\r\n\t1. Emphasizing the unique power of the molecular docking method in new drug discovery; \r\n\t2. Demonstration of how the molecular docking technique has led to the discovery of new molecules in cancer therapy, proteasome, and STAT3 inhibition, and the treatment of Alzheimer's disease; \r\n\t3. Underlining the importance of molecular docking-based modeling methods in the various branches of biotechnology
\r\n
\r\n\tWe hope that this book will be a common point where researchers working in the fields of life sciences and drug development will eventually meet.
",isbn:"978-1-80356-468-5",printIsbn:"978-1-80356-467-8",pdfIsbn:"978-1-80356-469-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"8c918a1973786c7059752b28601f1329",bookSignature:"Dr. Erman Salih Istifli",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",keywords:"Protein-Ligand Interaction, Lead Discovery, Molecular Recognition, Enzyme-Ligand Interaction, Mutant Enzymes, Alanine Screening, Proteasome Inhibitors, Signal Transducers, Transcription Activators (STATs), DNA Recognition Motifs, Neoplastic Cells, Amyloid-Beta Proteins",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 3rd 2022",dateEndSecondStepPublish:"May 4th 2022",dateEndThirdStepPublish:"July 3rd 2022",dateEndFourthStepPublish:"September 21st 2022",dateEndFifthStepPublish:"November 20th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A multidisciplinary researcher working in the fields of cytogenetics, molecular genetics, and bioinformatics-based molecular modeling (currently on the structural biology of COVID-19 and the treatment of Alzheimer’s disease). Dr. Istifli previously joined the molecular cytogenetics group at the Max Planck Institute for Molecular Genetics in Berlin, Germany where he contributed experimentally to the identification of four candidate genes (GRIA2, GLRB, NPY1R, and NPY5R).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"179007",title:"Dr.",name:"Erman Salih",middleName:null,surname:"Istifli",slug:"erman-salih-istifli",fullName:"Erman Salih Istifli",profilePictureURL:"https://mts.intechopen.com/storage/users/179007/images/system/179007.JPG",biography:"Dr. Erman Salih İstifli received his Ph.D. from Biology Department of Cukurova University, Insitute of Science and Letter. In his doctoral study, Dr. İstifli focused on the elucidation of the genotoxic and cytotoxic effects of a commonly used anticancer agent (antifolate) on human lymphocytes. During his period of doctoral research, he joined the molecular cytogenetics group at the Max Planck Institute for Molecular Genetics in Berlin, Germany, and he focused there on investigating the molecular cytogenetic causes of some human rare diseases. During these studies, he contributed experimentally to the identification of four candidate genes (GRIA2, GLRB, NPY1R, and NPY5R) responsible for intelligence and obesity. He was assigned as an expert and rapporteur on eight candidate projects in the Marie-Sklodowska Curie-Actions Innovative Training Networks in 2016. In 2017, he completed the online theoretical and practical course 'Introduction to Biology - The Secret of Life', run by the Massachusetts Institute of Technology (MIT) on the edX platform. In April 2019, within the framework of Erasmus+ staff mobility program, he gave seminars on 'DNA microarrays and their use in genotoxicity' at Tirana University in Tirana, Albania. 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From chapter submission and review, to approval and revision, copy-editing 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:"8068",title:"Cytotoxicity",subtitle:"Definition, Identification, and Cytotoxic Compounds",isOpenForSubmission:!1,hash:"20a09223d92829b5478b5f241f6a03ce",slug:"cytotoxicity-definition-identification-and-cytotoxic-compounds",bookSignature:"Erman Salih Istifli and Hasan Basri Ila",coverURL:"https://cdn.intechopen.com/books/images_new/8068.jpg",editedByType:"Edited by",editors:[{id:"179007",title:"Dr.",name:"Erman Salih",surname:"Istifli",slug:"erman-salih-istifli",fullName:"Erman Salih Istifli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6969",title:"Lymphocytes",subtitle:null,isOpenForSubmission:!1,hash:"1aa8ac01c934ebdeedd5d7813036beef",slug:"lymphocytes",bookSignature:"Erman Salih Istifli and Hasan Basri İla",coverURL:"https://cdn.intechopen.com/books/images_new/6969.jpg",editedByType:"Edited by",editors:[{id:"179007",title:"Dr.",name:"Erman Salih",surname:"Istifli",slug:"erman-salih-istifli",fullName:"Erman Salih Istifli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10198",title:"Response Surface Methodology in Engineering Science",subtitle:null,isOpenForSubmission:!1,hash:"1942bec30d40572f519327ca7a6d7aae",slug:"response-surface-methodology-in-engineering-science",bookSignature:"Palanikumar Kayaroganam",coverURL:"https://cdn.intechopen.com/books/images_new/10198.jpg",editedByType:"Edited by",editors:[{id:"321730",title:"Prof.",name:"Palanikumar",surname:"Kayaroganam",slug:"palanikumar-kayaroganam",fullName:"Palanikumar Kayaroganam"}],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:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],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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1. Introduction
1.1 Objective and scope
The objective of this chapter is to introduce AM processes, which have been utilized in clinical practice for the fabrication of mechanically-robust and dimensionally-accurate bone tissue scaffolds for the treatment of osseous fractures, defects, and diseases (such as osteoporosis, bone tumor resection, and orthopedic trauma). Particularly, this chapter concentrates on PME, FDM, PJP, as well as DLP with a special focus on the PME-AM process. Figure 1 illustrates additively-manufactured biocompatible bone tissue scaffolds and constructs having porous internal structures. Please note that the phantom as well as the femur bone were composed of a medical-grade composite material [1, 2], while the cubic microporous scaffold was composed of PCL [3, 4, 5].
Figure 1.
Biocompatible bone scaffolds and constructs with microporous internal structures, which allow for not only cell incorporation and adhesion, but also diffuse proliferation for clinical practice (Source: [1, 2, 3, 4, 5]).
The aforementioned AM processes enable high-resolution, non-contact, and multi-material deposition of functional bio-inks, polymer materials, as well as composite materials for tissue engineering applications. In spite of their benefits and potential applications, the AM processes are intrinsically complex. The process complexity, to a great extent, stems from not only complex physical phenomena (such as phase change and non-Newtonian material deposition), but also dynamic material-process interactions. In addition, there are a broad range of design factors and process parameters (such as porosity, surface roughness, scaffold topology, nozzle diameter, material viscosity, as well as material deposition pressure, flow rate, and temperature) that contribute to the complexity of the AM processes. Consequently, investigation of the influence of the significant design and process parameters (in addition to their interactions) on the mechanical, biomedical, and morphological properties of the fabricated bone structures would be inevitable [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. In the absence of such knowledge, orthopedic surgeons and clinicians will be unable to efficiently treat osseous fractures in the presence of constraints, such as sex, age, bone density, and immune system rejection. Hence, the aim of this chapter is to introduce the AM processes and highlight their significant process parameters. The PME, FDM, PJP, and DLP processes will be reviewed in Sections 2.1–2.4, respectively. A review of other AM processes (i.e., powder bed fusion as well as binder jetting) used in clinical practice is given in Section 2.5. Finally, the conclusions are presented in Section 3.
2. AM processes for bone tissue engineering
2.1 Pneumatic micro-extrusion (PME)
PME is a material extrusion AM process [11], which has emerged as a robust high-resolution method for the fabrication of a wide range of biological tissues, scaffolds, and structures. Advanced PME systems, for example, Cellink BIO X (Boston, MA, USA), have a layer resolution and positioning precision of 100 and 10 μm, respectively.
As demonstrated in Figure 2, the PME process utilizes a high-pressure gas flow (typically air, supplied by a compressor) as a medium of transport and deposition. A polymer material (typically in powder form) is loaded into the deposition head’s cartridge (also known as barrel) and subsequently heated above the polymer’s melting temperature; this results in formation of a non-Newtonian molten polymer flow prior to deposition [3, 4, 5]. An internal/external air compressor or a pressure source (not shown), provides a steady pressure flow into the cartridge. Having high thermal conductivity, the cartridge allows for rapid melting of the loaded polymer material. The molten polymer is, subsequently, deposited on a heated/cooled free surface via a converging microcapillary nozzle with the aid of the pressurized gas flow. A fan with a filter at the top of the chamber not only delivers a clean air flow, but also aids in maintaining a fixed level (rate) of polymer solidification (and thus layer adhesion). The surface temperature is kept below the melting temperature of the polymer material. Spoerk et al. [12] observed that an optimal bed temperature would be critical for proper layer adhesion and thus accurate material deposition.
Figure 2.
(a) The material deposition chamber as well as the main components of the PME AM process; and (b) pneumatic micro-deposition of a polymer material (PCL) on a heated glass substrate using a converging microcapillary nozzle (Source: [3, 4, 5]).
Klemstine et al. [3] investigated the mechanical properties of biocompatible and biodegradable triply periodic minimal surface-based bone scaffolds, composed of PCL and fabricated using the PME-AM process. Having a molecular weight (Mn) as well as a density of approximately 50,000 and 1.145 g/mL (at 25°C), respectively, PCL is a semi-crystalline, hydrophobic polyester-based polymer, derived from caprolactone monomer using ring-opening polymerization. It has a glass transition temperature of −60°C and a melting temperature in the range of 59–64°C. In addition, PCL has a tensile strength and elasticity modulus (indicative of stiffness) of 16 MPa and 0.4 GPa, respectively [13]. The PME fabrication of the bone scaffolds was on the basis of a set of optimal process parameters, detailed in Table 1.
Parameter
Type
Level [unit]
Layer height (thickness)
Design
200 [μm]
Infill pattern
Design
Concentric
Nozzle size
Machine
200 [μm]
Bed temperature
Machine
10 [°C]
Print speed
Machine
2.5 [mm/s]
Deposition head temperature
Machine
180 [°C]
Deposition flow pressure
Machine
300 [kPa]
Pre-flow delay
Machine
900 [ms]
Post-flow delay
Machine
400 [ms]
Table 1.
The optimal PME process parameters used by Klemstine et al. for the additive fabrication of biocompatible bone scaffolds composed of PCL. Please note that the bone scaffold fabrication process was based on the Cellink BIO X 3D-bioprinting system (Source: [3]).
In a research work, Yu et al. [4] investigated the effects of influential scaffold design factors and process parameters—as listed in Table 2, including layer thickness, layer width, infill density, print speed, flow pressure, deposition head temperature, and infill pattern—on the dimensional accuracy as well as the mechanical properties of PME-fabricated PCL bone scaffolds. The assessment of the scaffold dimensional accuracy was based on not only a digital image processing platform established in the MATLAB environment, but also physical measurements (used to corroborate the veracity of the image-based assessment). The underlying algorithms embedded in the image-processing platform are discussed in detail in [14, 15]. Please note that the image-processing platform, in addition, allows for insitu characterization, monitoring, and ultimately control of the PME process.
The experimental design table established by Yu et al. to systematically study the influence of seven design and process parameters on the functional properties of PCL bone scaffolds fabricated using the PME process. Please note that the bone scaffold fabrication process was based on the Cellink INKREDIBLE+ 3D-bioprinting system (Source: [4]).
Figure 3 illustrates the influence of the deposition head temperature (as an example of the PME process parameters) on the morphology as well as the microstructure of the fabricated PCL bone scaffolds. It is implied from the figure that the scaffold diameter increases as a result of an increase in the deposition head temperature. This phenomenon, largely, stems from the fact that an increase in the deposition head temperature leads to a decrease in the polymer viscosity and consequently, an increase in material deposition rate (resulting in formation of larger bone scaffolds in diameter). Besides, Yu et al. [4] observed that the scaffold stiffness increased when the deposition head temperature increased from 100 to 125 [°C]; this trend can be due to the increased amount of deposited mass per scaffold structure as a result of a decline in the polymer viscosity (when the deposition head temperature increases).
Figure 3.
The influence of deposition head temperature (DHT) at six levels of 100, 105, 110, 115, 120, and 125°C on: (a, b) the morphology, and (c) the microstructure of PME-fabricated PCL bone scaffolds (Source: [4]).
Yeow et al. [4, 8] developed a 3D computational fluid dynamics (CFD) model with the aim to investigate the underlying non-Newtonian fluid dynamics of material transport and deposition in the PME process, formulated as a transient multi-phase flow problem. Demonstrated in Figure 4(a), the geometry of the CFD model consisted of a cartridge, a connector, as well as a microcapillary nozzle (having a diameter of 200 μm). It turned out that approximately five layers of inflation would be sufficient to obtain accurate solution near the wall boundaries. Shown in Figure 4(b), four boundary conditions were defined for the CFD model, including flow pressure inlet, stationery wall, volume fraction, and pressure outlet. Both the energy equation and the laminar viscous model were included in the CFD model (in addition to the continuity and momentum equations) respectively to account for the effects of viscous heating and to capture the effects of viscosity.
Figure 4.
(a) The main components of the PME deposition head assembly; (b) the boundary conditions defined for the 3D-CFD model; and (c) simulation of the velocity field in the PME deposition head under a flow pressure of 550 kPa (Source: [4, 8]).
It was observed that the transport of molten PCL through the micro-capillary nozzle (under a flow pressure of 550 kPa) would be a viscous flow having a Reynolds number (Re) of ≪1, implied from Figure 4(c). This PME material deposition regime is unlike that of the other additive manufacturing processes, such as AJP, where material deposition is intrinsically turbulent [14, 16, 17].
The following research works exemplify the use of PME in clinical practice. In a research work, Du et al. [18] demonstrated additive fabrication of mesoporous bioactive glass/silk fibroin composite scaffolds with high osteogenic ability using the PME process. The functional properties of the fabricated scaffolds were characterized on the basis of porosity, compressive strength, degradation, biocompatibility, as well as apatite forming ability. The results of an animal study showed that the mesoporous bioactive glass/silk fibroin composite scaffolds (loaded with human bone marrow mesenchymal stem cells) had not only more significant osteogenic potential, but also superior compressive strength and biocompatibility than mesoporous bioactive glass/polycaprolactone (PCL) scaffolds.
In addition, Du et al. [19] demonstrated 3D-fabrication of pearl/calcium sulfate composite scaffolds—characterized with high osteogenic ability, uniform interconnected macropores, high porosity, as well as improved mechanical properties—using PME integrated with a hydration process. The fabricated scaffolds not only showed satisfactory apatite-forming ability, but also stimulated the proliferation as well as differentiation of rat bone mesenchymal stem cells. The osteogenic potential of the scaffolds was assessed based on micro-computed tomography (μ-CT) imaging and histological analysis.
Park et al. [20] demonstrate a novel technique, combining 3D printing with spatial-temporal deposition and control of growth factors, with the aim to prevascularize bone tissues. Having osteogenic and vasculogenic potential, human dental pulp stem cells were deposited using the PME process together with bone morphogenetic protein-2 as well as vascular endothelial growth factor. An animal study was conducted where both micro-vessel formation and angiogenesis were observed.
Cui et al. [21] investigated 3D-fabrication of polyion complex hydrogel-based scaffolds incorporating multi-walled carbon nanotubes using PME for bone regeneration. The hypothesis of the work was that the addition of multi-walled carbon nanotubes would enhance bone repair efficiency. It was observed that the fabricated scaffolds not only were biocompatible with rat bone marrow-derived mesenchymal stem cells, but also had a high degree of osteogenic differentiation, mineralized matrix formation, and osteogenesis upregulation.
2.2 Fused deposition modeling (FDM)
Similar to PME, FDM is a material extrusion AM process, which has been extensively utilized in tissue engineering applications. As illustrated in Figure 5, in the FDM process, a polymer/composite material, typically in the form of a filament, is fed into a heat block (maintained at a temperature above the melting temperature of the polymer material) with the aid of a stepper motor; this leads to formation of a molten polymer flow. A non-Newtonian fluid, the molten polymer is, subsequently, passed through a converging microcapillary nozzle (made up of, e.g., hardened steel or brass) in order to increase the linear momentum of the molten polymer flow prior to deposition on a heated or unheated free surface. Finally, the built plate (also known as platen) is automatically translated downward (controlled as a function of layer height), and the next layer is deposited on top of the previous layer. In fact, the layer height controls the amount of overlap between two subsequent deposited vertical layers. Please note that layer-to-layer bonding is influenced by not only the extrusion temperature, but also the layer height.
Figure 5.
An FDM 3D-printing system, equipped with a Plexiglas enclosure and a fan installed to create a thermally uniform environment for steady-state material deposition. (a, b) Real pictures, and (c) a schematic diagram of the FDM deposition head assembly (Source: [1, 2, 22]).
Chaffins et al. [1] investigated the mechanical properties of FDM-fabricated medical-grade bone scaffolds composed of a biocompatible composite material (with low moisture absorption) containing polyamide, polyolefin, and cellulose fibers. The composite material has an elongation at break, elasticity modulus (stiffness), and ultimate strength of 4%, 850 MPa, and 23 MPa, respectively. The FDM fabrication of the bone scaffolds was on the basis of a set of optimal process parameters, detailed in Table 3. An equilibration time of 3 hours was taken with the aim to ensure thermal equilibrium (regulated by the chamber fan) and as a result, steady-state material deposition in the FDM process. Please note that the fan speed affects the rate of material solidification after deposition. With the aid of a slicer software program, that is, Cura (Ultimaker, Utrecht, the Netherlands), the 3D CAD models of the bone scaffolds were converted into a G-code, and consequently a tool-path was created prior to fabrication.
Parameter
Type
Level [unit]
Scaffold porosity (CAD-based)
Design
60 [%]
Number of shells
Design
1
Scaffold dimensions
Design
15 × 15 × 15 [mm]
Layer height (thickness)
Design
200 [μm]
Layer (line) width
Design
200 [μm]
Infill density
Design
100 [%]
Nozzle size
Machine
400 [μm]
Bed temperature
Machine
95 [°C]
Fan speed
Machine
83 [%] [10 Volts]
Print speed
Machine
15 [mm/s]
Deposition head temperature
Machine
235 [°C]
Flow (feed) rate
Machine
100 [%]
Steady state chamber temperature
Machine
37 [°C]
Build plate adhesion type
Machine
Brim
Table 3.
The optimal FDM process parameters used by Chaffins et al. for the additive fabrication of bone scaffolds composed of a biocompatible composite material. Please note that the bone scaffold fabrication process was based on the FT5−R2 3D-printing system (Folger Tech, Milford, NH, USA) (Source: [1]).
The following research works exemplify the use of FDM in clinical practice. In a research work by Lai et al. [23], porous bone scaffolds with biomimetic structure were fabricated, based on a novel composite material composed of magnesium, PLGA, and β-tricalcium phosphate for the treatment of bone defects. A steroid-associated osteonecrosis rabbit model was established to assess the biosafety as well as the osteogenic and angiogenic properties of the fabricated scaffolds. It turned out that the scaffolds led to an increase in blood perfusion in addition to vessel ingrowth after surgery (approximately in 4–8 weeks), observed respectively with the aid of dynamic contrast-enhanced magnetic resonance imaging and micro-computed tomography (μ-CT)-based angiography. Furthermore, the fabricated scaffolds led to significant bone formation with enhanced functional properties.
Deng et al. [24] demonstrated additive fabrication of bi-lineage constructive scaffolds (composed of manganese-doped β-tricalcium phosphate) for bone regeneration. The physicochemical properties and bi-lineage bioactivity of the fabricated scaffolds as well as the mechanism of stimulating osteochondral regeneration were characterized. It was observed that the addition of manganese to β-tricalcium phosphate not only reduced the lattice parameters and crystallization temperature, but also enhanced the density and the compressive strength of the fabricated scaffolds. The results of an animal study, in addition, showed that the ionic products from manganese-doped β-tricalcium phosphate improved the proliferation and promoted the differentiation of chondrocytes and rabbit mesenchymal stem cells. Furthermore, the results showed that the fabricated scaffolds significantly improved the regeneration of subchondral bone tissues, transplanted invivo.
Hassanajili et al. [25] demonstrated characterization of polylactic-acid/polycaprolactone/hydroxyapatite composite scaffolds, fabricated using a combined fabrication process where material extrusion was utilized for the fabrication of a negative mold (composed of poly(vinyl alcohol), soluble in water) for casting integrated with freeze drying/particle leaching method. Liquid replacement technique was utilized to measure scaffold porosity. Cell adhesion, scaffold cytotoxicity, cell viability, and mineral deposition (indicative of osteoinductive capacity) together with modulus of elasticity, porosity, and pore size were measured to characterize the functional properties of the fabricated bone scaffolds.
Oladapo et al. [26] investigated the functional characteristics of biomimetic bone scaffolds, composed of poly lactic acid (PLA) matrix reinforced with carbohydrate particles and fabricated using the FDM process. In fact, the presence of carbohydrate particles allows for ion or ionic group substitutions and enhances the kinetics of absorption and ultimately, the mechanical properties of fabricated scaffolds. The bioactivity, surface roughness, apparent porosity, as well as mechanical properties of the fabricated scaffolds were analyzed. It was observed that there was a significant, proportional relationship between the carbohydrate content and surface roughness. In addition, the presence of carbohydrate particles led to a decline in scaffold stiffness and compressive strength (when compared with pure PLA).
2.3 Polymer jet printing (PJP)
Demonstrated in Figure 6, the PJP process operates on the basis of simultaneous deposition (jetting) of build as well as support materials (composed of liquid photopolymers) on a free surface [7]. Both build and support materials are radiation-curable. Having a resolution of, for example, 600 and 1200 dots per inch (DIP), inkjet heads are utilized for the deposition of liquid photopolymers onto a build platform. Subsequently, the deposited photopolymers are immediately cured in situ using a UV light source; this mechanism allows for fabrication of layers on top of each other. The photopolymer materials undergo a chemical transformation and become solid upon irradiation of the UV light [11].
Figure 6.
(a-e) Real pictures of the main components of the PJP process including: (a) the deposition head assembly; (b) the roller; (c) the material deposition nozzles; (d) the build and support material cartridges shown by the letters B and S, respectively; and (e) the UV light assembly. (f) A schematic diagram of the PJP process. Please note that the deposition head assembly includes build as well as support material nozzles (Source: [7]).
Weese et al. [7] investigated the effects of four influential PJP process parameters, detailed in Table 4, on the mechanical properties of fabricated femur bone structures. The PJP process parameters include: (i) print direction, controlling the sequence of material deposition and layer formation; (ii) resolution factor, indicative of the resolution of material deposition; (iii) UV light intensity, controlling the intensity of the UV light source; and (iv) deposition head temperature.
Parameter
Type
Level [unit]
Print direction
Machine
[Unidirectional, bidirectional]
Resolution factor
Machine
[0.25, 2.00]
UV light intensity factor
Machine
[0.34, 1.35]
Deposition head temperature factor
Machine
[0.65, 1.95]
Table 4.
The PJP process parameters used by Weese et al. for the additive fabrication of femur bone structures (Source: [7]).
The additive fabrication of the femur bone structures was based on a PJP 3D-printing system (Objet30 Pro, Stratasys Ltd., Eden Prairie, MN, USA), having an accuracy of 100 μm. The 3D-printing system, in addition, allows for deposition of materials with a layer thickness of as small as 28 μm. A slicer software program, that is, Objet Studio (Stratasys Ltd., Eden Prairie, MN, USA), was similarly used to convent 3D CAD models into a G-code and create a tool-path. The build photopolymer material used for the fabrication of the femur bone structures had a polymerized density, water absorption, and glass transition temperature (Tg) of 1.17–1.18 [g/cm3], 1–1.5%, and 53°C, respectively. Furthermore, the build material had a stiffness as well as a tensile strength of 2–3 GPa and 50–65 MPa, respectively. Unlike the build material, the support material was soluble in a solution of 2% sodium hydroxide (NaOH) and 1% sodium metasilicate (Na2SiO3).
The following research work exemplifies the use of PJP in clinical practice. In a research work by Libonati et al. [27], synthetic composite structures (composed of acrylic-based photopolymers and having a pattern inspired by the microstructure of cortical bone) were designed and characterized. The composite structures were fabricated using the PJP process, and their functional performance in terms of fracture behavior was characterized by mechanical testing. It was observed that the cortical bone-inspired design would potentially enhance toughness amplification and would be essential for balance with material strength. In addition, the PJ-fabricated composite structures showed similar cortical bone-related failure mechanisms, including crack deflection, crack branching, constrained microcracking, as well as fibril bridging.
2.4 Digital light processing (DLP)
DLP is a vat-photopolymerization AM process. It is, to some extent, similar to the PJP process, where radiation-curable resins become a solid upon exposure to UV light through a process called photopolymerization. Figure 7 illustrates the main components of the DLP process. Once the first layer has been cured, the build platform is translated automatically upward, and the next later is cured on top of the previous cured later. The DLP process has been utilized for the high-resolution fabrication of 3D structures with complex internal geometries such as bone and dental implants. In a research work by Raines et al. [28], dental implants with complex internal structures were fabricated using the DLP process. The fabricated dental implants were composed of a biocompatible resin. The DLP process consists of several design and process parameters, as listed in Table 5. 3D-Sprint (3D Systems, Rock Hill, SC, USA) was the slicer software program of choice. Finally, the DLP 3D-printing system used in their work was FabPro 1000 (3D Systems, Rock Hill, SC, USA).
Figure 7.
(a) The main components of the DLP additive manufacturing process. (b) An X-ray microCT-based, biocompatible dental jaw model, fabricated using the DLP-AM process (Source: [28]).
Parameter
Type
Level [unit]
Scaffold porosity
Design
60 [%]
Number of shells
Design
1
Scaffold dimensions
Design
15 × 15 × 15 [mm]
Layer thickness
Design
100 [μm]
Cure depth
Machine
115 [μm]
Print resolution
Machine
454 × 454 dpi
Layer resolution
Machine
100 [μm]
Table 5.
The DLP process parameters used by Raines et al. for the fabrication of dental structures, composed of a biocompatible liquid photopolymer (Source: [28]).
2.5 A review of other AM processes used in clinical practice
2.5.1 Powder bed fusion
Pei et al. [29] demonstrated an integrated method for the biomechanical design as well as fabrication of bionic bone tissue implants using SLS additive manufacturing process with the aim to repair the femoral head. Composed of titanium, the fabricated implants were based on interconnected diamond-lattice pore units that would prevent stress shielding. FEA was utilized for design optimization and numerical characterization of the mechanical properties of the bone implants. On the basis of an animal study, it was observed that pore-unit parameters would significantly influence implant porosity, pore size distribution, and mechanical strength.
Zhang et al. [30] designed and fabricated porous scaffolds (composed of Ti6Al4V alloy and having diamond-lattice pore units with customized shape and tunable mechanical properties) using SLS process for bone tissue regeneration and ultimately femoral-head repair. The weak points within the structure of the scaffolds were analyzed using a FEA model. Struts diameters, pore size, as well as porosity were identified as critical implant design parameters. The biocompatibility and osteogenic potential of the fabricated scaffolds were assessed invivo based on an animal study.
Similarly, Zhao et al. [31] investigated the mechanical properties of porous titanium alloy scaffolds fabricated using SLS process for bone tissue reconstruction. Various scaffolds (including Diamond, Gyroid, Orthogonal, Truss, and Cube) were designed based on parameterization modeling. The mechanical characteristics of the designs as well as the SLS-fabricated scaffolds were assessed numerically using FEA and experimentally using mechanical testing, respectively. It was observed that the fabricated scaffolds were dimensionally accurate characterized with an error of <3% (when comparted with their reference CAD models).
2.5.2 Binder jetting
In a research work by Inzana et al. [32], composite bone scaffolds (composed of calcium phosphate and collagen) were fabricated using binder jet additive manufacturing process. Collagen was dissolved into a phosphoric acid-based binder solution to synthesize a collagen-incorporated calcium phosphate composite. The addition of collagen, to a great extent, improved the flexural strength of the fabricated scaffolds as well as cell viability. In addition, it was observed that the properties of the binder solution would play a significant role in the cytocompatibility, osteoconductivity, and mechanical strength of the fabricated bone scaffolds. Furthermore, to achieve reliable material deposition, the viscosity and surface tension of the collagen solution were reduced with the aid of physiologic heat treatment and Tween 80, respectively. To assess the healing potential, the fabricated scaffolds were implanted into a critically-sized murine femoral defect for 9 weeks; it tuned out that the implants not only were osteoconductive, but also led to new bone growth.
Zhou et al. [33] investigated the characteristics of synthesized composite materials composed of calcium phosphate powders (based on hydroxyapatite and β-tricalcium phosphate) as well as calcium sulfate powders for the fabrication of bone scaffolds using binder jet printing process (with a water-based binder). The printability of the composite materials was assessed in terms of powder bed packing, binder deposition regimes, particle size, calcium phosphate:calcium sulfate ratio, powder-binder wettability, and the strength of the fabricated scaffolds. It was observed that the compressive strength of the scaffolds increased as the ratio of calcium phosphate:calcium sulfate increased. In addition, the use of fine powders (i.e., ≤ 20 μm in diameter) led to slow binder penetration rate, large penetration depth, low wetting ratio, and insignificant green-state strength. Besides, the beta tricalcium phosphate-based powders had lower wetting ratio as well as green-state strength than the hydroxyapatite-based powders.
Bergmann et al. [34] demonstrated additive fabrication of customized bone substitute implants composed of bioresorbable β-tricalcium phosphate as well as bioresorbable and adjustable bioactive glass fabricated using binder jet printing process for swift maxillofacial or craniofacial defect repair. The fabricated scaffolds had a bending strength of approximately 15 MPa. In addition, the results of an X-ray powder diffraction (XRD) analysis revealed the presence of both calcium sodium phosphate and calcium silicate (that are biocompatible and biodegradable).
Similarly, Cox et al. [35] presented characterization of porous bone scaffolds, fabricated using binder jet printing process and composed of hydroxyapatite as well as poly(vinyl)alcohol (PVOH) composite powders (bound with the aid of a water-based binding agent). It was observed that scaffold mechanical stability, microstructure, and porosity would be significantly affected by the flowability of hydroxyapatite:PVOH precursor materials. The fabricated scaffolds were anisotropic, and failure at the boundaries of interlayer bonds was identified as the primary failure mechanism influencing the scaffolds’ functional performance. Furthermore, it turned out that invivo osteoconduction and osteointegration would be significantly enhanced by factors, such as scaffold porosity and interconnectivity in addition to powder bed packing and surface roughness.
3. Conclusions
In this chapter, advanced AM processes were analyzed with a focus on PME, FDM, PJP, as well as DLP. In addition, each AM process was characterized in terms of system components, underlying physical phenomena, and influential parameters. The AM processes are inherently complex, despite their benefits and engendered potential applications. The process complexity, to a great extent, stems from complex physical phenomena (such as non-Newtonian material deposition and phase change) as well as nonlinear material-process interactions. Furthermore, the 3D fabrication of bone tissue scaffolds and implants consists of a broad spectrum of design and process parameters, for example, scaffold porosity, material viscosity, and UV light intensity. Hence, investigation of the effects of the process parameters integrated with physics-based process characterization using computational methods, such as CFD and FEA, would be an inevitable need toward obtaining optimal material transport and deposition regimes for the fabrication of bone tissues with tunable medical properties.
Acknowledgments
This work was made possible by the NASA Established Program to Stimulate Competitive Research (EPSCoR), Grant # 80NSSC19M0054. Dr. Salary would like to sincerely thank the NASA West Virginia Space Grant Consortium (Morgantown, WV, USA). In addition, Dr. Salary would like to sincerely acknowledge the Marshall University Research Corporation (MURC) for supporting this work via the John Marshall Scholars Faculty Award. Furthermore, Dr. Salary would like to sincerely thank the West Virginia State’s Higher Education Policy Commission and the Community and Technical College System for the Open Education Resources (OER) Grant.
Dr. Salary also would like to thank the College of Engineering & Computer Sciences (CECS) at Marshall University, the Cabell Huntington Hospital and Medical Center (Huntington, WV, USA), as well as FibreTuff Biotechnology Company (Toledo, OH, USA).
Nomenclatures
AJP
aerosol jet printing
AM
additive manufacturing
CAD
computer-aided design
CFD
computational fluid dynamics
DHT
deposition head temperature
DLP
digital light processing
FDM
fused deposition modeling
FEA
finite element analysis
PCL
polycaprolactone
PJP
polymer jet printing
PME
pneumatic micro-extrusion
SLS
selective laser sintering
\n',keywords:"bone tissue engineering, regenerative medicine, advanced manufacturing",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80362.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80362.xml",downloadPdfUrl:"/chapter/pdf-download/80362",previewPdfUrl:"/chapter/pdf-preview/80362",totalDownloads:67,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:0,impactScoreQuartile:0,hasAltmetrics:0,dateSubmitted:"September 16th 2021",dateReviewed:"January 10th 2022",datePrePublished:"February 24th 2022",datePublished:null,dateFinished:"February 4th 2022",readingETA:"0",abstract:"This book chapter delineates advanced additive manufacturing processes used in clinical practice for high-resolution fabrication of mechanically-robust and dimensionally-accurate bone tissue scaffolds with a focus on pneumatic micro-extrusion, fused deposition modeling, polymer jet printing, and digital light processing. The main components as well as the underlying physics behind each process are explained. Furthermore, this chapter is integrated with a review of literature; the aim is to show how these additive manufacturing processes are potentially utilized in clinical practice for bone tissue engineering. This chapter serves as an introductory platform toward advanced studies and/or research works in the area of bone regenerative medicine. Finally, this chapter will be helpful to engineering and medical students as well as researchers from academia and industry.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80362",risUrl:"/chapter/ris/80362",book:{id:"10974",slug:null},signatures:"Roozbeh (Ross) Salary",authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Objective and scope",level:"2"},{id:"sec_3",title:"2. AM processes for bone tissue engineering",level:"1"},{id:"sec_3_2",title:"2.1 Pneumatic micro-extrusion (PME)",level:"2"},{id:"sec_4_2",title:"2.2 Fused deposition modeling (FDM)",level:"2"},{id:"sec_5_2",title:"2.3 Polymer jet printing (PJP)",level:"2"},{id:"sec_6_2",title:"2.4 Digital light processing (DLP)",level:"2"},{id:"sec_7_2",title:"2.5 A review of other AM processes used in clinical practice",level:"2"},{id:"sec_7_3",title:"2.5.1 Powder bed fusion",level:"3"},{id:"sec_8_3",title:"2.5.2 Binder jetting",level:"3"},{id:"sec_11",title:"3. Conclusions",level:"1"},{id:"sec_12",title:"Acknowledgments",level:"1"},{id:"sec_14",title:"Nomenclatures",level:"1"}],chapterReferences:[{id:"B1",body:'Chaffins A, Yu M, Claudio PP, Day JB, Salary RR. Investigation of the functional properties of additively-fabricated triply periodic minimal surface-based bone scaffolds for the treatment of osseous fractures. In: Proc. Paper No. 2004, ASME 2021 International Manufacturing Science and Engineering Conference (MSEC 2021), Virtual Conference (Due to the COVID-19 Pandemic); 21-25 June 2021; University of Cincinnati, Cincinnati, OH, USA. American Society of Mechanical Engineers'},{id:"B2",body:'Zhao D, Hart C, Weese NA, Rankin CM, Kuzma J, Day JB, Salary RR. Experimental and computational analysis of the mechanical properties of biocompatible bone scaffolds, fabricated using fused deposition modeling additive manufacturing process. In: Proc. Paper No. 8511, ASME 2020 International Manufacturing Science and Engineering Conference (MSEC 2020); 22-26 June 2020; Cincinnati, OH, USA. American Society of Mechanical Engineers. DOI: 10.1115/MSEC2020-8511'},{id:"B3",body:'Klemstine C, Abdelgaber Y, Lawrence L, Day JB, Claudio PP, Salary RR. Characterization of the compressive properties of triply periodic minimal surface (TPMS) polycaprolactone scaffolds for bone tissue engineering. In: Proc. Paper No. IMECE2021-72125, ASME International Mechanical Engineering Congress & Exposition (IMECE 2021), Virtual Conference; 1-5 November 2021. American Society of Mechanical Engineers'},{id:"B4",body:'Yu M, Yeow YJ, Lawrence L, Claudio PP, Day JB, Salary R. Characterization of the functional properties of PCL bone scaffolds fabricated using pneumatic microextrusion. Journal of Micro and Nano-Manufacturing. 2021;9(3):030905 (13 Pages). DOI: 10.1115/1.4051631'},{id:"B5",body:'Zhao D, Yu M, Lawrence L, Claudio PP, Day JB, Salary RR. Investigation of the influence of consequential design parameters on the mechanical performance of biodegradable bone scaffolds, fabricated using pneumatic micro-extrusion additive manufacturing process. In: Proc. Paper No. 8512, ASME 2020 International Manufacturing Science and Engineering Conference (MSEC 2020); 22-26 June 2020; Cincinnati, OH, USA. American Society of Mechanical Engineers. DOI: 10.1115/MSEC2020-8512'},{id:"B6",body:'Lawrence L, Day JB, Claudio PP, Salary RR. Investigation of the regenerative potential of human bone marrow stem cell-seeded polycaprolactone bone scaffolds, fabricated using pneumatic microextrusion process. In: Proc. Paper No. 1997, ASME 2021 International Manufacturing Science and Engineering Conference (MSEC 2021); 21-25 June 2021; University of Cincinnati, Cincinnati, OH, USA. American Society of Mechanical Engineers. DOI:10.1115/MSEC2021-63411'},{id:"B7",body:'Weese NA, Rankin CM, Zhao D, Hart C, Quinlan P, Day JB, Salary RR. Experimental optimization of polymer jetting additive manufacturing process using Taguchi design. In: Proc. Paper No. IMECE2020-24271, V02AT02A046, 7 Pages, ASME 2020 International Mechanical Engineering Congress and Exposition (IMECE 2020); 16-19 November 2020. American Society of Mechanical Engineers. DOI: 10.1115/IMECE2020-24271'},{id:"B8",body:'Yeow YJ, Yu M, Day JB, Salary RR. A computational fluid dynamics (CFD) study of material flow in pneumatic microextrusion (PME) additive manufacturing process. In: Proc. Paper No. 24325, ASME 2020 International Mechanical Engineering Congress and Exposition (IMECE2020); 16-19 November 2020; Portland, OR, USA. American Society of Mechanical Engineers. DOI: 10.1115/IMECE2020-24325'},{id:"B9",body:'Yu M, Lawrence L, Claudio PP, Day JB, Salary RR. Pneumatic microextrusion-based additive biofabrication of polycaprolactone bone scaffolds—part II: Investigation of the influence of polymer flow parameters. In: Proc. Paper No. 2002, ASME 2021 International Manufacturing Science and Engineering Conference (MSEC 2021), Virtual Conference (Due to the COVID-19 Pandemic); 21-25 June 2021; University of Cincinnati, Cincinnati, OH, USA. American Society of Mechanical Engineers'},{id:"B10",body:'Yu M, Yeow YJ, Lawrence L, Claudio PP, Day JB, Salary RR. Investigation of the effects of design and process parameters on the mechanical properties of biodegradable bone scaffolds, fabricated using pneumatic microextrusion process. In: Proc. Paper No. 24252, ASME 2020 International Mechanical Engineering Congress and Exposition (IMECE2020). 16-19 November 2020; Portland, OR, USA. American Society of Mechanical Engineers. DOI: 10.1115/IMECE2020-24252'},{id:"B11",body:'Gibson I, Rosen DW, Stucker B. Additive Manufacturing Technologies—3D Printing, Rapid Prototyping, and Direct Digital Manufacturing. New York, NY, USA: Springer; 2014. DOI: 10.1007/978-1-4939-2113-3'},{id:"B12",body:'Spoerk M, Gonzalez-Gutierrez J, Sapkota J, Schuschnigg S, Holzer C. Effect of the printing bed temperature on the adhesion of parts produced by fused filament fabrication. Plastics, Rubber and Composites. 2018;47(1):17-24. DOI: 10.1080/14658011.2017.1399531'},{id:"B13",body:'Jenkins M, Stamboulis A. Durability and Reliability of Medical Polymers. Philadelphia, PA, USA: Woodhead Publishing; 2012'},{id:"B14",body:'Salary R, Lombardi JP, Tootooni MS, Donovan R, Rao PK, Borgesen P, et al. Computational fluid dynamics modeling and online monitoring of aerosol jet printing process. Journal of Manufacturing Science and Engineering. 2017;139(2):021015. DOI: 10.1115/1.4034591'},{id:"B15",body:'Salary R, Lombardi JP, Tootooni MS, Donovan R, Rao PK, Poliks MD. In situ sensor-based monitoring and computational fluid dynamics (CFD) modeling of aerosol jet printing (AJP) process. In: Proc. Paper No. 8535, ASME 2016 11th International Manufacturing Science and Engineering Conference (MSEC 2016); 27 June–1 July 2016; Virginia Tech, Blacksburg, VA, USA. American Society of Mechanical Engineers. p. V002T004A049. DOI: 10.1115/MSEC2016-8535'},{id:"B16",body:'Salary R, Lombardi JP, Weerawarne DL, Rao PK, Poliks MD. A computational fluid dynamics (CFD) study of material transport and deposition in aerosol jet printing (AJP) process. In: Proc. Paper No. 87647, ASME 2018 International Mechanical Engineering Congress & Exposition (IMECE 2018); 9-15 November 2018; Pittsburgh, PA, USA. American Society of Mechanical Engineers. DOI: 10.1115/IMECE2018-87647'},{id:"B17",body:'Salary R, Lombardi JP, Weerawarne DL, Rao P, Poliks MD. A computational fluid dynamics investigation of pneumatic atomization, aerosol transport, and deposition in aerosol jet printing process. Journal of Micro and Nano-Manufacturing. 2021;9(1):010903. DOI: 10.1115/1.4049958'},{id:"B18",body:'Du X, Wei D, Huang L, Zhu M, Zhang Y, Zhu Y. 3D printing of mesoporous bioactive glass/silk fibroin composite scaffolds for bone tissue engineering. Materials Science and Engineering: C. 2019;103:109731. DOI: 10.1016/j.msec.2019.05.016'},{id:"B19",body:'Du X, Yu B, Pei P, Ding H, Yu B, Zhu Y. 3D printing of pearl/CaSO4 composite scaffolds for bone regeneration. Journal of Materials Chemistry B. 2018;6(3):499-509. DOI: 10.1039/C7TB02667F'},{id:"B20",body:'Park JY, Shim J-H, Choi S-A, Jang J, Kim M, Lee SH, et al. 3D printing technology to control BMP-2 and VEGF delivery spatially and temporally to promote large-volume bone regeneration. Journal of Materials Chemistry B. 2015;3(27):5415-5425. DOI: 10.1039/C5TB00637F'},{id:"B21",body:'Cui H, Yu Y, Li X, Sun Z, Ruan J, Wu Z, et al. Direct 3D printing of a tough hydrogel incorporated with carbon nanotubes for bone regeneration. Journal of Materials Chemistry B. 2019;7(45):7207-7217. DOI: 10.1039/C9TB01494B'},{id:"B22",body:'E3D-v6 Assembly. Open Source Creative Commons (CC BY-NC-SA 3.0) License, UK. Available from: https://e3d-online.dozuki.com/'},{id:"B23",body:'Lai Y, Li Y, Cao H, Long J, Wang X, Li L, et al. Osteogenic magnesium incorporated into PLGA/TCP porous scaffold by 3D printing for repairing challenging bone defect. Biomaterials. 2019;197:207-219. DOI: 10.1016/j.biomaterials.2019.01.013'},{id:"B24",body:'Deng C, Yao Q, Feng C, Li J, Wang L, Cheng G, et al. Retracted: 3D printing of bilineage constructive biomaterials for bone and cartilage regeneration. Advanced Functional Materials. 2017;27(36):1703117. DOI: 10.1002/adfm.201703117'},{id:"B25",body:'Hassanajili S, Karami-Pour A, Oryan A, Talaei-Khozani T. Preparation and characterization of PLA/PCL/HA composite scaffolds using indirect 3D printing for bone tissue engineering. Materials Science and Engineering: C. 2019;104:109960. DOI: 10.1016/j.msec.2019.109960'},{id:"B26",body:'Oladapo BI, Zahedi S, Adeoye A. 3D printing of bone scaffolds with hybrid biomaterials. Composites Part B: Engineering. 2019;158:428-436. DOI: 10.1016/j.compositesb.2018.09.065'},{id:"B27",body:'Libonati F, Gu GX, Qin Z, Vergani L, Buehler MJ. Bone-inspired materials by design: Toughness amplification observed using 3D printing and testing. Advanced Engineering Materials. 2016;18(8):1354-1363. DOI: 10.1002/adem.201600143'},{id:"B28",body:'Raines R, Day JB, Salary RR. Experimental characterization of the mechanical properties of medical-grade dental implants, fabricated using vat-photopolymerization additive manufacturing process. In: Proc. Paper No. 85436, ASME 2022 International Manufacturing Science and Engineering Conference (MSEC 2022); 27 June–1 July 2022; Purdue University, West Lafayette, IN, USA. American Society of Mechanical Engineers'},{id:"B29",body:'Pei X, Zhang B, Fan Y, Zhu X, Sun Y, Wang Q, et al. Bionic mechanical design of titanium bone tissue implants and 3D printing manufacture. Materials Letters. 2017;208:133-137. DOI: 10.1016/j.matlet.2017.04.128'},{id:"B30",body:'Zhang B, Pei X, Zhou C, Fan Y, Jiang Q, Ronca A, et al. The biomimetic design and 3D printing of customized mechanical properties porous Ti6Al4V scaffold for load-bearing bone reconstruction. Materials and Design. 2018;152:30-39. DOI: 10.1016/j.matdes.2018.04.065'},{id:"B31",body:'Zhao L, Pei X, Jiang L, Hu C, Sun J, Xing F, et al. Bionic design and 3D printing of porous titanium alloy scaffolds for bone tissue repair. Composites Part B: Engineering. 2019;162:154-161. DOI: 10.1016/j.compositesb.2018.10.094'},{id:"B32",body:'Inzana JA, Olvera D, Fuller SM, Kelly JP, Graeve OA, Schwarz EM, et al. 3D printing of composite calcium phosphate and collagen scaffolds for bone regeneration. Biomaterials. 2014;35(13):4026-4034. DOI: 10.1016/j.biomaterials.2014.01.064'},{id:"B33",body:'Zhou Z, Buchanan F, Mitchell C, Dunne N. Printability of calcium phosphate: Calcium sulfate powders for the application of tissue engineered bone scaffolds using the 3D printing technique. Materials Science and Engineering: C. 2014;38:1-10. DOI: 10.1016/j.msec.2014.01.027'},{id:"B34",body:'Bergmann C, Lindner M, Zhang W, Koczur K, Kirsten A, Telle R, et al. 3D printing of bone substitute implants using calcium phosphate and bioactive glasses. Journal of the European Ceramic Society. 2010;30(12):2563-2567. DOI: 10.1016/j.jeurceramsoc.2010.04.037'},{id:"B35",body:'Cox SC, Thornby JA, Gibbons GJ, Williams MA, Mallick KK. 3D printing of porous hydroxyapatite scaffolds intended for use in bone tissue engineering applications. Materials Science and Engineering: C. 2015;47237-247. DOI: 10.1016/j.msec.2014.11.024'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Roozbeh (Ross) Salary",address:"salary@marshall.edu",affiliation:'
Departments of Mechanical and Biomedical Engineering, College of Engineering and Computer Sciences, Marshall University, Huntington, WV, USA
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1. Introduction
The creation of new companies poses various challenges for most people. However, some fractions face particularly difficult challenges in terms of resources: students, people in developing countries, and refugees.
Over the past years, the number of student entrepreneurs has been increasing [1]. In general, students are provided with a good framework as universities put much effort into supporting them. For example, they offer entrepreneurship programmes and courses or business incubators for entrepreneurs [1] and students can use university resources for little money [1]. However, the support students receive from their universities is not sufficient for founding a start-up and many barriers are faced all the same. Shambare [2] identifies four main barriers that student entrepreneurs are confronted with: lack of entrepreneurial support, lack of exposure to businesses, whereby lack of exposure and lack of entrepreneurial support and equivalent resources pose the most significant barriers. Bailetti [3] mentions two types of barriers: institutional and regional barriers. Student entrepreneurs often are not accepted by society and lack business experience and commercial skills. On the other hand, they face “regulatory, legal, administrative, employment, financial, and partnership burdens” [3]. Sometimes the support of a business expert for receiving funding is required. The access to financial and network resources also presents a challenge as students do not have access to [3]. This is supported by a study conducted by Ruda, Martin, & Danko [4] who identified four clusters regarding the start-up barriers faced by students. In addition to the monetary constraints, they also mention student entrepreneurs have small networks.
Another group facing similar barriers is the group of entrepreneurs in developing countries. It is a common assumption that not much entrepreneurship exists in these countries, but this is not true. Entrepreneurship plays an important role as it helps developing countries to grow and leads to increased innovation and employment [5]. Nevertheless, entrepreneurship in developing countries is more difficult than in developed countries. Entrepreneurs in developing countries often are based in less wealthy locations. Besides, people in developing countries do not receive the same education as people in developing countries, which limits their capabilities to access financial resources and capital [5, 6]. Another barrier is the lack of knowledge about market conditions and requirements [5]. Often, the government even hinders entrepreneurial activities on purpose by setting up high entry barriers in the form of administrative fees as higher tax income can be generated off bigger enterprises [7]. As a consequence, entrepreneurs have to pay large sums for setting up their business or need to go through a very complex and time-consuming administrative process [7], which is very costly and, thus, hinders the establishment of new firms [6]. In comparison to developed countries, developing countries do not have a social security system as tax money is used to pay for essential public goods. Consequently, no public safety net is available, and families need to save and protect their money and even support other family members financially. This complicates investments in new businesses even more [7].
The third group that is examined is the group of refugee entrepreneurs. As the refugee population is continuously growing, the likelihood of refugee enterprises is very high [8]. Meister & Mauer [9] and Embiricos [8] provide a concise summary of the barriers refugee entrepreneurs are facing. Both authors attest refugees lack knowledge about the host country’s culture, language, and ways of doing business, therefore complicating their entrepreneurial aspirations. Resulting from their flight from another country, they do not possess big networks in the host country and often face discrimination by society and economy [8, 9]. Moreover, the insecurity about their asylum status and a denial of their asylum claims ruin all of the investments made [10]. Until this claim is granted by the authorities, it is difficult to get access to financial resources due to low creditworthiness [8, 9]. Labour market regulations and legal frameworks directed at asylum seekers make the foundation of a business a time-consuming matter, too [10]. Similar to entrepreneurs in developing countries, refugees save money to support their families, resulting in the limitation of financial resources to be used for founding a business [10].
Even though the investigated groups seem to be very different from each other, it appears that they are similar with regards to the challenges faced when intending to found a business related to resources.
This leads to the research question, what can be done to detect tools and approaches for those groups to enable them to create a start-up without or low resources.
2. Conceptual framework
The conceptual model on which the chapter is based (Figure 1) shows that the process of successfully founding a start-up and creating a business without resources consists of two concepts according to two phases. In this paper, both concepts are presented, the concept of Bricolage and the concept of Growth Hacking, according to their deployment in those phases; addressing and including selected neighbourhood strategies, such as Bootstrapping and Guerrilla Marketing.
Figure 1.
Conceptual Framework.
This framework is anticipated and based on an approach that values the momentum and initiative of the individual with regard to economic success higher than economic algorithms and regularities. Thus a renewed confirmation of Schumpeter’s law [11, 12] according to the Austrian School of Economy. The Austrian School is a scientific view of economics that represents a heterodox doctrine in economics. The central logic is the idea of the evolutionary creation of knowledge by the individual, the entrepreneur and the consideration of the dynamic uncertainty of economic processes. The school emphasises the importance of individuals and their personal initiatives for economic processes (subjectivism). In addition, there is a negation of purely mathematical forms of representation of economic relationships (Lausanne School with its mathematically formulated models of neoclassicism) [13].
3. Bricolage
Bricolage, associated with its actor (i.e., bricoleur), serve as analogies to delineate a particular way of practical reasoning: “making do with current resources, and creating new forms and order from tools and materials at hand” [14]. Since its original conception, Bricolage has been extended to a range of different fields, such as entrepreneurship, innovation, organisation, and management. Contrary to the resource-creating mentality, Bricolage stands for a behaviour in which the bricoleur solves problems using only available means or resources. Bricolage is an activity where, contrary to the resource-creating mentality, only the resources of the repertoire are worked with making do with the means or resources at hand [15, 16].
In the field of entrepreneurship, Baker et al. [14] label “dependence on pre-existing contact networks -” as “network Bricolage” to analyse the founding process of new knowledge-based firms. The research finds that network Bricolage is prevalent in discovering founding opportunities and recruiting early members into organisations. Trying to understand how some entrepreneurs can “create something out of nothing in resource-constrained environments”, Baker and Nelson [17] integrate a range of related concepts and build a process model of Bricolage and firm growth to understand entrepreneurial behaviour. Together with resource seeking (continued attempt to acquire standard resources) and avoiding new challenges (by downsizing, disbanding, or remaining inert), entrepreneurial Bricolage is an alternative approach that organizations may adopt when facing with penurious environment. Bricolage is thus defined as “making do by applying combinations of the resources at hand to new problems and opportunities”. This means bricoleurs view resource limitations as both a problem and an opportunity. Such a notion of “the pursuit of opportunity through close regard to the resources at hand” is consistent with the claim that most entrepreneurial opportunities are more enacted than discovered [17].
In many cases, entrepreneurs draw on resources readily at hand, instead of searching broadly for, or planning for specific resources [14]. The entrepreneurship literature differentiates Bricolage and resource-seeking as two approaches and entrepreneurs make assessment by trading-off. They “engage in Bricolage at sometimes and in some domains and reject Bricolage at other times or for other activities”. There are admixtures of Bricolage and resource-seeking in entrepreneurial practice. Entrepreneurs may engage in network resource-seeking for founding but rely heavily on network Bricolage afterwards, while there are other cases, in particular in start-up firms, that the founding begins with the Bricolage and successfully transmits to accelerated growth afterwards through resource seeking [18].
Bricolage is frequently used interchangeably with the term “improvisation” and some suggest taking Bricolage as an element or correlate of improvisation [19, 20] or treating improvisation as a precursor to Bricolage [21]. However, they are not the same construct. Improvisation “consists of assembling elements based on simple rules in order to yield an original composition [15], and it is “occurring when the design and execution of novel action converge” [17]. Improvisation highlights an organization’s rapid degree of adaptation to a turbulent environment, whereas Bricolage is the “mixture of the precomposed and the spontaneous” and as sensemaking, Bricolage contributes to the capacity improvement for adaptation in destabilizing situations [15]. Improvisation framework complements the design precedes execution (DPE) approach, in which clear goals precede and are independent of action, while Bricolage may often occur during improvisation, but may occur in the implementation of pre-existing plans as well [14]. Baker et al. argue that improvisation implies Bricolage, but Bricolage does not imply improvisation [14], and they often “appear tightly linked empirically”, however, further studies are needed to understand their relationship [17].
Three approaches, i.e., causation, effectuation, and Bricolage, are most used as theoretical perspectives to describe the logic and behaviour underlying the entrepreneurial action or corporate venturing process [14, 22, 23]. Causation is a traditional, rational model of entrepreneurship, which identifies opportunities and makes plans before developing products or services. The causation processes “take a particular effect as given and focus on selecting between means to create that effect” [21]. Effectuation and Bricolage offer an alternative view to the causation approach, which posits the market provides opportunities, and the entrepreneur discovers them. Effectuation is positively associated with uncertainty, which generates more actions of control than prediction [16]. Effectuation processes “take a set of means as given and focus on selecting between possible effects that can be created with that set of means” [24]. Effectuation and Bricolage involve starting with a set of means. However, entrepreneurial Bricolage combines existing resources in creating solutions. Behaviours following a DPE model may also make use of Bricolage. Bricoleurs may use materials at hand both to see the possible results with current resources (effectuation) and to find out the means to meet the pre-existing goal through what is at hand (causation).
Bricolage deals with the question of how start-ups succeed in outperforming and even outgrowing their competitors despite limited resources and limited scope of networks. The mechanism of how Bricolage works is hardly comprehensible so far and worth addressing [22]. However, Bricolage is a process of continuous creation and utilization of practical knowledge and a process of exploitation of varied types of resources [15, 25]. A unique advantage for bricoleurs in resource-constrained start-ups is that they “enjoy great latitude in their processes of collecting and utilizing resources”, therefore, they can “find responses to the environmental constraints and dependencies they face” [15]. Despite its ability to overcome resource constraints, Bricolage can also lock the firm into a self-reinforcing cycle of activities that limit growth [23].
Bricolage depends on the existence of organizational memory, which allows an organization to maintain an inductively generated knowledge base on experiences [15]. With the link to resilience, Bricolage enables individuals and organizations to overcome the crisis by keeping flexibility in mobilizing available resources and taking trial and error tests [26]. Bricolage is viable in small firms since large organizations are more fragmented along professional or occupational boundaries [15]. It represents a particular process of engaging multiple actors and “gradually transform emerging (technological) paths to higher degrees of functionality [20]. Inside the Bricolage competencies, the improvisational competencies can impede the development of DPE competencies [14]. All these can be seen as positive points for start-ups with resource constraints. It is fair to say that the Bricolage approach is proving to be viable and potentially successful, especially for companies in problem situations, developing countries and under financial bottlenecks.
Both the resource-based view and the resource dependence theory highlight the new business’ need to acquire or have access to necessary resources to grow and survive [27]. However, many young and small firms confront the barriers of limited resources in finance, space, and skills. A similar approach of behavioural strategy to Bricolage is bootstrapping. Both approaches are resource management techniques that entrepreneurs use in resource-constrained environments [28] to find creative solutions to acquire necessary resources or exploit others underutilized resources [29]. Whereas Bricolage focuses on improvisation, bootstrapping focuses on a self-sustaining process that operates effectively without external/financial help [26]. Bootstrapping is often associated with financial resources since financial resources are often looked at as one of the most important resources [30]. Bootstrapping strategy is consistent with the pecking order theory which argues that due to the information asymmetry, firms prefer internal to external sources in managing resources [31].
Research deals with the categories of financial bootstrapping in small businesses. Four types of methods under bootstrapping are identified: (1) customer-related, (2) delaying payments, (3) owner-related financing and resource, and (4) joint-utilization of resources with other firms [32]. Winborg [33] further examines motives for using financial bootstrapping in new businesses and identified three groups of founders: cost-reducing bootstrappers, capital-constrained bootstrappers, and risk-reducing bootstrappers. The relative experience of the founder is the most significant influence for using bootstrapping. With the experience gained, the bootstrapping changes from initially focusing on reducing costs towards a proactive focus on reducing the risk in the business. By delineating the nature of bootstrapping strategy profiles, logics, and effects in small ventures, Malmstrom [28] identifies ‘quick-fix’, ‘proactive’, ‘efficient’ as three financial bootstrapping strategies for resource mobilization. ‘Quick-fix’ bootstrapping emphasizes temporary access to resources and prefer internally oriented activities for such purposes; ‘proactive bootstrapping’ focuses on operational resource issues; and ‘efficient bootstrapping’ prefers activities that are externally and vertically oriented, up, or down in the value creation chain.
Bootstrapping embraces the idea of “meeting the need for resources without relying on long-term external finance from debt holders or new owners” [32]. Bootstrapping has its pros and cons. On the one hand, it is often the speedier and more convenient way to gain access to large amounts of capital (e.g., through credit cards). It promotes lean organisations and maximizes internal efficiencies with limited resource sets [30] and helps keep ownership of the business, control over direction, and gain a sense of accomplishment [34]. On the other hand, bootstrapping firms take risks of cash flow shortages without outside capital, limitation on visibility and growth potential, drifting away from top-level help, and constraint on growth and financial performance [34]. Empirical study shows that if firms were only engaging in bootstrapping out of necessity instead of a strategic decision, bootstrapping often causes negative financial effects [27]. Nevertheless, financial bootstrapping provides useful insights by highlighting the innovative financing routes for small ventures by “acquiring the use of resources without borrowing money or raising equity financing from traditional sources” [35].
4. Growth hacking
4.1 Guide to a new smart concept
In 2010, Ellis [36] created the term Growth Hacking in a start-up surrounding. Especially interesting for start-ups, as those often have fewer financial and human resources compared to established companies [37]. Furthermore, Growth Hacking is delimited from other marketing strategies particularly for start-ups with low or non-budget. [38].
Growth Hacking describes intelligent, mostly free (online) marketing strategies, which primarily achieve companies to generate growth and – if products or software solutions are already available– to increase sales. Also, Growth Hacking is collecting direct feedback to build customer relations and use the feedback for direct improvement of the product and service. All channels and media available (at no or low cost), such as search engine optimisation, content marketing, social media, or viral marketing. [39] Only a few empirical research papers have been published on Growth Hacking, so empirical evidence is missing [40].
Thus, growth hacking, which is primarily data-based, is a practical promising strategy for new companies to effectively, efficiently and cost saving online tools or online-offline combinations to achieve ambitious objectives. Growth Hacking is also based on the ability of companies to collect relevant data and to analyse and store it in real time [41]. This also allows start-up companies to experiment and experience new marketing methods, whether or not they are successfully working.
The primary goal of start-ups is growth. Growth secures surviving and increase of value. Indicators for growth are measured by selected key figures, such as newsletter registrations, purchases, visitor klick rates or customer referrals. Thus, Growth Hacking is a process of rapid experimentation across different channels and development at the same time, to find the most effective and efficient way that contributes directly to the growth of the company [42]. One reason for this is the fact that start-ups, the development of products and their features directly into the growth process, which has a significant impact on their competitive advantage [43].
The growing digital change impacts the company’s digital and social media marketing [44, 45]. The need for marketing to act more flexibly got even more evident during the COVID-19 pandemic [46, 47]. To implement digital and social media marketing, start-ups, at first, need to provide the necessary knowledge and proactive agility. Shaltoni et al. [48] find that start-ups – and their stakeholders – are willing to engage if they perceive a greater benefit and compatibility with the corporate culture. Sun et al. [49] identifies further aspects that impact the willingness to integrate big data in a company “relative advantage, technological competence, technology resources, management support, competitive pressure, and regulatory environment.”
The advantages are addressing a wide range of customers, customer engagement and the possibility of specific placement targeting [44]. Neslin et al. [50] identifies for start-ups five challenges in customer channel management: data integration, understanding customer behaviour, channel evaluation, allocating resources across channels, and coordinating channel strategies. Also, in a report by McKinsey, the authors predict that the success of the company marketing during the unpredictable COVID-19 crisis will highly depend on “how effectively they can test, learn, and adapt.” [51]. The process which could support handling the opportunity is Growth Hacking.
Growth Hacking is a marketing strategy [52] that aims to increase growth by adapting digital marketing through testing and analysing, in repetitive cycles. Ellis and Brown [36] refer mainly to such as Dropbox, Uber, Instagram, and Facebook. Furthermore, those companies are offering software or artificial intelligence-related services.
But is Growth Hacking also applicable to companies offering physical products, as they cannot adopt their product as fast as software providers can?
In physical product selling markets the relationship between sellers and buyers is characterised as closer [53]. Furthermore, the focus is more on long-lasting relationships to reduce the risk [54]. Thus, relationship value leads to trust, satisfaction, and commitment, which result in loyalty [55]. Product companies need to provide more detailed information, as usually, buyers compare products in more detail [53]. Therefore, Habibi et al. [56] conclude that for products, a greater variety of communication channels and messages are needed. On the one hand, Gustafson et al. [57] relate the communication process of digital marketing, the diffusion, the transmission of information, conveyance as one relevant aspect. On the other hand, the researchers name the convergence process, which creates shared understanding and knowledge in the buying company [57].
Digital content marketing can enhance information flow and the customers’ trust [58]. Furthermore, perceived information quality influences customer loyalty [59]. Social selling is here to name as one opportunity, promotion via social media platforms [60]. Järvinen et al. [61] list several social media tools for start-up companies: blogs, Facebook, Flickr, discussion forums, Twitter, YouTube, webinars. As research has shown, the use of professional networks such as LinkedIn is particularly suitable, as well as Facebook [62]. Furthermore, buyers increase the relevance of digital content marketing; providing information in a journalistic format for the customer [58]. Moore et al. [62] find that salespeople use “social bookmarking, and presentation sharing storage sites” and “relationship-oriented social media significantly more often for prospecting, handling objections, and follow-up and after-sales service.” Firms also use e-mail marketing and newsletters [61]. Among other things, Growth Hacking can help to address and better coordinate these challenges by agility.
Agility marketing focuses on detecting and understanding changes repetitively and regularly, and responds fast to those changes thereafter [47]. Agility marketing consists of sensemaking, iteration, marketing decisions and speed. Leadership, employees, organisational and team factors influence the performance. Kalaignanam et al. [44] point out that reacting, however, deciding not to do so, is part of agile marketing. Homburg et al. [63] also talk about agile marketing in terms of “simplified structures and processes, fast decision making, and trial and error learning.”
Lean start-up describes an iterative process to develop and improve a product or process through the loop build-measure-learn [37]. The objective is to run the loop fast and often [37]. The central aspects of this methodology are learning from failures and mitigate invested resources [37, 64].
In their paper, Herttua et al. [52] differentiate Growth Hacking from viral marketing, guerrilla marketing and traditional marketing. For them, the difference to traditional marketing is that IT knowledge is necessary, as well as that it is not about shocking people as guerrilla marketing could intent and different from viral marketing, it focuses on people who share knowledge and not just information [52].
4.2 Neighborhood strategies
Whereas Growth Hacking can be combined and complemented with other low budget strategies, guerrilla marketing is a strategy with which start-ups design unusual marketing measures to stand out from the mass of advertising messages. It often involves offensive, creative, and unique advertising campaigns that appeal even to those who do not actually identify with the product or service or do not react to advertising due to sensory overload. Guerrilla marketing aims to achieve a surprise effect on large groups of people with a small budget and effort. Originally, the word comes from military operations and describes a tactic in warfare in which small, independently operating combat units operate covertly in the enemy’s hinterland and rely on the surprise effect on the opponent. The primary goal of such guerrilla tactics is to confuse the opponent with the help of the surprise effect and to strike in a targeted manner in order to then weaken him.
With guerrilla marketing, it is possible to address a very large part of one’s own target group, but beyond that, to create a sensation. Guerrilla marketing is not mass advertising. The more precisely the target group has been defined in advance and the smaller it is, the more effectively guerrilla marketing can be used. Like every marketing measure, guerrilla marketing also tries to trigger a reaction in the target group and encourage them to take action.
Guerrilla marketing has a variety of instruments at its disposal with which to convey its advertising message. Guerrilla marketing is known for being controversial and occasionally crossing boundaries. [65, 66].
These boundaries need to be weighed and exploited in a targeted way. Guerrilla marketing works best when the advertising campaign is so far unique and appears unexpected and surprising for the target groups and the competition.
Ambient marketing: Ambient marketing tries to surprisingly change the living environment of the target group. Frequently places or public spaces are fundamentally changed to attract attention. Public transport stops, airports or highly visible house walls are particularly suitable. [67].
Ambush marketing: Ambush marketing uses current topics in the media world and ties with them. This increases the relevance of the advertising and automatically generates more attention among the target group. If, for example, something negative about a company is revealed in the newspapers, the competitors could use this to their advantage [68].
Buzz marketing: Similar to promotional marketing, buzz marketing is about providing samples of one’s products or services among the target group. The goal is to get the product in people’s minds, get them to interact and share it with others on social media. [69].
Mosquito marketing: Smaller companies often lack the necessary level of awareness to apply advertising measures as effectively as possible. For example, weaknesses in the competition are identified, which are exploited to one’s own advantage through differentiation. In this way, unique selling points or special features that stand out from the competition are highlighted. [70].
Sensation marketing: As the name already suggests, sensation marketing tries to achieve a “wow effect” with the target group by attracting attention with spectacular advertising campaigns. Part of this marketing measure is to actively involve the audience, which is possible in the form of a spontaneous show, an event, or an installation at a specific location [66].
Viral marketing: In viral marketing, one specifically uses the possibilities of spreading one’s advertising message among customers through word of mouth. Social media in particular play an important role here, as the advertising messages can be spread very quickly and effectively by every possible person [71].
Linkbait: This is a special form of viral marketing that aims to generate backlinks.
Guerrilla marketing offers some advantages that speak for itself: low costs, enormous attention, quick impact, and a large reach both in the masses and specifically in the target group. One problem that can arise with guerrilla marketing is that the impact and spread of the advertising can only be influenced to a limited extent once it has been circulated. Since guerrilla marketing often specifically uses controversial or even offensive content, there is a risk of negative reception of the marketing measures.
According to Conway and Hemphill [72], Growth Hacking and agile marketing are much aligned. Growth Hacking adopts “the continuous cycle of improvement and the rapid iterative approach” and focuses on customer and revenue growth [36]. Thus, Herzberger and Jenny [73] regard Growth Hacking as an evolution rather than an innovation. After this classification and delimitation, the process of Growth Hacking is described in more detail in the following.
4.3 Growth hacking framework
Growth Hacking is a marketing technique to aim customer growth cost-efficiently through creativity, marketing techniques, data analysis and coding [36, 74]. Even though Ellis and Brown [36] define Growth Hacking, it is noted in the literature that a uniform definition is difficult to grasp [52, 72, 75, 76]. Analysing the existing data of customers and conducting surveys or interviews help get more insights to potential segment customers to figure out growth potential [36]. Analysing supports and detecting key customer trends can protect from misleading posts [77]. Therefore, tools, software and AI assist in evaluating the test [74].
The first step is about collecting ideas for hacks in an open-minded surrounding [36] and those need to be prioritised. Ellis and Brown [36] propose using the Impact, Confidence, and Ease of implementation (ICE) score system they developed. The following step is testing the preferred ideas. A/B tests can serve as a means of testing [52]. Furthermore, they propose conducting several tests a week and increasing the number of tests by time to improve results [36, 78]. After the test phase, the cycle restarts by analysing the results of the test.
Herzberger and Jenny [73], Bohnsack and Liesner [75] and Lennarz [74] propose a modified cycle. The Growth Hacking framework consists of three components, with their interaction or, in other words, their simultaneous application leading to Growth Hacking. The three components are (digital) marketing techniques, data analysis and testing, and coding and automation [74, 75, 76]. Conway and Hemphill [72] adapt the Growth Hacking framework by adding the product-fit step before the cycle. For them, the first step is to check the product-market fit and then, in the second step, to start with Growth Hacking. Ellis and Brown [36] also mention the product/market fit as a prerequisite to start Growth Hacking but do not integrate it as an element in their cycle. The idea of having a minimum viable product originates from the lean start-up. An initial product version enables gaining more information about customer needs. Then, those support developing the product and its promotion further [79]. A second prerequisite placed by Conway and Hemphill [72] before the cycle is, as already mentioned by Ellis and Brown [36], a multidisciplinary team with various skills [72]. Wahlandt and Heidel [80] propose for application in start-ups to divide Growth Hacking into three steps: development, implementation, and penetration.
Growth Hacking aims to increase growth by hacking which relates to creative ideas testing and adapting [42, 74]. To grow a company and its value, three customer groups are key: retaining customers, developing existing customers and acquiring new customers [81]. Hence balancing new and existing customers is necessary to secure financial performance [82]. Supporting the customer journey with a mixed team of sales and marketing representatives increases sales and customer loyalty [83]. So, it is relevant to follow the customer on the whole customer journey with Growth Hacking [36]. Big data provides new opportunities for companies along the customer journey. Five steps form the customer experience funnel: acquisition, activation, retention, referral, revenue. Acquisition, activation (developing) and retention were already mentioned above. Referral means a (potential) customer recommends the product to others [84]. Monetising, buying the product or, for example, a free download represents the fifth step: revenue [84]. Bohnsack and Liesner [75] identify 34 patterns for the customer journey that could facilitate the execution of Growth Hacking in a company. For example, for the activation phase, they propose using single sign-on or dynamic pricing for the revenue phase [75]. The growth of the customer base is also relevant for B2B companies [80].
According to Bussgang and Benbarak [85], in line with Herzberger and Jenny [73] Growth Hacking concerns owned (i.e., company website), paid (i.e., SEA) and earned media (i.e., likes on social media) as well as the product itself [36]. Different digital channels can serve for Growth Hacking. Ellis and Brown [36] classify them as viral/word-of-mouth (i.e., social media), organic (i.e., company website) and paid (i.e., SEA). Each channel has different opportunities and risks; besides, various efforts and inputs are necessary for the respective channel [80]. Gustafson et al. [57] point out that the right message and the right platform influence the speed and the quality of information sharing. Furthermore, the authors state besides the sources of information, for the buyer, the technique to gather and transform information into knowledge is relevant [57].
5. Conclusion, limitations, and further research
New and innovative concepts like Bricolage and Growth Hacking are increasingly finding their way into society. To survive and sometimes prosper under resource-constrained environments, and benefit from digitalisation and its associated opportunities, Bricolage and Growth Hacking offer the possibility to generate company growth. Bricolage provides a behavioural strategy that businesses can practice creativity to find solutions even under penurious environments.
The creation of new companies poses various challenges especially for the fractions who are short of resources, such as students, people in developing countries, and refugees.
Correspondingly, businesses with strong Bricolage capabilities in making use of inputs at hand can help firms explore and exploit new opportunities and win advantages in competitive markets. As digitalisation is predicted to grow, Growth Hacking provides the opportunity to improve performance by testing, analysing, and adapting [45]. The performance of a variety of digital marketing instruments applied by start-ups can be improved to generate growth, which is of high relevance for start-up companies [80].
Certain limitations restricted the study. As the topic of Growth Hacking is very current, only a limited amount of appropriate literature is available. The term was appeared in 2010 [36]. The research published since then is limited to small in comparison to other topics. So far, just a few research papers are published on growth hacking [40]. Due to the lack, this work has often drawn on other sources than on empirical research papers. Concluding more research on the topic is necessary to be able to make reliable statements on the quality of the model.
This paper proposes a two-phase conceptual model that embraces the business creation processes and marketing strategies. It seems that the two phases are separated and the processes are continuous, however, due to today’s dynamic, it is no longer entirely possible to separate the phases from each other, as they do not necessarily follow one another but shift, overlap and repeat during the creation of a new company. However, to depict this reality would have been too complex for this paper and needs further research. Notably, the application of bricolage and its linkage with growth hacking, as proposed in the framework, is not generalizable to all entrepreneurial endeavours under resource-constrained conditions. Also, for this purpose, pure literature research is not the most appropriate method. It would be advisable to conduct qualitative research or experiments (e.g., empirical case studies) to explore the topic in antecedents of acceptance or scepticism.
For future research, the concepts should be reviewed and aligned to current practices. There is an opportunity for future research to select sample cases and conduct longitudinal studies to examine processual features of entrepreneurial dynamics and capture the wide variability across start-ups. Furthermore, the subject is highly complex, and more applications should be considered than possible within the paper’s scope. There is a need for a deeper understanding of low resource company creation and development to evaluate the success. For future research, it would also be interesting to investigate how growth hacking through the internet influences the decision making and the buying time, if the fast accessibility decreases the decision time or whether the amount of information and the time to evaluate those extend the decision time.
\n',keywords:"Bricolage, Growth Hacking, Entrepreneurship of Students/Refugees/Developing Countries, Lacking Resources",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/77841.pdf",chapterXML:"https://mts.intechopen.com/source/xml/77841.xml",downloadPdfUrl:"/chapter/pdf-download/77841",previewPdfUrl:"/chapter/pdf-preview/77841",totalDownloads:202,totalViews:0,totalCrossrefCites:0,dateSubmitted:"April 14th 2021",dateReviewed:"July 11th 2021",datePrePublished:"August 17th 2021",datePublished:null,dateFinished:"August 4th 2021",readingETA:"0",abstract:"The chapter presents two smart concepts of creating a new business without or with only low budget. Thus, it applies particularly e.g., for either students, refugees and/or people from developing countries. “Bricolage” stands for a behaviour in which the actor solves problems using only available resources. Contrary to the resource-creating mentality, only the resources of the repertoire at hand are used. “Growth Hacking” as a new method, using digital approaches in particular, can achieve high sales in a short time. The relevance of data-driven marketing within the framework of a growth strategy. Working primarily with data is a promising strategy for companies that can effectively, efficiently and cost effectively using online tools or online-offline combinations to achieve their growth objectives. Thus, the two concepts are complementing each other by dedication to two different stages of a start-up process. Bricolage for creating the start-up and Growth Hacking for getting it successfully to the market and make it grow sustainably. The Chapter is describing the two concepts and their interdependence by offering a conceptual framework.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/77841",risUrl:"/chapter/ris/77841",signatures:"Thomas Baaken, Liguang Liu and Lea Lapornik",book:{id:"10917",type:"book",title:"Next Generation Entrepreneurship",subtitle:null,fullTitle:"Next Generation Entrepreneurship",slug:null,publishedDate:null,bookSignature:"Associate Prof. Burak Erkut and Dr. Vildan Esenyel",coverURL:"https://cdn.intechopen.com/books/images_new/10917.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83969-132-4",printIsbn:"978-1-83969-131-7",pdfIsbn:"978-1-83969-133-1",isAvailableForWebshopOrdering:!0,editors:[{id:"336103",title:"Associate Prof.",name:"Burak",middleName:null,surname:"Erkut",slug:"burak-erkut",fullName:"Burak Erkut"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Conceptual framework",level:"1"},{id:"sec_3",title:"3. Bricolage",level:"1"},{id:"sec_4",title:"4. Growth hacking",level:"1"},{id:"sec_4_2",title:"4.1 Guide to a new smart concept",level:"2"},{id:"sec_5_2",title:"4.2 Neighborhood strategies",level:"2"},{id:"sec_6_2",title:"4.3 Growth hacking framework",level:"2"},{id:"sec_8",title:"5. Conclusion, limitations, and further research",level:"1"}],chapterReferences:[{id:"B1",body:'Politis, D., Winborg, J., & Dahlstrand, Å. L. Exploring the resource logic of student entrepreneurs. ISBJ. 2011 Jan 07; 30(6): 659-683. Available from: https://journals.sagepub.com/doi/abs/10.1177/0266242610383445 DOI: 10.1177/0266242610383445'},{id:"B2",body:'Shambare, R. Barriers to Student Entrepreneurship in South Africa. JEBS. 2013 Jul; 5(7): 449-459. Available from: https://ojs.amhinternational.com/index.php/jebs/article/view/419 DOI: 10.22610/jebs.v5i7.410'},{id:"B3",body:'Bailetti, T. 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Role of big data and social media analytics for business to business sustainability: A participatory web context. IMM [Internet]. 2019 Apr [cited 2021 May 17];86:163-179. Available from: https://doi.org/10.1016/j.indmarman.2019.04.005'},{id:"B78",body:'Harvard Business Review [Internet]. Massachusets, USA: A Refresher on A/B Testing. 2017 Jun 28 [cited 2021 May 21]. Available from: https://hbr.org/2017/06/a-refresher-on-ab-testing'},{id:"B79",body:'Startup lessons learned [Internet]. Connecticut: Ries, E.; 2009. Minimum Viable Product: a guide.; 2009 Aug 3 [cited 2021 May 14]; about 6 screens]. Available from: http://www.startuplessonslearned.com/2009/08/minimum-viable-product-guide.html'},{id:"B80",body:'Wahlandt, V., & Heidel, B. Growth Hacking: Datengetriebenes Marketing als Wachstumsmotor für Unternehmen. TZ. 2019. (4):66-69.'},{id:"B81",body:'Gupta, S., Lehmann, D. R., & Ames Stuart, J. Valuing Customers. JMR. 2004 Feb 01; 41(1):7-18.'},{id:"B82",body:'Reinartz, W., Thomas, J. 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Available from: https://hbr.org/2016/02/every-company-needs-a-growth-manager'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Thomas Baaken",address:"baaken@fh-muenster.de",affiliation:'
MSB Münster School of Business, FH Münster – University of Applied Sciences, Germany
Science-to-Business Marketing Research Centre, Germany
MSB Münster School of Business, FH Münster – University of Applied Sciences, Germany
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Dr Alex Lazinica
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Alex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
Our business values are based on those any scientist applies to their research. We have created a culture of respect and collaboration within a relaxed, friendly and progressive atmosphere, while maintaining academic rigour.
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Integrity - We are consistent and dependable, always striving for precision and accuracy in the true spirit of science.
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Openness - We communicate honestly and transparently. We are open to constructive criticism and committed to learning from it.
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Disruptiveness - We are eager for discovery, for new ideas and for progression. We approach our work with creativity and determination, with a clear vision that drives us forward. We look beyond today and strive for a better tomorrow.
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Our Team
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Co-founded by Alex Lazinica and Vedran Kordic: “We are passionate about the advancement of science. As Ph.D. researchers in Vienna, we found it difficult to access the scholarly research we needed. We created IntechOpen with the specific aim of putting the academic needs of the global research community before the business interests of publishers. Our Team is now a global one and includes highly-renowned scientists and publishers, as well as experts in disseminating your research.”
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But, one thing we have in common is -- we are all scientists at heart!
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Sara Uhac, COO
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Sara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
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Adrian Assad De Marco
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Adrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
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IntechOpen Board Members
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Dr Alex Lazinica
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Alex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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As the science gets more advanced and the information about these two points becomes clearer, the view of this information might modify our understanding to these processes. Then, some topics might be dropped, and others might be raised or become more obvious. However, the feeding of halophyte forages as per se has several drawbacks and therefore, they have to be fed in mixed rations, fortifying these rations with energy supplements.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Salah A. Attia-Ismail",authors:[{id:"204190",title:"Emeritus Prof.",name:"Salah",middleName:"Abdelaty",surname:"Attia-Ismail",slug:"salah-attia-ismail",fullName:"Salah Attia-Ismail"}]},{id:"72082",doi:"10.5772/intechopen.92303",title:"Revalorization of Coffee Waste",slug:"revalorization-of-coffee-waste",totalDownloads:1081,totalCrossrefCites:4,totalDimensionsCites:10,abstract:"One of the household methods most used to prepare the coffee beverage is the coffee dripping method, which generates millions of tons of coffee waste (CW). Its disposition without control causes environmental matters due to the high consumption of oxygen during its discomposing process. However, the high availability, low cost, and chemical composition of CW (cellulose, hemicelluloses, lignin, ashes, protein, aliphatic acids, fats, and water) make them useful material for obtaining added-value products and bioenergy. In this chapter, the state of the art of different sustainable alternatives to revalorize CW is shown. CW has been successfully applied as an adsorbent for removing pollutants from wastewater and gas, a precursor for obtaining activated carbon, and a feedstock for producing energy and valuable products using mono-process extraction and biorefinery.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Felipe J. Cerino-Córdova, Nancy E. Dávila-Guzmán, Azucena M. García León, Jacob J. Salazar-Rabago and Eduardo Soto-Regalado",authors:null},{id:"56029",doi:"10.5772/intechopen.69614",title:"Production of Spineless Cactus in Brazilian Semiarid",slug:"production-of-spineless-cactus-in-brazilian-semiarid",totalDownloads:1888,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"The term “spineless cactus” is used in Brazil to designate cultivars of Opuntia ficus indica Mill and Nopalea cochenillifera Salm Dyck. The spineless cactus was consolidated in Brazilian semiarid as a strategic fundamental food resource in several production livestock systems, constituting a plant with enormous productive potential. Thus, the spineless cactus has been widely cultivated and used for several decades, by enabling the animal feeding in critical periods of year because of its characteristics, morpho‐anatomical and physiological (CAM), which makes it tolerant to long droughts, being a crop that presents high productivity in droughts conditions, when compared to other forages. Nevertheless, the spineless cactus is a crop relatively picky about soil and climate characteristics of region, presenting greater growth in fertile soils, as well as in regions where nighttime temperatures are cool and the air humidity is relatively high. Although the crop be adapted to long droughts periods, many times it’s necessary to perform irrigation in its production system, mainly in regions of low rainfall, for to supply its water needs, thus ensuring productivity and survival of crop. Therefore, the knowledge of characteristics of plant, as well as of appropriate management techniques to crop, is essential for the good performance of spineless cactus.",book:{id:"5978",slug:"new-perspectives-in-forage-crops",title:"New Perspectives in Forage Crops",fullTitle:"New Perspectives in Forage Crops"},signatures:"Wilma Cristina Cavalcante dos Santos Sá, Edson Mauro Santos,\nJuliana Silva de Oliveira and Alexandre Fernandes Perazzo",authors:[{id:"139631",title:"Dr.",name:"Edson Mauro",middleName:null,surname:"Santos",slug:"edson-mauro-santos",fullName:"Edson Mauro Santos"},{id:"180036",title:"Dr.",name:"Juliana",middleName:null,surname:"Oliveira",slug:"juliana-oliveira",fullName:"Juliana Oliveira"},{id:"203022",title:"MSc.",name:"Wilma",middleName:null,surname:"Sá",slug:"wilma-sa",fullName:"Wilma Sá"},{id:"207265",title:"Dr.",name:"Alexandre",middleName:null,surname:"Perazzo",slug:"alexandre-perazzo",fullName:"Alexandre Perazzo"}]},{id:"70151",doi:"10.5772/intechopen.89224",title:"The Harvest and Post-Harvest Management Practices’ Impact on Coffee Quality",slug:"the-harvest-and-post-harvest-management-practices-impact-on-coffee-quality",totalDownloads:1793,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Coffee is one of the most important agricultural commodities in the world. The coffee quality is associated with pre-harvest and post-harvest management activities. Each step starting from selecting the best coffee variety for plantation until the final coffee drink preparation determines the cupping quality. The overall coffee quality influenced by the factors which involve in changes the physicochemical properties and sensorial attributes, including the post-harvest operations. The post-harvest processing activities contribute about 60% of the quality of green coffee beans. The post-harvest operations include pulping, processing, drying, hulling, cleaning, sorting, grading, storage, roasting, grinding, and cupping. This chapter comprises the harvest and post-harvest operations of coffee and their impacts on coffee quality.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Mesfin Haile and Won Hee Kang",authors:null},{id:"69900",doi:"10.5772/intechopen.89508",title:"Coffee By-Products: Nowadays and Perspectives",slug:"coffee-by-products-nowadays-and-perspectives",totalDownloads:1144,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"Coffee is one of the most consumed products around the world; 2.25 billions of coffee cup are consumed everyday in the world. For coffee crop production, different by-products are produced, such as coffee peel, coffee husk, parchment, and spent coffee grounds. These by-products have several problems associated at the final disposition. In this book chapter, we study the main coffee varieties produced in the world, the by-products produced, and its composition and finally assess the potential of supramolecular solvents (SUPRAS) and water as green solvents for high-added-value compound extractions. Bioactive compounds were extracted from fresh and dried coffee peel in an acceptable rate for industrial applications. SUPRAS offer advantages in terms of rapidity (5 min) and simplicity (stirring and centrifugation at room temperature), thus avoiding costly processes based on high pressure and temperature. Extractions carried out using water as solvent is another technique of extraction mixing temperature (above 60°C) and time (4.5 min) obtained a beverage or solution with presence a bioactive compounds how caffeine, chlorogenic acid and polyphenols.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Laura Sofía Torres-Valenzuela, Johanna Andrea Serna-Jiménez and Katherine Martínez",authors:null}],mostDownloadedChaptersLast30Days:[{id:"71528",title:"A Detail Chemistry of Coffee and Its Analysis",slug:"a-detail-chemistry-of-coffee-and-its-analysis",totalDownloads:2331,totalCrossrefCites:5,totalDimensionsCites:6,abstract:"This review article highlights the detailed chemistry of coffee including its components; chemical constituents like carbohydrates, proteins, lipids, and caffeine; aromatic principles; oil and waxes; and minerals and acids. The high extent of caffeine can be found in the coffee plants; hence, in the second part of the study, various analytical methods are designed for the proper identification, separation, optimization, purification, and determination of caffeine present in coffee, tea, and marketed coffee. These analytical methods are appropriated for the separation and quantification of caffeine. The various analytical methods include spectroscopy methods like UV, IR, and NMR spectroscopy; chromatographic methods like paper, TLC, column, HPLC, and gas chromatography; and hyphenated techniques like LC–MS, GC–MS, and GC–MS/MS. This article compares and contrasts the amount of caffeine by various analytical methods.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Hemraj Sharma",authors:null},{id:"70151",title:"The Harvest and Post-Harvest Management Practices’ Impact on Coffee Quality",slug:"the-harvest-and-post-harvest-management-practices-impact-on-coffee-quality",totalDownloads:1793,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Coffee is one of the most important agricultural commodities in the world. The coffee quality is associated with pre-harvest and post-harvest management activities. Each step starting from selecting the best coffee variety for plantation until the final coffee drink preparation determines the cupping quality. The overall coffee quality influenced by the factors which involve in changes the physicochemical properties and sensorial attributes, including the post-harvest operations. The post-harvest processing activities contribute about 60% of the quality of green coffee beans. The post-harvest operations include pulping, processing, drying, hulling, cleaning, sorting, grading, storage, roasting, grinding, and cupping. This chapter comprises the harvest and post-harvest operations of coffee and their impacts on coffee quality.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Mesfin Haile and Won Hee Kang",authors:null},{id:"72400",title:"Factors Affecting Efficiency of Vegetable Production in Nigeria: A Review",slug:"factors-affecting-efficiency-of-vegetable-production-in-nigeria-a-review",totalDownloads:803,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"Vegetables are important for maintenance of good health; their production and marketing are veritable sources of employment and livelihood. To promote vegetables’ contribution to the above, there is a need for sustainable and efficient production process. The paper reviewed production, socioeconomic factors, and constraint affecting efficiency of production of three important vegetables (tomato, pepper, and onion). The review showed that socioeconomic factors found to increase technical efficiency in vegetable production were educational level, extension contact, and household size. Influence of farmer age on technical efficiency was inconclusive due to varied opinions. Increase in farm size, quantity of seed, amount of fertilizer, and agrochemical were found to have positive influence on output. Majority of the literature reviewed opined that increase in quantity of labour raises productivity; however, it must be utilized efficiently. The mean technical efficiency of the vegetables varied from the southern to the northern part of the country. The cross cutting constraints in vegetables production are pest and diseases, inadequate storage facilities, and high cost of improved inputs. The study recommends increase awareness and sensitization on optimum levels of resource use for increased productivity and appropriate intervention to constraints in the value chain.",book:{id:"10142",slug:"agricultural-economics",title:"Agricultural Economics",fullTitle:"Agricultural Economics"},signatures:"Iyabo Bosede Adeoye",authors:[{id:"317695",title:"Dr.",name:"Iyabo Bosede",middleName:null,surname:"Adeoye",slug:"iyabo-bosede-adeoye",fullName:"Iyabo Bosede Adeoye"}]},{id:"65591",title:"Insect Pest Management in Organic Farming System",slug:"insect-pest-management-in-organic-farming-system",totalDownloads:2595,totalCrossrefCites:1,totalDimensionsCites:4,abstract:"Due to the regulations of organic farming, few options remain for organic farmers to manage pests and diseases in their crops compared to conventional farming. However, major pests could still be managed through manipulation of the agroecosystem processes in advantage of the crops and disadvantage of pests. The limited number of active plant protection substances authorized for use in organic farming can provide support to natural and biological control agents in suppression of pests and diseases. This chapter highlights the principles and strategies of crop protection in organic farming, the cultural practices adopted, the active substances allowed for use to suppress pests, and the impacts on faunal and floral biodiversity. A case study of organic date palm cultivation is discussed.",book:{id:"6988",slug:"multifunctionality-and-impacts-of-organic-and-conventional-agriculture",title:"Multifunctionality and Impacts of Organic and Conventional Agriculture",fullTitle:"Multifunctionality and Impacts of Organic and Conventional Agriculture"},signatures:"Hamadttu Abdel Farag El-Shafie",authors:[{id:"192142",title:"Dr.",name:"Hamadttu",middleName:null,surname:"El-Shafie",slug:"hamadttu-el-shafie",fullName:"Hamadttu El-Shafie"}]},{id:"69412",title:"Soil Management and Water-Use Efficiency in Brazilian Coffee Crops",slug:"soil-management-and-water-use-efficiency-in-brazilian-coffee-crops",totalDownloads:806,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Brazil is a world leader in coffee production. However, currently, it coexists with recurrent and severe droughts, accompanied by intense heat, strong insolation and low relative humidity. As the cultivation is carried out primarily in the rainy season, these world climate variations have affected crops yields and fruits quality, requiring innovative actions that promote efficient use of water stored in the soil. Among several soil management practices that promote a more rational use of water, deep tillage combined with liming, gypsum and fertilizer amendments lead to an increase in effective depth of coffee roots, therefore reducing water stress. Moreover, intercropping with Urochloa sp. is highly efficient in enhancing soil structure, water infiltration and plant available water capacity. Additionally, other innovative techniques and practices are also introduced in this chapter.",book:{id:"8952",slug:"coffee-production-and-research",title:"Coffee",fullTitle:"Coffee - Production and Research"},signatures:"Bruno Montoani Silva, Geraldo César de Oliveira, Milson Evaldo Serafim, Carla Eloize Carducci, Érika Andressa da Silva, Samara Martins Barbosa, Laura Beatriz Batista de Melo, Walbert Junior Reis dos Santos, Thiago Henrique Pereira Reis, César Henrique Caputo de Oliveira and Paulo Tácito Gontijo Guimarães",authors:null}],onlineFirstChaptersFilter:{topicId:"27",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:315,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"38",title:"Pollution",coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",isOpenForSubmission:!0,editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",biography:"Ismail Md. Mofizur Rahman (Ismail M. M. Rahman) assumed his current responsibilities as an Associate Professor at the Institute of Environmental Radioactivity, Fukushima University, Japan, in Oct 2015. He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. Begum received her Ph.D. in Environmental Analytical Chemistry from Kanazawa University in 2012. She achieved her Master of Science (M.Sc.) degree with a major in Applied Chemistry and a Bachelor of Science (B.Sc.) in Chemistry, all from the University of Chittagong, Bangladesh. Her work affiliations include Fukushima University, Japan (Visiting Research Fellow, Institute of Environmental Radioactivity: Mar 2016 to present), Southern University Bangladesh (Assistant Professor, Department of Civil Engineering: Jan 2015 to present), and Kanazawa University, Japan (Postdoctoral Fellow, Institute of Science and Engineering: Oct 2012 to Mar 2014; Research fellow, Venture Business Laboratory, Advanced Science and Social Co-Creation Promotion Organization: Apr 2018 to Mar 2021). The research focus of Dr. Zinnat includes the effect of the relative stability of metal-chelator complexes in the environmental remediation process designs and the development of eco-friendly soil washing techniques using biodegradable chelators.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"39",title:"Environmental Resilience and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",isOpenForSubmission:!0,editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",slug:"jose-navarro-pedreno",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",biography:"Full professor at University Miguel Hernández of Elche, Spain, previously working at the University of Alicante, Autonomous University of Madrid and Polytechnic University of Valencia. 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He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"4",type:"subseries",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. 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