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",isbn:"978-1-83881-111-2",printIsbn:"978-1-83880-992-8",pdfIsbn:"978-1-83881-112-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"acb2875b3bfc189c9881a9b44b6a5184",bookSignature:"Dr. Abdo Abou Jaoudé",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11865.jpg",keywords:"Linear Operators, Normal Operators, Spectral Theorem, Applications, Differential Operators, Integral Operators, Functional Calculus, Complex Variables, Complex Analysis, Theory, Recent Advances, Latest Trends",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 13th 2022",dateEndSecondStepPublish:"June 21st 2022",dateEndThirdStepPublish:"August 20th 2022",dateEndFourthStepPublish:"November 8th 2022",dateEndFifthStepPublish:"January 7th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Abdo Abou Jaoudé is a pioneering Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé. He holds two PhDs in Mathematics and Prognostics from the Lebanese University and Aix-Marseille University. His research interests are in the field of mathematics.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"248271",title:"Dr.",name:"Abdo",middleName:null,surname:"Abou Jaoudé",slug:"abdo-abou-jaoude",fullName:"Abdo Abou Jaoudé",profilePictureURL:"https://mts.intechopen.com/storage/users/248271/images/system/248271.jpg",biography:"Abdo Abou Jaoudé has been teaching for many years and has a passion for researching and teaching mathematics. He is currently an Associate Professor of Mathematics and Statistics at Notre Dame University-Louaizé (NDU), Lebanon. He holds a BSc and an MSc in Computer Science from NDU, and three PhDs in Applied Mathematics, Computer Science, and Applied Statistics and Probability, all from Bircham International University through a distance learning program. He also holds two PhDs in Mathematics and Prognostics from the Lebanese University, Lebanon, and Aix-Marseille University, France. Dr. Abou Jaoudé's broad research interests are in the field of applied mathematics. He has published twenty-three international journal articles and six contributions to conference proceedings, in addition to seven books on prognostics, pure and applied mathematics, and computer science.",institutionString:"Notre Dame University - Louaize",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Notre Dame University – Louaize",institutionURL:null,country:{name:"Lebanon"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"15",title:"Mathematics",slug:"mathematics"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"252211",firstName:"Sara",lastName:"Debeuc",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/252211/images/7239_n.png",email:"sara.d@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"10062",title:"Forecasting in Mathematics",subtitle:"Recent Advances, New Perspectives and Applications",isOpenForSubmission:!1,hash:"9a3ad05fef0502040d2a238ad22487c0",slug:"forecasting-in-mathematics-recent-advances-new-perspectives-and-applications",bookSignature:"Abdo Abou Jaoude",coverURL:"https://cdn.intechopen.com/books/images_new/10062.jpg",editedByType:"Edited by",editors:[{id:"248271",title:"Dr.",name:"Abdo",surname:"Abou Jaoudé",slug:"abdo-abou-jaoude",fullName:"Abdo Abou Jaoudé"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11066",title:"The Monte Carlo Methods",subtitle:"Recent Advances, New Perspectives and Applications",isOpenForSubmission:!1,hash:"d1488c96b5b4d4909e963b9a91b1632f",slug:"the-monte-carlo-methods-recent-advances-new-perspectives-and-applications",bookSignature:"Abdo Abou Jaoudé",coverURL:"https://cdn.intechopen.com/books/images_new/11066.jpg",editedByType:"Edited by",editors:[{id:"248271",title:"Dr.",name:"Abdo",surname:"Abou Jaoudé",slug:"abdo-abou-jaoude",fullName:"Abdo Abou Jaoudé"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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Cell junctions and polarity in epithelial cells. Substances cross the epithelial layer through the transcellular or paracellular routes or by transcytosis. Each scheme depicts the main molecular components of cellular junctions and its organization in the membrane. MAGI are inverted membrane-associated guanylate kinase-like proteins, ZO-1, -2 and -3 are Zonula Occludens-1, -2 and 3, Src is the protein homologous to the Rous sarcoma virus kinase, FAK is the focal adhesion kinase, LSR stands for the lipolysis-stimulated lipoprotein receptor, JAM is the junctional adhesion protein.
The complex organization and regulation of cell junctions and cell polarity in epithelial cells are adaptations to perform vectorial transport. A given substance crosses epithelial layers either through the
Recent research demonstrated that
Cellular junctions and plasma membrane polarity are highly regulated. For example, a progressive conversion of renal intercalated cells of the collecting tubules from α to β type comprises the inversion of the apical H+-ATPase and a basolateral Cl−/HCO3+ exchanger polarity, in response to the increase in the expression of hensin, a protein of the extracellular matrix [31, 32], and cysts embedded in collagen displace their TJs from the vicinity of the lumen toward the proximity of the external surface [33, 34].
\nCell junctions and plasma membrane polarity are crucial for the normal physiology of the organism, and its failure in several pathologies has disastrous consequences. To start with, it is common that the genetic elimination of crucial proteins, such as E-cadherin from the AJs or ZO-2, is lethal at embryonic stages [35, 36], but whenever an epithelial adhesion protein is not expressed, epithelia compartmentalization and vectorial transport are lost. For example, in hereditary familial hypomagnesemia with hypercalciuria and nephrocalcinosis, the lack of CLDN-16 and CLDN-19 impairs Ca2+ and Mg2+ reabsorption in the kidney [17, 37]; in cholestatic children’s liver disease, the absence of ZO-2 and TJs provokes the invasion of bile salts into the blood [38]; in pemphigus vulgaris, the depletion of Des by autoantibodies against the desmosomal cadherin desmoglein-3 results in the formation of skin blisters [39], which can also appear if HDes are disassembled by mutations in the integrin β4, an adhesion molecule of this cell junction [40]; loss of adhesion and augmented proliferation in colon cancer are elicited by mutations that increases the cytosolic and nuclear pools of β-catenin [27]; infection and inflammation boost
All junctions have a similar structural layout: they have transmembrane proteins that are the receptors for adhesion, and a series of membrane-associated proteins that bind the cytoplasmic aspect of transmembrane receptors to the actin, tubulin, or cytokeratin cytoskeleton to provide mechanical strength. Besides cell adhesion, cell junctions are sensors that inform, in and out, the state of extracellular environment to modulate cell’s proliferation, differentiation, and fate. Given that lysosomes are of paramount importance for cell junctions and plasma membrane polarity, it is necessary to briefly review the degradation routes where this organelle intervenes.
\nLysosomes are major degradative organelles of eukaryotic cells. They were first identified as cell compartments enriched in hydrolases [43], but now they are also recognized as providers of building blocks during starvation and powerful stations to sense nutrients and regulate transcription and cellular homeostasis [44]. Lysosomes have a highly acid lumen (pH 4.5–5.0) produced by a vacuolar H+-ATPase. The acidic pH is necessary for the hydrolysis of waste materials and drives the transport of sugars, amino acids, nucleotides, and lipids, through the single membrane of the organelle for recycling [45]. The lysosomal membrane owes its resistance against the activity of the hydrolases that it contains, to the expression of a prominent glycocalyx in its inner surface, formed by glycosylated transmembrane proteins such as the human LIMP-2 and its homologues in
Many intracellular proteins are ubiquitiated and degraded in the proteasome (Figure 2, 1). There are also several routes to deliver cellular material into the lysosomes: an
Protein Degradation pathways. (1)
A central regulator of lysosomal activity, particularly autophagy, is the target of rapamycin (mTOR), a multi-protein complex that includes the kinase mTOR itself, inhibited by rapamycin, the raptor adaptor, two intrinsic inhibitors of mTOR activity, DEPTOR and PRAS40, and a G-protein. The mTOR complex senses energy and nutrient availability, growth factors, and stress conditions to modify cell growth and proliferation. In normal conditions, mTOR localizes in the cytosol and triggers anabolic programs, like mRNA translation. Under starvation, mTOR is translocated to the cytosolic side of the lysosome membrane, where it initiates catabolic processes like autophagy [44].
\nA growing body of evidence suggests that lysosomes can function as Ca2+ stores and contact intimately to the endoplasmic reticulum, the peroxisome, and the mitochondria to deliver necessary lipids [61, 62] and that lysosomes can fuse to the plasma membrane to pour hydrolytic enzymes in the extracellular media that modify the extracellular matrix and induce differentiation [59]. Lysosomes induce cell death when its membrane is permeabilized and hydrolases such as cathepsin B, a Ca2+-sensitive protease, are released in the cytoplasm. Cell death induced by lysosomal damage is observed in tissue remodeling, elimination of excessive intracellular waste or metals, and the immune response to intracellular pathogens and neurodegenerative diseases [63, 64].
\nTo maintain compartmentalization and vectorial transport in epithelial cells, the synthesis and degradation of adhesion proteins must be closely coordinated. Nevertheless, epithelial cells must have certain degree of plasticity to modify cell junctions in response to the variable environment. Lysosomal activity is crucial in both situations.
\nTJs, also known as
Epithelia adjust the permeability of their paracellular route in response to physiological requirements, pathological conditions, and pharmacological challenges. One simple way to gaze epithelial permeability is to measure the transepithelial electrical resistance (TER) [92]: the higher the value of TER, the lower the paracellular permeability. On this regard, the renal system is very illustrative. Human kidneys filtrate 170 l of plasma but secrete only 1.7 l of urine. Water, proteins, sugars, and ions from the glomerular filtrate are reabsorbed, and the filtrate is steadily concentrated along the nephron. The epithelia that line this tubular surface in vertebrate species gradually increase their TER from approximately 10 Ω cm2 at the proximal convoluted tubule [93, 94] to several thousands of Ω cm2 at the collecting duct [95, 96] and up to hundreds of thousands of Ω cm2 at the bladder [97, 98]. A number of epithelial cell adaptations account for by this TER gradient: increments in cell size, reduction of the junctional membrane tortuosity, a progressive increase in the structural complexity of TJ strands, and the expression of a specific set of CLDNs in each nephron segment [15, 65]. CLDN-2 induces a low TER phenotype in renal MDCK cells [99], from cation and water-selective channels [83, 100, 101], and it is expressed in proximal tubules [102–104], where it is necessary for the uptake of Na+, water and, likely, Ca2+ [105]. CLDN-4 induces a high-resistance phenotype upon the epithelial cells that express it [106–108], including those at the distal nephron segment epithelium [102–104].
\nThe fluids that bathe apical membranes, such as urine, semen, and milk, are radically different from each other, but the interstitial milieu that contacts the basolateral membranes has a constant composition maintained by homeostatic mechanisms. This difference suggests that substances in the apical media might regulate specific epithelial properties. Several substances in the extracellular milieu induce TER changes in canine MDCK cells [109]. One of them is EGF [110], a substance previously known to increase the TER of epithelial kidney pig LL-CPK1 cells [111]. Urinary EGF reduces the cellular CLDN-1 and CLDN-2 protein level and increases CLDN-4 one [110]. EGF decreases the cellular level of CLDN-2 [112] through the simultaneous activation of Src kinase, extracellular regulated kinases 1/2 (ERK1/2) [113, 114], and the transcription factor STAT3 [114] that, in turn, may accelerate clathrin-mediated endocytosis and lysosomal degradation of CLDN-2 [113], block CLDN-2 [115], and trigger CLDN-4 [116] transcription in MDCK cells. In lung cancer cells though, EGF increases CLDN-2 through the activation of the EGF/EGFR/MEK and cFos pathway [117]. It would be interesting to find out the molecular mechanisms that fail in cancer and provoke the opposite response.
\nThe response elicited by EGF is transient, reaches a maximal value of TER at 15 h, and slowly decreases to control values at 24 h. This downregulation is provoked by the induction of the synthesis of prostaglandin E2 by the EGF itself that increases AmpC production, which in turn blocks the activation of ERK1/2 [118].
\nIt is not clear which vesicular compartment participates in the CLDN-2 degradation induced by EGF. The observation that the knockdown of Rab14 induces the lysosomal degradation of CLDN-2 in MDCK cells [119] opens the possibility that EGF somehow be able to inactivate this Rab protein.
\nThe induction of CLDN-2 downregulation by EGF is blocked by bafilomycin A1 and chloroquine, indicating that it may be performed by autophagy (Figure 3). A schematic representation of the mechanisms of EGF effect on CLDNs is shown in Figure 4. The induction of selective autophagy by EGF can be seen as a differentiation or protective effect. In this respect, autophagy has been observed in Caco-2 cancer colon cells deprived of nutrients, where selective autophagy of CLDN-2 is activated, resulting in an increase in TER [120]. Moreover, in porcine gut IPEC-1 epithelial cells, the deprivation of nonessential amino acids induces an apoptotic process that degrades CLDN-1 and ZO-1, but if autophagy is inhibited with 3MA, degradation of adhesion proteins and apoptosis is potentiated, indicating that autophagy has a protective role in these cells [121]. Finally, the injured spinal cord in rats induces the degradation of p120 and β-catenins, as well as CLDN-5 and occludin, in blood vessels of endothelia. This degradation is performed through selective autophagy, considering that these proteins associate to LC3II and p62. The administration of retinoic acid potencies autophagy and improves movement of the injured rats [122].
\nEpidermal growth factor (EGF) induces CLDN-2 degradation in a bafilomycin 1A-sensitive manner. Epithelial dog kidney cells (MDCK) confluent monolayer grown on filters were incubated 15 h in control condition, EGF, bafilomycin A1 (Baf), or EGF plus Baf. (A) Transepithelial electrical resistance measurements. (B) Densitometric analysis of the cellular content of CLDN-2 measured by immunoblot. (C) CLDN-2 Immunofluorescence of cells incubated in the indicated conditions.
EGF triggers a Src-ERK1/ERK2-STAT3 cascade to induce the degradation of CLDN-2 in the lysosomes. Occupancy of EGFR by its ligand induces the simultaneous phosphorylation of the kinases Src, ERK1/ERK2, as well as the phosphorylation of the transcription factor STAT3. The phosphorylated STAT3 is translocated into the nucleus, where it upregulates the transcription of CLDN-4 at the same time downregulates that of CLDN-2. In the cytoplasm, the same cascade plays a role in the induction of CLDN-2 endocytosis and CLDN-4 exocytic fusion, events that result in the lysosomal degradation of CLDN-2, an insertion of CLDN-4 at the TJs, and an increment of the degree of sealing of the TJs.
In the eighteenth century, William Withering used extracts of the herb foxglove (
The activation of the Src-EGFR-ERK1/2 cascade by OUA regulates cell adhesion in a concentration-dependent manner: 10 nM OUA, a concentration near the hormonal level, increases the degree of sealing of the TJs, inducing the transcription, translation, and expression at the TJs of CLDNs [139], and 300 nM or higher concentrations of OUA promote cell detachment resulting from TJ, AJ, De, GAPJ, and FA disassembly, endocytosis, and posterior degradation of their cell adhesion molecules [140]. Occludin, CLDN-2, and CLDN-4 endocytoses are clathrin-dependent [141]. 300 nM but not 10 nM OUA increases p62 signal and its colocalization with CLDN-2 in MDCK cells; degradation of CLDNs at 300 nM OUA is inhibited with NH4Cl and bafilomycin A1 [141], suggesting that ouabain activates CLDN-2 degradation through autophagy (Figure 5). OUA increments the size of intracellular structures that bind an antibody against Rab11, a recycling endosome marker, indicating that OUA is not inducing recycling of CLDN-2 (Figure 6). The mechanism of OUA action is shown in Figure 7.
\nHigh ouabain concentrations increase autophagy. Control MDCK cells have their CLDN-2 localized at the TJs, in a normal quantity, and in the cytoplasm in numerous spots (green); p62 shows no colocalization with CLDN-2. Upon incubation in media containing ouabain (OUA) 10 nM images remains unchanged, indicating that low OUA concentration does not activate autophagy. On the contrary, the incubation with OUA 300 nM decreases CLDN-2 all around the cell and increases p62 that colocalizes with internalized CLDN-2 (white arrows). This result supports the observation that 300 nM OUA increases autophagy of CLDN-2. Confluent monolayers of MDCK cells were grown on coverslips overnight and then incubated with control media, ouabain 10 nM or 300 nM for 20 h. Barr corresponds to 10 μm.
Ouabain does not induce recycling of CLDN-2. MDCK cells monoloyers were plated on glass coverslips overnight and incubated in control conditions (control) or in media with OUA 10 or 300 nM for 6 h. Cells were stained with antibodies against CLDN-2 and Rab11, a small GTP-binding protein of the recycling endosome. At this time, CDLN-2 has not been degraded yet and does not colocalize with Rab11 at any condition, suggesting that CLDN-2 is not internalized through the recycling endosome. Nevertheless, ouabain 10 nM decreases the intensity of the signal and the number of spots observed in the cytoplasm, implying that low OUA concentrations decrease recycling, while 300 nM increases the signal as it corresponds to cells with very active endocytosis. These results indicate that under OUA stimuli there seems to be a very active endocytic pathway, but CLDN-2 is not being recycled nor internalized through it.
A high concentration of ouabain induces endocytosis and lysosomal degradation of claudins. OUA induces the formation of the signalosome (structure enclosed by the interrupted line), a caveolar complex including some Na+,K+-ATPases, and their associated Src and EGF receptors (EGFR). OUA activates the Src-ERK1/ERK2 pathway, which induces the clathrin- and dynamin-dependent endocytosis of TJ components. Our results indicate that there are two types of endocytic vesicles: one containing a core complex with essential TJ proteins, such as ZO-1, OCLN, and CLDN-4, and a second one consisting of components that confer a differentiated functional characteristic to TJs, such as CLDN-2, that makes TJs permeable to water and Na+. Src-ERK1/ERK2 pathway is also required to reduce CLDN-2 and ZO-1 mRNA levels. Surprisingly, during the OUA-induced aperture of the TJs, the cellular content of CLDN-4 and OCLN mRNAs increases.
The final outcome of the treatment with high concentrations of OUA is the detachment and death of OUA-sensitive cells [132, 137, 140, 142]. Ionic imbalance that results from the inhibition of the enzyme has been considered the prime cause of cell death given the fame of the Na+,K+-ATPase as an ion transporter. However, cells do not detach when they are cultured in low K+ medium [137], which mimics the diminished [K+]i content induced by OUA. The cytotoxic action of OUA in humans and rodent cells depends on the features of the type α subunit expressed, rather than by any downstream components of the cell death machinery [142]. In this respect, epithelial cells expressing a OUA-resistant isoform of Na+,K+-ATPase do not detach when they are incubated in low K+- or K+-free medium [137, 143]. Therefore, ionic imbalance by itself is not sufficient to detach cells; OUA and the activation of kinases (p38 tyrosine kinases, Src, and ERK1/2) are necessary (Figure 7), a finding that agrees with the triple role of the Na+,K+-ATPase: transporter, signaling receptor, and cell-cell adhesion molecule [144].
\nRenal hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive disease characterized by abundant renal Mg2+ and Ca2+ wasting that causes renal parenchymal calcification and renal failure. It can only be cured through renal transplantation. The illness results of the lack of stable expression of CLDN-16 and/or CLDN-19 caused by mutations in
In chordates, AJs are Ca2+-dependent cell-cell adhesions between neighboring epithelial cells at the lateral domain, immediately below the TJs (Figure 1, red). In prechordates, AJs present an inverted localization with respect to the TJs: AJs are the most apical junction of the lateral membrane, placed over the septated junctions. AJs consist of the nectin-afadine and the cadherin-catenin complexes. The nectin’s complex forms a scaffold necessary for the assembly of the AJs [156–159], whereas the cadherins serve as homotypic adhesion receptors [160, 161]. The associated plaque proteins catenins and afadins, in turn, bind the receptors to the cytoskeleton of actin [162, 163]. The homotypic adhesion of cadherin plays an important morphogenetic role because it underlays the selection and association of cells of the same type to form specific tissues, a process denominated “cell sorting” [164]. Based on the fact that there are numerous cadherins in the unicellular choanoflagellate
In a normal epithelium, β-catenin is mostly associated to E-cadherin at the plasma membrane, and the cytosolic pool of β-catenin is kept low by degradation in the proteasome. However, a proliferation signal, triggered by a Wnt ligand, impedes the β-catenin degradation and induces its accumulation in the nucleus to activate proliferation (Figure 8B) [27]. E-cadherin is degraded by lysosomes through an endocytic route [166]. The cytoplasmic domain of E-cadherin has an endocytosis signal that is normally masked by
Degradation of E-cadherin and β-catenin involves endosomal lysosomal and autophagyc routes. (A) Normal conditions. When nutrients abound, E-cadherin and β-catenin are degraded through the endocytic-lysosomal and proteasomal routes, respectively. (B) Starvation. Under nutrient shortage, β-catenin switches to a selective macro autophagy for degradation. Wnt represents the WNT signaling cascade, TCF4 is the transcription factor 1.
GAPJs are molecular ducts that communicate the cytoplasm of contiguous cells and allow the epithelium to respond coordinately to various stimuli or extracellular signals (Figure 1, yellow). These junctions are made up of tetraspan proteins: connexins in chordates and innexins in prechordates [172]. Six connexins polymerize to form a hemichannel or connexon in a cell, which attaches to a connexon in the neighboring cell, forming in this manner an intercellular channel that can be opened by diverse stimuli. The dense clustering of tens to thousands of intercellular channels originates a GAPJ [173–175]. Connexins are associated with a scaffold of ZO-1 or ZO-3, vinculin, Src, and tubulin [176]. This association is important for the localization of connexons, the formation of the multimolecular clusters of intercellular channels in the plasma membrane, and the regulation of intercellular communication [177].
\nDes are cell-to-cell adhesion structures that confer mechanical strength to epithelia and cardiomyocytes. These junctions are composed of five main proteins: the desmosomal cadherins, desmogleins, and desmocollins are the receptors for adhesion. Their cytoplasmic tails bind to plaque proteins of the armadillo family, plakoglobin and plakophilin (Figure 1) [178]. The armadillo proteins attach to another plaque protein, desmoplakin, which, in turn, links the protein cluster to the cytoskeleton made of intermediary filaments of cytokeratin [179]. Observations in tissues and cultured cells have shown that Des can adopt a Ca2+-dependent adhesion state that progresses to a Ca2+-independent hyper-adhesion state, a process that requires PKC activation [22, 180–182].
\nGAPJs are extremely stable junctional structures: as soon as they are formed, they become indestructible [183, 184]. Nevertheless, they are very dynamic due to the fact that connexins have a very short half-life of only 1–5 h [185]. Consequently, there is a permanent turnover that involves the closure of the intercellular conduction by several stimuli, for example, the binding of EGF to its receptor. The central portion of the GAPJ is then internalized, including the bound hemichannels and membrane of the neighboring cell, forming a peculiar structure named annular GAPJ (Figure 9) [186]. In some conditions, annular GAPJ may be recycled back to the plasma membrane [187] although, usually, they are degraded through autophagy; yet, the precise mechanism, the kind of autophagy involved, and the fate of the cells depend on the trigger and/or the cellular context [185, 187–189]. A mechanism that stops autophagy implicates the hijacking of components of the initiation of autophagy, for example, Atg16, by the connexins themselves. On nutrient starvation, connexins release Atg16, the blockade is lost and autophagy proceeds [190].
\nBig portions of GAPJ and complete desmosomes (Des) are degraded by nonselective autophagy. The central portion of the GAPJs is internalized and degraded by autophagy. Dependent on the cell type and condition, complete Des are internalized and degraded by autophagy, and halves of Des are degraded by autophagy and in the proteasome.
On liver cells of BRL 3A expressing connexin-43, cadmium inhibits GAPJ intercellular communications and induces the degradation by autophagy of connexin-43 as well as apoptosis. Inhibition of autophagy exacerbates Cd2+-induced inhibition of the intercellular communication and apoptotic cell death [188] revealing the protective role that autophagy plays on cell fate.
\nDes are also very stable structures which can reach a hyper-adhesion state insensitive to Ca2+ depletion [191]. It has been shown that a half of Des is internalized after extracellular Ca2+ depletion in a PKC- and actin-dependent process [182, 192]. Internalized half desmosome is then transported by kinesins and microtubules toward the centrosome and remains there without recycle to the plasma membrane. Degradation proceeds in lysosomes and proteasomes [193]. In mouse epidermis, the complete Des are engulfed and internalized [192]. Nevertheless, the degradation mechanism is different when disassembly is triggered with autoantibodies from pemphigus vulgaris patients; in this case, Des disassemble in smaller complexes made of the autoantibody, desmoglein-3, and plakoglobin that are endocyted and delivered to the lysosomes through the endocytic route [194].
\nFAs, also known as focal contacts, and HDes are the cellular junctions that attach cells to the extracellular matrix. HDes are common in stratified epithelia and bind epithelial cells to the underlying extracellular matrix (Figure 1, blue) [6] . The adhesion receptors of both, FAs and HDes, are transmembrane proteins of the family of integrins, which exist as heterodimers of α and β subunits form. There are 19 α-integrins and 8 β-integrins that combine to form 25 existing heterodimers in mammals [195, 196]. HDes provide stable adhesion and mechanical resistance to epithelial tissues by anchoring the extracellular matrix to the cytokeratin cytoskeleton, through a protein complex that includes the adhesion receptors α6β4 integrin, BP180, and the tetraspanin CD151, and the intracellular adapter proteins plectin and BP230 [6]. The expression of several HDes proteins depends on the transcription factor SOXF [197]. While the extracellular region of integrins of FAs binds the extracellular matrix, the cytosolic portion contacts specific plaque proteins such as focal adhesion kinase (FAK) and paxillin, which are important signaling proteins. Other protein components of the FA plaque, such as talin, vinculin, and α-actinin, bind the adhesion receptors to the actin microfilaments [5, 198, 199].
\nFAs are essential in cell migration and, therefore, for embryogenesis, wound healing, immune cell function, cancer progression, and promoting metastasis [200]. Cell migration requires endocytosis and recycling of integrins given by endocytic signals in its cytoplasmic tail. These signals bind either clathrin or caveolin-1 to induce integrin endocytosis. Once inside the cell, integrins anchored to protein complexes are sent to the early endosomes, where they can be sorted either to late endosomes and lysosomes for degradation (Figure 10, 1) or to recycling endosomes and plasmatic membrane for the assembly of new FAs. A short loop for recycling requires Rab4 proteins and is generally activated in response to growth factors (Figure 10, 2); the long loop is Rab11 and Arf6 dependent and delivers integrins to the perinuclear recycling compartments (PNRCs) and, from there, to the cell membrane (Figure 10, 3) [190]. The actin cytoskeleton is essential to the recycling pathway; in fact, depletion of the actin-related protein (Arp) 2/3 or the nucleating-promoting factors such as the members of the Wiskott-Aldrich syndrome protein (WASP) blocks recycling and induces delivery to the lysosomes [5, 198].
\nFA disassembly is linked to autophagy in two ways: a nonselective autophagy triggered by extreme stress condition, such as starvation or hypoxia (Figure 10, 4), and a selective autophagy for housekeeping and quality control that includes ubiquitin-tagged substrate association of them with an autophagic cargo receptor (ACR) attached to LC3II. This autophagy provokes the disassemby of FA Under starvation, β1 integrin is degraded in autophagosomes in cervix adenocarcinoma epithelial HeLa cells. This autophagy is inhibited by high mTOR activity at the leading edge during migration, which promotes increased motility [201], whereas the activation of selective autophagy promotes FA disassembly in metastatic mammary epithelial cells (4T1) [202]. Thus, the inhibition of autophagosome reduces cancer cell’s malignancy, indicating that selective authophagy is also a cell migration regulator (Figure 10).
\nAutophagy is crucial for the recycling of integrins in focal adhesions during migration. Cell migration requires continuous recycling of integrins. (1) Integrin endocytic pathway degradation. (2) Integrin short loop recycling; vesicular transport of integrins from the EE to the Rab4 containing RE, and from there back to the plasma membrane. (3) Integrin long loop recycling; vesicles transport integrins from EE to Rab11 containing RE, later on, to a perinuclear recycling compartment (PNRC) and then to the plasma membrane. (4) During starvation, integrins are endocyted and directed to the AP. (5) Cell migration leading edge. FA´s protein paxillin is recognized by autophagic cargo receptors (ACR) and degraded by selective macroautophagy, which induces FAs disassembly through a mTOR dependen pathway. In the leading edge, FAs must be first formed and then degraded to allow motility. Autophagy plays a crucial role in this process.
Besides migration, autophagy is linked to anoikis, a type of cell death due to detachment from the substrate. Loss of integrin-mediated adhesion initiates autophagy, which delays anoikis and downregulates apoptotic signals. This process affords cells time to reattach; however, in cancer cells, high autophagic activity after detachment provides resistance and promotes malignancy, allowing the cell to support stress condition, increase motility, and resist anoikis [203, 204].
\nAlthough there are several illnesses produced by the lack of HDes protein expression, little is known about HDes degradation.
\nLysosomal degradation mechanisms are crucial for the formation, differentiation, and degradation of epithelial cell junctions. Epithelial cells use selective autophagy to degrade claudin-2, in response to the stimulation with the epidermal growth factor. Ouabain, at a concentration close to the hormonal, does not induce autophagy of tight junction proteins and, at high concentrations though, induces lysosomal degradation that can involve autophagy. The precise sequence of events and outcome of each lysosomal degradation mechanism is context dependent; nevertheless, it is clear that the degradation through macroautophagy of large plaque of complete communicating junctions and desmosomes, as well as of desmosomal halves, takes place either in natural tissues or in cultured cells. It is also clear that the desmosomal transition from weak to strong adhesion stages requires lysosomal activity, that β-catenin undergoes selective autophagy in some conditions and that E-cadherin degradation is performed in lysosomes through an endocytic route.
\nElectrospinning (ES), as a nanotechnology, exhibits strong evolution of materials used across a broad spectrum from bioactive (microorganisms-infused for biomedical applications) to manufacturing (adhesion, proliferation, and differentiation of the mimetic for mechanical, chemical and electrochemical applications) nanofibers [1]. The advent of bioeconomy and innovation technological development presented opportunities for remarkable progress in the expansion of methods and multiple applicability for the electrospun nanofibers. Waste biomass and other recyclable materials are also finding use in ES as an adaptable and sustainable innovative approach for making ultrathin fibers [2]. Valorization of biomass waste materials such as plant biomass, waste plastic, industrial effluent and other waste biomass streams have been processed through various technologies to produce a wide range of higher hierarchical recycled fibrous products. These including biodegradable bio plastic, filtration membranes, nanofibers as macro, micro and nanomaterials. Advancement in innovative ES techniques allows for intrinsic control of the physicochemical factors, including physical (morphology, diameter, orientation); surface (volumetric dispersion, porosity and thickness) and chemical (functional groups) characteristics of the final product [2].
Electrospinning method entails the utilization of voltage to create an electric field, polymer solution of specific concentration and electrospinning pump to introduce the spinneret onto collector plate. The resulting products are electrospun nanofibers characterized by their fibrous morphology, three-dimensional (3D) porous framework, nanoscale and chemical character that enable unique capabilities across multiple fields; which are difficult to create using conventional methods. Thermally induced phase separation nanofibers, and electrospun nanofiber scaffolds, for example, are being developed and are widely regarded as an emerging technology and a potential strategy for biosensing, drug delivery, soft tissue regeneration, hard tissue regeneration, and wound healing. The capacity to alter numerous control aspects of the functional scaffold, such as fiber geometrical features and alignment, architecture, and subsequent material performance, is the technique’s most prominent feature [1]. More importantly, electrospinning allows for the creation of a wide range of novel materials, including polymer alloys, nanoparticles, and active agents.
Nanofiber preparation employing the ES method has proved to be a future-proof materials technology, with numerous appealing characteristics such as outstanding mechanical properties and large specific surface areas. Due to the versatility, utility, and simplicity of the ES technology, the fibers produced are particularly appealing for numerous applications from a simple process capable of producing diverse morphologies [3]. The use of metal organic frameworks (MOFs) due to its flexible and functionalized molecular structures, nanofibers composites were fabricated as a novel molecular system with highly engineered structures for tailored applications. The usage of MOFs/carbon nanofibers (CNFs) as good electrode materials in energy transformation and storage technologies that include supercapacitors, sensors, and electrocatalysts is one of the most basic applications [4].
Electrospinning for materials technology of the future have seen a wide range of innovations of the technology including home-made re-designing of the technology to improve the ES apparatus reproducibility. Thus hybrid electrospun structures on different types of polymers have been developed and optimized to create products for various applications [5]. This chapter explores electrospinning innovation technology and the materials of the future, their properties and characteristics and applications. The focus materials of the future will be products fabricated from recyclable waste biomass materials as a way of valorization for higher hierarchical bioeconomic products.
The ability to tailor structural and morphological aspects of electrospun materials, such as the surface topography of nanofibers, and their porosity that allows enhanced mimicking of the manufactured material matrix, has sparked interest in the ES technology. This is accomplished by the ability to modify the electrospinning assembly in numerous ways in order to combine polymers with a wide range of materials (incorporate active materials such as drugs, inorganic catalysts, growth factors, functional groups and DNA/RNA as necessary in the various applications of the fabricated nanofibers [6]. Figure 1 is a schematic diagram showing a simple set up of the electrospinning system.
Schematic illustration of vertical electrospinning setup [
Mokhtari et al. compared the technical assembly of the electrospraying and the electrospinning systems. This is because the two systems have different mechanisms of performing the fabrication of carbon materials they produce in unique distinct ways as shown in Figure 2. Electrospinning (Figure 2a) supports the formation of micro-scale and in some cases nano-scale fibers while the formation of thin films is facilitated by the electrospraying system (Figure 2b) aids in the formation of thin films [7]. As a result of insufficient polymer-chain entanglements in the polymer chains network, it was discovered that applying a high voltage below the minimum concentration causes electrospraying rather than electrospinning.
(a) Schematic drawing of a typical electrospray setup. (b) Schematic drawing of a typical electrospinning setup.
It was observed that varying the ratio of the polymer solution and the electrospinning potential difference results in the formation of unique materials ranging from beaded carbon deposits, heterogeneous fibers, uniform fibers, and entangled fibers [7]. Advanced efforts to improve electrospinning performance and the quality of the nanofibers while increasing cost-effective productivity of electrospinning and other nanofiber assembly technologies include integration of key concepts of conventional fiber production methods with nanotechnology. Electro-blowing, gas-jet/gas-assisted electrospinning, and solution blowing, which advanced from melt blowing, combined with electro-centrifugal processing, centrifugal spinning, near field electrospinning with dip-pen nanolithography, and XanoShear, which combines shearing with wet spinning, are among the merged electrospinning conceptual technologies [8].
A look into a study of electrospinning as a versatile technique for fibrous material manufacturing in advanced fabrication of the electrospun biopolymer-based biomaterials compared the conventional needle-based and an innovative needless-based electrospinning processes. Figure 3 presents the unique feature of the needless-based ES process is that the polymer solution is positioned in a bath and a high voltage polarized spinning mandrill is immersed into the bath.
Electrospinning setups needle-based (left) and needleless (right) [
When the rotating mandrill comes into contact with the grounded collection electrode, it collects a thin layer of polymer solution, which is subsequently subjected to an electric field. The electrostatic forces of the field at the needle’s tip, or the thin layer of polymer solution at the rotating mandrill, overcome the solution’s surface tension, pushing it to form several or a single Taylor cone, as illustrated in Figure 4. On its way to the collector, the charged polymer jet from the cones is ejected and extended. The solvent evaporates from the solution, weakening the continuous jet of pure polymer and depositing it in a fibrous form on the collector [2].
Needleless roller for electrospinning of polymer solutions.
A needleless mechanism performs the electrospinning of the polymer solution from the surface of a revolving roller. The roller is partially immersed in a tank containing material to be electrospun, as shown in Figure 4. On the roller’s surface, a layer of consistently new material is generated by a rotating roller. When compared to needle electrospinning, the technique produces a large number of Taylor cones on the roller’s surface, resulting in the technology’s industrial applicability in mass manufacture of nanofibers materials [9].
Complex fibrous nanostructures have been prepared through manipulation of many experimental parameters of a multifluid electrospinning process. This is an innovative shift from the traditional single-fluid blending electrospinning process. However, there are difficulties in using multifluid processes, such as compatibility concerns of set up parameters including fluids, rate of stock feed and average proportions, interfacial tensions, and electrospinning sustainability [10]. Mass production of nanofibers using electrospinning was determined through the development of the macromolecular ES principle. The molecular flow in the spinning process, as well as the molecular direction in nanofibers, can be tailored to advance the electronic, and physico-chemical properties of nanofibrous materials, which influence their applications, molecular orientation in nanofibers, and structural hierarchical significance [11]. Several recent methods were developed to manufacture nanofibers using macromolecular ES processes. For example, industrial yarn production processes were only applicable for solution electrospinning via the innovative conceptualized gas-assisted melt ES. (GAME) as shown in Figure 5.
Macromolecular electrospinning equipment showing a possible laminar flow in the suction tube [
The unique characteristic of the innovative technique is the observed occurrence that turbulent air applies a pulling force, subsequently leading to an increase in output and a 10% reduction in melt jet width, with an additional 20-fold thinning when the air jet temperature is increased [12].
Multi-temperature control electrospinning (MTCES) is a practical way to spin molten polymers on a submicron level fiber than the conventional molten/solution ES. The molten precursor polymer was treated to quad-heating regions in the proposed MTCES design: needle, nozzle, rotating area, and collector to augment and regulate fiber size and morphology. The nozzle, spinning thermal parameters and dimensions, electric field, and flow rate of the MTCES are all adjusted to change the fiber diameter [13]. The MTCES setup is depicted in Figure 6. The technical mechanism demonstrates that the jet propagation begins to bend significantly near the collector at 25°C, and at 80°C, a strong melt jet propagation increases the dwelling time of the jet in the rotary region, demonstrating a distinct multi-control ES scheme, which was characterized by extensive preliminary work and models that used the same or similar setup schemes.
The multi-temperature control electrospinning setup showing the multi-heating zone melt electrospinning [
Energy materials have been fabricated by ES techniques as an alternative to fossil fuels and environmental mitigation initiatives. The nanofibrous materials produced by ES are extensively used in electrochemical energy storage devices. This is because the materials have inherent excellent properties, including an increased surface area, high dimensional ratio, good flexibility, high permeability, with several functionalities. A shift from the conventional ES methods saw the development of innovative enhanced ES techniques that produce nanofibers with novel special hierarchical nanostructures [14].
The core-shell structure was chosen because of its distinctive features, which can help to improve the preferred properties. Co-electrospinning creates core-shell fibers by filling two distinct precursor solutions into the double nozzles, as shown in Figure 7 [14].
Scheme for coaxial electrospinning [
The simplicity of setup and low cost, together with the ability to fabricate nanofibers with a wide range of compositions and morphologies, has aided ES technology’s innovative advancement. Electrospinning-created nanofibrous structures provide appealing extracellular matrix conditions for the fixing, migration, and variation of materials matrix, including those giving rise to hard structure regeneration. The creation of structural materials regenerating nanofibers has been utilized by ES technology developments, which include material simulating composite/hybrid configurations and surface functionalization such as mineralization [16].
A special trifluid electrospinning technology was also developed as an innovation to the co-electrospinning process. This advancement provided for complex multi-chamber nanostructures for designing novel functional nanomaterials. The complex structure consisted of a collective shell and two independent openings of a multi-chamber nanostructure, with each having its own unique complex property, and these compartments form a total composite assembly within a region limited by nanofiber diameter. The sheath-separate-core fused nanostructure synchronized the functionalities of the three ES monolithic nanocomposites to afford a smart regulated release profile of a multi-chamber nanostructure, with each chamber characterized by distinct intrinsic complex property, and the structural compartments constituting a whole fused structure inside a section restricted by the diameter of nanofiber as shown in Figure 8 [17].
Designs of the complex spinneret for implementing trifluid electrospinning: (a) a digital image showing a full view of the spinneret; (b) front view; (c) side view; and (d) a diagram about the organization of a structural outlet from three inlets [
Precision electrospinning, enabled by recent improvements in ES technology, is being envisioned as a viable option for fabricating 3D nanofibrous materials with a desired microstructure. Internal access to setup parameters such as solvent and fiber collecting method has increased intrinsic control of final nanofibrous architecture creation mechanism, as shown in Figure 9 [18].
Setup used to form 3D nanofibrous scaffold using a negatively charged electrode or negative ion generator [
Plastic and other waste materials from industrial, domestic and agricultural activities, are the modern scourge on the face of the planet. The global call for re-use and recycle is gaining tremendous recognition with scientist scrambling for innovative ways of using waste materials in the circular economy. Waste biomass has been explored as an alternative source of polymers that may be used in wide range of ES processes targeting specific valorized products. As new materials use emerge and novel materials are electrospun into nanofibers, it is becoming increasingly critical to grasp current breakthroughs in biomass conversion into polymer sources for nanofibrous structures in order to fully exploit their potential. Advancements in waste biomass conversion technologies such as bio digestion, pyrolysis of plastic, and waste agricultural plant biomass wastes into bio oils and other polymers have preceded this.
Biomass is organic substances that is renewable and comprises plants and animals matter and may be combusted for heat or treated into renewable polymeric materials or fuels using a range of technologies. Most of the biomass end up as environmental waste materials that contaminate the land, rivers and oceans. Waste biomass include waste plant materials from crops, animal waste (dung and sewage), industrial waste in the form of effluent coming from industries such as petrochemical, food processing, textile dye effluent, pharmaceutical, and solid waste biomass including plastics, plant residues, (bagasse and other dregs), timber offcuts and sawdust, pulp and paper processing waste etc. These various biomass waste streams may be used as an alternative source of polymeric materials that may be used in electrospinning to produce materials for the future. Three classes of the waste biomass will be discussed namely synthetic waste biomass, natural flora waste biomass and natural fauna-based waste biomass.
Plastic is the largest solid waste biomass on the face of the earth’s surface while textile and pharmaceutical effluent are major synthetic liquid waste biomass. Unless great strides are made to valorize these waste streams and find hierarchical bioeconomic applications of these materials, they will persist in the environment as contaminants. Due to its tunable features, including wettability, surface charge, transparency, elasticity, porosity, and surface to volume proportion, various polymeric fibrous nano materials have been developed as simulated extracellular matrix. Using ES nanofibers of natural polymers (NPs) and synthetic polymers (SPs) as simulated extracellular matrix for tissue regeneration, a comprehensive investigation identified five basic kinds of nanofibrous polymers. NP–NP composites, NP–SP composites, SP–SP composites, cross-linked, and modified polymers with mineral materials are some of the polymers available [19]. Polycaprolactone (PCL), polylactic acid (PLA), poly(lactic-co-glycolic acid) (PLGA), and polyethylene terephthalate (PET) are some of prevalent well-known synthetic polymers [20, 21].
In recent years, a variety of processing technologies have been utilized in the manufacture of polymeric fibrous nano materials, including drawing, 3D printing, template synthesis, phase separation, self-assembly, ES, and so on. Synthetic ES nanofibrous materials processing allows for internal control of the electrospinning mechanism and foster chemical crosslinking to generate covalent connections between polymeric fibers. In either in situ electrospinning or post-spinning crosslinking, this manipulation is done to target qualities of the material of application in which the fibers will be used. Highly porous electrospun nanofibrous membranes, for example, have sparked a lot of interest in water filtering applications. Figure 10 presents some of the common synthetic biomass materials used in ES of nanofibers. The creation of a reduced pore size and its distribution is highly favored by a thicker membrane with a lower mean fiber diameter, albeit the influence of membrane thickness is rather restricted. A high flux microfiltration (MF) sheath was fabricated based on efficient control of the total composite structure containing the electrospun layer thickness of 200 ± 10 m and a mean fiber diameter of 100 ± 20 nm [22].
Synthetic polymers used in electrospinning of nanofibrous materials.
A previous study looked at the spinnibility of various polymers, such as aqueous poly(ethylene oxide) (PEO) dispersed in alcohol-to-water mixtures. Fiber production was found to be possible with viscosities ranging from 1 to 20 poises and superficial tensions of 35−55 dynes/cm. Electrospinning, however, was not feasible at viscosities more than 20 poises due to flow instability produced by the solution’s high cohesiveness [23].
Spongy pomelo peels, rice husk, rice straw, sugar cane bagasse, coffee beans, coconut shells, and peanut shells have all been investigated as alternative sources of carbonaceous materials from biomass. In comparison to other carbonaceous precursors, these and other natural plant/floral biomass resources have grown increasingly appealing due to their availability, low cost, easy accessibility, and environmental friendliness. As a result, floral biomass has gotten a lot of attention in the electrospinning, biomedical, and energy storage fields [24]. Okara, soy pulp, or tofu dregs, for example, is a pulp made up of insoluble components of the soybean that remain after pureed soybeans are filtered for soy milk and tofu manufacture. Recent reviews have reported on the feasibility of ES fibrous nano materials made from a variety of decomposable and biocompatible matter, including natural proteins like floral and faunal collagen, gelatin, silk, chitosan, and alginate [25].
The preparation of the waste floral/plant biomass for ES of nanofibrous materials involves a number of steps that extract plant proteins in the insoluble parts of the waste biomass. Silk fibroin (SF), for example, is made by degumming raw silk fibers twice with a 0.5% (W/W) NaHCO3 base medium at 100°C, over half an hour period followed by rinsing with warm dH2O. At 70°C for 6 h, degummed silk (SF) is dispersed in a ternary aqueous medium of calcium chloride-ethanol-water (1:2:8 in molar ratio). The SF was filtered and lyophilized after 3 days of dialysis using cellulose hollow sheath (250-7u; Sigma) in dH2O to get the regenerated SF sponges. Dispersing the SF sponges in 98% methanoic acid (Aldrich) for 3 h makes SF solutions. The molar quantities of SF solutions for electrospinning range from 3% to 15% by weight [26].
Extracted silk fibroin was used to prepare silk electrospinning as presented in Figure 11. Electrospun SF nanofibers with varied silicon fibroin concentrations of 3%, 6%, 9%, and 12% are shown in SEM micrographs. The most prevalent natural polymers used as ES nanofiber materials include chitosan, collagen, gelatin and silk [20, 21]. Natural polymer nanofibers present distinguished features like biodegradability and biocompatibility, a phenomenon that makes them suitable materials in biological environments. Figure 12 presents some of the abundant natural polymers adapted for ES nanofibers production. Chitin and its over 50% deacetylated derivative, chitosan, for example, are commonly used natural polysaccharides as scaffolds. Blending with other materials are thus required to tailor-make materials with a set of acceptable features and attributes in order to achieve a stronger composite. Chitin/silk fibroin (chitin/SF) nanofibers, for example, were used to make novel ECM scaffolds [27].
SEM micrographs of electrospun SF nanofibers with concentration of (a) 3%, (b) 6%, (c) 9%, and (d) 12% [
Natural polymers used in electrospinning of nanofibrous materials.
Biocompatibility and biological activity are two characteristics of natural polymers. However, these polymers have some drawbacks, such as engineering and processing difficulties due to poor mechanical strength, restricted processing and manufacturing capacities, batch-to-batch variability, and the possibility of pathogen transmission [20]. Collagen and proteoglycans, for example, make up the majority of the body’s natural extracellular matrices (ECMs), which vary in composition depending on tissue type. Nanofibrous scaffolds made of collagen fused with glycosaminoglycans (GAGs), the major constituent of proteoglycans like condroitin sulfates and hyaluronic acid, are suitable for creating a perfect scaffold that mimics the natural ECM. Collagen and GAGs’ utility, on the other hand, has been limited because of their exorbitant price and poor mechanical qualities. In biomedical applications, this phenomenon can be addressed by fusing natural polymers such as proteins polymeric strands and polysaccharides fibrous materials, which can improve biotic transformation of cells and accelerate tissue development [27].
Most of the insoluble floral biomass is in the form of lignocellulosic and chitin material. The success of tapping into the floral biomass as a resource for ES of nanofibrous material depends on the ability to depolymerize the lignin and chitin long polymer chains. It is these polymers that will be used for ES processes to produce electrospun nanofibers. Recently, there has been renewed interest in producing carbon fibers from sustainable cellulosic precursors [28]. The abundance and cost effectiveness of cellulose as a material generator, as well as the relatively ecologically friendly fiber production methods used preceded this interest. Recent research on regenerated cellulose fibers from a fluid crystalline fabrication route as a carbon fiber precursor generated strands with a modulus of 140 GPa for the shell area and 40 GPa for the core area, indicating that CNFs resulting from nano-sized cellulosic precursors are even more competent as physical reinforcement than micron-sized fibers; because of their reduced diameters, providing a greater surface area for bonding and stress transfer [29].
Animal manure, agricultural residues, organic portion of municipal solid garbage, industrial waste biomass, and natural vegetation cycle waste are all examples of enormous amounts of organic waste produced by many sectors. Similarly, fauna waste biomass, primarily in the form of keratin, a durable, fibrous protein found in advanced vertebrates (mammals, birds, and reptiles) and human epithelial cells, has been widely employed in ES for the creation of nanofibrous materials. Millions of tons of keratin-containing biomass are produced by the food business, particularly the meat market, slaughterhouses, and wool manufacturers. These sectors are rapidly expanding, with the United States, Brazil, and China accounting for more than 40 million tons of fauna-based biomass annually [30]. Inadequate management of these organic wastes can harm the environment by polluting water and air, lowering people’s quality of life [31].
If controlled with scientific interventions, organic waste no longer persists as garbage, but instead becomes a rich source of substrate, polymers, and molecules for the production of a variety of value ES nanofibrous products [32]. Detailed studies explored potential applications of the fauna generated organic waste in the production of biogas for energy production. Human waste is disposed of as sewage in the form of biological wastewater. Technological advances unravelled biological wastewater treatment plants (WWTP) as an approach to converting biomass into rich materials for precursor molecules for polymerization in ES nanofibrous material fabrication or for energy production [33]. Fauna waste biomass in the form of dung (Figure 13), piggery or fowl wastewater treatment with purple phototrophic bacteria was explored as a promising platform for electrospinning biomass resource recovery process under optimized operational conditions [34].
Fauna biomass: cow dung is co-digested with sewage for production of gas in an anaerobic bio digester.
It is important to note that fauna waste biomass is a natural phenomenal bio digestive process of converting lignocellulosic and chitin organic biomass and transform it into shorter chains of polysaccharides and other polymeric substrates for ES nanofibrous materials production. Anaerobic bio digestion followed by catalytic polymerization of biogas molecules such as methane, ethane and propane, will produce tailor-made polymeric materials that may be used in electrospinning production of carbon nanofibrous materials. Figure 14 is an advanced industrial scale bio digestion plant for production of biogas.
Sewage treatment plant for gas production.
Bio digestion of fauna waste biomass is a significant alternative supply of materials for electrospinning of nanofibrous materials when modern methods are used. Previous research on bio digestion of fauna waste biomass for methane production found that the influence of pre-treatment results in a substantial increase in gas production of up to 67%, with a 52% methane content in the biogas. As a result, it was determined that pretreatment of both feed and biomass improves biogas output but not methane content [35]. According to recent studies, the valorization of bio or organic waste is being prioritized in order to tackle the rapid accumulation of waste generated from food production activities, as well as to create sustainable feedstock for industrial materials and chemicals in place of fossils and synthetic materials (see Section 3.1). Biogas, compost, and small platform molecules are currently produced from biowaste via anaerobic bio digestion, fermentation, and thermo-chemical methods as shown in Figure 15. There are currently no commercial low-temperature chemical methods for valorizing organic lignin fractions as feedstock for modified compounds. Thus, research has been conducted to fill this technological gap, demonstrating that moderate thermal hydrolysis of municipal bio-waste manure reserve is a safe, environmentally sustainable, and affordable process for transforming lignin-like material from compost into value-added specialty chemicals for the production of ES nanofibrous materials (Figure 15) [37].
Auger/screw pyrolysis reactor concept using heat carrier [
Biomass is a readily available and long-lasting ES material that may be turned into carbon based smart energy storage device and other uses. For carbon nanofiber manufacture, many strategies were used to meet various goals, including an increased productivity, easy dimensional parameters manipulation, energy efficient, and a high turnover. Nonetheless, several critical features of biomass-based fibrous carbon nano materials are yet to be extensively studied, thus information gaps still exist for each process to be supplied. As a result, more research is needed to expand our knowledge of the essential characteristics of various processes in order to generate highly desirable precursor materials for ES fibrous carbon nano materials manufacture from organic matter for sustainable materials manufacturing and energy smart storage applications [38].
An example of fauna waste biomass material rich in extractable materials for ES nanofibers materials is feathers from the poultry industry. Chicken feathers, comprises 90% raw keratin protein and 70% amino acids, can be employed as one of the primary sources for extracting keratin. Keratin is used in a variety of industries, including biotechnology, waste management, cosmetics, and medicine [39]. Waste feathers can be converted into keratin in a cost-effective and environmentally beneficial manner. Keratin is an insoluble protein of the cytoskeletal element with a size of 8–10 nm that belongs to a group known as intermediate filaments (IFs). Keratin is a fibrous protein with a helical structure, as seen in Figure 16, and is the ecosystem’s third most prevalent natural biomass polymer after chitin and cellulose [41].
An α-helix and β-pleated sheet keratin and the molecular structure [
Electrospun fibers fabricated from waste biomass sources has resulted in manufacturability of bioactive electrospun nanofibers and has been reported as potential drug delivery agents [42], wound dressing with antibacterial activity, filtration, cosmetics, protective clothing, electrical applications [43] catalysis [44], food industry [44], facial mask [45], and smart energy storage devices, such as supercapacitors as illustrated in Figure 17.
Applications of nanofibers in different fields for day to day activities.
Natural biopolymer electrospun products are made up of ultrafine fibers that are reusable, nontoxic, biocompatible, biodegradable and antibacterial properties. The fibers have been reported to possess excellent physical and chemical characteristics such as high degrees of crystallinity, aspect ratio, large specific surface area, number of surface hydroxyl groups, thermal resistance and excellent mechanical properties [45, 46]. However, the substantial chemical and energy consumption associated with the isolation of macro-sized fibers to nano-sized fibers creates manufacturing hurdles for waste bioactive electrospun nanofibers [46]. As a result, findings on waste bioactive electrospun nanofibers are still in their infancy in the literature [46].
In the biomedical field, literature reports on manufactured products made from biomass electrospun fibers range from medication delivery agents to biomaterials [42], wound dressing with antibacterial activity, facial mask [45], and tissue regenerative biomedical applications as presented in Figure 18.
Illustration of various applications of bioactive electrospun fibers in the biomedical field [
The ultrafine fibers have been previously reported to result in high-performance filters and applicability in facial masks [45, 47]. Various ultrafine fiber filters have been created that can filter particles larger than 10 nm with excellent efficiency. Spider-web network filters are described in the literature as having a combination of extremely efficient, long-range electrostatic property, low air resistance, and great transparency [45, 47]. Viruses can be blocked by ultrafine fiber filters [47]. Irrespective of the challenges associated with the fabrication of bioactive electrospun fibers products. The choice of polymer used aid in fabricating fibers with antimicrobial activities [45].
Figure 19a presents a typical electrospinning technology. Choice of polymer, concentration, flow rate, needle, and tip-to-collector distance all affect fiber quality. Figure 19b shows various types of electrospun fibers. The structure of a hybrid filter that works as both a filter and a hydrophobic layer is shown in Figure 19c and d.
(a) Scheme of electrospinning technology. (b) Various SEM images of electrospun nanofibers. (c) Scheme of generally utilized masks. (d) The proposed structure of electrospun ultrafine fibrous masks.
Facial masks constructed from electrospun biomass possess key characteristic performance features that has the potential to outcompete with the masks in the market. Advantages of biomass electrospun masks vary from the transparent, reusability, antiviral, degradable smart masks that possess filtration, thermal stability, and water resistance [45]. The facial mask technique has a wide range of possible uses, including filtration systems in water treatment, protective garments, and cosmetics [45].
As a result of the structure and bioactivity of loaded pharmaceuticals remaining unaltered during the spinning process, electrospun drug-delivery agents drew interest. They also reduced in vitro drug burst release and can contain a range of biomolecules [48]. Drug delivery agents fabricated from all forms of cellulose polymer results in drug delivery systems that are hydrophilic, eco-friendly, bio-degradable, and biocompatible [42].
Incorporation of NPs, natural biomass onto the polymer through the electrostatic interaction between their functional groups has a stabilizing effect on NPs [44, 49]. These electrospun catalyst found application in catalysis, supercapacitors, corrosion inhibition, and within the food industry natural polymers [44, 49].
Carbon-based supercapacitors with a large interactive surface and high permeability have sparked interest in natural floral and faunal waste materials, owing to the growing ecological consciousness. Electrospun cellulose-based supercapacitors are still in the laboratory stage, despite their rich carbon abundance of roughly 44%, great stability, and exceptional permeability linked with its hierarchical conformation and exceedingly efficient rigid lateral chains in cellulose [49]. The energy density of cellulose-based supercapacitors is low [49]. Hence the poor electrical performance and cell voltage. Another limitation is time consumption associated with economic factor in the optimization stage of cellulose electrospun mats.
As an alternate technique for increasing the electrochemical properties of lignin/cellulose nanofiber electrodes, creating compound electrode materials with a lignin/cellulose backbone can be used to address these constraints [49, 50]. Literature presented flexibility, wide surface area, outstanding mechanical flexibility, and particularly good electrical conductivity, composite nanofibers and ES activated carbon fiber network (ACFN) as attributes to improved performance. When employed as supercapacitor electrodes, they have a high electrical performance, a phenomenon attributed to their pseudo-capacitance [51, 52]. As a result, ACFNs lignin/cellulose nanofiber composites could be an attractive electrode material for biomass-based flexible supercapacitors [49]. Furthermore, when the electrolyte penetrates the micropores of the electrospun mats, as shown in Figure 20, the characteristics of the electrospun biomass composites can be adjusted, allowing for the wettability feasible with the preferred electrolyte [53].
Supercapacitive cell with thin film-coated carbon powder-based electrodes and free-standing and flexible flexible carbon nanofiber electrodes in conjunction with a polymer electrolyte [
In aqueous electrolytes, heteroatoms have been reported to enhance wettability of carbonaceous surfaces [54]. Lignin has a lot of oxygen functional groups and a lot of active hydrophilic surface. However, biomass-derived ECNF p-doped performed worse relative to the commercial CF. The lower performance could be attributable to the starting material’s higher number of oxygen functional groups. P-doping has been reported to block micro/mesopores, reduce conductivity and electron transport [50]. Jet viscosity of the polymer was not measured, as such further research still has to be done.
As a result, environmentally friendly biomass electrospun fibers with improved performance in working electrochemical devices have demonstrated that the fabrication of future smart energy storage materials will be ecologically viable, providing a completely green alternative to the powering of transportation and conventional storage [50].
The versatility of waste biomass electrospun fibers, as well as their controllable physical and chemical properties, make them a model technique for electrode fabricating and flow media for a variable of smart energy devices, with the ability to reduce mass transport and activate overpotentials, thereby increasing competence [50]. Natural biomass is being used as a polymer of choice because of its capacity to infuse sustainable principles in electrochemical device materials. This also contributes to their capacity to increase the use of renewable electricity through their application [50]. Lignin is a waste by-product derived from natural flora that has been documented to exist in three different types: Different molecular weights and mechanical and thermal stabilities of kraft (KL), ethanol organosolvents (EOL), and phosphoric acid lignin (PL) [50]. For vanadium redox couples, electrospun carbon nanofibers produced from PL and KL at 9 kV demonstrated excellent cyclic voltammetry electrochemical performance. Figure 20 clearly illustrates potential electrical products that can be fabricated from waste biomass electrospun fibers. Redox flow batteries (RFBs), fuel cells, and metal air batteries are some of the potential products shown in Figure 20 [50]. The use of electrospun material in RFBs is still in its infancy and requires further development. Nonetheless, the improved redox couple’s catalytic activity of waste biomass electrospun fibers provides an alternate solution to commercial electrodes’ high overpotential when discharge current density is large [50].
Electrospun fibers made from waste biomass have the potential to be used in redox flow batteries because they form microstructures with large surface areas and mass transport qualities in the electrodes. Similarly, improved biomass electrospun fiber applicability in fuel cells and metal air batteries offers a conductive-advanced structure for the gas diffusion layers that can dope and/or support catalytic nanoparticles, as well as electrochemically active fibers [50].
The advancement of electrospinning (ES) technologies and the industrial production of ES fibrous carbon nano materials to suit or facilitate different bioeconomic uses was aided by technical innovation. It may be inferred that the capacity to change the electrospinning assembly in various ways, in order to combine different materials with a wide variety of properties as well as incorporate active elements, will have a substantial impact on the production of materials in the future. By combining essential concepts from traditional fiber manufacturing techniques with nanotechnology, the performance of electrospinning technology and the quality of nanofibers can be increased. In comparison to other carbonaceous precursors, natural flora and fauna waste biomass for future electrospinning material technology has become increasingly appealing due to its abundance, low cost, easy accessibility, and environmental friendliness. Most of the insoluble floral biomass is in the form of lignocellulosic and chitin material while the soluble biomass is in the form of proteins and polysaccharides. Fauna waste biomass is mainly in the form of keratin. Millions of tons of keratin biomass are produced by industry, particularly the meat market, slaughterhouses, and wool manufacturers. The determination of marketable low thermal chemical procedures to valorize bio and organic waste lignin fractions as feedstock for commercial chemicals will be the focus of future work aimed at advancing electrospinning materials.
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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. 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Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. 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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.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation"},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and 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.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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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. 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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. 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