline – PBS (positive control). Photographic records were made for analysis of the wound area evolution by morphometry. Twelve days after treatment, the skin samples around the lesion were removed for subsequent histological analysis. Concerning the rate of wound contraction, we observed that DAP showed the best percentage of contraction at day 3. In the treatments using MSCs, a negative value of wound contraction was observed for the isolated MSCs, as well as a lower contraction value for the association of the MSC + DAP when compared to PBS group. Histopathological analysis showed diminished tissue lesion and less intense inflammation in MSCs and DAP groups. This could indicated potential use of stem cells in regenerative therapies after loxoscelic accidents.

Nanocellulose is cellulose in the form of nanostructures, i.e. features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, e.g. in bacterial cellulose; nanofibers, e.g. in electrospun matrices; nanowhiskers and nanocrystals. These structures can be further assembled into bigger 2D and 3D nano-, micro- and macro-structures, such as nanoplatelets, membranes, films, microparticles and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluonacetobacter), plants (trees, shrubs, herbs), algae (Cladophora) and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology and biomedical applications, e.g. for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.

Plants of the genus Zingiber (Family Zingiberaceae) are widely used throughout the world as food and medicinal plants. They represent very popular herbal remedies in various traditional healing systems; in particular, rhizome of Zingiber spp. plants has a long history of ethnobotanical uses because of a plethora of curative properties. Antimicrobial activity of rhizome essential oil has been extensively confirmed in vitro and attributed to its chemical components, mainly consisting in monoterpene and sesquiterpene hydrocarbons such as α-zingiberene, ar-curcumene, β-bisabolene and β-sesquiphellandrene. In addition, gingerols have been identified as the major active components in the fresh rhizome, whereas shogaols, dehydrated gingerol derivatives, are the predominant pungent constituents in dried rhizome. Zingiber spp. may thus represent a promising and innovative source of natural alternatives to chemical food preservatives. This approach would meet the increasing concern of consumers aware of the potential health risks associated with the conventional antimicrobial agents in food. This narrative review aims providing a literature overview on Zingiber spp. plants, their cultivation, traditional uses, phytochemical constituents and biological activities.

To better understand the shape memory materials and self-healing materials, a new series of liquid-crystalline shape memory polyurethane (LC-SMPU) composites, named SMPU-OOBAm, were successfully prepared by incorporating 4-octyldecyloxybenzoic acid (OOBA) into the PEG-based SMPU. The effect of OOBA on the structure, morphology and properties has been carefully investigated. The results demonstrate that SMPU-OOBAm have liquid crystalline properties, triple-shape memory properties and self-healing properties. The incorporated OOBA promotes the crystallizability of both soft and hard segments of SMPU, and the crystallization rate of the hard segment of SMPU decreases when the OOBA-content increases. Additionally, the SMPU-OOBAm forms a two-phase separated structure (SMPU phase and OOBA phase), and it shows two-step modulus changes upon heating. Therefore, the SMPU-OOBAm shows triple-shape memory behavior, and the shape recovery ratio decreases with an increase in the OOBA content. Finally, SMPU-OOBAm shows self-healing properties. The new mechanism can be ascribed to the heating-induced “bleeding” of OOBA in the liquid crystalline state and the subsequent re-crystallization upon cooling. This successful combination of liquid crystalline properties, triple-shape memory properties and self-healing properties make the SMPU-OOBAm composites with many promise applications in smart optical devices, smart electronic devices and smart sensors.

Though Cyber Physical Systems (CPS) become very popular in last the decade, dependability of CPS is still a critical issue and related survey is rare. We try to spell out the jigsaw of technologies and figure out the technical trends of dependable self-managing CPS. This survey first recalls the motivation and the similar concepts. By analyzing four generic architectures, we summarize the common characteristics and related assurance technologies, and propose a more generic environment-in-loop processing flow of CPS and a formal interaction flow between physical space and cyber space. Further, the similarity between correctness and dependability is formally analyzed and the new five research questions of dependable self-managing CPS are presented. Then we review the critical technologies and related correctness verification & validation (V&V) methods, the architectures for dependable self-managing CPS. Further, the detail dependability management and V&V technologies are surveyed, which covers the areas of running-time fault management methods and whole life cycle V&V technologies, maintenance and available tool sets. For holistic CPS development, Modeling techniques and MDE (model driven engineering) based V&V methods are analyzed in detail. Then we complete the jigsaw of technologies and figure out the missing part. Further, we propose the technical challenges and the further direction. To our best knowledge, this is the first comprehensive survey on dependable self-managing CPS development and evaluation.

Vitrimers are covalent network materials, comparable in structure to classical thermosets. Unlike normal thermosets, they possess a chemical bond swap mechanism that makes their structure dynamic and suitable for activated welding and even autonomous self-healing. The central question in designing such materials is the trade-off between autonomy and material stability: The swap mechanism facilitates the healing but it also facilitates creep, which makes the perfectly stable self-healing solid a hard goal to reach. Here, we address this question for the case of self-healing vitrimers made from star polymers. Using coarse-grained molecular dynamics simulations, we study the adhesion of two vitrimer samples and find that they bond together on timescales that are much shorter than the stress relaxation time. We show that the swap mechanism allows the star polymers to diffuse through the material through coordinated swap events, but the healing process is much faster and does not depend on this mobility.

The advancement of bioconcrete over cementitious composites has brought us to the application of microbes in the field of construction materials. Certain microbes like bacteria, algae, and fungi have been discussed in the review. The purpose of applying these microbes in the matrix is mainly to enhance the concrete’s strength and other properties such as durability, resistance, and self-healing ability. As these microbes are able to induce calcite biomineralizations, the process is also known as Microbiologically Induced Calcite Precipitation (MICP). Some known microorganisms with their mentioned ability are Bacillus subtilis and Bacillus cohnii (bacteria), Chlorella vulgaris and Spirulina platensis (algae), and Trichoderma reesei, Aspergillus niger, and Neurospora crassa (fungi). The paper provides a “state-of-the-art” review of research into the effects of bioconcrete and discusses the overall methodologies of every medium with their physiological, physicochemical and bioengineering properties in the light of recent researches done so far in the same field.

Artificial Intelligence (AI) has seen increased application and widespread adoption over the past decade despite, at times, offering a limited understanding of its inner working. AI algorithms are, in large part, built on weights, and these weights are calculated as a result of large matrix multiplications. Computationally intensive processes are typically harder to interpret. Explainable Artificial Intelligence (XAI) aims to solve this black box approach through the use of various techniques and tools. In this study, XAI techniques are applied to chronic wound classification. The proposed model classifies chronic wounds through the use of transfer learning and fully connected layers. Classified chronic wound images serve as input to the XAI model for an explanation. Interpretable results can help shed new perspectives to clinicians during the diagnostic phase. The proposed method successfully provides chronic wound classification and its associated explanation. This hybrid approach is shown to aid with the interpretation and understanding of AI decision-making processes.

The use of flexible sensors has tripled over the last decade due to the increased demand in various fields including health monitoring, food packaging, electronic skins and soft robotics. Flexible sensors have the ability to be bent and stretched during use and can still maintain their electrical and mechanical properties. This gives them an advantage over rigid sensors that lose their sensitivity when subject to bending. Advancements in 3D printing have enabled the development of tailored flexible sensors. Various additive manufacturing methods are being used to develop these sensors including inkjet printing, aerosol jet printing, fused deposition modelling, direct ink writing, selective laser melting and others. Hydrogels have gained much attention in the literature due to their self-healing and shape transforming. Self-healing enables the sensor to recover from damages such as cracks and cuts incurred during use and this enables the sensor to have a longer operating life and stability. Various polymers are used as substrates on which the sensing conductive material is placed. Polymers including polydimethylsiloxane (PDMS), polyvinyl acetate (PVA), and Kapton are extensively used in flexible sensors. The most widely used nanomaterials in flexible sensors are carbon and silver, however, other nanomaterials such as iron, copper, manganese dioxide and gold are also used to provide controlled levels of conductivity or other functional properties.

This study aimed to investigate the healing effect of advanced platelet-rich fibrin (A-PRF) clot membranes in the reduction of palatal wounds resulting from free gingival graft (FGG) harvesting, in the re-epithelization rate and in the pain experience after surgery. Twenty-five patients requiring soft tissue augmentation (gingival recession coverage or keratinized gingiva augmentation) participated in this prospective randomized clinical study. After FGG harvesting, the test group (n=14) received A-PRF clot membranes at the palatal wound and the control group (n=11) a gelatin sponge. Epithelialization rate of the palatal wound, wound healing area, correspondent percentage of reduction and post-surgical pain experience were assessed. The follow-up period was 90 days. There was a significantly higher reduction of the palatal wound area in the A-PRF group vs. the control group, at 7 (p<0.001), 14 (p=0.009) and 30 days (p<0.001) follow-up. The maximum difference between groups was attained at 30 days (91.5% for A-PRF vs. 59.0% for the control group). At 14 days a significant difference in the proportion of patients showing total epithelization was found: 64.3% for A-PRF vs. 9.1% for the control group (p=0.012). At 90 days, both groups showed total recovery. Overall, the control group experienced a higher level of pain and discomfort until the 14th day, being significantly higher on the second day (p=0.013). The results suggest that A-PRF membranes haste the healing process by promoting a greater reduction along the recovery period and an apparent less painful postoperative period.

Background and Objectives: Acute compartment syndrome (ACS) is an emergency condition of the lower limb in which prophylactic fasciotomy is required to prevent complications. A negative pressure wound therapy (NPWT) used to the treatment of fasciotomy wounds provide beneficial clinical results. This study aimed to exchange the authors’ experience of using the NPWT installation system on the lower limb wounds after fasciotomy in ACS. Materials and Methods: This is a retrospective study enrolled consecutive patients with ACS, who underwent fasciotomy and was treated with the NPWT installation system at Department of Vascular Surgery, Provincial Hospital in Kielce from April 2016 to July 2017. Results: The study enrolled 15 patients with a diagnosis of ACS (87% men, mean age 65 years old). An open four-compartment fasciotomy (87%) or two-compartment fasciotomy (13%) was performed. The NPWT was applied on the first day after fasciotomy in 87% of patients. Therapy was initiated by the negative pressure of 125 mm Hg, which maintained at this level until the therapy was finalized. In 80% of patients, the vacuum-assisted wound closure (VAC) dressing changes were performed every 3 days. The first approximation of fasciotomy wounds margins occurred on the 4th day after surgery among 67% of individuals. The average time of using VAC on fasciotomy wounds was 9 days. The average time to definitive closure edges of fasciotomy wounds was 12 days. The average time of hospital stay was 17 days. Conclusions: Our experience indicates the legitimacy of using NPWT in wound treatment after fasciotomy in ACS. The NPWT enables faster primary closure of wounds, reduces edema, as well as decreases hospitalization time.

There are various biomaterials in nature, but none fulfills all the requirements. Cellulose, eco-friendly material-based biopolymers, have been advanced biomedicine to satisfy most market demand and circumvent many ecological concerns. This review aims to present an overview of the state of the art in cellulose's knowledge and technical biomedical applications. It included an extensive bibliography of recent research findings for fundamental and applied investigations. The chemical structure of cellulose allows modifications and simple conjugation with several materials, including nanoparticles, without tedious efforts. Cellulose-based materials were used for biomedicine applications such as antibacterial agents, antifouling, wound healing, drug delivery, tissue engineering, and bone regeneration. They advanced the applications to be cheap, biocompatible, biodegradable, easy for shaping and processing into different forms, with suitable chemical, mechanical and physical properties.

In this changing world, we all are surrounded by the surmountable risk of getting injured. Amongst various risk factors, major burns are the most distressing and catastrophic. Burn wounds are not easy to heal via natural healing process and ultimately ended up with scar formation. If the degree of burn is high then the loss of tissue and its function is very common. To fasten-up the natural burn wound healing; zinc, an essential trace element is found to be very much effective. But due to its’ particle size limitation, less contact with wounded cells and tissues, and high inherent toxicity restrict its use. Needlessly, zinc is an element with dual action i.e. both antimicrobial and wound healing it is a prime choice to apply its aptitude in burn wound healing. To overcome the documented limitations zinc has converted to nanoparticle form. Zinc oxide nanoparticles, in particular, have attained ample of interest due to their unique properties and potential antimicrobial activity along with wound healing activity which makes it promising for the healing of topical burn wounds. Plant mediated green synthesis of nano-metal oxide particles is gaining a lot of significance due to its simplicity, eco-friendliness and extensive antimicrobial activity and recommended as an appealing substitute to not only physical methods but also chemical methods avoiding the use of the high rate of toxic chemicals and extreme surroundings. This study includes ZnO NPs role in burn wound healing with Phyto-mediated synthesis methods to provide evidence of their potential applications. Additionally, it provides an overview of traditional methods used for the synthesis of ZnO nanoparticles and characterization techniques to obtain information concerning the size, shape and optical properties along with toxicity and safety concern of ZnO NPs and its biomedical applications.

Self-assembled structures mostly arises through enzyme-regulated phenomena in nature under persistent conditions. Enzymatic reactions are one of main biological processes in fabrication and construction of supramolecular hydrogel networks required for biomedical applications. The enzymatic processes provide a unique opportunity to integrate hydrogel formation. In most of cases, structure and substrates of hydrogels are adjusted by enzyme catalysis due to the chemo-, regio- and stereo-selectivity of enzymes. Hydrogels processed by using various enzyme schemes showed remarkable characteristics as dynamic frames for cells, bioactive molecules and drugs in biomedical applications. A novel class of enzyme-mediated crosslinking hydrogels mimics the extracellular matrices by displaying unique physicochemical properties and functionalities like water-retention capacity, drug loading ability, biodegradability, biocompatibility, biostability, bioactivity, optoelectronic properties, self-healing ability, shape memory ability. In recent years, many enzymatic systems investigated hydrogel cross-linking. Results of biocompatible hydrogel products show that these mechanisms of crosslinking can fulfill requirements for variety of biomedical applications including tissue engineering, wound healing and drug delivery.

Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges in size from one to one hundred nanometers. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism that it is tested on, all have a large determining factor on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signaling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress, as well as the effects of nanosilver on the responses to such stresses, are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis, as well as other pathway alterations are examined in this review.

Lytic bacteriophages have the efficacy to act and eradicate pathogenic bacteria as an attractive tool in the near future. Bacteriophages specifically kill multidrug-resistant bacteria even which have the capacity to form biofilms. The present review mainly focused on the efficacy of bacteriophages and cocktails as therapeutic agents against predominate MDR-bacteria and their biofilms which are isolated from septic wound infections. The body of evidence includes data from studies investigating bacteriophages from sewage samples as novel antibacterial and antibiofilm agents against pathogenic bacteria. The goal of this review is to present an overview on predominant bacteria from septic wound infection, the biofilm-forming capacity of bacteria, lytic effect of bacteriophages and phage cocktails with an emphasis on the application of bacteriophages against septic wound causing bacteria.

Cyber Physical Systems (CPS) has been a popular research area in the last decade. The dependability of CPS is still a critical issue, and rare survey has been published in this domain. CPS is a dynamic complex system, which involves various multidisciplinary technologies. To avoid human error and to simplify management, self-management CPS (SCPS) is a wise choice. And to achieve dependable self-management, systematic solution is necessary to verify the design and to guarantee the safety of self-adaptation decision, as well as to maintain the health of SCPS. This survey first recalls the concepts of dependability, and proposes a generic environment-in-loop processing flow of self-management CPS, and then analyzes the error sources and challenges of self-management through the formal feedback flow. Focus on reducing the complexity, we first survey the self-adaptive architecture approaches and applied dependability means; then we introduce a hybrid multi-role self-adaptive architecture, and discuss the supporting technologies for dependable self-management at the architecture level. Focus on dependable environment-centered adaption, we investigate the verification and validation (V&V) methods for making safe self-adaptation decision and the solutions for processing decision dependably. For system-centered adaption, the comprehensive self-healing methods are summarized. Finally, we analyze the missing pieces of the technology puzzle and the future directions. In this survey, the technical trends for dependable CPS design and maintenance are discussed, an all-in-one solution is proposed to integrate these technologies and build a dependable organic SCPS. To the best of our knowledge, this is the first comprehensive survey on dependable SCPS building and evaluation.

(1) Background: Reactive oxygen species (ROS) play a crucial role in the preparation of the normal wound healing response. Therefore, a correct balance between low or high levels of ROS is essential. Antioxidant dressings that regulate this balance is a target for new therapies. The purpose of this review is to identify the compounds with antioxidant properties that have been tested for wound healing and to summarize the available evidence on their effects. (2) Methods: A literature search was conducted and included any study that evaluated the effects or mechanisms of antioxidants in the healing process (in vitro, animal models, or human studies). (3) Results: Seven compounds with antioxidant activity were identified (Curcumin, N-acetyl cysteine, Chitosan, Gallic Acid, Edaravone, Crocin, Safranal, and Quercetin) and 46 studies reporting the effects on the healing process of these antioxidants compounds were included. (4) Conclusions: These results highlight that numerous novel investigations are being conducted to develop more efficient systems for wound healing activity. The application of antioxidants is useful against oxidative damage and accelerates wound healing. Designing biomaterials that can scavenge excess reactive oxygen species requires new technologies and further research, especially human studies.

Given their severity and non-healing nature, diabetic chronic wounds are a significant concern to the 30.3 million Americans diagnosed with diabetes mellitus (2015). Peripheral arterial diseases, neuropathy, and infection contribute to the development of these wounds, which lead to an increased incidence of lower extremity amputations. Early recognition, debridement, offloading, and controlling infection are imperative for timely treatment. However, wound characterization and treatment are highly subjective and based largely on the experience of the treating clinician. Many wound dressings have been designed to address particular clinical presentations, but a prescriptive method is lacking for identifying the particular state of chronic, non-healing wounds. The authors suggest that recent developments in wound dressings and biosensing may allow for the quantitative, real-time representation of the wound environment, including exudate levels, pathogen concentrations, and tissue regeneration. Development of such sensing capability could enable more strategic, personalized care at the onset of ulceration and limit the infection leading to amputation. This review presents an overview of the pathophysiology of diabetic chronic wounds, a brief summary of biomaterial wound dressing treatment options, and biosensor development for biomarker sensing in the wound environment.

Self-healing is the capability of materials to repair themselves after damage has occurred, usually by interaction between molecules or chains. Physical and chemical processes are applied for the preparation of self-healing systems. There are different approaches for these systems such as heterogeneous systems, shape memory effects, hydrogen bonding or covalent-bond interaction, diffusion and flow dynamics. Self-healing mechanisms can occur in particular by heat and light exposure or by reconnection without direct effect. The applications of these systems display an increasing trend in both R&D and industry sectors. Moreover, self-healing systems and their energy storage applications are currently getting great importance. This review aims to provide general information on recent developments in self-healing materials and their energy applications in view of the critical importance of self-healing systems for lithium-ion batteries (LIBs). In the first part of the review, an introduction about self-healing mechanisms and design strategies of self-healing materials is given. Then, selected important healing materials in the literature for the anodes of LIBs are mentioned in the second part. The results and future perspectives are stated in the conclusion section.

1) Introduction: Negative pressure wound therapy (NPWT) is a frequently applied open abdomen (OA) treatment. There are only a few experimental data supporting this method and describing the optimal settings and pressure distribution in the abdominal cavity during this procedure. The aim of our study was to evaluate pressure values at different points of the abdominal cavity during NPWT in experimental abdominal compartment syndrome (ACS) animal model. 2) Methods: In this study (permission Nr. 13/2014/UDCAR) 27 Hungahib pigs (15.4- 20.2 kg) were operated. ACS was generated by implanting a plastic bag in the abdomen through mini-laparotomy and filled with 2100- 3300 ml saline solution (37 C°) to an intraabdominal pressure (IAP) of 30 mmHg. After 3 hours, NPWT (Vivano Med ® Abdominal Kit, Paul Hartmann AG, Germany) or Bogota bag was applied. NPWT group was divided into -50, -100 and 150 mmHg suction group. Pressure distribution to the abdominal cavity was monitored at 6 different points of the abdomen via a multichannel pressure monitoring system. 3) Results: The absolute pressure levels were significantly higher above than below the layer. The values of the pressure were similar in the midline than laterally. Amongst the bowels, the pressure values changed periodically between 0 and -12 mmHg which might be caused by the peristaltic movements. 4) Conclusions: The porcine model of the present study seems to be well applicable for investigating ACS and NPWT. It was possible to provide valuable for clinicians. The pressure was well distributed by the protective layer to the lateral parts of the abdomen and this phenomenon did not change considerably during the therapy.

This review describes the positive effects of growth hormone on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on the vascular endothelium improving its dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease inducing the generation of new collateral vessels able to bypass a major artery occlusion. We include some preliminary data from a trial in which GH or placebo is given to elder people suffering from critical limb ischemia, showing the effects of the hormone on plasma markers of inflammation, and stating that the administration of GH in short periods of time is safe and effective even in diabetic patients. We also analyze how Klotho may have strong relationships with GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH to repair the damaged tissue. Lastly, we show how GH induces wound healing by increasing the blood flow to the ischemic tissue. In summary, we postulate that short-time GH administration is useful for treating cardiovascular diseases.

Cancers have been interpreted either as somatic evolution of cheater cells that escape replication regulation or alternatively as non-healing wounds. Both the interpretations have substantial support as well as glaring anomalies but the two have not been put together to make a coherent synthesis. We argue here that mechanisms and pathways to escape the normal regulation of cell proliferation do not need to evolve de novo. Mechanisms to override the normal regulation have already evolved for wound healing and tissue regeneration. Almost all of the hallmarks of cancer are also seen in the wound healing process. This suggests that cancer develops not by any de novo gain of function but by exaptation of pre-evolved wound healing functions. Somatic evolution that makes the wound healing triggers constitutive is not mutation limited but selection limited and the selective forces are dependent on the tissue microenvironment. Some mechanisms for such selection have been suggested. Many more need to be investigated. A series of mechanisms have evolved to minimize the risk of cancers which may fail in an altered lifestyle context. We support our synthesis with multiple lines of evidence and also make differential testable predictions. This evolutionary perspective suggests novel lines of research and also has translatable implications for cancer prevention.

Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymph­angiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptors. The activating cleavage of VEGF-C is mediated by at least five different proteases: plasmin, ADAMTS3, prostate-specific antigen, cathepsin D, and thrombin. All of these proteases except for ADAMTS3 can also activate VEGF-D. Processing by different proteases results in distinct forms of the "mature" growth factors, which differ in affinity and receptor activation potential. The “default” VEGF-C-activating enzyme ADAMTS3 does not activate VEGF-D and therefore, VEGF-C and VEGF-D do function in different contexts. VEGF-C itself is also regulated in different contexts by different proteases. During embryonic development, ADAMTS3 activates VEGF-C. In contrast, thrombin and plasmin likely activate VEGF-C/-D during tissue injury-induced lymphangiogenesis, and PSA and cathepsin D perhaps during tumor-associated pathological lymphangio­genesis. Additionally, cathepsin D from saliva might activate latent VEGF-C/-D upon wound licking, thereby accelerating healing. Similar to tyrosine kinase receptors and VEGFs themselves, these activating proteases could be targeted to modulate angiogenesis and lymphangiogenesis in relevant diseases.

Background: Chronic lower limb ulcers (CLLU) have an important burden to the individual and the healthcare system. However, there is a lack of information about the cost of CLLU in Argentina.Objective: To determinate the number and cost of consultation and hospitalization associated to CLLU in a public hospital in Argentina. Methods: Retrospective observational study. Cost estimation were calculated based on days of stay, treatments and laboratory tests in a inpatient population and the number of consultations, treatments and laboratory tests, in a outpatient population. Results: In 2013 and 2014, the overall number of consultation with ICD-10 codes was 7,224 and the number of inpatient was 359. The mean age for male and female outpatient consultations was 59.53(±13.06) years and 59.04(±10.93), respectively. For CLLU male and female inpatient, the mean age was 63.9(±10.4) years and 54.5(±8.6) years, respectively. The length of stay was 22.88 days. There was a mean of 0.41 surgeries per patient where 25% were amputations. The mean annual cost in a single public hospital was US$4,053.65 per inpatient and US$3,589.24 per outpatient. Conclusion: Cost information allows new public health policies to reduce socioeconomic burden due to CLLU.

Wounds are structural and functional disruptions of the skin that occur because of an accident. Chronic wounds are caused by a breakdown in the finely coordinated cascade of events that occurs during wound healing. Wound healing is a long process that split into at least three continuous and overlapping processes: an inflammatory response, a proliferative phase that leads to tissue repair, and third one is tissue remodeling. Therefore, wound healing studies are extensively studied to develop techniques that can achieve maximum recovery with minimum scar. Several growth hormones and cytokines secreted at the wound site tightly regulate wound healing processes. The traditional approach for wound management has been represented by topical treatments. Metal nanoparticles (e.g., silver, gold, zinc) are increasingly being employed in dermatology due to their favorable effects on wound healing, as well as in treating and preventing bacterial infections. The development of wound dressings materials has now been used to overcome the issues of external environments. The impregnated nanomaterials have provided moist environment that removes the exudates and avoid maceration. This review highlights the mechanism and focus on the current advancement of various nanoparticles impregnation material for wound healing process that can protect wound from infection and maintain the optimum exchange of gases.

Background: Selection and application of suture materials, has gained more importance especially with the increasing number of patients seeking oral surgeries. Since lying in a bacterial-filled environment, sutures make the tissue prone to infection. Suture material plays an important role in the reduction of the risk of infection. This study aimed to assess the success rate of an antibacterial suture named Vicryl Plus in preventing bacterial growth in the surgical site of the mandibular third molar. Methods: 27 patients were included in this double-blinded randomized clinical trial study. Surgical Extraction of the mandibular wisdom tooth was done and the incision was managed by randomly using Vicryl Plus and Vicryl sutures. After 7 days, sutures were removed and assessed microbiologically. Predominant species of Streptococcus mutans and Lactobacillus were assessed as well as the total number of colonies on each suture. Results: There was a significant difference between two suture materials in colony number-length ratio of lactobacillus (p-value= 0.031) and total bacterial colonies (p-value=0.016); but not for S. mutans species (p-value=0.201). Conclusion: Antibacterial Vicryl suture can be a useful tool for the reduction in the rate of surgical site infection in high-risk cases and situations.

We report the development of an extrinsic self-healing coating system that shows no fluorescence from the intact coating, yellowish fluorescence in cracked regions, and greenish fluorescence in healed regions, thus allowing the separate monitoring of cracking and healing of coatings. This fluorescence monitoring self-healing system consisted of a top coating, an epoxy matrix resin containing mixed dye-loaded in single microcapsule. The dye-loaded microcapsules consisted of a poly(urea-formaldehyde) shell encapsulating a healing agent containing MAT-PDMS and styrene, a photo-initiator and a mixture of two dyes, one that fluoresces only in the solid state (DCM) and a second that fluoresces dramatically increased in the solid than solution state (4-TPAE). A mixture of the healing agent, photo-initiator and the two dyes was yellow due to fluorescence from DCM. On UV curing of this mixture, however, the color changed from yellow to green and the fluorescence intensity increased due to fluorescence from 4-TPAE in the solid state. When a self-healing coating embedded with microcapsules containing the DCM/4-TPAE dye mixture was scratched, the damaged region exhibited a yellowish color that changed to green after healing. Thus, the self-healing system reported here allows the separate monitoring of cracking and healing based on changes in fluorescence color.

innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan can be used to create biocompatible and biodegradable scaffolds with 3D architectures similar to human structures, allowing their efficient and safe use as tissue engineering and drug delivery systems in chronic wounds. Locally heated tumors above polymer lower critical solution temperature can induce its conversion into a hydrophobic form, enhancing drug release until the thermal stimulus is gone, where a lower release is due to the swelling of the material. This paper integrates the relevant reported contributions of bioengineered scaffolds for thermo-responsive drug delivery in wound healing. Therefore, we present a comprehensive review that aims to demonstrate the capacity of these systems to provide spatially and temporally controlled release strategies for one or more drugs used in wound healing. In this sense, the novel manufacturing techniques of 3D-printing and electrospinning are explored for the tuning of their physicochemical properties to adjust therapies according to the patient’s convenience, as well as reduce drug toxicity and side effects.

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition include bacterial contamination, tissue perfusion, and mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments.In this review, we discuss bioengineering advances in non-invasive detection of biologic and physiologic factors of the healing wound, visualizing and modeling the ECM, and computational tools to efficiently evaluate the complex data acquired from the wounds to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the matrix, linearity of collagen, and live tracking of components within the ECM. Computational modeling of the matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed.

Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signalling takes part in all four wound healing phases: hemostasis, inflammation, proliferation and remodelling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration and treatment of dermal diseases, including the stem cell-derived, plant-derived and engineered EVs.

Dermal wound healing describes the progressive repair and recalcitrant mechanism of damaged skin and eventually reformatting and reshaping the skin. Many probiotics, nutraceuticals, metal nanoparticles have been associated with improved healing process of intra and inter tissue wounds. Despite the vast nature on material based wound healing mediators, the exact mechanism on material-cellular interaction is still point of repent issue particularly in diabetics and pathological condition. The use of bioengineered alternative agents will likely only continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new additional products continue to cut costs and improve wound healing process. This review article provides an update of the various remedies with confirmed wound healing activities by a diverse group of agents from previous experiments conducted by various researchers

Crohn’s disease is an inflammatory bowel disease whose prevalence is increasing worldwide. Among medical strategies, the dietary therapy with exclusive enteral nutrition is recommended as first line option, at least for children, because it induces clinical remission and mucosal healing. Modulen®, a polymeric TGF-β2 enriched formula, has a good palatability and is widely used. For the first time in the literature, this review outlines and discusses the clinical outcomes obtained with this therapy, as well as the potential mechanisms of action of its compounds. It can be explained by its TGF-β2 content but also by its protein and lipid composition. Further well-designed studies are required to improve our knowledge and to optimize therapeutic strategies.

. Sealants and adhesives are used in the repair and preservation of damaged solid organs. This study examines the matrix metalloproteinases (MMP) activity in the healing of liver injuries treated with two biological adhesives (Tachosil® and GelitaSpon®) as well as that of a new elastic cyanoacrylate (Adhflex®). Methods. We induced in 90 male rats hepatic lesions using a Stiefel biopsy punch in the liver. Wound healing was assessed 2, 6, and 18 days after injury by quantifying MMP1, 2, 8, 9, and 13 tissue levels. The histopathological repair was evaluated by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining and CD31, CD68 immunohistochemical marker. The three sealants used contributed to the complete healing of hepatic lesions. Both histopathology and MMP findings point to the fact that degradation with Adhflex® is slower and causes a strong inflammatory reaction at the onset of healing. Results. All the MMPs measured showed higher values early in the healing process in animals treated with Adhflex® and Tachosil, expression for MMP2 and MMP9 being significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant greater values of MMP8 and MPP13 than the Adhflex group. Animals treated with Adhflex® showed a sustained overexpression in all MMPs even at the latest wound healing stages. Conclusion. Notably, the overexpression of the MMPs did not negatively influence the histological healing process of liver injuries. Since all hepatic trauma injuries should be treated as emergencies, any easy-to-use and rapid sealant, like Adhflex®, could be considered an adequate treatment option.

A phosphate/molybdate and cerium-modified phosphate/molybdate conversion coatings were deposited on a carbon steel surface and their protective and self-healing abilities were evaluated. Surface morphology and inner structure of the coatings were examined using FE-SEM-FIB and TEM techniques, chemical composition and element distribution depth profiles in conversion layers were determined using EDX measurements, whereas XPS was applied for the analysis of Mo and Ce oxidation states. Voltammetric measurements and EIS were performed to assess the corrosion behavior of the samples. The higher protective and stronger self-healing abilities were found for phosphate/molybdate/cerium conversion coating deposited in a sulphate-containing solution. This was attributed to higher values of both: total cerium and Ce(IV) content in the conversion layer as well as to lower number of structural defects in the coating. It was demonstrated that the micro-structural characteristics of protective coatings are also important in determining self-healing abilities.

Background. Adhesives and sealants can be used to repair and preserve solid damaged organs. This study explores the activity of different matrix metalloproteinases (MMP) during the healing of liver injuries treated with two biological adhesives (Tachosil and GelitaSpon) and a new synthetic elastic cyanoacrylate (Adhflex®). Methods. Liver traumatic injuries were experimentally induced in 90 male Wistar rats using a Stiefel biopsy punch in the liver. Wound healing was evaluated 2, 6, and 18 days after injury by determining MMP1, 2, 8, 9, and 13 expression. The histopathological repair was assessed by hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining. The three sealants used supported complete healing of the liver lesions. Both histopathology and MMP findings indicate that the degradation process of Adhflex® is slower and produces a strong initial inflammatory reaction. Results. All the MMPs measured disclosed higher values at early stage of the healing process in animals treated with Adhflex® and Tachosil, being the expression of for MMP2 and MMP9 significantly higher in the Adhflex-treated group. Animals treated with Tachosil had significant higher values of MMP8 and MPP13 than the Adhflex-treated group. Animals treated with Adhflex® showed a maintained overexpression in all the MMPs tested even at the latest wound healing stages. Conclusion. Notably, this MMPs overexpression did not influence negatively the histological healing process of the hepatic injuries. Given that all hepatic trauma injuries should be considered emergencies, any easy-to-use and rapid sealant, such as Adhflex®, could be considered as a suitable treatment option.

In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk aggravating factors for the development of chronic skin lesions. Stem cells regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of 3D bioprinted scaffolds. With this review we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, towards their relevance in the skin regeneration field.

This retrospective study aimed to investigate the effect of known risk factors on nonsurgical periodontal treatment (NSPT) response using a pocket depth fine-tuning multilevel linear model (MLM). Thirty-seven patients (24 males and 13 females) with moderate to severe chronic periodontitis were treated with nonsurgical periodontal therapy. Follow-up visits at 3, 6, and 12 months included measurement of several clinical periodontal parameters. Data were extracted from a database system. Probing depth (PD) and Clinical Attachment Loss (CAL) reductions after NSPT in an overall of 1416 initially affected sites (baseline PD ≥ 4 mm), distributed on 536 teeth, were analyzed against known risk factors at three hierarchical levels (patient, tooth and site). The variance component models fitted to assess the three-level variance of PD and CAL decrease for each post-treatment follow-up showed that all levels contributed significantly to the overall variance (P < 0.001). Patients that underwent NSPT and were continually monitored had very curative results. All three hierarchical levels included risk factors who had impact on the to influence the magnitude of PD and CAL reduction. Specifically, the tooth’s type, surfaces involved and teeth mobility site-level risk factors showed the highest influence on these reductions, being highly relevant factors for the NSPT success.

Regeneration is usually regarded as a unique plant or some animal species process. In reality, regeneration is a ubiquitous process in all multicellular organisms. It ranges from response to wounding by healing the wounded tissue to whole body neoforming (remaking of the new body). In a larger context, regeneration is one facet of two reproduction schemes that dominate the evolution of life. Multicellular organisms can propagate their genes asexually or sexually. Here I present the view that the ability to regenerate tissue or whole-body regeneration is also determined by the sexual state of the multicellular organisms (from simple animals like hydra and planaria to plants and complex animals). The above idea is manifested here by showing evidence that many organisms, organs, or tissues show inhibited or diminished regeneration capacity when in reproductive status compared to the same organism organs or tissues in nonreproductive conditions or by exposure to sex hormones.

Taiwan cobra (Naja atra) bites account for approximately 20% of all venomous snakebites in Taiwan. In Taiwan, the rates of wound necrosis and secondary infection from Taiwan cobra bites are higher than those associated with other venomous snakebites. Clinical tools to evaluate the infection risk after Taiwan cobra bites are lacking. Therefore, in this study, we developed a useful clinical tool to evaluate the infection risk after Taiwan cobra bites. Moreover, we investigated wound infection bacteriology. We analyzed the data of patients bitten by N. atra who had undergone freeze-dried neurotoxic antivenin treatment in emergency rooms of the Chang Gung Memorial Hospital network, which comprises seven hospitals and the largest medical system in Taiwan, from January 2001 to May 2017. Because patients with wound necrosis required antibiotics for infection treatment, we included only patients with wound infection but without tissue necrosis in the development of our Cobra Bacteriology of Infections in Taiwanese snake Envenomation (Cobra BITE) score by using univariate and multiple logistic regression. In total, 8,295,497 emergency department visits occurred from January 2001 to May 2017, and 195 patients were diagnosed has having cobra bites. Among them, 23 and 30 patients had wound necrosis and wound infection, respectively. The wound infection rate was 27.2% (53/195). Regardless of whether the patients had necrosis, Enterococcus faecalis and Morganella morganii were the main bacteria identified in the culture report. Gentamicin, ceftriaxone, ciprofloxacin, and levofloxacin are the ideal first-line antibiotics for treating N. atra bite wounds in Taiwan. As per our Cobra BITE score, the three factors predicting secondary wound infection after cobra bites are hospital admission, a white blood cell count (in 103/µL) × by neutrophil–lymphocyte ratio value of ≥114.23, and the use of antivenin medication. The area under the receiver operating characteristic curve for the Cobra BITE score system was 0.88. The ideal sensitivity and specificity were 0.89 and 0.76, respectively, and the optimal cutoff point for Cobra BITE score was 7. The Hosmer–Lemeshow p value was 0.4. In conclusion, our Cobra BITE study established a new practical clinical tool for clinicians to evaluate infection risk after N. atra bites. This score system enables the assessment of wound infections after N. atra bites, and it could be modified and improved in future for other Naja spp. bites.

Micellar Casein Concentrate (MCC) is manufactured from microfiltration (MF) of skim milk utilizing ceramic or polymeric membrane filtration. While ceramic filtration has higher efficiency, use of polymeric is cost effective and the process is familiar to several US dairy processors. The aim of the present study was to develop an optimized membrane filtration process to produce MCC using spiral wound polymeric membrane filtration (SW MF) system by systematic selection of transmembrane pressure (TMP) and level of diafiltration (DF). Using skim milk as feed material, preliminary lab-scale MF experiments were conducted using 0.5 µm polyvinylidene fluoride (PVDF) membrane. Three TMP (34.5, 62.1, and 103.4 kPa) and three levels of DF (70, 100, and 150%) along with a process without DF as control were used in the study. Effect of TMP and effectiveness of DF on flux rates, SP removal, casein to total protein (CN/TKN) ratio, casein to true protein (CN/TP) ratio, rejection of casein (rej CN) and SP (rej SP) were evaluated. At all TMP values used in the study, the overall flux (O Flux) increased with the level of DF. Highest O Flux of 30.77 liter per meter square per hour (LMH) was obtained with 34.5 kPa pressure and 150% DF. The impact of DF was more pronounced at lower pressures than at the higher pressures used in the study. With controlled DF, instantaneous flux was maintained within 80% of initial flux for the entire process run. For all the experiments, casein has a rejection of 0.97 to 1.0, while serum protein has the lowest rejection of 0.10 at 34.5 kPa pressure and 150% DF level. Use of 34.5 kPa and DF level of 150 % contributed to 81.45% SP removal, and casein to true protein ratio of 0.96. SP removal data from the lab-scale experiments were fitted into a mathematical model using DF and square of TMP as factors. The model predicts SP removal within 90-95% of actual SP removal got from the pilot plant experiments.

Bone marrow derived adult human mesenchymal stem cells (hMSCs) possess therapeutic qualities that enable them to enhance wound repair. However, the mechanisms by which this occurs remains poorly understood. Basic mechanisms may include the directed migration of delivered cells to target sites and/or the production and release of soluble factors that act at a distance. Allogeneic and even xenogeneic cells may effectively participate in wound repair. Labeled hMSCs were delivered to full-thickness skin wounds that were created in immunologically competent mice. The delivery occurred on day 3 post-wounding using two different carriers; one which released cells and one which retained cells. The fates of the delivered cells were tracked for up to 25 days. During this period, released cells migrated as a tight cohort deep into the wound to reach the subdermal vascular plexus. Simultaneously, enhanced formation of granulation tissue was evident. This migration of hMSCs was not essential in that enhanced granulation tissue formation and wound contraction occurred when cells were retained in the carrier matrix. This provided further evidence for the release of therapeutic factors by hMSCs to sites of injury.

Hydrogels are used for various biomedical applications due to their biocompatibility, capacity to mimic the extracellular matrix, and ability to encapsulate and deliver cells and therapeutics. However, traditional hydrogels have a few shortcomings, especially regarding their physical properties, thereby limiting their broad applicability. Recently, researchers have investigated the incorporation of nanoparticles (NPs) into hydrogels to improve and add to the physical and biochemical properties of hydrogels. This brief review focuses on papers that describe the use of nanoparticles to improve more than one property of hydrogels. Such multifunctional hydrogel nanocomposites have enhanced potential for various applications, including tissue engineering, drug delivery, wound healing, bioprinting and biowearable devices.

The vertebrate annexin superfamily (AnxA) consists of 12 members of a calcium (Ca²⁺) and phospholipid binding protein family which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca²⁺-controlled regulation of a broad range of membrane events. In this review, we identify and discuss several themes of annexin actions that hold a potential therapeutic value, namely the regulation of the immune response and the control of tissue homeostasis, and that repeatedly surface in the annexin activity profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically clinical point of view.

Current clinical treatment options for symptomatic, partial-thickness rotator cuff tear (sPTRCT) offer only limited potential for true tissue healing and improvement of clinical results. In animal models, injections of adult stem cells isolated from adipose tissue into tendon injuries evidenced histological regeneration of tendon tissue. However, it is unclear whether such beneficial effects could also be observed in a human tendon treated with fresh, uncultured, autologous, adipose derived regenerative cells (UA-ADRCs). A specific challenge in this regard is that UA-ADRCs cannot be labeled and, thus, not unequivocally identified in the host tissue. Therefore, histological regeneration of injured human tendons after injection of UA-ADRCs must be assessed using comprehensive, immunohistochemical and microscopic analysis of biopsies taken from the treated tendon a few weeks after injection of UA-ADRCs.

The indole-3-pyruvic acid pathway is the major route for auxin biosynthesis in higher plants. Tryptophan aminotransferases (TAA1/TAR) and members of the YUCCA family of flavin-containing monooxygenases catalyze the conversion of L-tryptophan via indole-3-pyruvic acid into indole-3-acetic acid (IAA). It has been described that locally produced jasmonic acid (JA) in response to mechanical wounding, triggers de novo-formation of IAA through the induction of two YUCCA genes, YUC8 and YUC9. Here, we report the direct involvement of a small number of basic helix-loop-helix transcription factors of the MYC family in this process. We show that the JA-mediated regulation of YUC8 and YUC9 gene expression depends on the abundance of MYC2, MYC3, and MYC4. In support of this observation, seedlings of myc knockout mutants displayed a strongly reduced response to JA-mediated IAA formation. In addition, transactivation assays provided experimental evidence for the binding of the MYC transcription factors to a particular tandem G-box motif abundant in the promoter regions of YUC8 and YUC9, but not in those of the other YUCCA genes. Moreover, we clearly demonstrate that YUC8ox and YUC9ox overexpressing plants show less damage after spider mite infestation, thereby underlining a role of auxin in plant responses toward biotic stress cues.

The vertebrate annexin superfamily (AnxA) consists of 12 calcium (Ca2+) and phospholipid binding proteins which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca2+-controlled regulation of membrane events. In this review, we discuss several themes of potential therapeutic value, namely the regulation of the immune response and the control of tissue homeostasis, that repeatedly surface in the annexin action profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically clinical point of view.

The effective treatment for chronic wounds constitute one of the most common worldwide health care problem due to the presence of high levels of proteases, free radicals and exudates in the wound, which constantly activate the inflammatory system avoiding the tissue regeneration. In this study, we describe a multifunctional bioactive and resorbable membrane with in-built antioxidant agent for the continuous quenching of free radicals as well as to control inflammatory response helping to promote the wound healing process. To reach that goal synthesized statistical copolymers of N-vinylcaprolactam (V) and 2-hydroxyethyl methacrylate (H) have been conjugated with catechol bearing hydrocaffeic acid (HCA) molecules. The natural polyphenol (catechol) is the key molecule responsible for the mechanism of adhesion of mussels, and provides the functionalized polymer conjugate a continuous antioxidant response, antiinflammatory effect, UV screen and bioadhesion in the moist environment of the human body, all of them key features in the wound healing process. Therefore, these novel mussel-inspired materials have an enormous potential of application and can act very positively, favoring and promoting the healing effect in chronic wounds.

Honey is a complex sweet food stuff with well-established antimicrobial and antioxidant properties. It has been used for millennia in a variety of applications, but those most noteworthy include treatment of surface wounds, burns and inflammation. A variety of substances in honey have been suggested as the key component to its antimicrobial potential; polyphenolic compounds, hydrogen peroxide, methylglyoxal and bee-defensin 1. These components vary greatly across honey samples due to botanical origin, geographical location and the individual bee. The use of medical grade honey, Medihoney and Revamil, in the treatment of surface wounds and burns has been seen to improve the healing process, reduce healing time, reduce scarring and prevent microbial contamination. Therefore, medical grade honeys should be used for these treatments and reduce the demand for antibiotic usage. In this review, we aim to outline the constituents of honey and how they affect the antibiotic potential of honeys in a clinical setting.

The Kalanchoe genus is composed of more than 100 species that usually thrive in tropical environments, which have been used in folkloric medicine to treat various illnesses, including dermatological conditions. With this, the present study assesses the pharmacognostical and pharmacological properties of different species of the Kalanchoe genus as elements for a potential treatment for dermatological-related conditions, from findings of existing literature and studies. It was analyzed that the Kalanchoe pinnata plant, or one of the most common species of Kalanchoe, have been observed to have distinct morphological and microscopic characteristics. Further, it was discovered that different species of Kalanchoe have anti-inflammatory, antioxidant, antibacterial, and wound healing properties, which enable the plant to be used for dermatological products that are available to the market. With this, it is recommended that further studies be conducted in other understudied species of Kalanchoe regarding their pharmacological properties, as well as the use of other structures of the Kalanchoe plant for treatment of various dermatological conditions.

Wound healing involves a complex cascade of cellular, molecular, and biochemical responses and signaling processes. It consists of successive interrelated phases, the duration of which depends on multifactorial processes. Wound treatment is a major healthcare issue that can be resolved by development of effective and affordable wound dressings based on natural materials and biologically active substances. Proper use of modern wound dressings can significantly accelerate wound healing with minimal cosmetic defects. The innovative biotechnologies for creating modern natural interactive dressings are based on sulfated polysaccharides from seaweeds with their unique structures and biological properties, the availability of their sources in the form of wild bushes, and in the form of aquaculture, as well as with a high potential for participation in process control wound healing. These natural biopolymers are a novel and promising biologically active source for designing wound dressings based on alginates, fucoidans, carrageenans, and ulvans, which serve as active and effective therapeutic tools. The aim of this review is to summarize available information about the modern wound dressing’s technologies based on seaweed-derived polysaccharides, including those successfully implemented in commercial products, with the emphasis on promising and innovative designs. The further prospect of using marine biopolymers is related to the need to analyze the results of numerous in vitro and in vivo experiments, summarize clinical trial data, develop a scientifically based approach and relevant practical recommendations for the treatment of wounds.

Cutaneous wound healing is a complex multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically and biologically injured area resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics is therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring and eliminate chronic wounds. Following the global trend towards automation, miniaturization and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay or cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.

Micro-blade design is an important factor in the cutting of single cells and other biological structures. This paper describes the fabrication process of three dimensional (3D) micro-blades for the cutting of single cells in a microfluidic “guillotine” intended for fundamental wound repair and regeneration studies. Our microfluidic guillotine consists of a fixed 3D micro-blade centered in a microchannel to bisect cells flowing through. We show that the Nanoscribe two-photon polymerization direct laser writing system is capable of fabricating complex 3D micro-blade geometries. However, structures made of the Nanoscribe IP-S resin have low adhesion to silicon, and they tend to peel off from the substrate after at most two times of replica molding in poly(dimethylsiloxane) (PDMS). Our work demonstrates that the use of a secondary mold replicates Nanoscribe printed features faithfully for at least 10 iterations. Finally, we show that complex micro-blade features can generate different degrees of cell wounding and cell survival rates compared with simple blades possessing a vertical cutting edge fabricated with conventional 2.5D photolithography. Our work lays the foundation for future applications in single cell analyses, wound repair and regeneration studies, as well as investigations of the physics of cutting and the interaction between the micro-blade and biological structures.

This study examines the matrix metalloproteinase (MMP) activity in the healing of liver injuries treated with biological adhesives Tachosil^® and GelitaSpon^® and the elastic cyanoacrylate Adhflex^®. Hepatic lesions were induced in male rats using a Stiefel biopsy punch. Healing was assessed 2, 6, and 18 days after injury by quantifying tissue levels of MMP1, 2, 8, 9, and 13. Histopathological repair was evaluated using hematoxylin-eosin, Masson’s trichrome, and Periodic Acid Schiff (PAS) staining and immunohistochemical markers CD31 and CD68. The sealants contributed to complete healing. Histopathology and MMP findings indicate that Adhflex^® has slower degradation and a strong inflammatory reaction at the onset of healing. Early on, all MMPs showed higher levels in Adhflex^® and Tachosil^®-treated animals, and MMP2 and MMP9 expressions were significantly higher in the Adhflex-treated group at 18 days post-injury (T3). The Adhflex^® group had significantly higher MMP8 and MPP13 levels than other treated groups and showed a sustained overexpression of all MMPs, even in the latest healing stages. Notably, the overexpression did not negatively influence the histological healing process. All hepatic trauma injuries should be treated as emergencies, and any easy-to-use and rapid sealant like Adhflex^® could be considered as an option for treating liver trauma.

Introduction: Wound healing is a multifaceted biological process, and diabetic wounds add more complexity to it. In diabetic wounds, the combination of chloroform fractions of Achyranthes aspera L. (A.aspera) leaves with β-Glucans has not been investigated. The additive effect of these two (A.aspera + β-Glucans) would benefit the inflammatory phase of diabetic wounds, as improper treatment will lead to chronic injuries. Therefore, the goal of this research work was to assess the in-vivo wound healing and anti-inflammatory effects of a combination of chloroform fractions of A.aspera leaves and β-Glucans in a variety of wound models in STZ-induced diabetic rats. Methods: Preliminary phytochemical analyses of A.aspera were conducted to identify various phytoconstituents in the test extract. Acute and sub-acute dermal toxicity tests of A.aspera were carried out on mice and rats, respectively, to see whether there were any abnormalities. Excision and incision wound models, cotton pellet-induced granuloma models, rat paw edema and burn wounds were used to test wound healing and anti-inflammatory actions. To induce diabetes, streptozotocin (STZ) was administered intraperitoneally at a dosage of 65 mg/kg (i.p.). A.aspera (10% w/w) and β-Glucans (2% w/w) ointments were tested separately and in combination for wound healing activities. Silver sulfadiazine (1 % w/w) ointment was used to treat the positive control groups. Excision wound model rats that had been treated with basic ointment were used as negative controls, as were incision wound model rats that had not been treated. A.aspera (400 mg/kg, po) and β-Glucans (30 mg/kg, po) were tested separately and in combination for anti-inflammatory efficacy. Positive control groups were given indomethacin (10 mg/kg, po) for cotton pellet-induced granuloma and rat paw oedema models. Negative controls for both anti-inflammatory activity models were provided 2% Tween 80. The groups were made up of six rats, and the treatments were given topically and orally to assess wound healing and anti-inflammatory effects. The levels of hydroxyproline and hexosamine and the antioxidant enzymes (SOD and CAT) in the granulation tissue were measured in excision wound model. Healed excision wound skin was examined histopathologically. Results: The A.aspera and β-Glucans combination resulted in a significant percentage of wound contraction and a shorter epithelialization time (P<0.01). The combination was found to be the most effective, with the highest percentage of edema reduction (55 %; p<0.01). The combination also exhibited favourable hydroxylamine, hexosamine and anti-oxidant profiles supported by histopathology data. Conclusion: This research showed that the immunomodulatory effect of β-Glucans had significantly enhanced the wound healing, anti-inflammatory, and anti-oxidant potential of A.aspera in diabetic wounds.

Objectives Bone fractures are very common diseases, which can be caused by impact injuries or physiological disorders. Thus, the present review aimed to study the use of medicinal plants in the healing mechanism of bone fractures. Evidence acquisition Through research in the PubMed, Google Academic, and Scielo databases, this article reviews 11 ethnopharmacological studies and 34 preclinical studies on the biological actions of different plants in bone fracture healing mechanism. Results Indian tribes have highlighted in the plants ethnopharmacological study for various diseases, including bone fractures. However, despite the large citations of traditional use, technical-scientific studies are still scarce in the literature. Chenopodium ambrosioides, Piper sarmentosum, quadrangular Cissus, Ricinus communis and Radix salvia miltiorrhiza plants were the most studied in the literature regarding their osteogenic, angiogenic, anti-inflammatory and remodeling effects, acting on bone receptors, stimulating bone metabolism, increasing minerals uptake, and assisting in free radicals breakdown. Conclusion Thus, the medicinal plants use is promising in the field of bone regeneration, as well as being alternative when conventional therapies are unfeasible, increasing herbal medicines demand and popularity.

Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of inflammatory bowel disease (IBD) including Crohn’s disease. Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation. This review focuses on the role of UPR in the pathogenesis in IBD from an immunologic perspective. The roles of macrophage and mesenchymal cells in the UPR from in vitro and in vivo animal models are discussed. The links between ER stress and other signaling pathways such as senescence and autophagy are introduced. Recent advances in the understanding of the epigenetic regulation of UPR signaling are also updated here. The future directions of development of the UPR research and therapeutic strategies to manipulate ER stress levels are also reviewed.

Numerous cases and a shortage of resources usually limit wild animal rescue. New technology implemented might save these severely injured wild animals from the situation of euthanasia by easing the requirement of intensive medication. Three-dimensional (3D) technologies provide precise and accurate results that improve the quality of the medical application. These 3D tools have become relatively low-cost and accessible in the past years. In the medical field of exotic animal, turtle shell defect is highly challenging because of inevitable water immersion. This report is the first attempt to apply the combination of 3D scanning, computer-aid design (CAD), and 3D printing to make a protective device that frees the wound from exposure to water or infection sources. The presenting techniques successfully extricate a wild freshwater turtle from an extensive shell defect within a short period. Integration of multiple sciences to 3D technology can provide a facile model for veterinary medical applications.

In recent years, photobiomodulation (PBM) has been recognized as a physical therapy in wound management. Despite several published research papers, the mechanism underlying photobiomodulation is still not completely understood. The investigation about application of blue light to improve wound healing is a relatively new research area. Tests in selected patients evidenced a stimulation of the healing process in superficial and chronic wounds treated with a blue LED light emitting at 420 nm; a study in animal model pointed out a faster healing process in superficial wound, with an important role of fibroblasts and myofibroblasts. Here we present a study aiming at evidencing the effects of blue light on the proliferation and metabolism in fibroblasts and keratinocytes. Different light doses were used to treat the cells, evidencing inhibitory and stimulatory effects. Electrophysiology was used to investigate the effects on membrane currents, while Raman spectroscopy revealed the mitochondrial Cytochrome C (Cyt C) oxidase dependence on blue light irradiation. In conclusion, we observed that the blue LED light can be used to modulate the activity of human fibroblasts, and the effects in wound healing are particularly evident when studying the fibroblasts and keratinocytes co-cultures.

A sustainable solution for crack maintenance in geopolymers is necessary if they are to be the future of modern green construction. This study thus aimed to develop self-healing biogeopolymers that could potentially rival bioconcrete. First, a suitable healing agent was selected from Bacillus subtilis, B. sphaericus, and B. megaterium by directly adding their spores in the geopolymers and subsequently exposing them to a large amount of nutrients for 14 days. SEM-EDX analysis revealed the formation of biominerals for B. subtilis and B. sphaericus. Next, the effect of biochar-immobilization and co-culturing (B. sphaericus and B. thuringiensis) on the healing efficiencies of the geopolymers were tested and optimized by measuring their ultrasonic pulse velocities weekly over a 28-day healing period. The results show that using co-cultured bacteria significantly improved the observed efficiencies, while biochar-immobilization had a weak effect but yielded an optimum response between 0.3-0.4 g/mL. The maximum crack width sealed was 0.65 mm. Through SEM-EDX and FTIR analyses, the biominerals precipitated in the cracks were identified to be mainly CaCO3. Furthermore, image analysis of the XCT scans of some of the healed geopolymers confirmed that their pulse velocities were indeed improving due to the filling of their internal spaces with biominerals. With that, there is potential in developing self-healing biogeopolymers using biochar-immobilized spores of bacterial cultures.

: Over time, we have come to recognize a very complex network of physiological changes enabling wound healing. An immunological process enables the body to distinguish damaged cells and begin a cleaning mechanism by separating damaged proteins and cells with matrix metallopro-teinases, a complement reaction, and free radicals. A wide variety of cell functions help to rebuild new tissue, dependent on energy provision and oxygen supply. Like in an optimized "biorector," disturbance can lead to prolonged healing. One of the earliest investigated local factors is the pH of wounds, studied in close relation to the local perfusion, oxygen tension, and lactate concentration. Granulation tissue with the wrong pH can hinder fibroblast and keratinocyte division and pro-liferation, as well as skin graft takes. Methods for influencing the pH have been tested, such as occlusion and acidification by the topical application of acidic media. In most trials, this has not changed the wound's pH to an acidic one, but it has reduced the strong alkalinity of deeper or chronic wound. Energy provision is essential for all repair processes. New insights into the metabolism of cells have changed the definition of lactate from a waste product to an indispensable energy provider in normoxic and hypoxic conditions. Neovascularization depends on oxygen provision and lactate, signaling hypoxic conditions even under normoxic conditions. An appropriate pH is necessary for successful skin grafting; hypoxia can change the pH of wounds. This review describes the close interconnections between the local lactate levels, metabolism, healing mechanisms, and pH. Furthermore, it analyzes and evaluates the different possible ways to support metabolism, such as lactate enhancement and pH adjustment. The aim of wound treatment must be the optimization of all these components. Therefore, the role of lactate and its influence on wound healing in acute and chronic wounds will be assessed.

Ulmus species have been widely used in Korean folk medicine because of their anti-inflammatory and antimicrobial properties. We intended to investigate the wound healing effect of the powder of Ulmus parvifolia (UP) root bark in a mouse wound healing model. We also determined the mechanisms of effects of Ulmus parvifolia (UP) in skin and skin wound healing effect using keratinocyte model. in vivo experiments showed that the wound lesions in the mice decreased by U. parvifolia with 200 mesh size of root bark powder and significantly reduced by treatment with UP, compared with those treated with U. macrocarpa (UM). Results from in vitro experiments also revealed that UP extract promoted the migration of human skin keratinocytes. UP powder treatment upregulated the expression of the matrix metalloproteinase-2 and -9 protein and significantly increased transforming growth factor (TGF)-β levels. We confirmed that topical administration of the bark powder of exerted a significant effect on skin wound healing by upregulating the expression of MMP and transforming growth factor-β. TGF-β In, Our study suggests that U. parvifolia may be a potential candidate for skin wound healing including epidermal skin rejuvernation.

Bacterial infections occur when wound healing fails to reach the final stage of healing, usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site accompanied very often by an increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies, such as polymers, scaffolds, films and wound dressings, organic and inorganic nanoparticles, to combat infection and modulate the healing rate have been discussed as well. New technologies such as CRISPR-Cas are taken into consideration as potential future tools for AMP delivery in skin therapy.

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diaminopyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against Methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent.

Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes, and significantly increased the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.

Wound healing is a process through which skin maintains itself. Once a wound occurs, the inflammatory and proliferative stages are instigated in reaction to injury. It is established that wound restorative comprises four stages including haemostasis, inflammation, proliferation, and remodeling. The amelioration of wound healing is very challenging as tumors can develop at the site of chronic injury. There are numerous plants, plant extracts and plant based natural products were widely used by tribal communities from ancient times for the treatment of cuts, burns, scars, burns and wounds. The therapeutic potential of these plants is recognized due to the presence of phytomolecules such as phenolic compounds, flavonoids, triterpenoids, saponins, tannins, alkaloids and glycosides. The plant used for the treatments of wound healing includes Achillea millefolium, Andrographis paniculata, Boswellia sacra, Calendula officinalis, Crocus sativus, Curcuma longa, Ehretia laevis, Ehretia microphylla, Glycyrrhiza glabra, Malva sylvestris, Rosmarinus officinalis and Salvia officinalis. This assemblage comprises the structures of phytomolecules isolated from the different extracts of these plants, mechanistic insights and important key findings responsible for wound healing. The mechanistic insights involved in wound healing are similar to cytotoxic, anti-inflammatory and antioxidant agents such as ROS generation, DNA fragmentation and western blotting. This review article is an effort to bridge the gaps in the prevailing literature and thus offers gigantic scope for researchers and academicians betrothed in validation of the customary claims and development of safer and efficient and worldwide recognized natural potential candidates as drugs for healing of wounds, burns and cuts.

Herein, we report results of the study of the composite ferroelectric scaffolds based on vinylidene fluoride-tetrafluoroethylene copolymer (VDF-TeFE) and polyvinylpyrrolidone (PVP) produced by electrospinning and their application as a wound-healing material. The physicochemical properties of ferroelectric composite polymer scaffolds depending on the content of PVP (in the range from 0 to 50 wt %) including morphology, composition and crystalline structure were studied. The cytotoxicity of materials and the proliferative activity of cells during their cultivation on the surface of formed scaffolds are reported. It has been found that the optimal PVP content in the VDF-TeFE composite scaffolds is 15 wt%. On a model of a full-thickness contaminated wound in vivo, it was shown that piezoelectric scaffolds based on VDF-TeFE copolymer containing 15 wt% PVP provide better wound healing results in comparison with standard gauze dressings impregnated with a solution of an antibacterial agent.

The human papillomavirus (HPV) type 16 E7 oncogene is critical to carcinogenesis and highly conserved. Previous studies identified a preponderance of non-synonymous E7 variants amongst HPV16-positive cancer-free controls compared to those with cervical cancer. To investigate the function of E7 variants, we constructed full-length HPV16 E7 genes and tested variants at positions H9R, D21N, N29S, E33K, T56I, D62N, S63F, S63P, T64M, E80K, D81N, P92L, and P92S (found only in controls); D14E, N29H (CIN2), and P6L, H51N, R77S (CIN3). We determined the steady-state level of cytoplasmic and nuclear HPV16 E7 protein. All variants from the controls showed a reduced level of steady-state E7 protein, with 7/13 variants having deficient protein levels. In contrast, 2/3 variants from the CIN3 precancer group had near-normal E7 levels. We assayed the activity of representative variants in stably transfected NIH3T3 cells. The H9R, E33K, P92L, and P92S variants found in control subjects had lower transforming activity than D14E and N29H variants (CIN2); and the R77S (CIN3) had activity only slightly reduced from wildtype E7. In addition, R77S and WT E7 caused increased migration of NIH3T3 cells in a wound-healing assay as compared with H9R, E33K, P92L, and P92S (controls) and D14E (CIN2). These data provide evidence that the E7 variants found in HPV16-positive cancer-free women are partially defective for transformation and cell migration further demonstrating the importance of fully active E7 in clinical cancer development.

Contact-based co-culture of fibroblasts and keratinocytes is important to study the structure and functions of the wound bed. Co-culture of these two cell types in direct contact with each other has been challenging, requiring high serum concentrations (up to 10%), feeder systems and a range of supplemental factors. These approaches are not only technically demanding, but also present scientific, cost and ethical limitations associated with high-serum concentrations. We have developed two reduced-serum approaches (1-2%) to support contact-based co-culture of human dermal fibroblasts (HDFa) and human epidermal keratinocytes (HaCaT). The two approaches include (1) Specialized cell culture media for each cell type mixed in a 1:1 ratio (KGM+FGM), and (2) Minimal media supplemented with cell-specific growth factors (MEM+GF). Co-culture could be successfully achieved by co-seeding (two cell types were introduced simultaneously), or in a layered fashion (keratinocytes seeded on top of confluent fibroblasts). With wound scratch assays, the co-cultured platforms could demonstrate cell proliferation, migration and wound closure. The reduced-serum conditions developed are simple, easy to formulate and adopt, and based on commonly-available media components. These contact-based co-culture approaches can be leveraged for wound and skin studies, and tissue bioengineering applications, potentially reducing concerns with high-serum formulations.

The prevalence for chronic, non-healing skin wounds in the general population, most notably diabetic foot ulcers, venous leg ulcers and pressure ulcers, is approximately 2% and is expected to increase, driven mostly by an aging population and the steady rise in obesity and diabetes. Non-healing wounds often become infected, increasing the risk of life-threatening complications, which poses a significant socioeconomic burden. Aiming at an improved management of infected wounds, a variety of wound dressings incorporating antimicrobials (AMDs), namely polyhexanide (poly(hexamethylene biguanide); PHMB), have been introduced in the wound care market. However, many wound care professionals agree that none shows comprehensive and optimal antimicrobial activity. This manuscript summarizes and discusses studies on novel PHMB-releasing membranes (PRMs) for wound dressings, detailing their preparation, physical properties relevant in the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall effi-cacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.their preparation, physical properties relevant in the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall efficacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.

Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodeling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants. In this review, we will examine how certain strategies that specifically target and activate mast cells can be used to treat and resolve infections, augment vaccines and heal wounds. Although these strategies may be protective in certain circumstances, mast cells activation may be deleterious if not carefully controlled and any therapeutic strategy using mast cell activators must be carefully explored.

Background: Recently, the management of musculoskeletal disorders with the patients' own stem cells, isolated from the walls of small blood vessels, which can be found in great numbers in the adipose tissue, has received considerable attention. On the other hand, there are still misconceptions about these adipose-derived regenerative cells (ADRCs) that contain vascular-associated pluripotent stem cells (vaPS cells) in regenerative medicine. Methods: Based on our previous publications on this topic, we have developed a concept to describe the significance of the ADRCs/vaPS cells in the field of orthobiologics as briefly as possible and at the same time as precisely as possible. Results: The ADRCs/vaPS cells belong to the group of orthobiologics that are based on autologous cells. Because the latter can both stimulate a patient’s body's localized self-healing power and provide new cells that can integrate into the host tissue during the healing response when the localized self-healing power is exhausted, this group of orthobiologics appears more advantageous than cell-free orthobiologics and orthobiologics that are based on allogeneic cells. Within the group of orthobiologics that are based on autologous cells, enzymatically isolated, uncultured ADRCs/vaPS cells have several advantages over non-enzymatically isolated cells/microfragmented fat as well as over uncultured bone marrow aspirate concentrate and cultured cells (adipose-derived stem cells, bone marrow-derived mesenchymal stem cells). Conclusions: The use of ADRCs/vaPS cells can be seamlessly integrated into modern orthopedic treatment concepts, which can be understood as the optimization of a process which - albeit less efficiently - also takes place physiologically. Accordingly, this new safe and effective type of treatment is attractive in terms of holistic thinking and personalized medicine.

Vimentin has been reported to play diverse roles in cell processes such as spreading, migration, and cell-matrix adhesion. Here, we use vimentin knock out cells (Vim KO) to assess how vimentin impacts cell spreading, morphology, and myofibroblast transformation of human corneal fibro-blasts. Overall, loss of vimentin did not significantly impact corneal fibroblast spreading, as indicated by Vim KO morphology and mechanical activity (traction force). However, we found that Vim KO cells had reduced elongation in response to PDGF as compared to controls. Furthermore, absence of vimentin did not completely block TGFβ induced myofibroblast transformation, since αSMA protein expression was detected in Vim KO cells. Nonetheless, the degree of transformation and amount of αSMA protein was reduced as compared to control cells. Proteomics showed that Vim KO cells cultured in TGFβ had a similar pattern of protein expression as controls. One exception included periostin, an ECM protein associated with wound healing and fibrosis in other cell types, which was highly expressed only in Vim KO cells. We also demonstrate for the first time that LRRC15, a protein previously associated with myofibroblast transformation of cancer-associated fibroblasts, is also expressed by corneal myofibroblasts. Overall, our data shows that vimentin has a limited, yet measurable impact on corneal fibroblast spreading and myofibroblast transformation. We also identified novel proteins that may regulate corneal myofibroblast transformation in the presence and/or absence of vimentin.

Chemical composition analysis of açaí extracts revealed higher levels of total polyphenol content in purple açaí samples for both commercial (4.3 – 44.7 gallic acid equivalents mg/g) and non-commercial samples (30.2 – 42.0 mg/g) compared to white (8.2 – 11.9 mg/g) and oil samples (0.8 – 4.6 mg/g). The major anthocyanin compounds found in purple açaí samples were cyanidin-3-glucoside and cyanidin-3-rutinoside with total concentrations in the range of 3.6 – 14.3 cyanidin-3-glucoside equivalents mg/g. The oligomeric proanthocyanidins were quantified in the range of 1.5 – 6.1 procyanidin B1 equivalents mg/g. Moreover, açaí presented significant levels of calcium, magnesium, manganese, iron, zinc and copper, essential minor and trace elements, in comparison with other berries. All of the açaí extracts at 50 μg/mL potently inhibited the release of reactive oxygen species in lipopolysaccharide-stimulated RAW 264.7 macrophage cells, but none inhibited the release of nitric oxide. Furthermore, all the açaí samples demonstrated potential as wound healing agents due to the high levels of migration activity in human fibroblast cells.

Based on its large surface area and covering the whole human body, the skin body’s largest organ and its main function is protection. Injuries and wound healing involving the skin offer valuable lessons shared with and of relevance to other organ systems and the diseases that impact them. Arguably the most complex human body process, wound healing is a multifaceted process that involves multiple cells and the extracellular matrix (ECM), with each component playing a specific role in the different stages of the healing process. Importantly, studies indicate that cells with stem cell-like properties are present within many of the human tissues and play key roles in case of tissue and cellular injury. Cell-to-cell and cell-to-ECM interactions are salient in wound healing subsequent to an injury. Microenvironment related factors and the variations therein including hypoxia or the abundance of oxygen, the presence/absence of growth factors and cytokines add to the complexity of the wound healing process and impact cell function and result in compromised or enhanced wound healing. This expert review critically examines the advances in biochemical and analytical tools that are enable the analysis of numerous cells and molecules within the wound microenvironment, revealing great cellular heterogeneity as well as novel molecular targets of importance to enhance wound healing. In a broader angle, we emphasize the ways in which wound healing is significant in the search for perfect skin after injury and in many common complex human diseases including cancer. In all, wound healing is a centrepiece of integrative biology research and applications in medicine as well as dermatology as discussed in this review.

Background: In 2014 the World Health Organization (WHO) warned of an emerging world-wide crisis of antibiotic resistant microorganisms. In response, government and professional organizations recommended that health care systems adopt antimicrobial stewardship programs (ASPs). In the United States, the Centers for Medicare Services (CMS) mandated antimicrobial stewardship in the hospital inpatient setting. Effective January 1, 2020, the Joint Commission required ambulatory centers that prescribe antibiotics, such as wound centers, to institute an ASP. Chronic wounds often remain open for months, during which time patients may receive multiple courses of antibiotics and numerous antimicrobial topical treatments. The wound clinician plays an integral role in reducing antimicrobial resistance in the outpatient setting: antibiotics prescribed for skin and soft tissue infections are among the most common in an outpatient setting. One of the most challenging aspects of antimicrobial stewardship in treating chronic wounds is the inaccuracy of bacterial and infection diagnosis. Methods: Joint Commission lists five elements of performance (EP): (1) Identifying an antimicrobial stewardship leader, (2) establishing an annual antimicrobial stewardship goal, (3) implementing evidence-based practice guidelines related to the antimicrobial stewardship goal, (4) providing clinical staff with educational resources related to the antimicrobial stewardship goal, and (5) collecting, analyzing, and reporting data related to the antimicrobial stewardship goal. This article focuses on choosing and implementing an evidence-based ASP goal for 2020. Discussion: Clinical trials have demonstrated the ability of fluorescence imaging (MLiX) to detect clinically significant levels of bacteria in chronic wounds. Combined with clinical examination of signs and symptoms of infection, the MLiX procedure improves the clinician’s ability to diagnose infection and can guide antimicrobial use. In order to satisfy the elements of performance, the MLiX procedure was incorporated into the annual ASP goal for several wound care centers. Clinicians were educated on the fluorescence imaging device and guidelines were instituted. Collection of antimicrobial utilization data is underway.

Despite being under development for decades, RNA therapeutics have only recently emerged as viable platform technologies. The COVID-19 mRNA vaccines have demonstrated the promise and power of the platform technology. In response, novel RNA drugs are entering clinical trials at an accelerating rate. As the skin is the largest and most accessible organ, it has always been a preferred target for drug discovery. This holds true for RNA therapies as well, and multiple candidate RNA-based drugs are currently in development for an array of skin conditions. In this mini review, we catalog the RNA therapies currently in clinical trials for different dermatological diseases. We summarize the main types of RNA-related drugs and use examples of drugs currently in development to illustrate their key mechanism of action.

Background : Diabetic wounds are very easy to experience complications in the form of infection due to bacterial invasion, and sugar conditions blood which tall encourage the growth of bacteria.Bacteria that can cause infection in diabetic wounds wrong one is staphylococci aureus . Wound diabetes can treated with honey. Honey contains antibacterial , antioxidant and hydrogen peroxide properties that help kill bacteria dangerous. Objective : The purpose of this study was to determine the effect of the wound dressing contains honey against bacterial colonization Staphylococcus aureus on wound diabetic . Methods : The research design used is pre-experimental with o ne-group pre-test and post-test design . Sampling method using consecutive sampling as many as 7 respondents. Results : Analysis data use test dependent t-test and obtained score p value 0.000 ( p value < = 0.05), so could concluded there is influence care wound use honey to colonization bacteria Staphylococcus aureus in wounds diabetic Diabetes Mellitus patients in the region work Public health center Banjarmasin . Conclusion : best Use honey as product care wound because nature the antibacterial which could prevent infection and speed up process healing wound .

Dysregulation of the arsenal of cells, growth factors, cytokines, proteases, and proteins involved in wound healing (WH), could delay the healing process. Plants and plant-derived molecules (PDMs) have been used as medicines for skin wounds. This study aimed to select and evaluate the pro-healing capacity of PMDs. Thirty-three PDMs and 10 therapeutic targets (TTs) were chosen for molecular docking and PDMs: aristolochic acid (AA), α-copaene, selinenes, β-caryophyllene (BC), and BCoxide, and TTs: metalloproteinase (MMP) 3, MMP13, and tumor necrosis factor (TNF α) for molecular dynamics. The bests inhibitor was AA, but because of its toxicity, BC and BCoxide were chosen for evaluation in HaCat cells and BALB/c mice excisional model. Both compounds were not toxic, and higher percentages of lesion area closure (LAC) were induced by BC treatment (p<0.05). All mice healed; however, an initial delay of LAC was induced by 0.05, 0.1% BCoxide, 0.1% BC, and allantoin. At the end of treatment, lower numbers of mast cells, level of cellular infiltrates (except 1% BCoxide and 0.05, 0.5%BC), epidermal thickness tendency (except 0.1, 0.5% BCoxide), and higher values of SC-thickness, and collagen fibers only by 0.5% BC treatment compared with untreated control (p<0.05) were observed. Our results show that BC is a promising multitarget candidate for wound healing treatment and optimization campaigns.

Plantago major L. is a worldwide available plant that has been used traditionally for several medical application due to its properties such as wound healing, anti-inflammatory, antimicrobial etc. This work aimed to develop and evaluate nanostructured PCL electrospun dressing with P. major extract encapsulated in nanofibers for application in wound healing. The extract from leaves was obtained by extraction in a mixture of water:ethanol= 1:1 of the freeze-dried extract presented a minimum inhibitory concentration (MIC) for Staphylococcus Aureus susceptible and resistant to methicillin of 5.3 mg/mL, a high antioxidant capacity, but a low content of total flavonoids. Electrospun mats without defects were successfully produced using two P. major extract concentrations based on MIC value. The extract incorporation in PCL nanofibers was confirmed by FTIR and contact angle measurements. The PCL/P. major extract was evaluated by DSC and TGA demonstrating that incorporation of the extract decreases the thermal stability of the mats as well as the degree of crystallinity of PCL-based fibers. The P. major extract incorporation on electrospun mats produced a significant swelling degree (more than 400%) and increased the capacity of adsorbing wound exudates and moisture, important characteristics for skin healing. The extract-controlled release evaluated by in vitro study in PBS (pH, 7.4) shows that P. major extract delivery from the mats occurs in the first 24 h, demonstrating their potential capacity to be used in wound healing.

Supramolecular structures are of great interest due to their applicability in various scientific and industrial fields. These fields of scientific action include promising applications i biomedical areas, in sensing, and in conductive and electrical phases. The sensible definition of supramolecular molecules is being set by investigators, who, because of the different sensitivities of their methods and observational timescales, may have different views as to what constitute these supramolecular structures. Besides, diverse polymers can be found to offer unique avenues for multifunctional systems with properties in medicine industrial applications. Aspects of this review provide different conceptual strategies to address molecular design, properties, and potential applications of self-assembly materials and the use of metal coordination as a feasible and useful strategy for constructing complex supramolecular structures. In this order of appreciations and ideas order, it is that this review report involves classic topics such as hydrogels that range from their relationship with drug delivery systems, to metallo-supramolecular materials, through applications in ophthalmic systems, in applications that require adhesiveness and electrically conductive hydrogels. This review also addresses systems that are largely based on hydrogel chemistry and the enormous opportunities to design very specific structures for applications that demand enormous specificity.

Hydrogels prepared from natural polymer have attracted extensive attentions in biomedical fields such as drug delivery, wound healing, and regenerative medicine due to their good biocompatibility, degradability and flexibility. This review outlines the commonly used natural polymer in hydrogel preparation, including cellulose, chitosan, collagen/gelatin, alginate, hyaluronic acid and starch. The polymeric structure and process/synthesis of natural polymers are illustrated, and natural polymer-based hydrogels including the hydrogel formation and properties are elaborated. Subsequently, the biomedical application of hydrogels based on natural polymer in drug delivery, tissue regeneration, wound healing and other biomedical field is summarized. Finally, the future perspectives of natural polymers and hydrogels based on them are discussed. For natural polymer, novel technologies such as enzymatic and biological methods are developed to improve the structural properties and the development of new natural based polymers or natural polymer derivatives with high performance is still very important and challenging. For natural polymer-based hydrogels, novel hydrogel materials, like double-network hydrogel, multifunctional composite hydrogels and hydrogel microrobots are designed to meet the advanced requirements in biomedical application, and new strategies such as dual-crosslinking, microfluidic chip, micropatterning and 3D/4D bioprinting, have been explored to fabricate advanced hydrogel materials with designed properties for biomedical application. Overall, natural polymeric hydrogels have attracted increasing interests in biomedical application, and the development of novel natural polymer-based materials and new strategies/methods for hydrogel fabrication is badly desirable and still challenging.

Although research has long established that the interaction with the natural environment is associated with better overall health and well-being outcomes, the Western model mainly focuses on treating the symptoms. In Aotearoa-New Zealand, the Indigenous Māori have long demonstrated significantly more negative health outcomes than non-Māori. Little research has examined the causes compared to Western populations or the role of the natural environment in health outcomes for Māori. An exploration of rongoā Māori (traditional healing system) was conducted to ascertain the importance of landscape in the process of healing. Eight rongoā healers or practitioners took part in semi-structured narrative interviews from June to November 2020. Transcribed interviews were analysed using an interpretative phenomenological analysis and Kaupapa Māori techniques. The findings show how rongoā is underpinned by a complex set of cultural values and beliefs, drawing from the connection to wairua (spirit), tinana (body), tikanga and whakaora (customs and healing), rākau (plants), whenua (landscape) and whānau (family). Incorporating such constructs into the landscape can foster our understanding of health and well-being and its implications for conceptualising therapeutic environments and a culturally appropriate model of care for Māori and non-Māori communities.

Cold plasma (CP) is an ionised gas containing excited molecules and ions, radicals, free electrons, and emits electric fields and UV radiation. CP is potently antimicrobial and can be applied safely to biological tissue, birthing the field of plasma medicine. Reactive oxygen and nitrogen species (RONS) produced by CP affect biological processes directly or indirectly via the modification of cellular lipids, proteins, DNA, and intracellular signalling pathways. CP can be applied at lower levels for oxidative eustress to activate cell proliferation, motility, migration, and antioxidant production in normal cells, mainly potentiated by the unfolded protein response, Nrf2-activated antioxidant response element and PI3K/Akt pathway, which also activates NFκB. At higher CP exposures, inactivation, apoptosis and autophagy of malignant cells can occur via degradation of PI3K/Akt and MAPK-dependent and -independent activation of the master tumour suppressor p53, leading to caspase-mediated cell death. These opposing responses validate a hormesis approach to plasma medicine. Clinical applications of CP are becoming increasingly realised in wound healing, while clinical effectiveness in tumours is currently coming to light. This review will outline advances in plasma medicine and compare the main redox and intracellular signalling responses to CP in wound healing and cancer.

Chronic wounds are associated with considerable patient morbidity and present a significant economic burden to the healthcare system. Often, chronic wounds are in a state of persistent in-flammation and unable to progress to the next phase of wound healing. Placental-derived bio-materials are recognized for their biocompatibility, biodegradability, angiogenic, an-ti-inflammatory, anti-microbial, anti-fibrotic, immunomodulatory, and immune privileged prop-erties. As such, placental-derived biomaterials have been used in wound management for more than a century. Placental-derived scaffolds are composed of an extracellular matrix (ECM) that can mimic the native tissue, creating a reparative environment to promote ECM remodeling, cell migration, proliferation, and differentiation. Reliable evidence exists throughout the literature to support the safety and effectiveness of placental-derived biomaterials in wound healing. How-ever, differences in source (i.e., anatomical regions of the placenta), preservation techniques, decellularization status, design, and clinical application have not been fully evaluated. This re-view provides an overview of wound healing and placental-derived biomaterials, summarizes the clinical results of placental-derived scaffolds in wound healing, and suggests directions for future work.

The management of wounds is a significant issue that impacts individuals, healthcare systems, and society at large. This study evaluates Rigemed D (RD), a novel compound extracted from Bovine Colostrum with a unique combination of 20 different growth factors and exosomes, known for its exceptional properties in promoting cell proliferation and regeneration. This study aims to determine the effects of different doses of RD on cell survival (using CCK8) and to assess its antioxidant effect using the Comet assay in the presence of hydrogen peroxide (H2O2) on two human cell types, fibroblasts and immortalised keratinocytes (HaCat cell line). The study results revealed that RD, at doses of 1, 1.5, and 2 % v/v, significantly improved cell viability four, six, and 12 times, respectively, compared to the control group (p < 0.00001). Furthermore, the Comet assay showed a two-fold reduction in DNA damage in RD-treated cells at 2% v/v without and with H2O2 (p < 0.001). The effect of RD on cell proliferation and migration was evaluated using a scratch assay on fibroblasts and HaCat cells. The findings demonstrated a four-fold increase in cell proliferation and migration at 1 and 24 hours (p < 0.001). Immunohistochemistry confirmed this claim (p < 0.001). Also, angiogenesis induction of RD was assessed on human vein umbilical endothelial cells (HUVEC), showing that RD significantly enhanced the proliferation of endothelial HUVEC cells (p < 0.0001). In conclusion, RD is a promising vitalising compound with exceptional capabilities in promoting cell proliferation, migration, and regeneration. It also shows a significant antioxidant effect and has the potential to support all phases of wound healing involving cell proliferation, re-epithelialisation, angiogenesis, and tissue maturation. Hence, the present formulation presents a promising foundation for developing a 3D bio-printed membrane, potentially expediting the wound healing process.

The capability of radially polymerized bio-dendrimers and hyperbranched polymers for medical applications is well established. Among them, perhaps the most important are those that involve interactions with the regenerative mechanisms of cells. Dendritic polymers due to their distinctive architecture may play a multitude of roles such as protein biomimicry (collagen, elastin, hydroxy apatite production), gene and drug delivery (cell differentiation, antimicrobial protection), surface chemistry and charge modulation (adhesion to cells and tissues), polymer cross-linking (eye, skin and internal organ wound healing). The review highlights all the different categories of hard and soft tissues that may be remediated with their contribution. The reader will be also exposed to the incorporation methods to established biomaterials such as scaffolds, the functionalization strategies, and the synthetic paths for the assembly from biocompatible building blocks and natural metabolites.

Although a slight imbalance between oxidative and antioxidative mediators is part of normal physiology that enables cell aging and the removal of dead cells, burns disturb this equilibrium locally and systemically. Topical burn dressings may attenuate local and systemic oxidative stress and positively influence the post-burn clinical course. This review integrated knowledge regarding the impact of burn dressings on oxidative stress. Using keywords and in-text searches, literature was identified from PubMed, Google Scholar, and Google articles, and studies on local or topical applications of wound dressings and associated oxidative stress were selected. As im-balances between oxidative mediators and antioxidative agents significantly contribute to organ dysfunction and healing disturbance, we investigated oxidative stress on organs, metabolic changes, clinical results, and oxidative parameters influenced by applied dressings. We found positive local and systemic effects of external burn dressings in laboratory and animal tests; however, such studies were rare in humans. Nevertheless, we identified successful cases of semi-occlusive, occlusive, and biologically active dressings that reduce oxidative stress in hu-man burns. In particular, we highlight promising clinical and laboratory results from lac-tate-releasing dressings. Our review provides an invaluable resource for future development and clinical applications of burn dressings.

Background:This study evaluated the effect of low-level laser therapy on postoperative pain and wound healing in children undergoing primary molar extractions.Methods:40children,6-10years of age, systemically healthy, and had atraumatic extraction indications of bilateral primary molar teeth were included in the study. First session randomly selected tooth was extracted under local anesthesia. In the control group, only the clot formation on the socket was observed and photographed. Other group extraction's performed 2weeks later. The LLLT group treated with980nm wavelength Doctor Smile Wiser diode laser and photographed. Non-epithelialized surface measurements performed with the ImageJ program. Pain assessment was performed with Wong-Baker Pain Scale. Statistical analyzes were performed with SPSS software.Results: There was no statistically significant difference in Wong-Baker values(p&gt;0.05). The laser group had more '0' values on days 1 and7; same values as the control group were recorded on other days. In soft tissue healing 3rd day evaluations, non-epithelialized surface of laser socket was found to be smaller than control group, and measurement results were found to be statistically significant(p&lt;0.05). The other days' measurement results were not statistically significant(p&gt;0.05).Conclusions:Although LLLT not found to be very effective in reducing postoperative discomfort after extraction of primary molars, it provides better wound healing in extraction sockets.

Reducing the costs of repairing concrete structures damaged due to the appearance of cracks and reducing the number of people involved in the process of their repair is the subject of a multitude of experimental studies. Special emphasis should be placed on research involving industrial by-products, the disposal of which has a negative environmental impact, as is the case in the research presented in this paper. The basic idea was to prepare a mortar with added granulated blast furnace slag from Smederevo Steel Mill and then treat artificialy produced cracks with a Sporosarcina pasteurii DSM 33 suspension under the conditions of sterile demineralized and water from Danube river in order to simulate natural conditions. The results show a bio-stimulated healing efficiency of 32.02% in sterile demineralized water and 42.74% in Danube water already after 14 days. The SEM images clearly show calcium carbonate crystals as the main compound that has started to fill the crack, and the crystals are much more developed under the Danube water conditions. As a special type of research, microscopic images of cracks were classified into those with and without the presence of bacterial culture. By applying convolutional neural networks (ResNet 50), the classification success rate was 91.55%.

After surgery, oral cavity healing occurs in a hostile environment and requires proper oral care and hygiene to accelerate recovery. The aim of the current study is to investigate and compare the bioreactivity characteristics of chlorhexidine based (CHX) mouth rinse and a novel bone bioactive liquid (BBL) mouth rinse on oral healing within seven days application post-surgery. A randomized, double blind clinical trial conducted in 81 patients. The mouth rinses were applied twice a day for a period of 7 days. The visual analog scale (VAS) protocol was applied to measure pain index. Early wound healing score (EHI) was determined in evaluate the oral cavity healing progress. No adverse effects were observed using the mouth washes, but CHX resulted in teeth staining. CHX and BBL were sufficient to reduce pain over a period of 7 days. However, the BBL group demonstrated a statistically significant reduction in VAS stating day 4. Relative to CHX group, the EHI scores were significantly higher in the BBL group, independent from the tooth location. No gender differences were observed in both VAS and EHI scores. Relative to the commercially available CHX, BBL mouth rinse reduced pain and accelerated oral cavity healing. Suggesting an improvements of oral cavity microenvironment at the wound site that mediates soft tissue regeneration.

This study develops an efficient, low-temperature process for formulating a nanoemulsion-based gel encapsulating Pituranthos tortuosus's essential oil, investigating its wound healing potential. The novel process ensured stable encapsulation of the medicinal plant's oil. The nanoemulsion was characterized using dynamic light scattering and transmission electron microscopy, followed by in vitro and in vivo tests to examine wound healing efficacy. Results revealed the gel's excellent stability, high encapsulation efficiency, and significant wound-healing effects. This research provides a new method for formulating Pituranthos tortuosus's essential oil nanoemulsion-based gel, emphasizing the potential role of plant-based therapies in healthcare advancement, and invites further exploration into the therapeutic applications of essential oil-encapsulating nanoemulsions.

Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, like diabetic foot ulcers, have increased significantly in the last years due to the rise of an aging population. A better understanding of the infectious pathophysiological mechanisms is urgently needed along with new options for the treatment of wound infections and wound healing disorders. New advances in the preparation of biocompatible dressing materials that can be loaded with antimicrobial drugs may improve the topical treatment of infected wounds. In this study, we investigated the antimicrobial activity of polyvinylpyrrolidone (PVP) foils loaded with ciprofloxacin (Cipro-foils) in the presence of acetic acid as co-solvent. We used ex vivo human wounds that were infected with two bacterial strains: Methicillin-Resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PAO1). The effectiveness of the treatment was demonstrated by the quantification of the living bacteria extracted from the wound and the detection of released immunological mediators in skin extracts and in the skin culture media. We found that Cipro-foils effectively treated the infection with both PAO1 and MRSA. Other than PAO1, MRSA had not proteolytic effects. MRSA infections increased cytokines expression and release. Interestingly, treatment with Cipro-foils could partially counteract these effects.

Wound infection is a common complication of chronic wounds. It can impair healing, which may not occur without external help. Antimicrobial dressings (AMDs) are a type of external help to infected chronic wounds. In this study, highly porous membranes made of only chitosan and containing the antiseptic polyhexanide (poly(hexamethylene biguanide); PHMB) were prepared by cryogelation, aiming to be used in AMDs. These membranes exhibited high water swelling capacity, fast water absorption and high water vapor transmission. The best drug loading method involved simultaneous loading by soaking in a PHMB solution and sterilization by autoclaving, resulting in sterilized, drug-loaded membranes. The drug release kinetics was comparable to that of a commercial PHMB-releasing AMD assayed under the same conditions. These membranes exhibited high antibacterial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are bacterial species commonly found in infected wounds, and blood clotting activity. The obtained results suggest that these membranes may be suitable for use in the development of AMDs.

Wounds represents a medical problem that contribute importantly to patient morbidity and to the healthcare costs in several pathologies. In Hidalgo, Mexico, Bacopa procumbens plant has been traditionally used for wound healing care for several generations; in vitro and in vivo experiments were design to evaluate the effects of bioactive compounds obtained from B. procumbens aquoethanolic extract and to determine the key pathways involved in wound regeneration. Bioactive compounds were characterized by HPLC- QTOF-MS and proliferation, migration, adhesion, and differentiation studies were done on NIH/3T3 fibroblasts. Polyphenolic compounds from Bacopa procumbens (PB) regulated proliferation and cell adhesion; enhanced migration reducing the artificial scratch area; and modulated cell differentiation. PB compounds were included in a hydrogel for topical administration on rat excision wound model. Histological, histochemical and mechanical analysis showed that PB treatment accelerates wound closure in at least 48 h; reduce inflammation, increasing cell proliferation and deposition and organization of collagen in earlier times. These changes resulted in the formation of a scar with better tensile properties. Immunohistochemistry and RT-PCR molecular analyses demonstrated that treatment induces: i) overexpression of transforming growth factor beta (TGF-β); and ii) the phosphorylation of Smad 2/3 and ERK1/2, suggesting the central role of some PB to enhance wound healing, modulating TGF-β activation.

Developing novel wound dressings containing medicinal plant extracts can have several potential benefits, including improving the therapeutic value of the dressings and reducing the cost of producing wound dressings. In this study, we prepared foam dressing containing Eclipta prostrata leaf extract and gelatin (Eclipta prostrata dressing). Chemical composition was verified using Fourier transform infrared spectroscopy (FTIR), and pore structure was obtained by scanning electron microscopy (SEM). The physical properties, including absorption and dehydration properties, were also evaluated. The chemical properties were measured to determine the pH environment after being submerged with Eclipta prostrata dressings. The results revealed that the Eclipta prostrata dressing had a pore structure with an appropriate pore size (313.25 ± 76.51 µm and 383.26 ± 64.45 µm for the Eclipta prostrata A and Eclipta prostrata B dressings, respectively). The Eclipta prostrata B dressing was more consistent porosity, resulting in a higher absorption capacity and faster dehydration rate. According to physical properties, the Eclipta prostrata B dressing is best used on low-exuding wounds. Furthermore, the Eclipta prostrata A and B dressings make a slightly acidic environment. Therefore, our foam dressing will not interfere wound healing process.

Plant extracts have been evaluated to determine their bioactivities and their potential use in wound healing. In this study, a conductive composite material, based on graphene oxide (GO), nanocellulose (CNF) and tannins (TA) from pine bark, reduced using polydopamine (PDA), was developed for wound dressing. The amount of CNF and TA was varied in the composite material and a complete characterization including SEM, FTIR, XRD, XPS, TGA was performed. Also, the conductivity, mechanical properties, cytotoxicity, and in vitro wound healing of the materials were evaluated. The results showed a successful physical interaction between CNF, TA and GO. In-creasing the CNF amount in the composite reduced the thermal properties, surface charge and conductivity of the material, but its strength, cytotoxicity and wound healing performance were improved. The TA incorporation slightly reduced the cell viability and migration, which may be associated with the doses used and the chemical composition of the extracts. However, the in vitro obtained results demonstrated that these composite materials can be suitable for wound healing.

Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury termed the response to injury wound healing (RTIWH) mechanism. When injured, regional brain endothelial cells initially undergo activation and dysfunction with initiation of hemostasis, inflammation (peripheral leukocytes and innate microglia and perivascular macrophage cells), proliferation (astrogliosis), remodeling, repair, and resolution phases if the injurious stimuli are removed. In conditions wherein the injurious stimuli are chronic as occurs in obesity, metabolic syndrome, and type 2 diabetes mellitus this process does not undergo resolution and there is persistent RTIWH with remodeling. Indeed, the brain is unique, in that it utilizes its neuroglia: the microglia cell along with peripheral inflammatory cells and its astroglia instead of peripheral scar-forming fibrocytes/fibroblasts. The brain undergoes astrogliosis to form a gliosis scar instead of a fibrosis scar to protect the surrounding neuropil from regional parenchymal injury. One of the unique and evolving remodeling changes in the brain is the development of enlarged perivascular spaces (EPVS), which is the focus of this brief review. EPVS are important since they serve as a biomarker for cerebral small vessel disease and also represent an impairment of the effluxing glymphatic system that is important for the clearance of metabolic waste from the interstitial fluid to the cerebrospinal fluid and disposal. Therefore, it is important to better understand how the RTIWH mechanism is involved in the development of EPVS that are closely associated with and important to the development of premature and age-related cerebrovascular and neurodegenerative diseases with impaired cognition.

Tissue regeneration is an essential requirement for wound healing and recovery of organs’ dysfunction. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium. In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity in a concentration-dependent manner. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated by topical application of ERCM solution (4 x 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. The results indicate that ERCM from AMSCs containing a large amount of GFs and NFs improve wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production.

Medicinal plants for bone grafts are promising because they are free from infecting microorganisms and biocompatible. We report a novel study evaluating osteoregeneration of bone grafts from extracts of Alternanthera brasiliana and Fridericia platyphylla after bone injury induced by radius fracture in rats. Grafts were obtained using 2% chitosan gel and 0.5% hydroalcoholic extract. The rats were randomly divided into four experimental groups (N= 12): Negative control (NC) - Chitosan gel; Positive control (PC) - bovine mineral bone graft (Lumina Bone®, fine powder 0.5); F. platyphylla Graft (FRID) - 0.5% bone graft; A. brasiliana Graft (ABRA) - 0.5% bone graft. The animals were evaluated for three periods, 30, 60, and 90 days after fracture induction. Bone alkaline phosphatase (BSAP) and radiographic and histological evaluations were followed. After 90 days, there was an increase in BSAP for the ABRA group on the newly formed bone matrix but not for FRID, indicating the presence of active osteoblasts. Additionally, mature bone tissue and bone remodeling were observed, and a conspicuous presence of type I collagen for both FRID and ABRA. We demonstrated that FRID and ABRA grafts produced early bone neoformation. New perspectives for these species as a graft are suggested.