Transient Anomalous Diffusion MRI Measurement Discriminates Porous Polymeric Matrices Characterized by Different Sub-Microstructures and Fractal Dimension.

Considering the current development of new nanostructured and complex materials and gels, it is critical to develop a sub-micro-scale sensitivity tool to quantify experimentally new parameters describing sub-microstructured porous systems. Diffusion NMR, based on the measurement of endogenous water's diffusion displacement, offers unique information on the structural features of materials and tissues. In this paper, we applied anomalous diffusion NMR protocols to quantify the subdiffusion of water and to measure, in an alternative, non-destructive and non-invasive modality, the fractal dimension dw of systems characterized by micro and sub-micro geometrical structures. To this end, three highly heterogeneous porous-polymeric matrices were studied. All the three matrices composed of glycidylmethacrylate-divynilbenzene porous monoliths obtained through the High Internal Phase Emulsion technique were characterized by pores of approximately spherical symmetry, with diameters in the range of 2-10 µm. Pores were interconnected by a plurality of window holes present on pore walls, which were characterized by size coverings in the range of 0.5-2 µm. The walls were characterized by a different degree of surface roughness. Moreover, complementary techniques, namely Field Emission Scanning Electron Microscopy (FE-SEM) and dielectric spectroscopy, were used to corroborate the NMR results. The experimental results showed that the anomalous diffusion α parameter that quantifies subdiffusion and dw = 2/α changed in parallel to the specific surface area S (or the surface roughness) of the porous matrices, showing a submicroscopic sensitivity. The results reported here suggest that the anomalous diffusion NMR method tested may be a valid experimental tool to corroborate theoretical and simulation results developed and performed for describing highly heterogeneous and complex systems. On the other hand, non-invasive and non-destructive anomalous subdiffusion NMR may be a useful tool to study the characteristic features of new highly heterogeneous nanostructured and complex functional materials and gels useful in cultural heritage applications, as well as scaffolds useful in tissue engineering.

Tackling Current Biomedical Challenges With Frontier Biofabrication and Organ-On-A-Chip Technologies.

In the last decades, biomedical research has significantly boomed in the academia and industrial sectors, and it is expected to continue to grow at a rapid pace in the future. An in-depth analysis of such growth is not trivial, given the intrinsic multidisciplinary nature of biomedical research. Nevertheless, technological advances are among the main factors which have enabled such progress. In this review, we discuss the contribution of two state-of-the-art technologies-namely biofabrication and organ-on-a-chip-in a selection of biomedical research areas. We start by providing an overview of these technologies and their capacities in fabricating advanced in vitro tissue/organ models. We then analyze their impact on addressing a range of current biomedical challenges. Ultimately, we speculate about their future developments by integrating these technologies with other cutting-edge research fields such as artificial intelligence and big data analysis.

4D printing in biomedical applications: emerging trends and technologies.

Nature's material systems during evolution have developed the ability to respond and adapt to environmental stimuli through the generation of complex structures capable of varying their functions across direction, distances and time. 3D printing technologies can recapitulate structural motifs present in natural materials, and efforts are currently being made on the technological side to improve printing resolution, shape fidelity, and printing speed. However, an intrinsic limitation of this technology is that printed objects are static and thus inadequate to dynamically reshape when subjected to external stimuli. In recent years, this issue has been addressed with the design and precise deployment of smart materials that can undergo a programmed morphing in response to a stimulus. The term 4D printing was coined to indicate the combined use of additive manufacturing, smart materials, and careful design of appropriate geometries. In this review, we report the recent progress in the design and development of smart materials that are actuated by different stimuli and their exploitation within additive manufacturing to produce biomimetic structures with important repercussions in different but interrelated biomedical areas.

Photocurable Biopolymers for Coaxial Bioprinting.

Thanks to their unique advantages, additive manufacturing technologies are revolutionizing almost all sectors of the industrial and academic worlds, including tissue engineering and regenerative medicine. In particular, 3D bioprinting is rapidly emerging as a first-choice approach for the fabrication-in one step-of advanced cell-laden hydrogel constructs to be used for in vitro and in vivo studies. This technique consists in the precise deposition layer-by-layer of sub-millimetric hydrogel strands in which living cells are embedded. A key factor of this process consists in the proper formulation of the hydrogel precursor solution, the so-called bioink. Ideal bioinks should be able, on the one side, to support cell growth and differentiation and, on the other, to allow the high-resolution deposition of cell-laden hydrogel strands. The latter feature requires the extruded solution to instantaneously undergo a sol-gel transition to avoid its collapse after deposition.To address this challenge, researchers are recently focusing their attention on the synthesis of several derivatives of natural biopolymers to enhance their printability. Here, we present an approach for the synthesis of photocurable derivatives of natural biopolymers-namely, gelatin methacrylate, hyaluronic acid methacrylate, chondroitin sulfate methacrylate, and PEGylated fibrinogen-that can be used to formulate tailored innovative bioinks for coaxial-based 3D bioprinting applications.

PredyCLU: A prediction system for chronic leg ulcers based on fuzzy logic; part II-Exploring the arterial side.

Peripheral arterial disease (PAD) and its most severe form, critical limb ischaemia (CLI), are very common clinical conditions related to atherosclerosis and represent the major causes of morbidity, mortality, disability, and reduced quality of life (QoL), especially for the onset of ischaemic chronic leg ulcers (ICLUs) and the subsequent need of amputation in affected patients. Early identification of patients at risk of developing ICLUs may represent the best form of prevention and appropriate management. In this study, we used a Prediction System for Chronic Leg Ulcers (PredyCLU) based on fuzzy logic applied to patients with PAD. The patient population consisted of 80 patients with PAD, of which 40 patients (30 males [75%] and 10 females [25%]; mean age 66.18 years; median age 67.50 years) had ICLUs and represented the case group. Forty patients (100%) (27 males [67.50%] and 13 females [32.50%]; mean age 66.43 years; median age 66.50 years) did not have ICLUs and represented the control group. In patients of the case group, the higher was the risk calculated with the PredyCLU the more severe were the clinical manifestations recorded. In this study, the PredyCLU algorithm was retrospectively applied on a multicentre population of 80 patients with PAD. The PredyCLU algorithm provided a reliable risk score for the risk of ICLUs in patients with PAD.

The Role of Biofilm in Central Venous Catheter Related Bloodstream Infections: Evidence-based Nursing and Review of the Literature.

BACKGROUND: Biofilm is a fundamental component in the pathogenesis of infections related to the use of the central venous catheter (CVC,) which can represent an important health issue in everyday practice of nursing and medical staff. OBJECTIVE: The objective of the following review is to analyze the components of biofilm and their role in catheter-related infection determinism in an evidencebased nursing perspective in such a way as to give health professionals useful suggestions in the prevention and management of these complications. METHODS: The following databases were consulted for the bibliographic search: Medline, Scopus, Science Direct. Biofilm can be the cause of CVC extraction and can lead to serious haematogenic infectious complications that can increase the morbidity and mortality of affected patients. RESULTS: Updated pathophysiologic knowledge of biofilm formation and appropriate diagnostic methodology are pivotal in understanding and detecting CVC-related infections. Lock therapy appears to be a useful, preventive, and therapeutic aid in the management of CVCrelated infections. New therapies attempting to stop bacterial adhesion on the materials used could represent new frontiers for the prevention of CVC-related infections. CONCLUSION: The correct evidence-based nursing methods, based on the use of guidelines, provides the opportunity to minimize the risks of infection through the implementation of a series of preventive measures both during the CVC positioning phase and in the subsequent phase, for example, during device management which is performed by medical and nursing staff.

3D bioprinting of hydrogel constructs with cell and material gradients for the regeneration of full-thickness chondral defect using a microfluidic printing head.

Osteochondral (OC) tissue is a biphasic material comprised of articular cartilage integrated atop subchondral bone. Damage to this tissue is highly problematic, owing to its intrinsic inability to regenerate functional tissue in response to trauma or disease. Further, the function of the tissue is largely conferred by its compartmentalized zonal microstructure and composition. Current clinical treatments fail to regenerate new tissue that recapitulates this zonal structure. Consequently, regenerated tissue often lacks long-term stability. To address this growing problem, we propose the development of tissue engineered biomaterials that mimic the zonal cartilage organization and extracellular matrix composition through the use of a microfluidic printing head bearing a mixing unit and incorporated into an extrusion-based bioprinter. The system is devised so that multiple bioinks can be delivered either individually or at the same time and rapidly mixed to the extrusion head, and finally deposited through a coaxial nozzle. This enables the deposition of either layers or continuous gradients of chemical, mechanical and biological cues and fabrication of scaffolds with very high shape fidelity and cell viability. Using such a system we bioprinted cell-laden hydrogel constructs recapitulating the layered structure of cartilage, namely, hyaline and calcified cartilage. The construct was assembled out of two bioinks specifically formulated to mimic the extracellular matrices present in the targeted tissues and to ensure the desired biological response of human bone marrow-derived mesenchymal stem cells and human articular chondrocytes. Homogeneous and gradient constructs were thoroughly characterized in vitro with respect to long-term cell viability and expression of hyaline and hypertrophic markers by means of real-time quantitative PCR and immunocytochemical staining. After 21 days of in vitro culture, we observed production of zone-specific matrix. The PCR analysis demonstrated upregulated expression of hypertrophic markers in the homogenous equivalent of calcified cartilage but not in the gradient heterogeneous construct. The regenerative potential was assessed in vivo in a rat model. The histological analysis of surgically damaged rat trochlea revealed beneficial effect of the bioprinted scaffolds on regeneration of OC defect when compared to untreated control.

3D bioprinted hydrogel model incorporating ß-tricalcium phosphate for calcified cartilage tissue engineering.

One promising strategy to reconstruct osteochondral defects relies on 3D bioprinted three-zonal structures comprised of hyaline cartilage, calcified cartilage, and subchondral bone. So far, several studies have pursued the regeneration of either hyaline cartilage or bone in vitro while-despite its key role in the osteochondral region-only few of them have targeted the calcified layer. In this work, we present a 3D biomimetic hydrogel scaffold containing ß-tricalcium phosphate (TCP) for engineering calcified cartilage through a co-axial needle system implemented in extrusion-based bioprinting process. After a thorough bioink optimization, we showed that 0.5% w/v TCP is the optimal concentration forming stable scaffolds with high shape fidelity and endowed with biological properties relevant for the development of calcified cartilage. In particular, we investigate the effect induced by ceramic nano-particles over the differentiation capacity of bioprinted bone marrow-derived human mesenchymal stem cells in hydrogel scaffolds cultured up to 21 d in chondrogenic media. To confirm the potential of the presented approach to generate a functional in vitro model of calcified cartilage tissue, we evaluated quantitatively gene expression of relevant chondrogenic (COL1, COL2, COL10A1, ACAN) and osteogenic (ALPL, BGLAP) gene markers by means of RT-qPCR and qualitatively by means of fluorescence immunocytochemistry.

3D-Printing of Functionally Graded Porous Materials Using On-Demand Reconfigurable Microfluidics.

Tailoring the morphology of macroporous structures remains one of the biggest challenges in material synthesis. Herein, we present an innovative approach for the fabrication of custom macroporous materials in which pore size varies throughout the structure by up to an order of magnitude. We employed a valve-based flow-focusing junction (vFF) in which the size of the orifice can be adjusted in real-time (within tens of milliseconds) to generate foams with on-line controlled bubble size. We used the junction to fabricate layered and smoothly graded porous structures with pore size varying in the range of 80-800 µm. Additionally, we mounted the vFF on top of an extrusion printer and 3D-printed constructs characterized by a predefined 3D geometry and a controlled, spatially varying internal porous architecture, such as a model of a bone. The presented technology opens new possibilities in macroporous material synthesis with potential applications ranging from tissue engineering to aerospace industry and construction.

Engineering Human-Scale Artificial Bone Grafts for Treating Critical-Size Bone Defects.

The manufacturing of artificial bone grafts can potentially circumvent the issues associated with current bone grafting treatments for critical-size bone defects caused by pathological disorders, trauma, or massive tumor ablation. In this study, we report on a potentially patient-specific fabrication process in which replicas of bone defects, in particular zygomatic and mandibular bones and phalanxes of a hand finger, were manufactured by laser stereolithography and used as templates for the creation of PDMS molds. Gas-in-water foams were cast in the molds, rapidly frozen, freeze-dried, and cross-linked. Since bone matrix consists essentially of collagen and hydroxyapatite, biomimetic scaffolds were fabricated using gelatin and hydroxyapatite in a ratio very similar to that found in bone. The obtained composite scaffolds were excellent replicas of the original bone defects models and presented both a superficial and internal porous texture adequate for cellular and blood vessels infiltration. In particular, scaffolds exhibited a porous texture consisting of pores and interconnects with average size of about 300 and 100 µm, respectively, and a porosity of 90%. In vitro culture tests using hMSCs demonstrated scaffold biocompatibility and capacity in inducing differentiation toward osteoblasts progenitors. In vivo cellularized implants showed bone matrix deposition and recruitment of blood vessels. Overall, the technique/materials combination used in this work led to the fabrication of promising mechanically stable, bioactive, and biocompatible composite scaffolds with well-defined architectures potentially valuable in the regeneration of patient-specific bone defects.

Endovascular repair versus open repair in the treatment of ruptured aortic aneurysms: a systematic review.

INTRODUCTION: Rupture of abdominal aortic aneurysm remains a fatal event in up to 65% of cases and emergency open surgery (ruptured open aneurysm repair or rOAR) has a great intraoperative mortality of about 30-50%. The introduction of endovascular repair of abdominal aortic aneurysm (ruptured endovascular aneurysm repair or rEVAR) has rapidly challenged the conventional approach to this catastrophic event. The purpose of this systematic review is to compare the outcomes of open surgical repair and endovascular interventions. EVIDENCE ACQUISITION: A literature search was performed using Medline, Scopus, and Science Direct from August 2010 to March 2017 using keywords identified and agreed by the authors. Randomized trials, cohort studies, and case-report series were contemplated to give a breadth of clinical data. EVIDENCE SYNTHESIS: Ninety-three studies were included in the final analysis. Thirty-five (50.7%) of the listed studies evaluating the within 30 days mortality rates deposed in favor of rEVAR, while the others (comprising all four included RCTs) failed detecting any difference. Late mortality rates were found to be lower in rEVAR group in seven on twenty-seven studies (25.9%), while one (3.7%) reported higher mortality rates following rEVAR performed before 2005, one found lower incidence of mortality at 6 months in the endovascular group but higher rates in the same population at 8 years of follow-up, and the remaining (66.7%) (including all three RCTs) failed finding any benefit of rEVAR on rOAR. A lower incidence of complications was reported by thirteen groups (46.4%), while other thirteen studies did not find any difference between rEVAR and rOAR. Each of these two conclusions was corroborated by one RCTs. Other two studies (7.2%) found higher rates of tracheostomies, myocardial infarction, and acute tubular necrosis or respiratory, urinary complications, and acute renal failure respectively in rOAR group. The majority of studies (59.0%, 72.7%, and 89.3%, respectively) and all RCTs found significantly lower rates of length of hospitalization, intensive care unit transfer, and blood loss with or without transfusion need in rEVAR group. The large majority of the studies did not specified neither the type nor the brands of employed stent grafts. CONCLUSIONS: The bulk of evidence regarding the comparison between endovascular and open surgery approach to RAAA points to: 1) non-inferiority of rEVAR in terms of early (within 30 days) and late mortality as well as rate of complications and length of hospitalization, with trends of better outcomes associated to the endovascular approach; 2) significantly better outcomes in terms of intensive care unit transfer and blood loss with or without transfusion need in the rEVAR group. These conclusions reflect the results of the available RCTs included in the present review. Thus rEVAR can be considered a safe method in treating RAAA and we suggest that it should be preferred when technically feasible. However, more RCTs are needed in order to give strength of these evidences, bring to definite clinical recommendations regarding this subject, and assess the superiority (if present) of one or more brands of stent grafts over the others.

Co-axial wet-spinning in 3D bioprinting: state of the art and future perspective of microfluidic integration.

Nowadays, 3D bioprinting technologies are rapidly emerging in the field of tissue engineering and regenerative medicine as effective tools enabling the fabrication of advanced tissue constructs that can recapitulate in vitro organ/tissue functions. Selecting the best strategy for bioink deposition is often challenging and time consuming process, as bioink properties-in the first instance, rheological and gelation-strongly influence the suitable paradigms for its deposition. In this short review, we critically discuss one of the available approaches used for bioprinting-namely co-axial wet-spinning extrusion. Such a deposition system, in fact, demonstrated to be promising in terms of printing resolution, shape fidelity and versatility when compared to other methods. An overview of the performances of co-axial technology in the deposition of cellularized hydrogel fibres is discussed, highlighting its main features. Furthermore, we show how this approach allows (i) to decouple the printing accuracy from bioink rheological behaviour-thus notably simplifying the development of new bioinks-and (ii) to build heterogeneous multi-materials and/or multicellular constructs that can better mimic the native tissues when combined with microfluidic systems. Finally, the ongoing challenges and the future perspectives for the ultimate fabrication of functional constructs for advanced research studies are highlighted.

Novel biomarkers for cardiovascular risk.

Cardiovascular disease refers to different diseases involving the heart and/or the arteries and/or the veins. Cardiovascular disease, overall considered, is a notable source of morbidity and mortality worldwide. Therefore, several research studies are dedicated to explore, by means of biomarkers, the possiblity to calculate the cardiovascular risk both for the onset and for the complications of the related clinical manifestations such as coronary artery disease, carotid artery stenosis, peripheral artery disease, arterial aneurysm, chronic venous disease and venous thromboembolism. This review discusses the most updated information in the area of the novel biomarkers related to omics, imaging techniques and clinical data, that may help physicians in order to improve the knowledge and the management of the cardiovascular risk.

Emergent treatment of carotid stenosis: an evidence-based systematic review.

INTRODUCTION: Stroke is one of the major causes of death in the world, but above all is the condition most associated with severe long-term disabilities. It is clear that this condition therefore requires the best therapeutic approach possible to minimize the consequences that this can lead to. The major issues concern the type of treatment to be used for revascularization (carotid endarterectomy [CEA] or stenting of the carotid artery [CAS]) and the timing of the treatment itself. Many studies have been conducted on this issue, but a definitive and unanimous verdict has not yet been reached on account of the great variety of results obtained from the various study group. The aim of this review is to analyze the latest scientific findings focused on revascularization following a symptomatic carotid stenosis (SCS). EVIDENCE ACQUISITION: We searched all publications addressing treatments and timing of approach to SCS. Randomized trials, cohort studies and reviews were contemplated in order to give a breadth of clinical data. Medline and Science Direct were searched from January 2013 to April 2017. EVIDENCE SYNTHESIS: Of the 819 records found, 76 matched our inclusion criteria. After reading the full-text articles, we decided to exclude 54 manuscripts because of the following reasons: 1) no innovative or important content; 2) insufficient data; 3) no clear potential biases or strategies to solve them; 4) no clear endpoints; and 5) inconsistent or arbitrary conclusions. The final set included 22 articles. CONCLUSIONS: CEA is considered a less problematic method than CAS, especially for patients over the age of 75; CAS remains recommended in patients with a favorable anatomy or high surgical risks. Studies that showed more solid results seem to lead to the conclusion that optimal timing may be between 2 days and the end of the first week from the onset of symptoms in patients who are appropriate candidates for surgery.

Skin tears and risk factors assessment: a systematic review on evidence-based medicine.

Skin tears represent a common condition of traumatic wounds, which may be encountered in some categories of individuals at the extremes of age, such as infants and the elderly. Despite the high prevalence and cost of these lesions, there has been little investigation into the risk factors that lead to this condition. The aim of this review was to systematically evaluate the main risk factors involved in development of skin tears. We planned to include all the studies dealing with risk factors related to skin tears. Only publications in English were considered. We excluded all the studies that did not properly fit our research question and those with insufficient data. Of the 166 records found, 24 matched our inclusion criteria. After reading the full-text articles, we decided to exclude seven articles because of the following reasons: (1) not responding properly to our research questions and (2) insufficient data; the final set included 17 articles. From a literature search, we found the following main issues related to risk factors, which have been described in detail in this section: age-related skin changes, dehydration, malnutrition, sensory changes, mobility impairment, pharmacological therapies and mechanical factors related to skin care practices. Our findings clearly show that in frail populations (especially infant and elderly), the stratification risk, as a primary prevention strategy, is an effective tool in avoiding the development of chronic wounds. The development and the implementation of prevention strategies based on appropriate knowledge of the risk factors involved and the adoption of correct techniques during skin care practices could reduce or even avoid the onset of skin tears.

PLA short sub-micron fiber reinforcement of 3D bioprinted alginate constructs for cartilage regeneration.

In this study, we present an innovative strategy to reinforce 3D-printed hydrogel constructs for cartilage tissue engineering by formulating composite bioinks containing alginate and short sub-micron polylactide (PLA) fibers. We demonstrate that Young's modulus obtained for pristine alginate constructs (6.9 ± 1.7 kPa) can be increased threefold (up to 25.1 ± 3.8 kPa) with the addition of PLA short fibers. Furthermore, to assess the performance of such materials in cartilage tissue engineering, we loaded the bioinks with human chondrocytes and cultured in vitro the bioprinted constructs for up to 14 days. Live/dead assays at day 0, 3, 7 and 14 of in vitro culture showed that human chondrocytes were retained and highly viable (∼80%) within the 3D deposited hydrogel filaments, thus confirming that the fabricated composites materials represent a valid solution for tissue engineering applications. Finally, we show that the embedded chondrocytes during all the in vitro culture maintain a round morphology, a key parameter for a proper deposition of neocartilage extracellular matrix.

Microfluidic Bioprinting of Heterogeneous 3D Tissue Constructs.

3D bioprinting is an emerging field that can be described as a robotic additive biofabrication technology that has the potential to build tissues or organs. In general, bioprinting uses a computer-controlled printing device to accurately deposit cells and biomaterials into precise architectures with the goal of creating on demand organized multicellular tissue structures and eventually intra-organ vascular networks. The latter, in turn, will promote the host integration of the engineered tissue/organ in situ once implanted. Existing biofabrication techniques still lay behind this goal. Here, we describe a novel microfluidic printing head-integrated within a custom 3D bioprinter-that allows for the deposition of multimaterial and/or multicellular within a single scaffold by extruding simultaneously different bioinks or by rapidly switching between one bioink and another. The designed bioprinting method effectively moves toward the direction of creating viable tissues and organs for implantation in clinic and research in lab environments.

Engineering Muscle Networks in 3D Gelatin Methacryloyl Hydrogels: Influence of Mechanical Stiffness and Geometrical Confinement.

In this work, the influence of mechanical stiffness and geometrical confinement on the 3D culture of myoblast-laden gelatin methacryloyl (GelMA) photo-crosslinkable hydrogels was evaluated in terms of in vitro myogenesis. We formulated a set of cell-laden GelMA hydrogels with a compressive modulus in the range 1 ÷ 17 kPa, obtained by varying GelMA concentration and degree of cross-linking. C2C12 myoblasts were chosen as the cell model to investigate the supportiveness of different GelMA hydrogels toward myotube formation up to 2 weeks. Results showed that the hydrogels with a stiffness in the range 1 ÷ 3 kPa provided enhanced support to C2C12 differentiation in terms of myotube number, rate of formation, and space distribution. Finally, we studied the influence of geometrical confinement on myotube orientation by confining cells within thin hydrogel slabs having different cross sections: (i) 2,000 µm × 2,000 µm, (ii) 1,000 µm × 1,000 µm, and (iii) 500 µm × 500 µm. The obtained results showed that by reducing the cross section, i.e., by increasing the level of confinement-myotubes were more closely packed and formed aligned myostructures that better mimicked the native morphology of skeletal muscle.

Microfluidic-enhanced 3D bioprinting of aligned myoblast-laden hydrogels leads to functionally organized myofibers in vitro and in vivo.

We present a new strategy for the fabrication of artificial skeletal muscle tissue with functional morphologies based on an innovative 3D bioprinting approach. The methodology is based on a microfluidic printing head coupled to a co-axial needle extruder for high-resolution 3D bioprinting of hydrogel fibers laden with muscle precursor cells (C2C12). To promote myogenic differentiation, we formulated a tailored bioink with a photocurable semi-synthetic biopolymer (PEG-Fibrinogen) encapsulating cells into 3D constructs composed of aligned hydrogel fibers. After 3-5 days of culture, the encapsulated myoblasts started migrating and fusing, forming multinucleated myotubes within the 3D bioprinted fibers. The obtained myotubes showed high degree of alignment along the direction of hydrogel fiber deposition, further revealing maturation, sarcomerogenesis, and functionality. Following subcutaneous implantation in the back of immunocompromised mice, bioprinted constructs generated organized artificial muscle tissue in vivo. Finally, we demonstrate that our microfluidic printing head allows to design three dimensional multi-cellular assemblies with an exquisite compartmentalization of the encapsulated cells. Our results demonstrate an enhanced myogenic differentiation with the formation of parallel aligned long-range myotubes. The approach that we report here represents a robust and valid candidate for the fabrication of macroscopic artificial muscle to scale up skeletal muscle tissue engineering for human clinical application.

Skin grafting for the treatment of chronic leg ulcers - a systematic review in evidence-based medicine.

Skin grafting is one of the most common surgical procedures in the area of non-healing wounds by which skin or a skin substitute is placed over a wound to replace and regenerate the damaged skin. Chronic leg ulcers are an important problem and a major source of expense for Western countries and for which many different forms of treatment have been used. Skin grafting is a method of treatment that decreases the area of chronic leg ulcers or heals them completely, thus improving a patient's quality of life. Skin grafting is an old technique, rediscovered during the first and second world wars as the main treatment for wound closure. Nowadays, skin grafting has a pivotal role in the context of modern wound healing and tissue regeneration. The aim of this review was to track and to analyse the specific outcomes this technique achieved, especially in the last decade, in relation to venous, arterial, diabetic, rheumatoid and traumatic leg ulcers. Our main findings indicate that autologous split-thickness skin grafting still remains the gold standard in terms of safety and efficacy for chronic leg ulcers; skin grafting procedures have greater success rates in chronic venous leg ulcers compared to other types of chronic leg ulcers; skin tissue engineering, also supported by genetic manipulation, is quickly expanding and, in the near future, may provide even better outcomes in the area of treatments for long-lasting chronic wounds.