Immunomodulation of Skin Repair: Cell-Based Therapeutic Strategies for Skin Replacement (A Comprehensive Review)

The immune system has a crucial role in skin wound healing and the application of specific cell-laden immunomodulating biomaterials emerged as a possible treatment option to drive skin tissue regeneration. Cell-laden tissue-engineered skin substitutes have the ability to activate immune pathways, even in the absence of other immune-stimulating signals. In particular, mesenchymal stem cells with their immunomodulatory properties can create a specific immune microenvironment to reduce inflammation, scarring, and support skin regeneration. This review presents an overview of current wound care techniques including skin tissue engineering and biomaterials as a novel and promising approach. We highlight the plasticity and different roles of immune cells, in particular macrophages during various stages of skin wound healing. These aspects are pivotal to promote the regeneration of nonhealing wounds such as ulcers in diabetic patients. We believe that a better understanding of the intrinsic immunomodulatory features of stem cells in implantable skin substitutes will lead to new translational opportunities. This, in turn, will improve skin tissue engineering and regenerative medicine applications. Keywords: biomaterials; chronic wounds; immunomodulation; intrinsic immune cell signals; regenerative medicine; skin substitutes; skin tissue engineering; wound healing

Negative index metamaterial combining magnetic resonators with metal films

We present simulation results of a design for negative index materials that uses magnetic resonators to provide negative permeability and metal film for negative permittivity. We also discuss the possibility of using semicontinuous metal films to achieve better manufacturability and enhanced impedance matching.Comment: 6 pages, 3 figure

High-Yield Production and Transfer of Graphene Flakes Obtained by Anodic Bonding

We report large-yield production of graphene flakes on glass by anodic bonding. Under optimum conditions, we counted several tens of flakes with lateral size around 20-30 {\mu}m and few tens of flakes with larger size. 60-70% of the flakes have negligible D peak. We show that it is possible to easily transfer the flakes by wedging technique. The transfer on silicon does not damage graphene and lowers the doping. The charge mobility of the transferred flakes on silicon is of the order of 6000 cm^2/V s (at carrier concentration of 10^12 cm^-2), which is typical for devices prepared on this substrate with exfoliated graphene.Comment: 17 pages, 6 figures; ACS Nano 201

Plasmon-assisted direction-and polarization-sensitive organic thin-film detector

Utilizing Bragg surface plasmon polaritons (SPPs) on metal nanostructures for the use in optical devices has been intensively investigated in recent years. Here, we demonstrate the integration of nanostructured metal electrodes into an ITO-free thin film bulk heterojunction organic solar cell, by direct fabrication on a nanoimprinted substrate. The nanostructured device shows interesting optical and electrical behavior, depending on angle and polarization of incidence and the side of excitation. Remarkably, for incidence through the top electrode, a dependency on linear polarization and angle of incidence can be observed. We show that these peculiar characteristics can be attributed to the excitation of dispersive and non-dispersive Bragg SPPs on the metal–dielectric interface on the top electrode and compare it with incidence through the bottom electrode. Furthermore, the optical and electrical response can be controlled by the organic photoactive material, the nanostructures, the materials used for the electrodes and the epoxy encapsulation. Our device can be used as a detector, which generates a direct electrical readout and therefore enables the measuring of the angle of incidence of up to 60\ub0 or the linear polarization state of light, in a spectral region, which is determined by the active material. Our results could furthermore lead to novel organic Bragg SPP-based sensor for a number of applications

Chronic obstructive pulmonary disease in older persons: A comparison of two spirometric definitions

SummaryBackgroundAmong older persons, we previously endorsed a two-step spirometric definition of chronic obstructive pulmonary disease (COPD) that requires a ratio of forced expiratory volume in 1sec to forced vital capacity (FEV1/FVC) below .70, and an FEV1 below the 5th or 10th standardized residual percentile (“SR-tile strategy”).ObjectiveTo evaluate the clinical validity of an SR-tile strategy, compared to a current definition of COPD, as published by the Global Initiative for Obstructive Lung Disease (GOLD-COPD), in older persons.MethodsWe assessed national data from 2480 persons aged 65–80 years. In separate analyses, we evaluated the association of an SR-tile strategy with mortality and respiratory symptoms, relative to GOLD-COPD. As per convention, GOLD-COPD was defined solely by an FEV1/FVC<.70, with severity staged according to FEV1 cut-points at 80 and 50 percent predicted (%Pred).ResultsAmong 831 participants with GOLD-COPD, the risk of death was elevated only in 179 (21.5%) of those who also had an FEV1<5th SR-tile; and the odds of having respiratory symptoms were elevated only in 310 (37.4%) of those who also had an FEV1<10th SR-tile. In contrast, GOLD-COPD staged at an FEV1 50–79%Pred led to misclassification (overestimation) in terms of 209 (66.4%) and 77 (24.6%) participants, respectively, not having an increased risk of death or likelihood of respiratory symptoms.ConclusionRelative to an SR-tile strategy, the majority of older persons with GOLD-COPD had neither an increased risk of death nor an increased likelihood of respiratory symptoms. These results raise concerns about the clinical validity of GOLD guidelines in older persons

Phase II trial of sagopilone, a novel epothilone analog in metastatic melanoma

BackgroundSagopilone is a novel fully synthetic epothilone with promising preclinical activity and a favourable toxicity profile in phase I testing.MethodsA phase II pharmacokinetic and efficacy trial was conducted in patients with metastatic melanoma. Patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate haematological, and organ function, with up to 2 previous chemotherapy and any previous immunotherapy regimens. Sagopilone, 16 mg m⁻², was administered intravenously over 3 h every 21 days until progression or unacceptable toxicity.ResultsThirty-five patients were treated. Sagopilone showed multi-exponential kinetics with a mean terminal half-life of 64 h and a volume of distribution of 4361 l m⁻² indicating extensive tissue/tubulin binding. Only grade 2 or lower toxicity was observed: these included sensory neuropathy (66%), leukopenia (46%), fatigue (34%), and neutropenia (31%). The objective response rate was 11.4% (one confirmed complete response, two confirmed partial responses, and one unconfirmed partial response). Stable disease for at least 12 weeks was seen in an additional eight patients (clinical benefit rate 36.4%).ConclusionSagopilone was well tolerated with mild haematological toxicity and sensory neuropathy. Unlike other epothilones, it shows activity against melanoma even in pretreated patients. Further clinical testing is warranted