Cell Viability Assessment of PEDOT Conducting Polymer-Coated Microneedles for Skin Sampling.

Recently, transdermal monitoring and drug delivery have gained much interest, owing to the introduction of the minimally invasive microneedle (MN) device. The advancement of electroactive MNs electrically assisted in the capture of biomarkers or the triggering of drug release. Recent works have combined conducting polymers (CPs) onto MNs owing to the soft nature of the polymers and their tunable ionic and electronic conductivity.

PEDOT coated microneedles towards electrochemically assisted skin sampling.

Skin sampling is a diagnostic procedure based on the analysis of extracted skin tissues and/or the observation of biomarkers in bodily fluids. Sampling using microneedles (MNs) that minimize invasiveness is gaining attention over conventional biopsy/blood lancet. In this study, new MNs for electrochemically assisted skin sampling are reported, specifically tailored for combined skin tissue biopsy and interstitial fluid (ISF) extraction.

Collagen Functionalization of Polymeric Electrospun Scaffolds to Improve Integration into Full-Thickness Wounds.

Background: Electrospun fibers are widely studied in regenerative medicine for their ability to mimic the extracellular matrix (ECM) and provide mechanical support. In vitro studies indicated that cell adhesion and migration is superior on smooth poly(L-lactic acid) (PLLA) electrospun scaffolds and porous scaffolds once biofunctionalized with collagen.

Methods: The in vivo performance of PLLA scaffolds with modified topology and collagen biofunctionalization in full-thickness mouse wounds was assessed by cellular infiltration, wound closure and re-epithelialization and ECM deposition.

The development of microfluidic-based western blotting: Technical advances and future perspectives.

Over the past two decades significant technical advancement in the field of western blotting has been made possible through the utilization of microfluidic technologies. In this review we provide a critical overview of these advancements, highlighting the advantages and disadvantages of each approach. Particular attention is paid to the development of now commercially available systems, including those for single cell analysis.

Plasma-Functionalised Dressings for Enhanced Wound Healing.

Fundamental knowledge about cell-surface interactions can be applied in the development of wound dressings and scaffolds to encourage wounds to heal. As surfaces produced with acid-functionalised monomers encourage keratinocyte adhesion, proliferation and migration, whilst amine functionalisation enhances fibroblast proliferation and migration in vitro, standard care wound dressings were plasma-coated with either acrylic acid or allylamine and applied to 6 mm excisional wounds on the backs of mice to test their effectiveness in vivo. At day 3, the rate of wound healing was increased in mice treated with dressings that were plasma-coated with allylamine compared to uncoated dressings, with a significantly reduced wound area.

Influence of Acidic pH on Wound Healing In Vivo: A Novel Perspective for Wound Treatment.

There has been little understanding of acidification functionality in wound healing, highlighting the need to study the efficacy of wound acidification on wound closure and cellular activity in non-infected wounds. This study is focused on establishing the healing potential of wound acidification in non-infected wounds. Acidic buffers, constituting either phosphoric or citric acid, were employed to modify the physiological pH of non-infected full-thickness excisional murine wounds.

Wound Healing from an Actin Cytoskeletal Perspective.

Wound healing requires a complex cascade of highly controlled and conserved cellular and molecular processes. These involve numerous cell types and extracellular matrix molecules regulated by the actin cytoskeleton. This microscopic network of filaments is present within the cytoplasm of all cells and provides the shape and mechanical support required for cell movement and proliferation.

Increased Expression of Flightless I in Cutaneous Squamous Cell Carcinoma Affects Wnt/β-Catenin Signaling Pathway.

Cutaneous squamous cell carcinoma (cSCC) accounts for 25% of cutaneous malignancies diagnosed in Caucasian populations. Surgical removal in combination with radiation and chemotherapy are effective treatments for cSCC. Nevertheless, the aggressive metastatic forms of cSCC still have a relatively poor patient outcome.

Overexpression of during Murine Embryonic Development Increases Symmetrical Division of Epidermal Progenitor Cells.

Epidermal progenitor cells divide symmetrically and asymmetrically to form stratified epidermis and hair follicles during late embryonic development. Flightless I (Flii), an actin remodelling protein, is implicated in Wnt/β-cat and integrin signalling pathways that govern cell division. This study investigated the effect of altering Flii on the divisional orientation of epidermal progenitor cells (EpSCs) in the basal layer during late murine embryonic development and early adolescence.

Multifunctional ultrasmall AgNP hydrogel accelerates healing of S. aureus infected wounds.

The increasing emergence of antibiotic resistance coupled with the limited effectiveness of current treatments highlights the need for the development of new treatment modalities. Silver nanoparticles (AgNPs) are a promising alternative with broad-spectrum antibacterial activity. However, the clinical translation of AgNPs have been hampered primarily due to the delivery of unsafe levels of silver ions (Ag) resulting in cellular toxicity and their susceptibility to aggregation resulting in loss of efficacy.

Treatment of murine partial thickness scald injuries with multipotent adult progenitor cells decreases inflammation and promotes angiogenesis leading to improved burn injury repair.

Stem cells have been shown to have potential as a new therapy for burns and promote wound healing through decreasing inflammation and increasing angiogenesis. Multipotent adult progenitor cells (MAPC® cells) are a subpopulation of bone marrow-derived stem cells with outstanding self-renewal and differentiation capacity. MAPC cells also secrete a wide range of cytokines which can affect cellular activities.

Multifunctional Roles of the Actin-Binding Protein Flightless I in Inflammation, Cancer and Wound Healing.

Flightless I is an actin-binding member of the gelsolin family of actin-remodeling proteins that inhibits actin polymerization but does not possess actin severing ability. Flightless I functions as a regulator of many cellular processes including proliferation, differentiation, apoptosis, and migration all of which are important for many physiological processes including wound repair, cancer progression and inflammation. More than simply facilitating cytoskeletal rearrangements, Flightless I has other important roles in the regulation of gene transcription within the nucleus where it interacts with nuclear hormone receptors to modulate cellular activities.

Systemic Delivery of Anti-Integrin αL Antibodies Reduces Early Macrophage Recruitment, Inflammation, and Scar Formation in Murine Burn Wounds.

Increased macrophage recruitment in the early stages of wound healing leads to an excessive inflammatory response associated with elevated fibrosis and scarring. This recruitment relies upon integrins on the surface of monocytes that regulate their migration and extravasation from the circulation into the wound site, where they differentiate into macrophages. The aim of this study was to determine if inhibiting monocyte extravasation from the circulation into burns would reduce macrophages numbers in burns and lead to reduced inflammation and scar formation.

Attenuation of Flightless I Increases Human Pericyte Proliferation, Migration and Angiogenic Functions and Improves Healing in Murine Diabetic Wounds.

Pericytes are peri-vascular mural cells which have an important role in the homeostatic regulation of inflammatory and angiogenic processes. Flightless I (Flii) is a cytoskeletal protein involved in regulating cellular functions, but its involvement in pericyte activities during wound healing is unknown. Exacerbated inflammation and reduced angiogenesis are hallmarks of impaired diabetic healing responses, and strategies aimed at regulating these processes are vital for improving healing outcomes.

Human multipotent adult progenitor cell-conditioned medium improves wound healing through modulating inflammation and angiogenesis in mice.

Background: Stem cell therapies have been widely investigated for their healing effects. However, the translation of these therapies has been hampered by the requirement to deliver live allogeneic or autologous cells directly to the wound in a clinical setting. Multipotent adult progenitor cells (MAPC® cells) are a subpopulation of bone marrow-derived adherent stem cells that secrete a wide range of factors known to accelerate the wound healing process.

Collagen-functionalized electrospun smooth and porous polymeric scaffolds for the development of human skin-equivalent.

Electrospun polymer fibers have garnered substantial importance in regenerative medicine owing to their intrinsic 3D topography, extracellular matrix microenvironment, biochemical flexibility, and mechanical support. In particular, a material's nano-topography can have a significant effect on cellular responses, including adhesion, proliferation, differentiation, and migration. In this study, poly(l-lactic acid) (PLLA), a biodegradable polymer with excellent biocompatibility was electrospun into fibers with either smooth or porous topologies.

Effect of Flightless I Expression on Epidermal Stem Cell Niche During Wound Repair.

Activation of epidermal stem cells (EpSCs) from their quiescent niche is an integral component of wound reepithelialization and involves Wnt/β-catenin (β-Cat) signaling and remodeling of the actin cytoskeleton. The aim of this study was to investigate the effect of Flightless I (Flii), a cytoskeletal protein and inhibitor of wound healing, on EpSC activation during wound repair. Genetically modified Flii mice ( knockdown: , wild type: WT, overexpressing: ) received two incisional wounds along the lateral axis of the dorsal skin.

Flightless I Expression Enhances Murine Claw Regeneration Following Digit Amputation.

The mammalian digit tip is capable of both reparative and regenerative wound healing dependent on the level of amputation injury. Removal of the distal third of the terminal phalange results in successful regeneration, whereas a more severe, proximal, amputation heals by tissue repair. Flightless I (Flii) is involved in both tissue repair and regeneration.

Combination of low calcium with Y-27632 rock inhibitor increases the proliferative capacity, expansion potential and lifespan of primary human keratinocytes while retaining their capacity to differentiate into stratified epidermis in a 3D skin model.

Human keratinocytes are difficult to isolate and have a limited lifespan. Traditionally, immortalised keratinocyte cell lines are used in vitro due to their ability to bypass senescence and survive indefinitely. However these cells do not fully retain their ability to differentiate in vitro and they are unable to form a normal stratum corneum in organotypic culture.

In vivo delivery of functional Flightless I siRNA using layer-by-layer polymer surface modification.

Gene silencing using small interfering RNA has been proposed as a therapy for cancer, viral infections and other diseases. This study aimed to investigate whether layer-by-layer polymer surface modification could deliver small interfering RNA to decrease fibrotic processes associated with medical device implantation. Anti-green fluorescent protein labelled small interfering RNA was applied to tissue culture plates and polyurethane using a layer-by-layer technique with small interfering RNA and poly-L-lysine.

Cytoskeletal regulation of dermal regeneration.

Wound healing results in the repair of injured tissues however fibrosis and scar formation are, more often than not the unfortunate consequence of this process. The ability of lower order vertebrates and invertebrates to regenerate limbs and tissues has been all but lost in mammals; however, there are some instances where glimpses of mammalian regenerative capacity do exist. Here we describe the unlocked potential that exists in mammals that may help us understand the process of regeneration post-injury and highlight the potential role of the actin cytoskeleton in this process.

Overexpression of the Flii gene increases dermal-epidermal blistering in an autoimmune ColVII mouse model of epidermolysis bullosa acquisita.

Epidermolysis bullosa (EB) is a severe genetic skin fragility syndrome characterized by blister formation. The molecular basis of EB is still largely unknown and wound healing in patients suffering from EB remains a major challenge to their survival. Our previous studies have identified the actin remodelling protein Flightless I (Flii) as an important mediator of wound repair.

IL-5-overexpressing mice exhibit eosinophilia and altered wound healing through mechanisms involving prolonged inflammation.

Leucocytes are essential in healing wounds and are predominantly involved in the inflammatory and granulation stages of wound repair. Eosinophils are granulocytic leucocytes and are specifically regulated by interleukin-5 (IL-5), a cytokine produced by T helper 2 (Th2) cells. To characterize more clearly the role of the IL-5 and eosinophils in the wound healing process, IL-5-overexpressing and IL-5-deficient mice were used as models of eosinophilia and eosinophil depletion, respectively.

Gender specific effects on the actin-remodelling protein Flightless I and TGF-beta1 contribute to impaired wound healing in aged skin.

Impaired wound healing in the elderly presents a major clinical challenge. Understanding the cellular mechanisms behind age-related impaired healing is vital for developing new wound therapies. Here we show that the actin-remodelling protein, Flightless I (FliI) is a contributing factor to the poor healing observed in elderly skin and that gender plays a major role in this process.