Experimental studies using nanosystems for CL treatment.
\r\n\tThe protection of biodiversity is a major target of the European Union Marine Strategy Framework Directive, requiring an assessment of the status of biodiversity on the level of species, habitats, and ecosystems including genetic diversity and the role of biodiversity in food web structure and functioning. The restoration of marine ecosystems can support the productivity and reliability of goods and services that the ocean provides to humankind, to maintain ecosystem integrity and stability. Some of the goods produced by the marine ecosystem services are fish harvests, wild plant and animal resources, water, some of the services provided recreation, tourism, breeding and nursery habitats, water transport, carbon sequestration, erosion control, and habitat provision.
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Marta Gonçalves",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10845.jpg",keywords:"Non-indigenous Species, Dynamics, Ecosystem Maturation, Ecological Succession, Water Quality, Recovery, Biodiversity, Environmental Status, Ecosystem Services, Goods Production, Carbohydrates, Carrageenan",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 14th 2022",dateEndSecondStepPublish:"June 22nd 2022",dateEndThirdStepPublish:"August 21st 2022",dateEndFourthStepPublish:"November 9th 2022",dateEndFifthStepPublish:"January 8th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Ana Marta Gonçalves (h-index 19) holds a Ph.D. in Biology, from the University of Coimbra, Portugal, in collaboration with Ghent University, in 2011. During her research career obtained several grants is highly international competitive calls, including the MARS award for young scientists funded by The Royal Netherlands Institute for Sea Research (NIOZ) and the Foundation for Science and Technology (FCT, Portugal) grants.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"320124",title:"Dr.",name:"Ana M.M.",middleName:"Marta",surname:"Gonçalves",slug:"ana-m.m.-goncalves",fullName:"Ana M.M. Gonçalves",profilePictureURL:"https://mts.intechopen.com/storage/users/320124/images/system/320124.jpg",biography:"Ana Marta Gonçalves obtained a Ph.D. in Biology with a specialization in Ecology from the University of Coimbra, Portugal, in collaboration with Ghent University, Belgium, in 2011. Currently, she is an auxiliary researcher at the Marine and Environmental Sciences Center (MARE), Portugal, where she is also a member of the Directive Board. 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Although not fatal as VL, CL is the most common form of leishmaniasis and a serious public health problem. According to the World Health Organization (WHO) estimates, CL is endemic in 87 countries, with almost 200,000 new cases reported in 2015 [1]. From 2005 to 2013, CL-associated morbidity increased by 175% of disability-adjusted life years (DALYs) [2]. The impact of CL may be much greater considering the high under-reported cases and estimation that one fourth of the world population (1.7 billion people) live in area at risk of infection [3]. In addition, inadequate disease control may promote the progression of CL to more morbid and undefined subforms, such as diffuse CL and mucosal leishmaniasis (ML).
In the great majority (>90%) of cases worldwide, CL is of the uncomplicated type, with 1–4 localized skin ulcers, not larger than 3–4 cm diameter, with a raised border and central depression [4]. Even with localized manifestation, current treatment is normally based in the daily administration of intramuscular or intravenous injections with antimonials, pentamidine, or amphotericin B for 20–30 days. Besides limited to few drugs, and occurrence of drug resistance, available CL treatment produces unacceptable systemic toxicity [5].
Ideally, CL chemotherapy as proposed by Drugs for Neglected Diseases initiative (DNDi) should be efficacious against all species, compatible in combination therapy, safe in pregnant and breastfeeding women, and administered by oral or topical route [6]. However, oral and topical therapies have shown limited efficacy.
The major challenge in CL treatment is the preferred intracellular parasite location in macrophage phagolysosomes. That hinders drug access, making treatment with conventional formulations especially difficult [7].
Thus, the search for new drugs with different mechanisms of action and innovative forms of drug delivery systems appropriate for the effective treatment of CL is urgently needed. In that context, nanotechnology has emerged as an interesting strategy to increase drug potency and reduce toxicity.
Nanotechnology consists of the development of systems, structures, or devices in the nanometric scale, presenting at least one novel/superior characteristic or property over the original [8]. The use of nanostructured particles for drug delivery is a promising strategy due to their versatility. Besides, they may: (i) protect the drug against physical, chemical, and/or enzymatic degradation, (ii) enhance the pharmacokinetic properties, and (iii) improve bioavailability. They may also be functionalized for drug release at a specific site and thereby reduce systemic toxicity [7]. Furthermore, leishmaniasis is a particularly interesting disease to be treated with drug-loaded nanoparticles since the parasites almost exclusively infect the highly phagocytic macrophages. In this way, the infected cells of the skin (CL) or deep organs (VL) take up the nanoparticulated drug, which will reach the parasitophorous vacuole and act directly on the parasite (Figure 1). This allows the drug to reach an effective intracellular concentration, allowing dose and toxicity reduction. Particle uptake may be further increased with surface functionalization with receptor-binding ligands like mannose or mannan [9].
Nanoparticle drug delivery to intracellular parasites. A drug-loaded lipid or polymeric nanoparticle (Np, yellow) reaches the
Interest in designing nanomedicines for CL has grown over the years, as seen by the steady increase in scientific publications. Several nanosystems, such as liposomes [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20], solid lipid nanoparticles [21, 22], lipid complexes [23, 24], lipid-core nanocapsules [25], polymeric particles [26, 27, 28, 29, 30, 31], inorganic nanoparticle [32, 33, 34, 35], cyclodextrins complexes [36, 37], and drug nanoparticles [38] have been tested
Routes | Drug | Nanosystem | Parasite | Efficacy | Ref |
---|---|---|---|---|---|
Amphotericin B | Chitosan and chondroitin sulfate nanoparticles | Yes | [26] | ||
Amphotericin B | Poloxamer 407-micelles | Yes | [27] | ||
Amphotericin B | PLGA-DMSA nanoparticles | Yes | [28] | ||
Amphotericin B | Liposome | No | [10] | ||
Amphotericin B | Liposome (Ambisome®) | Yes | [11] | ||
Amphotericin B | DSHemsPC-liposome | Yes | [12] | ||
Amphotericin B | Nanodisks | Yes | [23] | ||
Amphotericin B | PADRE-derivatized-dendrimer complexed with liposome | Yes | [13] | ||
Chalcone DMC | PLA Nanoparticles | Yes | [29] | ||
Nanoselenium | Inorganic nanoparticle | Yes | [33] | ||
Paromomycin | Solid lipid nanoparticle | Yes | [21] | ||
Paromomycin | Solid lipid nanoparticle | Yes | [22] | ||
Pentamidine | Methacrylate nanoparticles | Yes | [30] | ||
Pentavalent antimonial | Nanohybrid hydrosols | Yes | [38] | ||
Sodium stibogluconate | Liposome | Yes | [14] | ||
Quercetin | Lipid-core nanocapsules | Yes | [25] | ||
Meglumine antimoniate | Beta-cyclodextrin | Yes | [36] | ||
Meglumine antimoniate | Polarity-sensitive nanocarrier | Yes | [24] | ||
Amphotericin B | Liposome | No | [15] | ||
Amphotericin B | Gamma-cyclodextrin | Yes | [37] | ||
Chalcone CH8 | Liposome | Yes | [16] | ||
Paromomycin | Liposome | Yes | [17] | ||
Paromomycin | Liposome | Yes | [18] | ||
Meglumine antimoniate | Liposome | Yes | [19] | ||
Nanosilver | Inorganic nanoparticles | No | [32] [34] | ||
Nanosilver | Inorganic nanoparticles | No | |||
Amphotericin B | Liposome (Ambisome®) | No | [11] | ||
Chalcone CH8 | PLGA microparticles | Yes | [31] | ||
Nanosilver | Inorganic nanoparticles | Yes | [35] | ||
Meglumine antimoniate | Liposome | No | [20] | ||
Miltefosine | Liposome | Yes | [20] | ||
Paromomycin | Liposome | No | [20] | ||
Paromomycin | Solid lipid nanoparticle | Yes | [22] | ||
Sodium stibogluconate | Liposome | Yes | [14] |
Experimental studies using nanosystems for CL treatment.
Note: Chalcone DMC – 2’,6’-dihydroxy-4’-methoxychalcone; Chalcone CH8 – 3-nitro-2’-hydro-4’,6’-dimethoxychalcone; DMSA – dimercaptosuccinic acid; DSHemsPC – 1,2-distigmasterylhemi-succinoyl-sn-glycero-3-phosphocholine; PADRE – pan DR-binding epitope; PLA – poly(D,L-lactide); PLGA – poly(lactic-co-glycolic acid); UVB – ultraviolet B radiation.
Advances and challenges of nanotechnology use in leishmaniasis treatment, especially for VL, have been extensively reviewed recently [7, 39, 40]. Here, we attempted to identify some of the opportunities and challenges of using nanotechnology to improve CL treatment. For that, mainly
For more than 70 years, injectable pentavalent antimonials such as meglumine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®) have been the first-choice drugs in most countries. The paucity of new effective drugs in the market is due to lack of investment/economic interest for the discovery of therapeutic alternatives. The therapeutic regimen consists of intramuscular or intravenous daily injections for 20–30 days. The long period of treatment leads to the accumulation of antimony (Sb) in the tissues, producing myalgia, pancreatitis, pancytopenia, hepatic and cardiotoxicity [41]. Other limiting factors are drug resistance and increased therapeutic failure [42]. In India, its use in VL has been contraindicated due to the appearance of resistant
In Sb-refractory cases, injectable pentamidine, amphotericin B or paromomycin are used. Pentamidine acts on the DNA synthesis of the parasite and has similar efficacy to antimonials, but also produces side effects such as hypoglycemia, diabetes, tachycardia, hypotension, nephrotoxicity and pain at the site of administration [44]. Like antimonials, cases of pentamidine resistance have been increasing, compromising their use in many endemic regions [45].
Amphotericin B is a polyene antibiotic mostly used in VL and in the disfiguring CL form, mucosal leishmaniasis, administered intravenously for 20 days, usually under hospital admission. This is the most efficacious antileishmanial drug, but it produces serious side effects due to its low solubility (nephrotoxicity), and secondary affinity not only for the parasite ergosterol but also for the host cholesterol, causing hypokalemia and cardiotoxicity [5]. Formulations of amphotericin B in lipids have led to a marked improvement in their plasma solubility and bioavailability. Three lipid formulations are commercially available: unilamellar liposomes (Ambisome®), lipid complex (Abelcet®) and colloidal cholesterol suspension (Amphocil®). Among these, Ambisome® has the highest plasma half-life, lowest toxicity, and highest efficacy against VL and CL models [46, 47]. In some countries, Ambisome® is already recommended as the first-choice drug for the treatment of VL and ML difficult cases. However, its high cost, the undefined optimum dosing regimen, toxicity, and the greater uptake of liposomes by the liver make its widespread use in the treatment of CL unfeasible [48].
The interest in the administration of nanosystems by parenteral routes has been increased, mainly for VL, since they increase the drug bioavailability and depending on the charge, size and composition accumulate preferentially in organs such as liver. In addition, nanosystems can be conjugated to biological compounds, such as peptides, antibodies and mannose, favoring their targeting to macrophages [9]. Thus, even with the dose reduction, the encapsulated drugs present greater efficacy and reduction of toxic effects. To date, most experimental studies are conducted parenterally that include chitosan and chondroitin sulfate nanoparticles, Poloxamer 407-micelles, PLGA-DMSA nanoparticles, PADRE-derivatized dendrimer complexed with liposomes, PLA nanoparticles, solid lipid nanoparticles, methacrylate nanoparticles, and liposomes (Table 1). Since amphotericin B is currently the most potent antileishmanial agent, most studies have used it in order to improve its specificity and reduce its adverse effects [10, 11, 12, 23, 26, 27, 28]. Despite the promising effects of nanomedicines obtained so far, Ambisome® remains the only nanomedicine approved for leishmaniasis parenteral treatment.
Another interesting strategy in the treatment of CL is the use of inorganic nanoparticles, such as nanoselenium, nanosilver and nanotitanium dioxide. Despite the promising efficacy of injected nanosilver [35] and nanoselenium [33] in CL models, the use of nanosilver by topical route was ineffective [32, 34], probably due to the lack of nanoparticle permeation through the infected skin, since those particles were directly active against culture parasites. Nanosilver may act directly on the
The experimental parenteral routes are normally intravenous or intraperitoneal, the latter not applicable in clinical usage. An important issue to be considered when nanoparticles are intravenously injected is the possibility of thrombosis induction [50]. However, small and submicrometric they may be, larger aggregates can form and clog small veins [51]. Therefore, for safety reasons, intralesional, topical and oral routes should be preferable for CL treatment.
The oral route is recommended for both CL and VL due to the ease of administration, high patient compliance, and versatility to increase drug bioavailability. However, systemic adverse effects cannot be precluded.
Miltefosine, a hexadecylphosphocholine previously used to treat cancer, is the only oral drug approved in VL treatment, with good cure rates in India, Nepal, and Bangladesh. However, its teratogenic potential, poor efficacy in patients coinfected with VL and human immunodeficiency virus and recently high rates of clinical failures have increasingly restricted its use in combination therapy [52]. Data on the efficacy of miltefosine in CL treatment are inconclusive, with a large variation depending on the parasite species and geographical area [53].
Another oral drug, allopurinol, an inhibitor of xanthine oxidase, has been explored since 1982 when its activity was demonstrated
Local therapies are the ideal way to treat uncomplicated CL, as they avoid unnecessary systemic side effects. This topic was subdivided in topical and intralesional treatments due to their different delivery approaches.
Topical CL treatment may be provided with chemical drugs or physical methods, such as thermotherapy and cryotherapy. Thermotherapy is the application of high temperature (>50°C) at the center and border of each lesion, based on the inability of
Topical drug treatment of CL normally involves administration of drugs in the form of ointments, creams or gels. These should be ideal for uncomplicated CL due to reduced hospital costs, since it can be auto-applied [44]. The most studied topical formulations are paromomycin creams and gels. The low skin permeation of paromomycin requires association with strong permeants, such as methylbenzethonium chloride, urea and surfactant-associated gentamicin (WR-279396), which may produce local burn and skin irritation [68]. To circumvent that, some formulations have used the milder urea permeant; however, clinical efficacy remains variable depending on the parasite species and geographical area [4]. The results with the WR-279396 formulation are also conflicting, showing high efficacy in patients infected with
Recently, DNDi supported a Phase Ib and II clinical study in Colombia evaluating the safety, pharmacokinetics, and efficacy of Anfoleish, a cream formulation containing 3% amphotericin B [71]. However, limited efficacy was found after topical application in patients infected with
For an optimal topical formulation, the drug should be highly effective and have a high permeation through the skin, reaching the parasite in the deep dermal layer in effective concentrations. For the drug to successfully permeate the stratum corneum, it must possess adequate lipophilicity and a molecular size below 500 Da. The failure or partial success of the topical formulations of paromomycin (615 Da) and amphotericin B (924 Da) is directly related to the low permeability of these drugs through the skin, probably due to their high molecular size [72]. In addition, the typical morphology of CL ulcer with necrotic center and high borders influences the permeation of drugs. Although local inflammatory reaction may facilitate the permeation of more hydrophilic drugs [68], infected macrophages are located in the border of the lesions where epidermal thickening occurs, with hyperplasia and increased number of cell layers, which may hamper drug permeation.
Topical liposomes have emerged as an advantageous way to overlay this problem by increasing drug skin permeation. In fact, some studies have shown the efficacy of liposomes loaded with paromomycin [17, 18] or meglumine antimoniate [19] in
In the search for new active drugs for leishmaniasis, our group has been studying the chalcone CH8 (3-nitro-2’-hydro-4’,6’-dimethoxychalcone), a nitrosylated derivative of the plant-derived chalcone (DMC – 2’,6’-dihydroxy-4’-methoxychalcone), which demonstrated a high selectivity index (SI = 143) and antileishmanial activity
Notwithstanding, the high phospholipid cost and liposomal instability hinder their use for CL. Thus, other nanosystems such as gamma-cyclodextrin have been studied for amphotericin B skin delivery to improve drug solubility and topical efficacy in
Intralesional drug administration is an alternative local treatment for CL. This is especially appropriate for patients with uncomplicated localized CL—up to four lesions, each no more than 3 cm in diameter, as well as parenteral medication restrictions due to systemic toxicity. Besides the lesser toxicity, local subcutaneous injections can accelerate clinical cure and reduce hospital costs as less injections are needed [4]. Pentavalent antimonials are the most used drugs, showing 68–100% efficacy in different clinical studies, depending on the size of the lesions [78, 79, 80, 81]. Repeated injections are required due to the high solubility that favors rapid absorption into the circulation. Treatment generally consists of 1–5 injections around each lesion per day, twice a week. In addition to the pain inflicted, adverse effects like local hyperpigmentation and anaphylactic shock have been reported [82].
Amphotericin B has also been tested by intralesional route in Iran in patients refractory to antimony therapy, leading to complete lesion remission in 61% of the cases [83]. Due to the necrotizing effect of deoxycholate surfactant in amphotericin B formulation, the amount injected has to be as low as possible, reducing effectiveness. Thus, despite its high potential in CL, intralesional treatments need improvement, particularly as regards dose number reduction.
Intralesional drug-loaded nanoparticles have appeared as interesting drug delivery systems in CL due to direct drug delivery to the infected macrophages. However, for the formulation to be effective, drug chemistry, nanosystem choice, and treatment schedule must be finely adjusted. Lipid systems such as SLN loaded with paromomycin have been tested intralesionally in
In this context, polymeric particles have emerged as an interesting strategy for CL intralesional and single-dose treatment. The advantage of this system is that particles smaller than 6 μM can be easily phagocytosed by infected macrophages releasing the drug directly into the target, whereas the larger microparticles form a depot slowly releasing the drug into the site, allowing at only one dose the drug to remain in the site of infection for the time needed for healing. The size of the microparticles and their polymer composition ensures retention of the drug in the lesion and determines its release time. In this way, adverse systemic effects are avoided and the effectiveness of the drug is increased. Recently, the safety and efficacy of PLGA microparticles containing chalcone CH8 in the intralesional treatment was demonstrated in
Since nanomedicines can be more efficiently taken up by the infected macrophages than free drugs, and also be designed to cross skin and epithelial barriers, they have emerged as promising strategies to allow novel topical and oral treatments for CL. Noteworthy is the possibility to treat the disease with a single local injection with biodegradable polymeric particles. Despite the promising results obtained with the different nanomedicines in pre-clinical studies, so far none has so far progressed to clinical trials in CL. Therefore, further efforts must be made in order to have them in the near future in the antileishmanial therapy arsenal.
A.J. Sousa-Batista is a recipient of Rio de Janeiro State Research Foundation—FAPERJ post-doc grant # E-26/202.401/2017.
The authors have no conflict of interest to declare.
The design of scaffold materials that can guide tissue regeneration is a very challenging goal [1]. In addition, to support and promote the growth and differentiation of specific cells, an ideal scaffold requires careful control of the material’s structure in the range of nanometers to centimeters, and some natural materials with complex structure exist in nature, which provides ideas for the design of ideal scaffolds [2]. These natural materials, such as mammal bones, abalone pearl layers and fish scales, which are composed of multi-layer biominerals and biopolymers, have complex microstructure, which can control the crack growth and fracture in three-dimensional (3D) direction, producing much more strength and toughness than their constituent materials [3, 4, 5]. Jellyfish and sea anemones, with a water content of up to 90%, show that their gelatinous bodies exhibit exciting mechanical properties and are able to respond quickly to various environmental stimuli [6, 7, 8]. There are also some soft support tissues (such as tendons, ligaments, meniscus, and cartilage), showing softness, toughness and impact resistance [9]. Because of the beneficial properties of natural composite materials, the design of bionic materials has attracted significant attention. Bio-inspired material is considered as a kind of material inspired by nature or biology and then developed by simulating some characteristics [10], and usually, the bio-inspired materials provide better functions than synthetic materials [11].
\nHowever, there are still many limitations on the fabrication of bio-inspired materials using traditional material manufacturing technology because they cannot accurately control the distribution and spatial trend of micro-holes inside the materials, and it is challenging to produce the contour matching with natural materials [12, 13]. Recently, 3D bioprinting technology has become a promising tool for manufacturing materials with high-precision, which can overcome the limitations compare with the traditional methods, and finally can eventually produce complex and delicate biomimetic 3D structures. Also, 3D bioprinting technology realizes the automatic biological preparation of cell-laden structure through the layered deposition of bio-inks
In recent years, in tissue engineering development, many materials have been developed to meet the needs of 3D bioprinting. The most common 3D bioprinting materials are metals, engineering plastics, photosensitive resins, bioplastics and polymer hydrogels. The bio-inspired hydrogels are very similar to natural extracellular matrix (ECM) and display potential advantages in tissue engineering [19]. Bio-inspired hydrogel provides an adequate and porous microenvironment that allows good nutrition and oxygen to diffuse into the encapsulated cells and can be modified to guide cellular processes with various physical, chemical, and biological cues [20]. Besides, these hydrogels are usually non-toxic or low toxic and have good reproducibility. Next, the 3D bioprinting techniques used for the fabrication of bio-inspired hydrogels were summarized, and the materials used for 3D bioprinting were outlined. This chapter also focuses on the applications of bio-inspired hydrogels.
\nThere are several available 3D bioprinting techniques for fabricating bio-inspired hydrogels, including inkjet bioprinting, laser-assisted bioprinting, extrusion bioprinting, and stereolithography, as shown in \nFigure 1\n [21].
\nBioprinting techniques mainly include inkjet, laser-assisted, extrusion and stereolithography [
During the inkjet bioprinting process, biomaterials are selectively placed on the construction platform layer by layer until the required structure is formed. The first inkjet printers for bioprinting applications were improved versions of commercial two-dimensional ink printers [22]. For the inkjet bioprinting, the ink in the ink cartridge is replaced by biomaterials, and the paper is replaced by an electronically controlled lifting table to provide the control of the third dimension Z-axis in addition to the X-and Y-axes. The bioprinter based on inkjet printing technology is customized to process and print biomaterials with higher resolution, accuracy and speed [16]. Inkjet bioprinters use thermal or acoustic forces to spray droplets onto the substrate, which can support or form part of the final structure [23]. Thermal inkjet uses a heating element to induce the evaporation of a small volume of bioink in a reservoir, thereby forming and ejecting a small droplet. Therefore, in the printing process, this method keeps the cells at high temperature (300°C) for several microseconds (about 2 microseconds), which may lead to the formation of transient pores in the cell membrane [16]. Using the thermal inkjet printer, Solis et al., studied the effect of heat generated by the thermal ink-jet bio printer and found that the survival rate of Chinese hamster ovary (CHO) cells was 89% [24]. Such survival rate of cells could be greatly improved by using a piezoelectric inkjet printer, the generation and injection of droplets are realized by applying external voltage to control the mechanical deformation of piezoelectric transducer, which prevents the temperature from rising to the super physiological level [25]. Compaan et al. used alginate as the sacrificial material to prepare cell-supported silk fibroin hydrogels with a clear structure based on the piezoelectric inkjet 3D bioprinting system. The printed tubular structure has a diameter of 5 mm, a height of 2.5 or 5.0 mm and a thickness of about 400 microns. Moreover, the effect of citrate treatment on the printing was compared. The results showed that alginate removal and alginate removal could enable cells to extend and contact each other and form a cell network in the whole hydrogel [26].
\nThe advantages of inkjet bioprinting mainly include: low cost due to its similar structure to commercial printers, high printing speed due to the ability of the print head to support parallel operation mode, and relatively high unit survival rate (usually from 80–90%) determined by many experimental results. However, the risks of cells and materials exposed to thermal and mechanical stresses, low droplet directionality, uneven droplet size, frequent nozzle plugging, and unreliable cell encapsulation have brought considerable limitations to the application in tissue engineering [27].
\nThe typical laser-assisted biological printing device include pulsed laser beams, focusing systems, and donor bands that respond to laser stimuli, consisting of glass covered with laser energy absorbing layers, and biomaterial layers (such as cells/hydrogel composite) prepared in liquid and receiving substrates for ribbons. The principle of laser-assisted bioprinting is to apply high-energy pulse laser (usually near-infrared laser) to the donor color band coated with bioink. This laser pulse evaporates a part of the donor layer, forms a high-pressure bubble on the interface of the bioink layer, and pushes the materials containing cells to the receiving substrate [16, 25, 28]. Compared with inkjet bioprinting, laser-assisted bioprinting can avoid the problem of jamming cell or material, also can avoid direct contact with the printer and biological ink at the same time. The non-contact biological printing method can choose much more types of ink, resulting in printing materials with wider range of viscosity [28].
\nThe laser pulse energy, ECM thickness, and bioink viscosity can influence cell viability. The higher the laser energy is, the higher the cell death rate is, but the increase of membrane thickness and bioink viscosity will lead to an increase of cell viability. Guillotin et al. studied the effects of bioink viscosity, laser energy and printing speed on printing resolution. The microscale resolution and 5 kHz printing speed could be achieved, and the laser-assisted bioprinting could combine cells with ECM to produce soft tissue with high cell density
The extrusion bioprinting can fabricate 3D cell carriers for tissue regeneration. The prepolymer solutions need to be prepared first, and almost all types of prepolymer solutions with different viscosities and aggregates with high cell density can be printed with extruded bioprinters [28]. Different from printing small droplets onto the platform, the extrusion bioprinting continuously deposit hydrogel filaments within a diameter of 150–300 microns to generate 3D structures. Common extrusion bioprinting method includes pneumatic, piston-driven, and screw-driven dispensing. In pneumatic dispensing, air pressure provides the required driving force, while in piston and screw-driven dispensing, vertical and rotating mechanical forces start printing respectively [30]. There are three main factors that decide the printability of extrusion bioprinting, mainly including the adjustability of viscosity, the bioink phase before extrusion, and the material-specific bio-manufacturing window [31]. Extrusion bioprinters have been used to produce various tissue types, such as aortic valves, branching vascular trees, in vitro drug movement and tumor models [32]. Although the manufacturing time may be prolonged for high-resolution complex structures, the structures have been manufactured from the clinically related tissue size to the microtissue in the microfluidic chamber. Furthermore, it is convenient to combine cells with bioactive agents, because that the heating process is not involved [33]. Compared with inkjet 3D bioprinting, extrusion bioprinters can achieve a continuous flow of biomaterials, thus achieving the simplicity of operation and a broader selection of biomaterials, including polymers, acellular matrices, cellular hydrogels, spheres and aggregates [34].
\nAmong all the bioprinting technologies, stereolithography (SLA) 3D bioprinting display much more advantages over extrusion or ink-jet bioprinting technology [28]. SLA is based on the polymerization of photosensitive polymers, and the digital mirror array controls the light band in the projection field to achieve selective crosslinking of each layer of the hydrogel prepolymer solution [35]. No matter how intricate a layer’s pattern is, the printing time is the same because the whole pattern is projected on the printing plane. Therefore, the printer only needs a movable table in the vertical direction, which significantly simplifies the control of the printer. The cell encapsulated scaffold fabricated by the SLA system can achieve 100 μm resolution with printing time less than 1 hour, also maintain very high cell viability (90%) [36]. The above properties make SLA practical for fabricating delicate construct for tissue engineering. Arcaute et al. used composite lithography technology and two different molecular weight of polyethylene glycol (PEG) to prepare composite multilayer 3D structure of PEG hydrogel, and the properties of prepared hydrogel were influenced by photo-initiator and photosensitive polymer concentration. Besides, the prepared PEG hydrogel supports attachment, proliferation and differentiation of bovine chondrocytes, providing evidence for the applicability of resins for cartilage tissue engineering [37]. Valentin et al. prepared the sodium alginate precursor solution based on ion crosslinking, and different concentrations of cationic sources, such as barium carbonate, magnesium carbonate and calcium carbonate, and photo acid generator (PAG), diphenyliodonium nitrate were used, and the sodium alginate hydrogel was printed by SLA. The printed alginate hydrogel exhibited different mechanical and physical properties when crosslinked with two kinds of cations. The microstructures with variable height could be printed with optimized precursor formulations. Due to the high resolution, the 3D fabrication of natural and synthetic polyelectrolyte hydrogels via SLA enables lab-on-a-chip devices, soft sensors and actuators, and other biologically-inspired devices [38].
\nHydrogels are considered as the gold standard materials for 3D bioprinting because they can provide a flexible and hydrated cross-linked network, similar to the natural extracellular matrix, in which cells can survive [39]. The polymers prepared for hydrogels can be classified into natural and synthetic polymers [40]. The natural polymers include alginate, chitosan, hyaluronic acid, gelatin, and so on, and the synthetic polymers mainly include polyacrylamide (PAAm), polyvinyl alcohol (PVA), polyethylene glycol (PEG), polylactic acid (PLA), and so on [41, 42].
\nMost hydrogels prepared by natural polymers have the advantages of good hydrophilicity, good biocompatibility, specific enzymatic degradation, and contain various active functional groups and structural domains, and display better interaction with cells to promote cell proliferation and differentiation.
\nAlginate is extracted from alginate plants, is a kind of natural high molecular, composing of β-d-mannuronate (M) and α-l-guluronate (G). Alginate has been widely used in tissue engineering because of its advantages of abundant production, low price, good biocompatibility, and abundant functional groups, which are suitable for the preparation of bioink for 3D bioprinting [43, 44]. Alginate can react with CaCO3 to release bivalent Ca2+ and then form an ionic crosslinking hydrogel bonded with -COO- on G unit of alginate G unit, to achieve the controllability of alginate ion crosslinking. The alginate hydrogel has high toughness and good mechanical properties, but the degradation rate of the alginate hydrogel is not controllable [45].
\nChitosan is the product of deacetylation of chitin, which has a straight-chain structure and positive charge due to the presence of amino groups. Because of the useful biological function and biocompatibility, the degradation by microorganisms, chitosan has been widely concerned and applied in various industries [46]. The chitosan ink can be directly printed in air, and then the chitosan scaffold is refined by physical gelation. A chitosan hydrogel that satisfies both biocompatibility and mechanical properties has been obtained, and it has been confirmed that chitosan hydrogel can guide cell growth [47].
\n(A) Fabrication of rapid gelation and tough GelMA/HA-NB/LAP hydrogel for DLP-based printing. (B) the skin analogous with sophisticated two-layer gel structure was fabricated via 3D bioprinting. (a) the bioink was printed with a layer-by-layer style using a DLP-based 3D printer. (b, c) the structure of native skin was displayed in CAD images. (d) the lower layer view of the scaffold was shown. (e) CAD images of different designed microchannel size and the printed products. (f) the elastic compressibility of products. (g) Compressive Young’s modulus [
Gelatin is the hydrolysate of collagen, which contains many arginine-glycine-aspartic-acid (RGD) sequences and matrix metalloproteinase (MMP) target sequences, which enhance cell adhesion and cellular microenvironment remodeling respectively [48]. Because of biodegradability, biocompatibility, and low antigenicity, gelatin is attractive for bio-inspired hydrogel [49]. Lewis et al. used gelatin as a bioink to print into a specific 3D geometry using 3D bioprinting, which can regulate the biological processes of hepatocytes, enhance protein function, and facilitate cell proliferation and differentiation [50]. Another commonly used gelatin derivative is to acylate gelatin to form gelatin methacrylamide (GelMA) [51]. Zhou et al. used GelMA, N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitrosophenoxy) butanamide linked hyaluronic acid (HA-NB) and photo-initiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as biomimetic bioink to fabricated a bio-inspired 3D tissue construct via the digital light process (DLP)-based 3D bioprinting technology for ski regeneration (\nFigure 2\n) [52]. Bhise et al. used GelMA to carry out Hep G2/C3A cells to prepare biomimetic 3D liver structure hydrogel through bioprinting technology. A bionic human body chip of liver tissue was prepared by bioreactor. The toxicity response test of this chip in the test of acetaminophen is similar to that reported
Hyaluronic acid (HA) is a kind of biocompatible non-sulfated glycosaminoglycan composed of N-acetylglucosamine and D-glucuronic acid repeated disaccharide units [54]. It is abundant in tissues including cartilage, neurons and skin. HA is of intrinsic biological importance because it binds to receptors such as CD44, can be degraded by oxidative species and hyaluronidase, and is related to the function and structure of development, wound healing and adult tissues. Because of biocompatibility, biodegradability, and natural biological function, HA hydrogels are widely used in various application fields [55]. Besides, the HA hydrogel can energize cell viability and promote osteoblasts to differentiate into cartilage. Unlike collagen and other proteins, the sequence of HA is different from species and its antigenicity is low, so it is especially promising as an injectable hydrogel.
\nSeveral other natural polymers, such as collagen, agarose, carrageenan, fibrin, heparin, chondroitin sulfate, cellulose, hemicellulose, lignin, and so on, could be used for hydrogels using 3D bioprinting [21]. However, natural hydrogels lack adequate mechanical properties, especially when implanted
The hydrogels fabricated using synthetic polymers have the advantages of long service life, strong water absorption, and high gel strength [41]. Polyacrylamide (PA) is a general designation of acrylamide homopolymer and copolymer. PA is a kind of water-soluble polymer, which has many amide groups in its structure and is easy to form hydrogen bond, so it has good stability and flocculation and is easy to be chemically modified. Ahn et al. grafted poly (N-isopropylacrylamide) (PNIPAAm) onto the framework of sodium alginate and synthesized sodium alginate PNIPAAm polymer micelles by self-assembly in aqueous solution, and the micelles could be used for the encapsulation of anticancer drug adriamycin [56]. Polyethylene glycol (PEG) is another synthetic polymer, and it has no toxicity and irritation, has good biocompatibility, and can be discharged from the body through the kidney. It has been widely used in the field of biomedicine [57]. Gao et al. constructed the polyethylene glycol diacrylate (PEGDA) hydrogel with uniform distribution of human mesenchymal stem cells (hMSCs) inside by simultaneous photopolymerization with commercial thermojet printers. hMSCs filled in 3D PEGDA hydrogel showed no deposition during culture and showed a chondrogenic phenotype [58]. Wang et al. prepared an injectable hydrogel through
Polylactic acid (PLA) is a kind of polymer, which is made of lactic acid as the primary raw material, and through polymerization, in which the performance can be adjusted by the structure [60]. Senatov et al. prepared PLA/hyaluronic acid (HA) interconnected porous scaffold via a melt-wire method; the 3D printing technique avoided thermal degradation of PLA, the porosity and pore size of the scaffold could be well controlled. The porous PLA/HA scaffold with 15% HA has a considerable crack resistance and can work for a long time under the stress of 21 MPa, which was potential for bone tissue engineering applications [61].
\nPolyvinyl alcohol (PVA) is a synthetic water-soluble polymer, it has good biodegradation, biocompatibility, and no side effects on the human body [62]. PVA has been widely used in ophthalmology, wound dressing, artificial joint, and so on [42, 63]. Shi et al. prepared an injectable dynamic hydrogel using HA grafted with PVA and phenyl boric acid (PBA). The synthesized HA-PBA-PVA dynamic hydrogel has the reactive oxygen species reactivity and the scavenging activity of active oxygen. Furthermore, the hydrogel had good biocompatibility to the encapsulated neural precursor cells (NPC), and its ability to scavenge reactive oxygen species could protect the NPC cells from the damage of reactive oxygen species. The HA-PBA-PVA hydrogel could be used as bioink for 3D biological printing to prepare multilayer and cell loaded structures. The NPC cells showed good viability (85 ± 2% of living cells) after extrusion and maintained the excellent viability of 81 ± 2% of living cells after 3 days of culture. The results indicated that multifunctional injectable and ROS responsive self-healing HA-PBA-PVA dynamic hydrogels were expected to be candidates for 3D culture and 3D bioprinting [64].
\nBesides, there are also many other synthetic polymers for the fabrication of bio-inspired hydrogels, such as Pluronic and derivatives, PEG or polyethylene oxide (PEO) based block copolymers, poly(L-glutamic acid), poly(propylene fumarate), methoxy polyethylene glycol, and so on. Though, the synthetic polymers can precisely control their gel structure and properties and have better physical and chemical stability and more raw materials to prepare bio-inspired hydrogels. However, it is necessary to pay attention to the possible biocompatibility of unreacted monomers and residual initiators during the preparation of synthetic polymer materials, and the biocompatibility could be greatly improved via compositing or liking with natural polymers [65, 66, 67].
\nTissue regeneration research is aim to develop substitute for damaged or diseased tissues or organs using principles of life science, engineering and medicine synergistically. It is crucial to fabricate the substitute as scaffolds, which is inspired by the natural 3D structure of tissue. The natural ECM regulates essential cellular functions, such as adhesion, migration, proliferation, differentiation and morphogenesis [68]. It is important of mimicking the ECM with dynamic nature using 3D bioprinting techniques, and the bio-inspired hydrogels via such techniques displayed potential applications in tissue regeneration, such as cartilage tissue, vascularized engineered tissue, bone tissue, skin regeneration, heart tissue, aortic valve conduits, muscle-tendon, and so on [69]. For example, Alexander et al. displayed a chemically and mechanically biomimetic filler-free bioink for 3D bioprinting of soft neural tissues, as shown in \nFigure 3\n. The thiolated Pluronic F-127, dopamine-conjugated (DC) gelatin, and DC hyaluronic acid were used as bioinks via a thiol-catechol reaction and photocuring; the storage modulus of the cured bioinks ranged from 6.7 to 11.7 kPa. The micro-extrusion 3D bioprinting was used to fabricate free-standing cell-laden tissue constructs. The Rodent Schwann cells, rodent neuronal cells, and human glioma cell-laden tissue constructs were printed and cultured over seven days and exhibited excellent viability, which has implications in micro physiological neural systems for neural tissue regenerative medicine [70]. Several works could be found in a recent study that focuses on the specific properties of bio-inspired hydrogels for tissue regeneration, such as high strength structures [30]. Also, the enhancement of printing resolution and versatility is vital for tissue regeneration. For example, the self-healing hydrogels were used to support the direct 3D bioprinting with high resolution by utilizing shear-thinning hydrogels, then the constructs could be printed in any direction [71]. The bio-inspired hydrogels could be accomplished via
(A) Native ECM components of neural tissue were combined with a synthetic polymer for microextrusion 3D bioprinting of soft, free-standing neural tissues. (B) Two curing pathways, including UV light exposure, and chelation of dopamine groups with iron (III), are shown to the formulation of photocuring containing methacrylated dopamine-conjugated gelatin. With the increase of PF127-SH content, the compressive properties of inks cured through UV exposure or chelation increased.
The bio-inspired hydrogels via 3D bioprinting can be applied for wound dressing and wearable devices, which are considered as important applications, especially in recent years. Skin plays an essential role in protecting the body from external damages, such as abrasions, lacerations, and burns, and so on. The full-thickness defects of the dermis layers are the most challenging wounds to heal because of the limitation of self-repairing capability; thus, the skin regeneration of skin with skin appendages still remains a tough challenge [72]. 3D bioprinting is being applied to fabricate skin constructs using biomaterial scaffolds with or without cells, to address the need for skin tissues suitable for transplantation for wound healing therapy. The natural polymers, including cellulose, collagen and chitin, alginate, and hyaluronic acids are employed to synthesis skin constructs due to the favorable biocompatibility, biodegradation, low-toxicity or nontoxicity, high moisture content, high availability and mechanical stability [73]. Feifei et al. fabricated gelatin methacrylate (GelMA) based bioink to print functional living skin using DLP-based 3D printing (\nFigure 2\n), while the printed skin could promote skin regeneration and neovascularization via mimicking the physiological structure of natural skin [52].
\nFurthermore, the bio-inspired hydrogels could not only be functionalized on skin regeneration but also as medical wearable devices. The conductive hydrogels could be designed and fabricated to acquire electronic devices with conductive, capacitive, switching properties, image displaying, and motion sensing [74]. Meihong et al. developed conductive, healable, and self-adhesive hybrid network hydrogels based on conductive functionalized single-wall carbon nanotube (FSWCNT), PVA and polydopamine. The prepared hydrogel exhibits fast self-healing ability around 2 s, high self-healing efficiency of about 99%, and robust adhesiveness, which could be used for healable, adhesive, and soft human-motion sensors [75]. Zijian et al. synthesized a stretchable, self-healing and conductive hydrogel based on gelatin-enhanced hydrophobic association poly(acrylamide-
The bio-inspired hydrogels could also be used in drug delivery system, such as protein carriers, anti-inflammatory drug carriers, in the pharmaceutical industry [79]. Rana et al. designed a magnetic natural hydrogel based on alginate, gelatin, and iron oxide magnetic nanoparticles as an efficient drug delivery system, the drug doxorubicin hydrochloride (DOX) was loaded, the anticancer activity against Hela cells could be regulated by the release of DOX from hydrogels [80]. Maling et al. provided a proof-of-concept of detoxification using a 3D-printed biomimetic nanocomposite construct in the hydrogel. A bio-inspired 3D detoxification device by installing polydiacetylene (PDA) nanoparticles in a 3D matrix was fabricated using dynamic optical projection stereolithography (DOPsL) technology; the nanoparticles could attract, capture and sense toxins, while the 3D matrix with a modified liver lobule microstructure allows toxins to be trapped efficiently [36]. The bio-inspired hydrogels via multi-materials 3D bioprinting can easy regulate the loading and release profiles of drugs, which show potentials as biomedicines.
\nThe design paradigms shift from 2D to 3D has revolutionized the way of bio-inspired hydrogels for materials components, engineered constructs,
The future outlook of 3D bioprinting for fabrication of bio-inspired tissues for tissue engineering applications [
The 3D bioprinting has changed the way bio-inspired hydrogels fabricated, and expanded the applications of bio-inspired hydrogels, including tissue regeneration, wound dressing, wearable devices, and pharmaceutical applications, and so on. In this chapter, the available 3D bioprinting techniques were described, the advantages and disadvantages of each printing technology were outlined. Then, the natural and synthetic polymers used for the fabrication of bio-inspired hydrogels via 3D bioprinting were introduced. The applications of bio-inspired hydrogels were focused. At last, the future outlook of bio-inspired hydrogels for tissue engineering were summarized. The bio-inspired hydrogels produced from 3D bioprinting still lacking sufficient clinical evidence, as more clinical trials evaluating bio-inspired hydrogels are still required.
\nThis research was funded by the National Natural Science Foundation of China No. 31700840.
\nThe authors declare no conflict of interest.
ADSCs | adipose derived stem cells |
CAD | \n |
CAM | computer-aided manufacturing |
CHO | Chinese hamster ovary |
DLP | digital light process |
DOPsL | dynamic optical projection stereolithography |
DOX | doxorubicin hydrochloride |
ECM | extracellular matrix |
FSWCNT | functionalized single-wall carbon nanotube |
GelMA | gelatin methacrylamide |
HA | hyaluronic acid |
HA-SH | thiol hyaluronic acid |
hMSCs | human mesenchymal stem cells |
LAP | lithium phenyl-2,4,6-trimethylbenzoylphosphinate |
MMP | matrix metalloproteinase |
MRI | magnetic resonance imaging |
NB | N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2-methoxy-5-nitrosophenoxy) butanamide |
NPC | neural precursor cells |
PA | polyacrylamide |
PAAm | polyacrylamide |
PAG | photo acid generator |
PBA | phenyl boric acid |
PDA | polydiacetylene |
PEG | polyethylene glycol |
PEGDA | polyethylene glycol diacrylate |
PEO | polyethylene oxide |
PLA | polylactic acid |
PNIPAAm | poly (N-isopropylacrylamide) |
PVA | polyvinyl alcohol |
RGD | arginine-glycine-aspartic-acid |
SLA | stereolithography |
TA-PEGDA | tetraniline polyethylene glycol diacrylate |
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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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We examine first the routes of exposure of bees to agrochemicals used for crop protection and their application to crops, fate and contamination of water and plants around the fields. Most of the time, the exposure of bees to pesticides is through ingestion of residues found in the pollen and nectar of plants and in water. Honey bees are also exposed to pesticides used for the treatment of Varroa and other parasites. The basic concepts about the toxicity of the different kinds of pesticides are explained next. Various degrees of toxicity are found among agrochemicals, and emphasis is given to the classic tenet of toxicology, “the dose makes the poison,” and its modern version “the dose and the time of exposure makes the poison.” These two factors, dose and time, help us understand the severity of the impacts that pesticides may have on bees and their risk, which are analysed in the third section. Sublethal effects are also considered. The final section is devoted to some practical advice for avoiding adverse impacts of pesticides in beekeeping.",book:{id:"5163",slug:"beekeeping-and-bee-conservation-advances-in-research",title:"Beekeeping and Bee Conservation",fullTitle:"Beekeeping and Bee Conservation - Advances in Research"},signatures:"Francisco Sanchez-Bayo and Koichi Goka",authors:[{id:"74970",title:"Dr.",name:"Francisco",middleName:null,surname:"Sánchez-Bayo",slug:"francisco-sanchez-bayo",fullName:"Francisco Sánchez-Bayo"},{id:"192045",title:"Dr.",name:"Koichi",middleName:null,surname:"Goka",slug:"koichi-goka",fullName:"Koichi Goka"}]},{id:"50307",doi:"10.5772/62654",title:"From Extraction to Meliponiculture: A Case Study of the Management of Stingless Bees in the West-Central Region of Mexico",slug:"from-extraction-to-meliponiculture-a-case-study-of-the-management-of-stingless-bees-in-the-west-cent",totalDownloads:2743,totalCrossrefCites:5,totalDimensionsCites:9,abstract:"Currently, stingless bees' populations are declining due to environmental degradation. In this context, the authors have developed a research project in the central-western region of Mexico with the goal to generate strategies for conservation and sustainable management of stingless bees. The chapter aims to present the process of this investigation and its main results in terms of a) local knowledge and management strategies of stingless bees, and b) the social process of technological appropriation of meliponiculture by beekeepers. We recognized specific knowledge on the biology and ecology of stingless bees that result in a system for identifying species and management strategies of wild populations of these bees based on the extraction of nests. The implementation of an innovative productive activity based on the principles of meliponiculture and current techniques has been well received by producers, which has led to the formation of the Meliponicultores Michoacanos del Balsas Association, which grows five species of stingless bees. The research suggests that conservation associated with the use of bees (integral meliponiculture) can be enhanced in the region. Faced with the loss of biodiversity and environmental crisis, it is essential to maintain and enhance local knowledge of stingless bees and management practices. This represents an alternative to develop management schemes that allow the raising and breeding of these bees, while its products are obtained.",book:{id:"5163",slug:"beekeeping-and-bee-conservation-advances-in-research",title:"Beekeeping and Bee Conservation",fullTitle:"Beekeeping and Bee Conservation - Advances in Research"},signatures:"Alejandro Reyes-González, Andrés Camou-Guerrero and Salvador\nGómez-Arreola",authors:[{id:"179951",title:"Dr.",name:"Andres",middleName:null,surname:"Camou-Guerrero",slug:"andres-camou-guerrero",fullName:"Andres Camou-Guerrero"},{id:"185413",title:"MSc.",name:"Alejandro",middleName:null,surname:"Reyes-González",slug:"alejandro-reyes-gonzalez",fullName:"Alejandro Reyes-González"},{id:"192049",title:"Dr.",name:"Salvador",middleName:null,surname:"Gómez-Arreola",slug:"salvador-gomez-arreola",fullName:"Salvador Gómez-Arreola"}]},{id:"50170",doi:"10.5772/62395",title:"A Comprehensive Characterization of the Honeybees in Siberia (Russia)",slug:"a-comprehensive-characterization-of-the-honeybees-in-siberia-russia-",totalDownloads:2296,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"A comprehensive study of some populations of honeybee (332 colonies) in Siberia (Tomsk region, Krasnoyarsk Krai (Yenisei population), Altai) using morphometric and molecular genetic methods was conducted. Infestation of bees (132 colonies) by Nosema has also been studied. Three variants of the COI-COII mtDNA locus were registered: PQQ, PQQQ (typical for Apis m. mellifera), and Q (specific for southern races). It was established that 64% of bee colonies from the Tomsk region and all colonies studied from the Krasnoyarsk and the Altai territories originate from Apis m. mellifera on the maternal line. According to the morphometric study, the majority of bee colonies of the Tomsk region are hybrids; in some colonies the mismatch of morphometric and mtDNA data was observed. Moreover, the majority of bee colonies infected by Nosema were hybrids. Yenisei population may be considered as a unique Apis m. mellifera population. Microsatellite analysis (loci А008, Ap049, AC117, AC216, Ap243, H110, A024, A113) showed the specific distribution of genotypes and alleles for some loci in the bees, which differ by geographical location. Loci A024 and Ap049 are of considerable interest for further study as candidate markers for differentiation of subspecies; locus A008 can be considered informative for determining of different ecotypes of Apis m. mellifera.",book:{id:"5163",slug:"beekeeping-and-bee-conservation-advances-in-research",title:"Beekeeping and Bee Conservation",fullTitle:"Beekeeping and Bee Conservation - Advances in Research"},signatures:"Nadezhda V. Ostroverkhova, Olga L. Konusova, Aksana N. Kucher\nand Igor V. Sharakhov",authors:[{id:"180112",title:"Ph.D.",name:"Nadezhda",middleName:null,surname:"Ostroverkhova",slug:"nadezhda-ostroverkhova",fullName:"Nadezhda Ostroverkhova"},{id:"180249",title:"Ms.",name:"Olga",middleName:null,surname:"Konusova",slug:"olga-konusova",fullName:"Olga Konusova"},{id:"180342",title:"Prof.",name:"Aksana",middleName:null,surname:"Kucher",slug:"aksana-kucher",fullName:"Aksana Kucher"},{id:"180343",title:"Prof.",name:"Igor",middleName:null,surname:"Sharakhov",slug:"igor-sharakhov",fullName:"Igor Sharakhov"}]},{id:"50683",doi:"10.5772/63145",title:"Advances in Pharmacological Activities and Chemical Composition of Propolis Produced in Americas",slug:"advances-in-pharmacological-activities-and-chemical-composition-of-propolis-produced-in-americas",totalDownloads:2578,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Propolis is a resinous material produced by bees from the selective collection of plant exudates that are subsequently mixed with beeswax and salivary bee secretions. Propolis has been used in folk medicine, and certainly, several studies have validated its biological properties. The chemical composition and pharmacological activities of propolis collected through North (including Central America and Caribbean) and South America have been studied in the last years, and several papers have reported differences and similarities among the analysed geographical samples. Propolis has been classified according to its aspect and plant source; however, the ecological diversity present along the Americas provides a plethora of botanical resins. Herein, we summarize and discuss most of the studies performed at present on this profitable product for apiculture, attempting to compare the bioactivity, phytochemical diversity and botanical sources of honeybee propolis produced in Americas.",book:{id:"5163",slug:"beekeeping-and-bee-conservation-advances-in-research",title:"Beekeeping and Bee Conservation",fullTitle:"Beekeeping and Bee Conservation - Advances in Research"},signatures:"Efrain Alday, Moisés Navarro-Navarro, Adriana Garibay-Escobar,\nRamón Robles-Zepeda, Javier Hernandez and Carlos Velazquez",authors:[{id:"96966",title:"MSc.",name:"Moises",middleName:null,surname:"Navarro-Navarro",slug:"moises-navarro-navarro",fullName:"Moises Navarro-Navarro"},{id:"180409",title:"Dr.",name:"Carlos",middleName:null,surname:"Velazquez",slug:"carlos-velazquez",fullName:"Carlos Velazquez"},{id:"186351",title:"Dr.",name:"Ramón",middleName:null,surname:"Robles-Zepeda",slug:"ramon-robles-zepeda",fullName:"Ramón Robles-Zepeda"},{id:"186352",title:"MSc.",name:"Efrain",middleName:null,surname:"Alday",slug:"efrain-alday",fullName:"Efrain Alday"},{id:"186353",title:"Dr.",name:"Javier",middleName:null,surname:"Hernandez",slug:"javier-hernandez",fullName:"Javier Hernandez"},{id:"189161",title:"Dr.",name:"Adriana",middleName:null,surname:"Garibay-Escobar",slug:"adriana-garibay-escobar",fullName:"Adriana Garibay-Escobar"}]},{id:"71161",doi:"10.5772/intechopen.91196",title:"Detailed Review on Pesticidal Toxicity to Honey Bees and Its Management",slug:"detailed-review-on-pesticidal-toxicity-to-honey-bees-and-its-management",totalDownloads:1053,totalCrossrefCites:1,totalDimensionsCites:6,abstract:"This chapter deals with the effects of different pesticides used in agro-ecosystem on honey bees and other pollinators and probable measures to manage this escalating problem of global decline of managed as well as the wild insect pollinators. This chapter describes different routes from which pollinators, especially honey bees get exposed to the different toxicants, followed by poisoning symptoms in honey bees. Further, this chapter focuses on the classification of different toxicants in different classes as per their nature. Finally, the management of these different toxicants and their toxicity to avoid bee poisoning has been considered in the later portion of the chapter.",book:{id:"8929",slug:"modern-beekeeping-bases-for-sustainable-production",title:"Modern Beekeeping",fullTitle:"Modern Beekeeping - Bases for Sustainable Production"},signatures:"Gaurava Kumar, Swoyam Singh and Rukesh Pramod Kodigenahalli Nagarajaiah",authors:[{id:"305621",title:"Ph.D. Student",name:"Gaurava",middleName:null,surname:"Kumar",slug:"gaurava-kumar",fullName:"Gaurava Kumar"},{id:"315507",title:"Dr.",name:"Swoyam",middleName:null,surname:"Singh",slug:"swoyam-singh",fullName:"Swoyam Singh"},{id:"315508",title:"Dr.",name:"Rukesh",middleName:null,surname:"Pramod K.N.",slug:"rukesh-pramod-k.n.",fullName:"Rukesh Pramod K.N."}]}],mostDownloadedChaptersLast30Days:[{id:"50170",title:"A Comprehensive Characterization of the Honeybees in Siberia (Russia)",slug:"a-comprehensive-characterization-of-the-honeybees-in-siberia-russia-",totalDownloads:2302,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"A comprehensive study of some populations of honeybee (332 colonies) in Siberia (Tomsk region, Krasnoyarsk Krai (Yenisei population), Altai) using morphometric and molecular genetic methods was conducted. Infestation of bees (132 colonies) by Nosema has also been studied. Three variants of the COI-COII mtDNA locus were registered: PQQ, PQQQ (typical for Apis m. mellifera), and Q (specific for southern races). It was established that 64% of bee colonies from the Tomsk region and all colonies studied from the Krasnoyarsk and the Altai territories originate from Apis m. mellifera on the maternal line. According to the morphometric study, the majority of bee colonies of the Tomsk region are hybrids; in some colonies the mismatch of morphometric and mtDNA data was observed. Moreover, the majority of bee colonies infected by Nosema were hybrids. Yenisei population may be considered as a unique Apis m. mellifera population. Microsatellite analysis (loci А008, Ap049, AC117, AC216, Ap243, H110, A024, A113) showed the specific distribution of genotypes and alleles for some loci in the bees, which differ by geographical location. Loci A024 and Ap049 are of considerable interest for further study as candidate markers for differentiation of subspecies; locus A008 can be considered informative for determining of different ecotypes of Apis m. mellifera.",book:{id:"5163",slug:"beekeeping-and-bee-conservation-advances-in-research",title:"Beekeeping and Bee Conservation",fullTitle:"Beekeeping and Bee Conservation - Advances in Research"},signatures:"Nadezhda V. Ostroverkhova, Olga L. Konusova, Aksana N. Kucher\nand Igor V. Sharakhov",authors:[{id:"180112",title:"Ph.D.",name:"Nadezhda",middleName:null,surname:"Ostroverkhova",slug:"nadezhda-ostroverkhova",fullName:"Nadezhda Ostroverkhova"},{id:"180249",title:"Ms.",name:"Olga",middleName:null,surname:"Konusova",slug:"olga-konusova",fullName:"Olga Konusova"},{id:"180342",title:"Prof.",name:"Aksana",middleName:null,surname:"Kucher",slug:"aksana-kucher",fullName:"Aksana Kucher"},{id:"180343",title:"Prof.",name:"Igor",middleName:null,surname:"Sharakhov",slug:"igor-sharakhov",fullName:"Igor Sharakhov"}]},{id:"70501",title:"Southeast Asian Meliponiculture for Sustainable Livelihood",slug:"southeast-asian-meliponiculture-for-sustainable-livelihood",totalDownloads:1262,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Stingless bees (Apidae: Meliponini) are one of the most important pollinators of native plants and economic crops in tropical and subtropical parts of the world. They not only establish large perennial colonies with complex social organization but also have a diverse nesting biology. The economic utilization of a total of 60 stingless bee species in Asia has been reported. The current status of meliponiculture in Southeast Asia is mainly focused on pollination utilization and honey and propolis production. This chapter shows that small-scale beekeeping of stingless bees, which is suitable for the flowering pattern in the tropics, is one of the best potential alternative opportunities. The cost-effectiveness analysis based on production yield, investment cost, and profit-return rate is reviewed. Finally, a sustainable utilization of stingless bees is considered to be an enhancer of pollination services both in an agricultural crop and natural ecosystem.",book:{id:"8929",slug:"modern-beekeeping-bases-for-sustainable-production",title:"Modern Beekeeping",fullTitle:"Modern Beekeeping - Bases for Sustainable Production"},signatures:"Atsalek Rattanawannee and Orawan Duangphakdee",authors:[{id:"283087",title:"Ph.D.",name:"Atsalek",middleName:null,surname:"Rattanawannee",slug:"atsalek-rattanawannee",fullName:"Atsalek Rattanawannee"},{id:"306411",title:"Dr.",name:"Orawan",middleName:null,surname:"Duangphakdee",slug:"orawan-duangphakdee",fullName:"Orawan Duangphakdee"}]},{id:"50073",title:"Impacts of Pesticides on Honey Bees",slug:"impacts-of-pesticides-on-honey-bees",totalDownloads:3419,totalCrossrefCites:20,totalDimensionsCites:41,abstract:"This chapter focuses on the detrimental effects that pesticides have on managed honey bee colonies and their productivity. We examine first the routes of exposure of bees to agrochemicals used for crop protection and their application to crops, fate and contamination of water and plants around the fields. Most of the time, the exposure of bees to pesticides is through ingestion of residues found in the pollen and nectar of plants and in water. Honey bees are also exposed to pesticides used for the treatment of Varroa and other parasites. The basic concepts about the toxicity of the different kinds of pesticides are explained next. Various degrees of toxicity are found among agrochemicals, and emphasis is given to the classic tenet of toxicology, “the dose makes the poison,” and its modern version “the dose and the time of exposure makes the poison.” These two factors, dose and time, help us understand the severity of the impacts that pesticides may have on bees and their risk, which are analysed in the third section. Sublethal effects are also considered. The final section is devoted to some practical advice for avoiding adverse impacts of pesticides in beekeeping.",book:{id:"5163",slug:"beekeeping-and-bee-conservation-advances-in-research",title:"Beekeeping and Bee Conservation",fullTitle:"Beekeeping and Bee Conservation - Advances in Research"},signatures:"Francisco Sanchez-Bayo and Koichi Goka",authors:[{id:"74970",title:"Dr.",name:"Francisco",middleName:null,surname:"Sánchez-Bayo",slug:"francisco-sanchez-bayo",fullName:"Francisco Sánchez-Bayo"},{id:"192045",title:"Dr.",name:"Koichi",middleName:null,surname:"Goka",slug:"koichi-goka",fullName:"Koichi Goka"}]},{id:"50135",title:"Breeding Program Design Principles for Royal Jelly",slug:"breeding-program-design-principles-for-royal-jelly",totalDownloads:2780,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This research was carried out to infer the genetic value to produce royal jelly in Africanized Apis mellifera L. honeybees with the compilation of data collected from 2006 to 2011. Genetic information of the selected and accessed colonies was obtained using the total DNA extraction techniques of nurse honeybees’ thorax with molecular markers for MRJP3 protein and characterized in Apis mellifera L. From the information on the colonies and genealogical structure were predicted genetic values of the colonies and queens for the larvae acceptance trait (%), royal jelly per colony (g), and royal jelly per cup (mg). Animal model with Bayesian Inference was used from Multiple Trait Gibbs Sampling software in Animal Models, Gibbs chains 58,500 cycles resulting from 650,000 cycles with intervals and disposal of 65,000 and 10 withdraw, respectively. From the predicted values, the colonies were classified into upper and lower. To compare the average of the genetic values according to the genotypes, the average multiple comparison tests were proceeded and implemented in routine PROC GENMOD from the Statistical Analysis System. Environmental effects were considered, time and hive type (standard Langstroth) as having flat distribution and collection as chi-square distribution. The studies presented an increase in the alleles C and D and the alleles D and E—referring to MRJPs—found in the highest genetic value for royal jelly production. Alleles D, E, and C are important when evaluating the parameters larvae acceptance, royal jelly per colony, and royal jelly per cup and, occasionally, it was the DE genotype that stood out royal jelly production. Genotypes DE, DC, and EC are those that should be kept in this evaluation system for royal jelly production, and the other genotypes should be discarded because they had the worst performance for the parameters evaluated.",book:{id:"5163",slug:"beekeeping-and-bee-conservation-advances-in-research",title:"Beekeeping and Bee Conservation",fullTitle:"Beekeeping and Bee Conservation - Advances in Research"},signatures:"Katia Ostrovski-Tomporoski, Patrícia Faquinello, Fabiana Martins\nCosta-Maia, Maria Claudia Ruvolo-Takasusuki, Pedro da Rosa\nSantos and Vagner Arnaut de Toledo",authors:[{id:"92329",title:"Dr.",name:"Vagner",middleName:"De Alencar",surname:"Arnaut De Toledo",slug:"vagner-arnaut-de-toledo",fullName:"Vagner Arnaut De Toledo"},{id:"119608",title:"Dr.",name:"Maria Claudia",middleName:"Colla",surname:"Ruvolo-Takasusuki",slug:"maria-claudia-ruvolo-takasusuki",fullName:"Maria Claudia Ruvolo-Takasusuki"},{id:"180234",title:"Dr.",name:"Patricia",middleName:null,surname:"Faquinello",slug:"patricia-faquinello",fullName:"Patricia Faquinello"},{id:"180235",title:"Prof.",name:"Fabiana",middleName:null,surname:"Costa-Maia",slug:"fabiana-costa-maia",fullName:"Fabiana Costa-Maia"},{id:"180368",title:"M.Sc.",name:"Katia",middleName:"Regina",surname:"Ostrovski-Tomporoski",slug:"katia-ostrovski-tomporoski",fullName:"Katia Ostrovski-Tomporoski"}]},{id:"50521",title:"Rearing Bumble Bees for Research and Profit: Practical and Ethical Considerations",slug:"rearing-bumble-bees-for-research-and-profit-practical-and-ethical-considerations",totalDownloads:2928,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"The commercial production of bumble bee colonies is a multi-million dollar business worldwide. The pollination of greenhouse tomatoes is largely dependent on this industry. However, microparasites are prevalent in many of these colonies and can spread to wild populations of bumble bees. Academic researchers now commonly purchase colonies for their work. I believe that this raises some questions: (a) What is the danger of exacerbating the problem of spread of parasites and pathogens to wild population of bumble bees from field studies using purchased colonies? (b) How representative studies are done on only a few species, for example, B. terrestris, B. impatiens? (c) Does the purchase and use of these colonies give tacit approval to the industry, which may be having a detrimental effect on the native populations of bumble bees? This is an ethical issue. (d) Loss of “feeling for the organism” by researchers and particularly graduate students. These issues were discussed, and the classical method of bumble bee rearing which avoids these problems was described.",book:{id:"5163",slug:"beekeeping-and-bee-conservation-advances-in-research",title:"Beekeeping and Bee Conservation",fullTitle:"Beekeeping and Bee Conservation - Advances in Research"},signatures:"Robin E. Owen",authors:[{id:"101485",title:"Dr.",name:"Robin",middleName:"Edward",surname:"Owen",slug:"robin-owen",fullName:"Robin Owen"}]}],onlineFirstChaptersFilter:{topicId:"332",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:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",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:"July 5th, 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,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,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,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,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. 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Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"15",type:"subseries",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. 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This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"August 3rd, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:107,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",fullName:"Reda R. Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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