This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).

Summary Background Over the last few years, several articles on dermoscopy of non‐neoplastic dermatoses have been published, yet there is poor consistency in the terminology among different studies. Objectives We aimed to standardize the dermoscopic terminology and identify basic parameters to evaluate in non‐neoplastic dermatoses through an expert consensus. Methods The modified Delphi method was followed, with two phases: (i) identification of a list of possible items based on a systematic literature review and (ii) selection of parameters by a panel of experts through a three‐step iterative procedure (blinded e‐mail interaction in rounds 1 and 3 and a face‐to‐face meeting in round 2). Initial panellists were recruited via e‐mail from all over the world based on their expertise on dermoscopy of non‐neoplastic dermatoses. Results Twenty‐four international experts took part in all rounds of the consensus and 13 further international participants were also involved in round 2. Five standardized basic parameters were identified: (i) vessels (including morphology and distribution); (ii) scales (including colour and distribution); (iii) follicular findings; (iv) ‘other structures’ (including colour and morphology); and (v) ‘specific clues’. For each of them, possible variables were selected, with a total of 31 different subitems reaching agreement at the end of the consensus (all of the 29 proposed initially plus two more added in the course of the consensus procedure). Conclusions This expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This tool, if adopted by clinicians and researchers in this field, is likely to enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology. What's already known about this topic? Over the last few years, several papers have been published attempting to describe the dermoscopic features of non‐neoplastic dermatoses, yet there is poor consistency in the terminology among different studies. What does this study add? The present expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This consensus should enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology.

Novel additive manufacturing processes are increasingly recognized as ideal techniques to produce 3D biodegradable structures with optimal pore size and spatial distribution, providing an adequate mechanical support for tissue regeneration while shaping in-growing tissues. With regard to the mechanical and biological performances of 3D scaffolds, pore size and geometry play a crucial role. In this study, a novel integrated automated system for the production and in vitro culture of 3D constructs, known as BioCell Printing, was used only to manufacture poly(ε-caprolactone) scaffolds for tissue engineering; the influence of pore size and shape on their mechanical and biological performances was investigated. Imposing a single lay-down pattern of 0°/90° and varying the filament distance, it was possible to produce scaffolds with square interconnected pores with channel sizes falling in the range of 245-433 µm, porosity 49-57% and a constant road width. Three different lay-down patterns were also adopted (0°/90°, 0°/60/120° and 0°/45°/90°/135°), thus resulting in scaffolds with quadrangular, triangular and complex internal geometries, respectively. Mechanical compression tests revealed a decrease of scaffold stiffness with the increasing porosity and number of deposition angles (from 0°/90° to 0°/45°/90°/135°). Results from biological analysis, carried out using human mesenchymal stem cells, suggest a strong influence of pore size and geometry on cell viability. On the other hand, after 21 days of in vitro static culture, it was not possible to detect any significant variation in terms of cell morphology promoted by scaffold topology. As a first systematic analysis, the obtained results clearly demonstrate the potential of the BioCell Printing process to produce 3D scaffolds with reproducible well organized architectures and tailored mechanical properties.

In biomedicine, magnetic nanoparticles provide some attractive possibilities because they possess peculiar physical properties that permit their use in a wide range of applications. The concept of magnetic guidance basically spans from drug delivery and hyperthermia treatment of tumours, to tissue engineering, such as magneto-mechanical stimulation/activation of cell constructs and mechanosensitive ion channels, magnetic cell-seeding procedures, and controlled cell proliferation and differentiation. Accordingly, the aim of this study was to develop fully biodegradable and magnetic nanocomposite substrates for bone tissue engineering by embedding irondoped hydroxyapatite (FeHA) nanoparticles in a poly(1-caprolactone) (PCL) matrix. X-ray diffraction analyses enabled the demonstration that the phase composition and crystallinity of the magnetic FeHA were not affected by the process used to develop the nanocomposite substrates. The mechanical characterization performed through small punch tests has evidenced that inclusion of 10 per cent by weight of FeHA would represent an effective reinforcement. The inclusion of nanoparticles also improves the hydrophilicity of the substrates as evidenced by the lower values of water contact angle in comparison with those of neat PCL. The results from magnetic measurements confirmed the superparamagnetic character of the nanocomposite substrates, indicated by a very low coercive field, a saturation magnetization strictly proportional to the FeHA content and a strong history dependence in temperature sweeps. Regarding the biological performances, confocal laser scanning microscopy and AlamarBlue assay have provided qualitative and quantitative information on human mesenchymal stem cell adhesion and viability/proliferation, respectively, whereas the obtained ALP/DNA values have shown the ability of the nanocomposite substrates to support osteogenic differentiation.

Magnetic scaffolds for bone tissue engineering based on a poly(e-caprolactone) (PCL) matrix and iron oxide (Fe 3 O 4 ) magnetic nanoparticles were designed and developed through a three-dimensional (3D) fiber-deposition technique. PCL/Fe 3 O 4 scaffolds were characterized by a 90/10 w/w composition. Tensile and magnetic measurements were carried out, and nondestructive 3D imaging was performed through microcomputed tomography (Micro-CT). Furthermore, confocal analysis was undertaken to investigate human mesenchymal stem cell adhesion and spreading on the PCL/Fe 3 O 4 nanocomposite fibers. The results suggest that nanoparticles mechanically reinforced the PCL matrix; the elastic modulus and the maximum stress increased about 10 and 30%, respectively. However, the maximum strain decreased about 50%; this suggested an enhanced brittleness. Magnetic results evidenced a superparamagnetic behavior for these nanocomposite scaffolds. Micro-CT suggested an almost uniform distribution of nanoparticles. Confocal analysis highlighted interesting results in terms of cell adhesion and spreading. All of these results show that a magnetic feature could be incorporated into a polymeric matrix that could be processed to manufacture scaffolds for advanced bone tissue engineering and, thus, provide new opportunity in terms of scaffold fixation and functionalization.

The inability of the avascular region of the meniscus to regenerate has led to the use of tissue engineering to treat meniscal injuries. The aim of this study was to evaluate the ability of fibrochondrocytes preseeded on PLDLA/PCL-T [poly(L-co-D,L-lactic acid)/poly(caprolactone-triol)] scaffolds to stimulate regeneration of the whole meniscus. Porous PLDLA/PCL-T (90/10) scaffolds were obtained by solvent casting and particulate leaching. Compressive modulus of 9.5±1.0 MPa and maximum stress of 4.7±0.9 MPa were evaluated. Fibrochondrocytes from rabbit menisci were isolated, seeded directly on the scaffolds, and cultured for 21 days. New Zealand rabbits underwent total meniscectomy, after which implants consisting of cell-free scaffolds or cell-seeded scaffolds were introduced into the medial knee meniscus; the negative control group consisted of rabbits that received no implant. Macroscopic and histological evaluations of the neomeniscus were performed 12 and 24 weeks after implantation. The polymer scaffold implants adapted well to surrounding tissues, without apparent rejection, infection, or chronic inflammatory response. Fibrocartilaginous tissue with mature collagen fibers was observed predominantly in implants with seeded scaffolds compared to cell-free implants after 24 weeks. Similar results were not observed in the control group. Articular cartilage was preserved in the polymeric implants and showed higher chondrocyte cell number than the control group. These findings show that the PLDLA/PCL-T 90/10 scaffold has potential for orthopedic applications since this material allowed the formation of fibrocartilaginous tissue, a structure of crucial importance for repairing injuries to joints, including replacement of the meniscus and the protection of articular cartilage from degeneration.

The requirement of a multifunctional scaffold for tissue engineering capable to offer at the same time tunable structural properties and bioactive interface is still unpaired. Here we present three-dimensional (3D) biodegradable polymeric (PCL) scaffolds with controlled morphology, macro-, micro-, and nano-mechanical performances endowed with bioactive moieties (RGD peptides) at the surface. Such result was obtained by a combination of rapid prototyping (e.g., 3D fiber deposition) and surface treatment approach (aminolysis followed by peptide coupling). By properly designing process conditions, a control over the mechanical and biological performances of the structure was achieved with a capability to tune the value of compressive modulus (in the range of 60-90 MPa, depending on the specific lay-down pattern). The macromechanical behavior of the proposed scaffolds was not affected by surface treatment preserving bulk properties, while a reduction of hardness from 0.50-0.27 GPa to 0.1-0.03 GPa was obtained. The penetration depth of the chemical treatment was determined by nanoindentation measurements and confocal microscopy. The efficacy of both functionalization and the following bioactivation was monitored by analytically quantifying functional groups and/or peptides at the interface. NIH3T3 fibroblast adhesion studies evidenced that cell attachment was improved, suggesting a correct presentation of the peptide. Accordingly, the present work mainly focuses on the effect of the surface modification on the mechanical and functional performances of the scaffolds, also showing a morphological and analytical approach to study the functionalization/bioactivation treatment, the distribution of immobilized ligands, and the biological features.

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