Control values of proliferation and differentiation for MG63 osteoblast cells at 3, 7, and 14 days culture.
\r\n\tThe surgical approach to prostate cancer is traditionally considered a milestone in the treatment of this disease. To date, minimally invasive procedures like laparoscopy and robotic surgery are a gold-standard and will be described in the book. Also, there is a growing interest among the investigators on conservative techniques. For this reason, there are chapters on non-surgical techniques, like radiotherapy and brachitherapy and on experimental techniques, like high-intensity focused ultrasound or electroporation.
\r\n\tIt is well known that the key to success in treatment of prostate cancer is the ability to perform the best treatment available, but not all patients are good candidates to the same treatment. This book intends to provide the reader with a comprehensive overview of the wide range of treatments available for prostate cancer and aims to give more insight on the opportunities related to a multimodal approach.
In the last few years, the research on microfabricated devices or implants for biomedical applications has quickly advanced [1, 2]. The aim of biological implants is to reinforce or replace the damaged or diseased tissue [3]. The presence of a biomaterial in the body after implantation procedure always causes a biological reaction [4]. This is a host response to the new living conditions and suggests that the body is trying to adapt at the given situation [5].
\nEvery year, for a large number of patients, biomaterials save lives, relieve suffering, and improve the quality of life [6]. To achieve the needs of the biomedical society, materials comprise everything from metals and ceramics to glasses and polymers have been investigated [7].
\nBiomaterial performances can be improved by selectively modifying the surface properties. One simple solution could be the deposition of thin films useful for changing the chemical and physical properties of biomaterials and important in achieving the optimal surface [8]. There are many studies which demonstrated that the cell response is dependent on surface topography [4].
\nLaser processing of natural or synthetic biomaterials has been rapidly developed to produce biomimetic artificial organs, tissue engineering scaffolds, and other biomedical constructs [9]. The laser processing techniques are commonly grouped into three categories: polymerization (use of laser to induce cross-linking between biomaterial polymer chains), ablation (use of laser to selectively remove part of the biomaterial by thermal or chemical effects), and activation (use of laser to activate certain parts on the polymer chains for specific application) [9]. Relative to other methods, laser processing of biomaterials presents some advantages: reduced surface contamination and mechanical damage and the capability to produce three-dimensional components with complicated geometries by controlling the surface structuring [4].
\nThe physics behind the interaction of laser pulse with the solid surfaces can help us to better understand the laser ablation mechanism [10].
\nThis chapter will provide a brief overview in the field of laser ablation of biomaterials, starting with the explanation of ablation mechanism and then presenting some of its applications.
\nBiomaterials science is a multidisciplinary domain, which involves various features of materials science, clinical science, chemistry, physics, biology, and medicine [11, 12]. It is also an exciting and quickly growing field. It is to be mentioned that a biomaterial is different from a biological material, the last being produced by a biological system [13]. A biomaterial is a natural or synthetic material used in a medical device, projected to interact with biological systems for direct medical treatment [6, 7, 14]. Their usage within a physiologic medium needs some specific characteristics such as biocompatibility (to perform the function with an appropriate host response), efficiency, and reliability [7, 14]. These representative features have provided with an appropriate combination of chemical, mechanical, physical, and biological properties [14]. Biomaterials used in medical applications are rarely used as simple material, being mostly integrated into devices [1].
\nThe biocompatibility of a biomaterial implies its acceptance by the surrounding tissues and the whole body. Consequently, implanted biomaterials should not irritate the injured area, provoke an abnormal inflammatory response, stimulate allergic or immunologic reactions, and cause other diseases [15]. Besides these characteristics, the selection of biomaterials for the manufacturing of an implant device and/or as thin films for the functionality improvement of implant should also depend on appropriate mechanical properties (strength, stiffness, and fatigue), proper optical properties, proper density, sterility, and long-standing storage [15].
\nThe most commonly used metallic implants are based on titanium and its alloys due to their excellent mechanical properties and corrosion stability [16]. Unfortunately, studies in the field showed that bare titanium or other metallic implants can determine ion release into body [17]. To prevent, control or diminish the ion release, such implants are covered with thin films.
\nNowadays, there are a lot of experimental studies focused on the growing of thin, uniform, and adherent films from polymers, organic materials, and biomaterials [18].
\n\nHydroxyapatite (HA) named by Berndt et al. as “hydrated calcium phosphate mineral” is the main inorganic component of the hard tissues (bone and teeth) and is the most extensively studied materials for bone healing [1, 19, 20]. HA belongs to the “apatite” group of compounds, having the chemical formula Ca10(PO4)6(OH)2 and a Ca/P ratio of 1.67 [19, 21]. It can be termed as hydroxylapatite, calcium hydroxyapatite, or apatite and has a calculated density of 3.22 g/cm3 [19]. The vacancies or substitutions, which could occur within the structural lattice, have therefore the non-stoichiometry (deficiency of Ca2+ and OH− ions) of biological apatite. Research in the field demonstrated the poor crystallinity of the biological apatite [22]. On the contrary, synthetic HA is considered to be a stoichiometric material [19]. It is to be mentioned that the presence of some crystallographic sites in the structure of HA allows the atomic exchanges of specific elements with different ionic charges (Na+, Mg2+, HPO4, K+, CO32−, F−, Cl−, or trace elements such as Sr2+, Ba2+, and Pb2+) [19, 22].
\nThe maximum sintering temperature of HA, up to which its structure remains unperturbed, is 1300°C. If one exceeds this threshold, the HA decomposition cannot be avoided [23].
\nDue to the similarity with the human bone, hydroxyapatite was largely used in medical applications. The influence of some HA parameters with respect to the structural, mechanical, and biological properties has been investigated [19].
\nOne important feature of HA, used as thin film for medical implants, was the stability in the physiological media, presenting a dissolution rate of 0.1 mg/year [19, 24].
\nHydroxyapatite can be considered a “smart” ceramic due to its functionalities such as fixation improvement and stabilization of implant [19].
\nOctacalcium phosphate (OCP), with the chemical formula Ca8(HPO4)2(PO4)4∙5H2O and a structure similar to calcium OH-apatite, is more soluble, being present in the first stage of tissue growth [25, 26]. OCP has a Ca/P ratio of about 1.33 and can induce the ectopic development of a new bone tissue [26, 27]. A disadvantage of OCP is represented by the thermal instability of this material. The decomposition takes place at temperatures lower than those needed for ceramic sintering. It was observed that:
– at ~90°C, OCP lose water;
– at 180°C, the OCP structure undergoes changes by interlayer bond breaking;
– at 300°C, the pyrophosphate appears from OCP [28].
The immersion of OCP in physiological fluids induces the conversion into bone-like apatite spontaneously and irreversibly [29].\n
\nRelated studies revealed the potential use of synthetic OCP as bone substitute material in different forms, such as coatings and granules. Furthermore, the stoichiometry of synthetic OCP controls the osteoconductivity and biodegradability of this material and recommends it to use in bone regeneration [30].
\nBoanini et al. evaluate the possibility to deposit thin films of magnesium substituted OCP (Mg:OCP) and strontium substituted OCP (Sr:OCP) on Ti substrates [31].
\nManganese is essential for a normal growth and function of bones and muscles [32]. Furthermore, Mn2+ ions increase the capacity of integrins (transmembrane receptors that mediate cellular interactions) to bind and facilitate cell adhesion [33]. The doping of hydroxyapatites with Mn2+ ensures a better connection of bone-implant and makes easier the regeneration of bone tissue. It was demonstrated that Mn-doped HA has a higher thermal stability than pure HA [32]. The results obtained by György et al. demonstrated that carbonated HA doped with manganese (Mn-CHA) films should determine a faster osteointegration of the implanted device [34].\n
\nTo modify the biomaterial surface properties, several methods were applied [3]. One can mention chemical treatments, ion beam implantation, liquid immersion, thermal and plasma spray, electrophoretic processes or laser processing methods based on laser ablation [3].
\nLaser, a versatile source of energy, is for sure an attractive tool with prospective applications in communication and military technology, industry, scientific research, and medicine [35, 36]. The continuous development of lasers and the impossibility of other techniques to deposit or modify some materials leaded to use lasers for material processing [3, 36]. The interaction between laser beam and material is a complex action, which needs the understanding of capabilities and limitations of this process. It involves the incidence of electromagnetic radiation on the material surface, followed by reflection, refraction, absorption, scattering, and/or transmission phenomena (Figure 1) [37]. Absorption of radiation in materials is an important and desired phenomenon and is governed by the excitation of free or bound electrons, inside the bulk material [35, 37].
Possible phenomena generated by the interaction of laser beam with material.
Being the base of laser material processing, laser ablation consists in the removal of material from a substrate/target by absorption of laser energy [18, 38]. The ablation process always depends on the laser parameters like wavelength, energy, fluence, pulse duration, and the material properties, such as chemical structure, melting temperature, thermal diffusion rate, optical reflectivity, and the ambient medium [39, 40]. Laser ablation has significant applications in surface modification and deposition of thin films. Ablation is commonly determined by a phase transition from the liquid state to the vapor state. In function of the physical processes that take place, a classification of laser ablation in the following:
– thermal ablation: the predominant phenomenon is heat induced by laser and vaporization;
– photophysical ablation: the ablation rate is directly influenced by non-thermic excitation;
– photochemical ablation: the chemical bonds are interrupted by direct dissociation or by indirect transfer of energy via defects and impurities [41].
Laser ablation, also known as ablative photodecomposition, is of key importance in the field of material processing [38, 42]. Depending on the surface (from flat to rough), the ablation condition would gradually change [43]. The ablation process is also influenced by the laser beam parameters, thermo-optical properties, and ambient conditions [43]. The selection of proper parameters helps us to achieve the desired material modification [3]. In laser ablation, the stoichiometric transfer and controlled delivery of target composition to the substrate are possible, this process being a non-equilibrium process [44].
\nLaser ablation of biomaterials is physically defined by four main parameters:
The ablation threshold fluence initiates the plasma ignition and is described as the minimal energy of the laser pulse per surface unit [41].
\nDepending on the selected biomaterial and of laser processing parameters (wavelength, energy, and target-substrate distance), material removal during laser ablation is accompanied by a variety of mechanisms [3]. At high-laser intensities, a significant volume of the bulk material is directly excited producing plasma [3]. This can be considered as the fourth state of matter and consists of extremely excited atomic, molecular, ionic, and radical species [8]. The propagation and expansion processes of plasma are dominated by mechanical interactions [43].
\nIt is to be mentioned that a complex cascade of strongly related processes happens in the vicinity of the target surface during and after laser-material interaction [47]. Laser ablation of biomaterials is also based on the strong absorption of laser photons by the investigated material. To achieve a maximum absorption, the wavelength has to be carefully chosen [48].
\nIn the nanosecond regime, laser ablation is induced by rapid heating of the surface layer [49]. In our case, all experimental results were obtained on coatings deposited using a KrF* excimer laser (
The common method used for thin film synthesis and associated to laser ablation is pulsed laser deposition (PLD). In this process, the ablated material from target to substrate is pushed by the PLD plasma, which acts as a piston (Figure 2). Furthermore, the absorbed photons by irradiating a solid target with a laser beam of high intensity can generate the fusion and local vaporization of target. In PLD, ablation can be defined as the rapid boiling of material in a localized interaction volume on and in the vicinity of target surface (Figure 3) [50].
\nHA plasma expansion.
Schematically representation of laser ablation process. (a) The initial absorption of laser radiation (long arrows), the beginning of melting and vaporization. (b) The melted material propagates into solid, vaporization continues, and the interaction laser-plume becomes visible. (c) Absorption of incident laser radiation and plasma formation. (d) The melted material is ejected and re-solidification takes place [
The product of this interaction, known as laser ablation phenomenon, produces plasma of complex composition: photons, electrons, ions, atoms, molecules, clusters, and even liquid or solid particles [51]. The ejected material from the target is in a thermodynamic equilibrium and can be associated to thermic and non-thermic mechanisms. A substrate parallel with the irradiated target was used to collect the vaporized material. The deposition of a thin layer on the substrate is the result of repeated laser pulses [52]. The target ablation and deposition rate are dependent on the material or combination of materials present in the target. The ablation threshold is dependent of absorption coefficient and wavelength [53]. As compared to films deposited by other methods, PLD films also exhibit superior performances.
\nAn important feature of PLD is the stoichiometry preservation of the target in the deposited thin films by choosing proper ablation and deposition parameters [54, 55]. Furthermore, in PLD, the deposited material exhibits an excellent adherence to substrate, with a controlled growth rate and without contaminations. This technique also offers the possibility to deposit multi-layers and doped films with great versatility [54]. The variation in the experimental parameters offers the possibility to deposit crystalline structures from various complex materials deposited at room temperature [55].
\nNevertheless, PLD presents some limitations as low deposition rate, use of compounds that are not sensitive to thermal decomposition and degradation, and restricted deposition area [52].
\nA specific tool appropriate for ablation of organic and inorganic materials is matrix-assisted pulsed laser evaporation (MAPLE; Figure 4). The material ejection and film formation in MAPLE process are also generated by photophysical interaction between laser and target material [56]. MAPLE technique proved to be an appropriate method to obtain high quality thin films by gentle laser transfer onto any substrate of interest [57]. MAPLE emerged as an alternative to PLD in order to preserve the chemical bonding or conformation of delicate materials. On the other words, MAPLE, a less damaging technique, is used to transfer, from the condensed phase to the vapor phase, organic and polymeric compounds, including small and large molecular weight species [58].
Typical MAPLE experimental set-up.
MAPLE, a non-contact technique, preserves the PLD advantages, allowing a better control of film thickness and morphology and enhancing the adherence of film to substrate [59].
\nTo avoid significant material decomposition, one can optimize the MAPLE deposition conditions: laser wavelength, fluence, solvent type, concentration, target-collector separation distance, temperature, repetition rate, background gas, and pressure. The selected solvent should absorb most of the laser energy and should not react with the studied material [60].
\nIn case of MAPLE, a cryogenic complex target of a dilute/suspension mixture of a material to be deposited and an appropriate solvent is irradiated using a laser beam of low energy. The target is maintained frozen during the laser irradiation and deposition process using liquid nitrogen [59]. This technique is governed by two photothermal processes, which takes place in the matrix, the evaporation of frozen complex target and material release into the chamber. The conversion of photon energy (absorbed by solvent) in thermal energy generates material heating and solvent vaporization [61].
\nMAPLE offers the possibility to produce uniform, ultrastable, and nanostructured coatings [59].
\nIn an extension of laser ablation, laser spallation is a progressive process in which the laser pulse is applied on the rear surface [62]. As known, spallation is defined as a damage occurred at the interface between inner film and substrate. Some examples are interface delamination, film spallation, and film expulsion. As illustrated in Figure 5, spallation can be described as a dynamic tensile fracture [63].
Laser-induced film spallation process: schematic diagram [
\nIn 1992, Gupta et al. [64] used laser spallation to measure the strength of planar interfaces. To achieve this, a laser pulse of a high enough energy and a pre-determined duration was converted into a pressure pulse of a critical amplitude and width that was sent through the substrate toward the free surface with the coating [64].
\nExtreme superheating/deformation conditions generated by laser processing are related to mechanisms such melting and/or photomechanical damage/spallation [65]. By increasing the fluence over the spallation threshold, the composition of the ejected plume rapidly changes. The modifications consist in conversion from liquid deposits and large droplets to a blend of individual atoms, small droplets, and atomic clusters [66].
\nNevertheless, it was found that certain laser processing conditions can generate undesired and very detrimental rear surface spallation effect at the textured front surface, even if there are used laser conditions well below the spallation threshold for planar surfaces [67].
\nOne should take into account that coatings are obtained by successive ejected material from the target by each laser pulse. We will start the discussion by presenting some representative results from our studies related to the processing of hydroxyapatite by laser ablation.
\nIn Figure 6, the surface of a HA target before and after laser irradiation is presented. The morphology is characteristic to a material melted and then resolidified. The details presented in Figure 6c, at a higher magnification, are specific to HA solidification, in fractal form. All circular bumps indicated the presence of the bubbling phenomenon. Moreover, the cracks appeared on target surface are due to expansion-contraction cycles as a result of repeated heating/cooling processes.
SEM micrographs of HA target before (a) and after (b and c) laser irradiation.
Typical HA structures deposited by laser ablation at different laser fluences and studied by Scanning Electron Microscopy (SEM) are presented in Figure 7. It is obvious that the aspect of deposited coatings varies from acicular at low fluence to cauliflower aspect at high fluence, respectively.
\nIn case of samples HA1 and HA2, the coatings seem to be the product of material condensation originated from plasma. The droplets, even if they are present, are of small dimensions.
\nThese coatings were also investigated By Energy Dispersive X-ray Spectroscopy (EDS) and X-ray Photoelectron Spectroscopy (XPS). EDS gives us information about the composition, on the entire thickness of the layer, while XPS provided information exclusively from surface.
\nOnly three of the samples (HA1, HA3, and HA5) have been biologically investigated
SEM micrographs for HA coatings deposited at (a) 1.2 J/cm2 (HA1), (b) 1.8 J/cm2 (HA2), (c) 2.7 J/cm2 (HA3), (d) 5 J/cm2 (HA4), and (e) 7.5 J/cm2 (HA5).
From Figure 8a, one can observe that HA1 sample was destroyed, the coating being completed and dissolved in the culture medium. We could not identify cells on the sample surface. Figure 8b demonstrated a partial dissolution of HA3 coating. No cell was present on the sample surface. In case of HA5, one can observe an important coverage rate of the coatings deposited at 7.5 J/cm2 in the presence of cells. The morphology of the coating was not modified, while the osteoblasts present a polygonal flattened form.
\nSEM micrographs for HA coatings deposited at (a) 1.2 J/cm2 (HA1), (b) 2.7 J/cm2 (HA3), and (c) 7.5 J/cm2 (HA5) after 5 days of cell growth.
A similar investigations on HA coatings were conducted by Zhu et al. They analyzed the behavior of MC3T3-E1 cells cultured on the specimens after 7 days [68].
\nIn another study, some of the HA coatings grown by PLD using a laser fluence of 3 J/cm2 were thermally treated (at 400°C for 6h) in order to improve the crystallinity.
\nAfter a first examination, the SEM images of this type of structures did not revealed significant differences (Figure 9).
\nSEM micrographs of HA coatings deposited by PLD (a) with (HAt) and (b) without thermal treatment (HA).
SEM micrographs, at higher magnification, showed the differences induced by the thermal treatment (Figure 10).
SEM micrographs of HA coatings synthesized by PLD with (left) and without (right) thermal treatment.
It can be seen that HA coatings present a more rough morphology at nano level. The droplets’ shape is similar to that of snowballs, and the surface is made up of parallelepipedic structure. The thermal treatment induced the surface structure reorganization. There are no longer irregularities, and the appearance of the droplets is smooth.
\nThe Atomic Force Microscopy (AFM) analysis revealed differences between the two types of structures related to their roughness (Figure 11). The decrease in the rough value from 1.01 to 0.8 nm, at nanometric scale, proves the smoothing of the target.
AFM imaged for HA coatings deposited by PLD with (left) and without (right) thermal treatment.
EDS results showed that the value of Ca/P ratio diminishes from 2.04 (untreated sample - HA) to 1.63 (treated sample - HAt). The corroborated results demonstrated the importance of thermal treatment in obtaining crystalline hydroxyapatite, biocompatible, having a structure similar to stoichiometric HA.
\nHA coatings were also grown by other techniques, such as thermal spray, high velocity oxy-fuel (HVOF) techniques, and plasma spraying trying to find, as in PLD depositions, the optimal conditions for good film with applications in medicine [19, 69].
\nA thermal treatment was also applied to Mn-CHA and OCP films obtained by PLD. In case of Mn-CHA coating, the Ca/P atomic ratio obtained by XPS and EDS investigations was 1.64–1.66, close to the stoichiometric values.
\nThe morphologies of the two structures, OCP and Mn-CHA, are quite different. OCP has a porous and arborescent-like structure (Figure 12a and b), and Mn-CHA has a granular and more compact (Figure 12c and d). The surface morphologies of both calcium phosphates are well matched for bone tissue growth and osteointegration.
(a) Scanning and (b) Transmission Electron Microscopy (TEM) images of OCP coatings; (c) SEM and (d) TEM images of Mn-CHA coatings (reproduced with permission from Ref. [
In case of OCP coatings, XPS measurements showed the total dissolution and disappearance of coating after 7 days of immersion in simulated body fluid (SBF) (Figure 13a). SEM investigations confirmed this advanced dissolution. As for Mn-CHA, the SEM and XPS investigations demonstrated that the coatings preserve the basic composition even the intensity of Ca and P peaks decreased (Figure 13b). After 7 days of immersion in SBF, the surface becomes slightly smoother.
\nSome interesting results were obtained by laser ablation of Mg:OCP and Sr:OCP compounds using the MAPLE technique [31]. The X-ray Diffraction (XRD) patterns revealed that all MAPLE coatings are constituted of OCP. This remark is sustained by the presence of the strong low angle reflection 2
XPS spectra of (a) OCP and (b) Mn-CHA before and after degradation tests (reproduced with permission from Ref. [
EDS maps recorded for (a) Mg:OCP and (b) Sr:OCP coatings (reproduced with permission from Ref. [
To evaluate the proliferation and morphology of MG63 cells, one can also perform phalloidin staining on OCP, Mg:OCP, and Sr:OCP coatings deposited by MAPLE. The surface topography and chemical composition can influence cell behavior. Looking the images of MAPLE coating stain with phalloidin for 14 days, no visible differences were observed (Figure 15, left). Similar results are visible from SEM images of the same structures (Figure 15, right). Deeper studies showed that Mg:OCP and Sr:OCP coatings improved the proliferation and differentiation of MG63 cells.
Phalloidin staining (left) and SEM images (right) of MG63 cells after 14 days of culture grown on (a) OCP, (b) Mg:OCP, and (c) Sr:OCP (reproduced with permission from Ref. [
The biological analysis conducted on Mg:OCP and Sr:OCP coatings revealed no visible cytotoxic or inflammatory effects on osteoblast-like cells in all experimental times (Table 1).
Test MG63 | \n3 days | \n7 days | \n14 days | \n
---|---|---|---|
WST1 (450/625 nm) | \n1.564 ± 0.125 | \n3.132 ± 0.081 | \n3.303 ± 0.047 | \n
Alkaline Phosphatase (ALP) (μg/mg proteins) | \n1.20 ± 0.17 | \n2.33 ± 0.19 | \n1.65 ± 0.02 | \n
Collagen Type I Production (CICP) (ng/mg proteins) | \n9.9 ± 1.2 | \n11.3 ± 0.3 | \n11.1 ± 0.3 | \n
Osteocalcin (OC) (ng/mg proteins) | \n2.00 ± 0.09 | \n2.09 ± 0.18 | \n2.63 ± 0.22 | \n
Interleukin-6 (IL-6) (pg/mg proteins) | \n37 ± 9 | \n109 ± 5 | \n97 ± 3 | \n
Transforming Growth Factor -β1 (TGF-β1) (pg/mg proteins) | \n454 ± 34 | \n537 ± 67 | \n370 ± 26 | \n
Control values of proliferation and differentiation for MG63 osteoblast cells at 3, 7, and 14 days culture.
Mroz et al. also evaluated the performances of HA and OCP coatings deposited by PLD. The biological assays revealed that both layers are biocompatible with respect to human osteoblast cells, offering favorable conditions for their proliferation [71].
\nThis chapter highlighted the importance of laser ablation phenomenon that underlies the processing of biomaterials.
\nLaser ablation of biomaterials is an important and complex field. This domain was explored since long time, but there are a lot of natural or inorganic biomaterials, which wait to be developed and understood.
\nPLD and MAPLE techniques are of interest for thin film deposition, allowing varying some parameters to achieve the optimum conditions for the selected biomaterial. They permit the stoichiometric transfer. In case of PLD, the depositions are obtained from a solid target, as compared to MAPLE in which the target is a cryogenic mixture.
\nSensitive biomaterials can be processed only by MAPLE, to avoid the chemical decomposition. The deposition of calcium phosphates (CaP) as thin films can be done by both techniques. Physical-chemical and biological analyses in the field of CaP recommend these coatings as potential biomaterial for the development of medical implants.
\nThe authors acknowledge the support of UEFISCDI under the contracts 19_RO-FR/2014 and PCCA 244/2014.
\nSchwann cells (SCs) are glial cells present in the peripheral nerve system (PNS). The name was given in honor of the German scientist Theodore Schwann, who discovered them in the nineteenth century [1] although they were not the main subject of his research. At that time it was thought that this type of cells is very complex and that the cells merge to supply peripheral nerves. Ramon y Cajal, only about 100 years later, discovered the true structure of the peripheral nerves, composed of axons and SCs that are in a symbiotic connection with it [2]. In the following years, with the evolution of electron microscopy, the study of SC morphology has developed continuously, leading to a better understanding of their complex biology.
It is known that nerves in PNS are much easier to regenerate than those in the central nervous system (CNS). Ramon y Cajal sensed very well that there is a “symbiosis” between the axon and the Schwann cells. Kidd et al. [3] described the Schwann cell as one of the largest and most complex cells in the body, which can develop and evolve rapidly after injury. The origin of the Schwann cell is in the neural crest, and this differentiation is made by the regulation of Sox10 but also in the presence of Notch and endothelin signaling [4, 5].
After a peripheral nerve lesion, a series of cellular changes occur at both axons and Schwann cells, a phenomenon known as Wallerian degeneration: axonal degeneration and myelin destruction, followed by a dedifferentiation (an immature-like phenotype of SCs) and proliferation of Schwann cells [6].
The purpose of this chapter is to highlight the extremely important role of the Schwann cell in the regeneration of the peripheral nerve and its extraordinary plasticity in order to ensure this phenomenon.
What does peripheral nerve injury mean? This could mean a mechanical trauma, transection or crush, or a pathological condition, when could be affected sensory nerves, motor nerves or autonomic nerves. A peripheral neuropathy may affect one or many nerves, axon, or myelin in the first stage.
In the nerve transection, all nerve fibers are affected, while in a disease manifestation, only a number of nerve fibers are affected, others being normal (Figures 2A and 4).
Very briefly, in peripheral neuropathies, it may be an axonal primary damage or a myelin sheath primary damage. After a period both components of the nerve fiber are affected.
Primary axonal degeneration, whether it is nerve transection or a pathological manifestation, is essentially the same: it starts with a Wallerian degeneration in the distal part of nerve (Figure 1), following the myelin destruction. On semithin transverse sections (Figure 2B and C) and in electron microscopy images (Figure 3), the affected nerve fibers are seen to be in a process of necrobiosis. In electron microscopy images, autophagic vacuoles are seen, near the axon (Figure 3A) or in the exterior layer of SC, under the basal lamina (Figure 3B and C) and macrophages (Figure 3D). After the destruction of the nerve fiber, only irregular structures of myelin residues can be seen (Figure 3E) or myelin debris like ovoids and balls (Figure 4B and C). If it is a chronic process, many nerve fibers disappear, the density of myelinated fibers being very low (Figure 2D and E). When the myelin is affected in the first step, not all Schwann cells are suffering in the same time. One internode with a very thin sheath between two normal internodes may be observed: segmental demyelination (Figure 4A and B). When a myelin protein, PMP22, is genetically affected, in hereditary neuropathy with pressure palsies (HNPP), the nerve biopsy shows demyelination and focal hypermyelination structures, tomacula (sausage-like) (Figures 2F and 4D). In hypertrophic neuropathies, like Charcot-Marie-Tooth disease type 1A (CMT 1A) and chronic inflammatory demyelinating polyneuropathy (CIDP), some structures named “onion bulbs” are present, a result of concentric layers of Schwann cell processes and collagen around the axons (Figure 2E). It is a repetitive segmental demyelination and myelin regeneration.
Wallerian degeneration. After injury, axon and myelin sheath in the distal stump degenerate. Macrophages migrate to the site of lesion and with proliferating Schwann cells remove myelin debris. After the debris has been removed, dedifferentiated Schwann cells align forming bands of Bungner, guiding axonal sprout regeneration.
Peripheral nerve pathological modifications (sural nerve biopsy): (A) a very mild affected nerve, with a normal fiber density; some myelinated fibers with small and medium mean diameter with demyelination; (B) a severe axonal destruction, with disappearance of many large diameter axons and with a low-fiber density; a degenerated axon is present; (C) many degenerated axons and demyelination present in the rest of myelinated fibers; (D) a very severe neuropathy with disappearance of most of the myelinated fibers; (E) some small myelinated axons with onion bulbs; (F) a hypermyelinated fiber in an HNPP case (tomacula) in the center of the image; (G) regeneration aspect: cluster of small axons (arrow). Semithin cross sections stained with toluidine blue; (under oil immersion – 60× Objective).
Electron microscopy aspects of axonal degeneration (sural nerve biopsy). (A) A myelinated axon showing an autophagic vacuole between axon and myelin sheath. (B) A myelinated axon with an autophagic vacuole in the Schwann cell exterior cytoplasma: small myelin debris are seen. (C) The same aspect: an autophagic Schwann cell with many smaller or bigger fragments of myelin inside. (D) A macrophage with lipid droplets is present near myelinated axons. (E) Total myelin degradation; only irregular laminated structure is present, with no axon (cross sections; bar = 2 μm).
Teased nerve fiber (sural nerve biopsy) panel. (A) A nerve fiber with segmental demyelination near two other normal myelinated fibers. (B) Near normal fibers, a fiber with segmental demyelination (a thin internode) and a fiber with few myelin ovoids and balls (axonal degeneration). (C) More myelin ovoids in an axonal degeneration. (D) A tomacula in myelin sheath of a nerve fiber.
After a segmental demyelination, along the affected internode, several Schwann cells arrive which begin to remyelinate this portion, the sign of remyelination being more short internodes (Figure 5).
Peripheral nerve remyelination. In demyelinating peripheral neuropathies, the segmental demyelination is often seen. Following a Schwann cell degeneration, the lost myelin internode is replaced by some Schwann cells which generate myelin sheaths, resulting in many shorter internodes.
The sign of axonal regeneration is observed on semithin sections and consists of the presence of some clusters of axons with the same small mean diameter and thinner myelin sheath (Figure 2G).
After these images sowing just few aspects of pathological degradation of peripheral nerve, focusing on myelin sheath damage, let’s take a closer look at what happens in the Schwann cell, at the cellular and molecular level.
Investigating the evolution of the main proteins that enter the composition of myelin sheath during and after nerve injury has been a subject of study for many scientists. These proteins are P zero (P0), myelin basic protein (MPZ), and P2. The first two play an important role in maintaining the integrity and compactness of the myelin sheath. P2 is a lipid-binding protein and participates in fatty acid elongation and transport during the myelination process [7]. Myelin associated glycoprotein (MAG) is a transmembrane protein that is found in the periaxonal region and participates in SC-axon contact organization. It seems to be involved in the myelination process after injury [8]. P0 and MBP mRNA in the distal nerve portion after transection were found to be 20% lower than normal levels but have had normal levels after crushing [9, 10]. In the absence of a contact between SCs and the axon, the levels of mRNAs of P0 and MBP remained low, and mRNA of MAG was undetectable, long time after nerve transection, whereas MAG mRNA was undetectable after lesion; in the case of a crush injury, after a sudden and short decrease, the mRNA levels of these proteins were found to increase rapidly afterwards [10, 11].
To understand what plasticity of Schwann cells means, we need to understand what the starting point is for their differentiation and evolution.
During development, SCs surround bundles of axons and support them to outgrow by releasing growth factors such as nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), and neurotrophin (NT3) [12, 13, 14]. It follows a “radial sorting” of axons by extension of cellular process from Schwann cells, which begins to divide axon bundles into smaller ones and finally separate the neighboring axons with cell cytoplasm. Thus two types of fibers are formed: (i) unmyelinated Remak fibers, in which SC surrounds several small-sized axons (sensory and autonomic) and does not produce myelin, and (ii) myelinated fibers in which each large-sized axon is surrounded by a SC cell, 1:1 relationship, and a myelin sheath is formed by SC membrane spirally wrapping the axon [15]. Mesaxon is termed the point where the plasma membrane apposition is formed where the first encircling process meets itself. Remak SCs maintain the proliferative capacity of all the life [16].
During this stage, changes in cell morphology and gene expression occur, mediated by the transcription factor Krox-20 (or Egr-2) [17, 18, 19].
The differentiation of Schwann cells is controlled by some
Nrgs need protease involvement for Nrg1-ErbB interactions because Nrgs are synthesized as single-pass transmembrane proteins and shed from the cell surface by the proteolytic cleavage, thus permitting the interaction with ErbB receptors across the periaxonal space [33, 34].
Another enzyme implicated in Nrg1 cleavage is beta-amyloid converting enzyme (BACE1), a
An effect opposite to the BACE activity has tumor necrosis factor-alpha-converting enzyme (TACE), a neuronal alpha-secretase, cleaving Nrg1 into an inactive form [37]. TACE genetic inactivation in motor neurons caused hypermyelination like in Nrg1 overexpression.
Another factor that is essential in SCs-axon interaction, with a protection role for the axon, is
All these interactions described above are very important and may be modulated in the control of nerve regeneration.
PNS has a very good regenerative capacity, and this is largely due to Schwann cells that develop a high plasticity and can contribute very quickly to the regeneration of peripheral nerves after injury whether it is a trauma or a pathological condition. In these cases, SCs have the ability to transform into an immature-like form, which drives subsequent regeneration of the nerve. These processes of dedifferentiation into non-myelinating cells and redifferentiation after injury are characteristic of these glial cells in PNS, and in the last decade a significant progress has been made in the study of the molecular mechanisms and signaling pathways that regulate this plasticity (reviewed in [42]). More of this, the myelinating and non-myelinating SCs remain bipotential cells all the time, as demonstrated by grafting or nerve cross anastomosis experiments [43, 44, 45]. Many experimental studies on transgenic animals have shown that after nerve cut or crush, both types of SCs reprogram into proliferative progenitor-like repair SCs [46, 47]. This phenomenon involves downregulation of pro-myelinating genes, such as early growth response 2 (Egr-2 or Krox-20), POU domain class 3 transcription factor 1 (Pou3f1 or Oct-6), and myelin protein zero (MPZ)/myelin basic protein (MBP). There is also an upregulation of markers of dedifferentiated (immature) SCs like low affinity neurotrophin receptor (p75NTR), c-Jun, or glial fibrillary acidic protein (GFAP) [6].
After Wallerian degeneration following nerve injury, a downregulation of pro-myelinating genes occurs, and the myelin clearing phenomenon begins after myelin sheath disorganization, through a mechanism of autophagy or myelinophagy [48]. Macrophages also participate in this process, phagocytosing myelin and axonal debris. The recruitment of macrophages is also done by SCs [49, 50, 51].
One of the major problems of human SCs is that as their regenerative capacity decreases in time, they can no longer sustain axonal growth, and their numbers decrease greatly (reviewed in [52]).
Regarding the plasticity of Schwann cells, although not covered by this chapter, we just want to mention here that SC precursors can generate many and different cell types during embryogenesis, besides myelinating and non-myelinating SCs, such as endoneurial fibroblasts, melanocytes, and neurons [52].
After injury, SCs reacquire some capabilities from early development, like proliferation, production of growth factors, sorting, and myelination. A good review regarding the biology of Schwann cells is the one made by Kidd et al. [3].
SC behavior and fate is regulated by two sort of interactions: SCs-axon and SCs-extracellular matrix/basal matrix. After 48 hours following axonal transection, SCs downregulate the production of myelin protein mRNAs [53] and upregulate trophic factors and cytokines [12, 13, 14] like NGF, BDNF, GDNF, and LIF, molecules necessary in axonal regeneration promoting into distal stump (reviewed in [54]). After axonal injury/transection, the axon is rapidly destroyed by a nonapoptotic autonomous mechanism [55]. SCs begin myelin degradation after axon injury, disassembling first the myelin internode starting with Schmidt-Lantermann incisure swelling [56, 57], following the dissolution of myelin in bubbles, ovoids, and balls. Macrophages finish the myelin degradation by phagocytosis [58]. It is not known exactly how much the SCs contribute to myelin degradation compared to macrophage participation, but it seems that it depends on the volume of the internode [59, 60]. During myelin degeneration, changes occur in the SC microtubule network, lysosome, and endosome positioning [61].
After nerve crush or transection, between the two stumps, over the lesion site, fibroblasts form a bridge, interacting with SCs [62]. The newly formed vasculature participates also in guiding the growing axons through this bridge to the distal end [63]. After a period of persistence of distal nerve stumps, distal axons disappear and dedifferentiated SCs proliferate, align, and begin emitting processes, forming the bands of Bungner (Figure 1), offering a physical and trophic support for the regrowth of axon [44, 60].
After the axonal regeneration, SCs differentiate once more in non-myelinating and myelinating cells to finish the functional recovery of the nerve. The regenerated myelin internodes (Figure 5) are shorter and thinner than the rest of the original ones in the proximal part of nerve [64].
The molecular mechanisms that regulate SC plasticity are very complex and widely described in many studies in recent years (reviewed in [42]). Here we will briefly mention them.
One important transcriptional factor in SC reprogramming is
Another transcriptional regulator is
Nuclear factor kB (
In the recent years, a transcriptional repressor,
Other factors which are overexpressed in SC dedifferentiation are
mTOR complex 1 (
In the distal stump of the peripheral nerve after injury SCs respond by activating MAPK proteins like extracellular signal-regulated kinase (Erk), c-Jun N-terminal kinase (JNK), and p38 MAP kinase [66, 90, 91, 92, 93, 94, 95].
Erk activation is a pro-myelinating factor, and if Erk is inhibited, the SC differentiation and myelination are blocked, showed many
In conclusion, Erk signaling is required in differentiation (Erk low levels) but also in dedifferentiation (high Erk levels) of SCs after nerve lesion [99, 100].
Without insisting, we would like just to remember other MAPK proteins and signaling pathways involved in SC plasticity:
After nerve injury, inflammation is an important phenomenon that must be considered. Thus, Toll-like receptors (TLRs) are key factors in initiating the immune response. A number of such receptors are expressed by SCs: TLR3, TLR4, and TLR7 [103]. Some experimental studies showed an upregulation of TLRs following nerve injury, the effect being the inflammation trigger with macrophage recruitment and activation and myelin clearance via SCs [50, 104, 105].
SCs express receptors for axonal neuregulins, as it is showed in Ssection 2.2. The neuregulin/Erb2/3 signaling is strongly involved in immature SC development but not in the regulation of adult SC proliferation after injury. An
Neuregulin Nrg1 is still necessary for adult SC evolution after nerve injury [108, 109]. The absence of Nrg1 in adult axons results in remyelination defects after nerve crush experiments and also in a slower axon regeneration [110].
Although the peripheral nerve has a much greater regenerative capacity than the CNS nerve, the clinical recovery of patients with peripheral neuropathies is difficult, slow and often incomplete. Moreover, this capacity decreases with age.
The rate of nerve regeneration is approximately 1 mm/day, depending on the site of the lesion and on the patient age. SC plasticity diminishes with age, showing an altered expression of c-Jun [111] and a weak regenerative capacity [112, 113].
Understanding the signaling pathways that govern SC reprogramming and plasticity is essential for nerve repair and therapy.
For example, modulating Nrg1/ErbB signaling may improve myelin clearance, axonal regeneration, and finally functional nerve recovery after injury. An inappropriate overactivation of this pathway may lead to demyelinating neuropathies or tumors like neuroepithelioma and neuroplastic SC line [114, 115]. Experiments on transgenic mice with overexpression of Nrg1 showed hypertrophic neuropathies and malignant peripheral nerve sheath tumors [116]. The excessive activation of ErbB2 by
Another approach to stimulate SC regeneration and peripheral nerve functional recovery is the exogenous modulation by electric stimulation with low frequencies, photomodulation with low-level laser, and pharmacotherapy (with pharmacological agents, growth factors, bioproducts, or hormones) (reviewed by [119]).
Understanding Schwann cell biology and its extraordinary plasticity can lead to the development of new therapeutic approaches in peripheral nerve pathology and in the improvement of treatment methods in the case of traumatic nerve lesions. Peripheral neuropathies cause a significant morbidity and a decreased life quality. A better understanding of the many SC signaling pathways represents a very important approach for nerve regeneration as long as we have seen that SC is the main engine in nerve damage and repair after injury.
The recovery of the peripheral nerve, although better than that of the CNS nerve, is still quite complicated, difficult many times, and it is never perfect until the end. But in the last years, a huge amount of scientific data drew attention to the role of growth factors, transcriptional factors, inflammatory factors, hormones, and even exogenous modulation factors in the regulation of Schwann cell and of Schwann cell-axon interrelations, a complex integrated system.
It is expected that studies regarding SCs plasticity in peripheral nerve regeneration will continue and expand, improving not only the scientific knowledge but also a targeted more effective therapies, based on the pathology, personalized treatment and specific response of patients.
This work was supported by the Ministry of Education and Research in Romania, under the following grants: Program 1, The improvement of the National System of Research and Development and Subprogram 1.2—Institutional Excellence—Projects of Excellence Funding in RDI, Contract nr. 7PFE/16.10.2018; PN 19.29.02.01; by UEFISCDI, grant, Project PN-III-P1-1.2-PCCDI-2017-0782 (REGMED); and by COST 18125 AeroGels.
The authors declare no conflict of interest.
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However, some phage and bacteria do store genetic information in linear constructs, and the ends of these structures form either invertrons or hairpin telomeres. Hairpin telomere formation is catalyzed by a protelomerase, a unique protein that modifies DNA by a two-step transesterification reaction, proceeding via a covalent protein bound intermediate. The specifics of this mechanism are largely unknown and conflicting data suggests variations occur between different systems. These proteins, and the DNA constructs they produce, have valuable applications in the biotechnology industry. They are also an essential component of some human pathogens, an increased understanding of how they operate is therefore of fundamental importance. Although this review will focus on phage encoded protelomerase, protelomerases found from Agrobacterium and Borellia will be discussed in terms of mechanism of action.",book:{id:"6910",slug:"bacteriophages-perspectives-and-future",title:"Bacteriophages",fullTitle:"Bacteriophages - Perspectives and Future"},signatures:"Sophie E. Knott, Sarah A. Milsom and Paul J. Rothwell",authors:[{id:"298694",title:"Dr.",name:"Paul",middleName:null,surname:"Rothwell",slug:"paul-rothwell",fullName:"Paul Rothwell"},{id:"298695",title:"Ph.D. Student",name:"Sophie",middleName:null,surname:"Knott",slug:"sophie-knott",fullName:"Sophie Knott"},{id:"302001",title:"BSc.",name:"Sarah A",middleName:null,surname:"Milsom",slug:"sarah-a-milsom",fullName:"Sarah A Milsom"}]},{id:"73723",title:"Neuromuscular Effects and Rehabilitation in Guillain-Barré Syndrome Associated with Zika Virus Infection",slug:"neuromuscular-effects-and-rehabilitation-in-guillain-barr-syndrome-associated-with-zika-virus-infect",totalDownloads:545,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The 2015–2017 Zika Virus outbreak caused a high increase in patients with Guillain-Barré syndrome (GBS), a post infectious autoimmune disease of the peripheral nerves. The severity of GBS can range from mild impairment with fast recovery to complete paralysis including severe respiratory or autonomic failure. Recovery may take months and even years and may be incomplete despite disease modifying treatment with IVIG or plasma exchange. Therefore, optimal supportive care and effective rehabilitation remain crucial. Multidisciplinary rehabilitation is recommended but may be challenging in the acute phase because of limited patient participation due to profound muscle weakness and severe pain. Inactive denervated muscles will inevitably undergo rapid degeneration resulting in wasting, weakness, and contractures as major long-term complications in severely affected patients. In this chapter, the current evidence of rehabilitation on the short- and long-term motor function in GBS is reviewed, including newly obtained experiences with neuromuscular electrical stimulation (NMES). Rehabilitation remains an area lacking well designed and controlled clinical studies and thus a clear lack of evidence-based guidelines.",book:{id:"8990",slug:"current-concepts-in-zika-research",title:"Current Concepts in Zika Research",fullTitle:"Current Concepts in Zika Research"},signatures:"Thomas Harbo and Henning Andersen",authors:[{id:"310593",title:"M.D.",name:"Thomas",middleName:null,surname:"Harbo",slug:"thomas-harbo",fullName:"Thomas Harbo"},{id:"318823",title:"Prof.",name:"Henning",middleName:null,surname:"Andersen",slug:"henning-andersen",fullName:"Henning Andersen"}]}],onlineFirstChaptersFilter:{topicId:"427",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:18,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,annualVolume:11418,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,annualVolume:11419,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,annualVolume:11420,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,annualVolume:11421,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,annualVolume:11422,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"27",title:"Multi-Agent Systems",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",isOpenForSubmission:!0,annualVolume:11423,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:43,paginationItems:[{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82212",title:"Protein Prenylation and Their Applications",doi:"10.5772/intechopen.104700",signatures:"Khemchand R. 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Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. 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Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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