\r\n\t1. Geopolymers chemistry topic describes the chemical reaction models and chemical kinetic of the geopolymerization which occurs after mixing the aluminosilicate raw materials with an alkaline solution.
\r\n\t2. Advanced characterization of geopolymers topic includes innovative technologies applied on geopolymers characterization at the nanoscale level, meant to explain the bond between the reacted and nonreacted particles from the composition.
\r\n\t3. Sustainability with geopolymers topic should provide clear information about the characteristics and applications of the geopolymers which use as raw materials industrial waste. Moreover, environmental impact studies which offer a clear view of the effects produced by geopolymers manufacturing, compared to conventional materials, is included.
\r\n\t4. Geopolymers as functional materials topic will present key aspects in developing geopolymers with tailored properties that increase further the heavy metals adsorption capacity, offering outstanding opportunities for energy-efficient separations and process intensification, in terms of saving energy, reducing capital costs, minimizing environmental impact and maximizing the raw materials exploitation.
\r\n\t5. Reinforced structures topic describe the effects produced by the introduction, in the geopolymers matrix, of different types of reinforcing elements.
Three-dimensional printing—also known as rapid prototyping—was first introduced in 1980s; during past three decades, enormous changes and development have been performed by scientists through modifying this technology by uses, material, and also accuracy.
\nWith increasing attention of scientific societies, recently, scientific literature bolded feasibility of 3-D-printed tissues and organs and its usage within laborious clinical situations. Also, this technology was used largely in accurate and highly customized devices, such as tracheobronchial splints, bionic ears, and even more. Within the field of craniofacial surgery, 3-D surgical models have been used as templates to create bone grafts, tailoring bioprosthetic implants, plate bending, cutting guides for osteotomies, and intraoperative oral splints. Using 3-D models and guides has been shown to shorten operative time and potentially reduce the complications associated with prolonged operative times.
\nThe goal of surgical procedures for a clinician is to improve perioperative form, recovery of function, and also minimizing operative and postoperative morbidity. Many exciting and new technological advances have ushered in a new era in the field of oral and maxillofacial surgery over the last years, which within no exaggeration 3-D printing is the novelist and controversial one.
\nThe aim of this chapter is to introduce 3-D printing method and its role in the contemporary oral and maxillofacial surgery and to review current advantages of its application in the field of regenerative medicine.
\nThree-dimensional (3-D) printing has been utilized in diverse aspects of manufacturing to produce different objects from guns, boats, and food to models of unborn babies. From over 1450 articles related to 3-D printing listed in PubMed, nearly a third of them were solely published in the last 2 years [1].
\nThree-dimensional (3-D) printing is a manufacturing process that objects are fabricated in a layering method during fusing or depositing different materials such as plastic, metal, ceramics, powders, liquids, or even living cells to build a 3-D matter [2, 3]. It is a process of generating physical models from digital layouts [4, 5]. This technology demonstrates a technique that a product designed through a computer-aided scheme is manufactured in a layer-by-layer system [6]. This process is also cited as rapid prototyping (RP), solid freeform technology (SFF), or additive manufacturing (AM) [7].
\n3-D printing techniques are not brand new and have been existed since 30 years ago [8–10]. This technology is first introduced and invented by Charles Hull in 1986, and at first, it was utilized in the engineering and automobile industry for manufacturing polyurethane frameworks for different models, pieces, and instruments [11]. Originally, Hull employed the phrase “stereolithography” in his US Patent 4,575,330, termed “Apparatus for Production of Three—Dimensional Objects by Stereolithography” published in 1986. Stereolithography technique included subjoining layers over the top of each other, by curing photopolymers with UV lasers [12, 13].
\nSince then, 3-D models have been used for a diversity of different objectives. Since 1986, this process has started to accelerate and has honored recognition globally and has influenced different arenas, such as medicine.
\nThe developing agora for 3-D desktop printers encourages wide-ranging experimentations in that subject. Generally, medical indications of these printers are such as treatment planning, prosthesis, implant fabrications, medical training, and other usages [4].
\nHaving being used in military, food industry, and art, rapid prototyping is receiving a lot of attention in the field of surgery in the last 10 years [6, 14].
\nThe pioneering usage of stereolithography in oral and maxillofacial surgery was by Brix and Lambrecht in 1985. Later this technique was used by them for treatment planning in craniofacial surgery [15].
\nIn 1990, stereolithography was used by Mankovich et al. for treating patients having craniofacial deformities [16, 17]. They used it to simulate bony anatomy of the cranium using computed tomography with complete internal components [17, 18].
\nBy aiding in complex craniofacial reconstructions, 3-D printing has recently earned reputation in medicine and surgical fields [19–21].
\nToday, maxillofacial surgery can benefit from additive manufacturing in various aspects and different clinical cases [22]. This technique can help with bending plates, manufacturing templates for bone grafts, tailoring implants, osteotomy guides, and intraoperative occlusal splints [23–27]. Rapid prototyping can shorten surgery duration and simplify pre and intraoperative decisions. It has enhanced efficacy and preciseness of surgeries [10].
\nFrom first innovation till nowadays, there are different kind of technologies introduced for 3-D printing. Binder jetting (BJ), electron beam melting (EBM), fused deposition modeling (FDM), indirect processes, laser melting (LM), laser sintering (LS), material jetting (MJ), photopolymer jetting (PJ), and stereolithography (SL) are well-known technologies of 3-D printing [14, 28, 29].
\nThere are many different 3-D printing techniques. Benefits and disadvantages are factors to differ each technology system [14]. Among this variety of different techniques, there is a huge discussion and usage in oral and maxillofacial region for SL, FDM, and PJ [1, 28, 30].
\nEach technology has its own characteristics, properties, and advantages which \nTable 1\n summarizes some different three dimensional printing technologies.
\nTechniques | \nAdvantages | \nDisadvantages | \n
---|---|---|
Light cured resin | \n||
1. Stereolithography (SLA) Light sensitive polymer cured layer by layer by a scanning laser in a vat of liquid polymer. | \nRapid fabrication. Able to create complex shapes with high feature resolution. Lower cost materials if used in bulk. | \nOnly available with light curable liquid polymers. Support materials must be removed. Resin is messy and can cause skin sensitization and may irritate by contact and inhalation. Limited shelf life and vat life. Cannot be heat sterilized. High cost technology. | \n
2. Photojet—light sensitive polymer is jetted onto a build platform from an inkjet type print head, and cured layer by layer on an incrementally descending platform. | \nRelatively fast. High resolution, high-quality finish possible. Multiple materials available various colors and physical properties including elastic materials. Lower cost technology. | \nTenacious support material can be difficult to remove completely. Support material may cause skin irritation. Cannot be heat sterilized. High cost materials. | \n
3. DLP (digital light processing) Liquid resin is cured layer by layer by a projector light source. The object is built upside down on an incrementally elevating platform. | \nGood accuracy, smooth surfaces, relatively fast. Lower cost technology. | \nLight curable liquid polymers and wax-like materials for casting. Support materials must be removed. Resin is messy and can cause skin sensitization, and may be irritant by contact Limited shelf life and vat life. Cannot be heat sterilized. Higher cost materials. | \n
Powder binder | \n||
Plaster or cementaceous material set by drops of (colored) water from ‘inkjet’ print head. Object built layer by layer in a powder bed, on an incrementally descending platform. | \nLower cost materials and technology. Can print in color. Un-set material provides support Relatively fast process. Safe materials. | \nLow resolution. Messy powder. Low strength. Cannot be soaked or heat sterilized. | \n
Sintered powder | \n||
Selective laser sintering (SLS) for polymers. Object built layer by layer in powder bed. Heated build chamber raises temperature of material to just below melting point. Scanning laser then sinters powder layer by layer in a descending bed. | \nRange of polymeric materials including nylon, elastomers, and composites. Strong and accurate parts. Self-supported process. Polymeric materials—commonly nylon may be autoclaved. Printed object may have full mechanical functionality. Lower cost materials if used in large volume. | \nSignificant infrastructure required, e.g., Compressed air, climate control. Messy powders. Lower cost in bulk. Inhalation risk. High cost technology. Rough surface. | \n
Selective laser sintering (SLS)—for metals and metal alloys. Also described as selective laser melting (SLM) or direct metal laser sintering (DMLS). Scanning laser sinters metal powder layer by layer in a cold build chamber as the build platform descends. Support structure used to tether objects to build platform. | \nHigh strength objects can control porosity. Variety of materials including titanium, titanium alloys, cobalt chrome, stainless steel. Metal alloy may be recycled. Fine detail possible. | \nElaborate infrastructure requirements. Extremely costly technology moderately costly materials. Dust and nanoparticle condensate may be hazardous to health. Explosive risk. Rough surface. Elaborate post-processing is required: Heat treatment to relieve internal stresses in printed objects. Hard to remove support materials. Relatively slow process. | \n
Electron beam melting (EBM, Arcam). Heated build chamber. Powder sintered layer by layer by scanning electron beam on descending build platform. | \nHigh temperature process, so no support or heat treatment needed afterwards. High speed. Dense parts with controlled porosity. | \nExtremely costly technology moderately costly materials. Dust may be hazardous to health. Explosive risk. Rough surface. Less post-processing required. Lower resolution. | \n
Thermoplastic | \n||
Fused deposition modeling (FDM) First 3-DP technology, most used in ‘home’ printers. Thermoplastic material extruded through nozzle onto build platform. | \nHigh porosity. Variable mechanical strength. Low- to mid-range cost materials and equipment. Low accuracy in low cost equipment. Some materials may be heat sterilized. | \nLow cost but limited materials—only thermoplastics. Limited shape complexity for biological materials. Support material must be removed. | \n
As researchers aim to investigate new materials for 3-D printing in last decade, it is obvious to see variety of biomaterials with different properties and also different applications. As \nTable 2\n summarizes all biomaterials used within studies all over the world for generating scaffolds for bone tissue engineering, it has to be noticed that from this large spectrum of biomaterials just a whole bit of them are available for application in 3-D printing. As follows, we discuss four large categories of materials for 3-D printing of scaffolds and craniofacial tissues, which researches still aim to determine these materials complete properties and advantages.
\nComposed scaffolds | \nSynthetic scaffolds | \nNatural scaffolds | \n||
---|---|---|---|---|
Nano-hydroxyapatite/collagen/PLLA | \nCeramic | \nPolymeric | \nInorganic | \nOrganic | \n
Octacalcium phosphate/collagen | \nCalcium Magnesium Phosphate cement (CMPC) | \nPLGA | \nSilver | \nCollagen sponge | \n
Nano-hydroxyapatite/polyamide 6 | \nβTCP | \nPLG | \nCoral | \nPRP | \n
Nano-hydroxyapatite/polyamide66 | \nHA/TCP | \nPLLA | \nSilk fibroin protein | \nGelatin sponge | \n
Hydroxyapatite-coated PLGA | \nFlurohydroxyapatite | \nPGA | \nPremineralized silk fibroin protein | \nGelatin Hydrogel | \n
HA/PLGA | \nCa deficient hydroxyapatite (CDHA) | \nPLA | \nABB | \nPuraMatrix | \n
βTCP/collagen | \nPLA-PEG | \nDeer horn | \nAlginate | \n|
DBM/PLA | \nFibronectin-coated PLA | \nPartially demineralized bone matrix | \n||
Nano-hydroxyapatite/polyamide | \nPEG-DA | \nBio-Oss | \n||
OsteoSet | \nPEG-MMP | \nAllograft | \n||
Octacalcium phosphate precipitated (OCP) alginate | \nPVDC | \nFibrin sealant | \n||
Demineralized bone powders/PLA | \nPolycaprolactone | \nGelatin foam | \n||
Apatite-coated PLGA | \nCollagen gel | \n|||
Hyaluronic acid based hydrogel | \n
Types of scaffolds used in bone tissue engineering in maxillo-craniofacial region [51].
TCP, tri-calcium phosphate; HA, hydroxyapatite; DBM, demineralized bone matrix; PLGA, poly(lactic-co-glycolic acid); PLA, poly(
Polymer hydrogels are ideal candidates for the development of printable materials for tissue engineering. Hydrogels are known for remarkable tunability of rheological also presenting great mechanical, chemical, and biological properties; high biocompatibility; and similarity to native extracellular matrix (ECM) [32]. For three-dimensional printing of polymers and hydrogels, the use of materials with controlled viscosity should been noticed. This defines the range of printability of the ink. Polymer inks, which are typically printed in the prepolymer phase, need enough viscosity allowing structural support of subsequent printed layers, also enough fluidity to prevent nozzle clogging. For avoiding these difficulties, alginate hydrogels have been cross-linked with calcium ions immediately before the ink leaves the printing head or just after extrusions [33].
\nIn recent researches, for providing suitable ink for bioprinting applications, prepolymerized cell-laden methacrylated gelatin hydrogels have been used successfully [34, 35]. Synthetic hydrogels used for cell encapsulation may limit cell-cell interactions. These interactions are critical for efficient cell proliferation, differentiation, and finally, tissue development. This can represent one of the limitations of bioprinting cell-laden hydrogels which is not present in 3-D printed scaffolds with cells seeded onto or in bioprinting of dense cell aggregates, which will discuss as follow. Hence, the requirement for the development of ECM-derived hydrogels that have tunable physical and chemical properties, are compatible with high cell viability, and provide the adequate binding sites (RGDs) for cell attachment and matrix remodeling during their early proliferative stage [32].
\nSynthetic polymers are most commonly used materials for 3-D printing in biomedical applications [36, 37]. However, since high temperature is usually involved during the printing of these materials, the direct incorporation of cells or growth factors in the polymer mixture is generally avoided as the cell viability or bioactivity [37] cannot be maintained throughout the manufacturing process.
\nAlthough hydrogels provide great advantages for tissue engineering applications, such as the ability of exposing cells to highly hydrated 3-D microenvironments that is similar to the natural ECM [32]. In contrast, they generally present very low stiffness (in the kPa range) compared with the majority of load-bearing tissues in the craniofacial complex (in the GPa range). Therefore, reconstruction of tissues subjected to higher mechanical loads, such as bones and teeth, usually requires the use of ceramic materials or composite scaffolds which provide more mechanical advantages, where polymers are commonly combined with inorganic fillers to increase scaffold stiffness [38].
\nCeramic scaffolds are usually composed of calcium and phosphate mineral phases, such as hydroxyapatite [39] or b-tricalcium phosphate [40]. The noticeable ability of these scaffolds to upregulate osteogenesis due to inherent properties of the formation of a bioactive ion-rich cellular microenvironment, also as mentioned before their ability to mechanically provide space maintenance, makes these materials interesting choice for 3-D scaffold fabrication for craniofacial applications. In contrast, ceramic scaffolds are not compatible with cell encapsulation for bioprinting. In 3-D printed ceramic scaffolds, cells quickly populate the scaffold surface, which establishing close cell-cell interactions lead to promotion of cell proliferation and differentiation. On the other hand, ceramics with properties lead to lower rates of degradation than hydrogels, which aids in prolonged guided tissue remodeling and structural support. In contrast, ceramic scaffolds are too brittle for implantation in load-bearing defect sites. Ideal scaffolds would combine the high calcium content of calcium and phosphate ceramics with the outstanding toughness of natural bone, which perhaps can only be obtained by creating scaffolds that are biomimetically mineralized and hierarchically structured, as recent researches demonstrated that in [41].
\nFused deposition of ceramics (FDC) in a direct printing mode generally consists of extruding a slurry including a high content (>50% w/v) of inorganic components [42]. The manufacturing of such scaffolds follows 3 steps:
Mixture phase, which involves the preparation of the slurry. The bioceramic particles are mixed in a solvent (aqueous or nonaqueous) with a low concentration of organic polymers/surfactants, called the binder, to obtain adequate flowability.
Green ceramic and binder burnout phase involving the deposition of filaments of slurry following a predetermined pattern prior to drying and exposure to high temperature to burn out the organic component of the mixture.
Sintering phase, which involves the exposure of the green form to elevated temperature (above 1000°C) to initiate the migration of atoms between adjacent ceramic particles, hence creating physical bonds called “necks.”
It is critical for reproducible manufacturing of 3-D rapid prototyped bioceramics to have shape retention, a challenge that can be reached by adjusting the viscosity of the slurry and the evaporation rate of the solvent [43].
\nPrintable composites, which are usually in the form of copolymers, polymer-polymer mixtures, or polymer-ceramic mixtures [44], allow ability for the combination of variety of advantageous properties of their included components, which provide a remarkable candidate as “bioink”. Considering the advantages of polymer composite hydrogels, such as interpenetrating polymer networks (IPNs) or hybrid hydrogels [45], the incorporation of synthetic fillers to printable materials recently discussed in researches [33]. The addition of silicate fillers [38] and a range of nanoparticles have been used to synthesize different types of composite scaffolds [46] to promote greater control over viscosity and stiffness of polymer hydrogels. In addition, several of silica-containing hydrogels with higher expression of genes encoding morphogenetic cytokines, such as bone morphogenetic proteins (BMPs) seems promising [47]. The combination and manufacturing mixture of hydrogels with filler materials and/or natural peptides with morphogenetic capacity demonstrate great future for application in 3-D printing in aim to reach ultimate goal in regenerative craniofacial repair.
\nOver recent years, many of researches aimed to evaluate and study cell aggregates and spheroids for use in tissue engineering and regenerative medicine [48]. As this method cited correctly and appropriately as “scaffold-free printing,” in fact small quantities of hydrogel are used to facilitate cell aggregation. In this method for 3-D printing, or in an appropriate way called “bioprinting,” multicellular spheroids are deposited using extrusion printers and allowed to self-assemble into the desired 3-D structure (\nFigure 1\n). As it is clear, these systems allow direct fabrication of tissue constructs which in contrast to other methods have extremely high cell densities. Although in load-bearing tissues with high amount of mineral components and noticeable mechanical properties use of this methods still looks uncertain, the ability to position aggregates of heterotypic cells with microscale precision (\nFigure 2\n) seems promising as an excellent alternative to bioprint complex tissues consisting variety of cells [49].
\nSEM view of multicellular spheroids of HUSMCs (A), CHO cells (B) and HFBs (C) (adapted from Norotte et al. [50]).
Principles of spheroids bioprinting technology: (a) bioprinter (general view); (b) multiple bioprinter nozzles; (c) tissue spheroids before dispensing; (d) tissue spheroids during dispensing; (e) schematic view of continuous dispensing in air; (f) schematic view of continuous dispensing in fluid; (g) schematic view of digital dispensing in air; (h) schematic view of digital dispensing in fluid; (i) schematic view of bioassembly of tubular tissue construct using bioprinting of self-assembled tissue spheroids illustrating sequential steps of layer-by-layer tissue spheroid deposition and tissue fusion process (adopted from Mironov et al. [48]).
Researches aimed to investigate novel technologies for 3-D printing and introduced some novel methods including phase-separation, self-assembly, electrospinning, freeze drying, solvent casting/particulate leaching, gas foaming, and melt molding [52]. Using scaffolds, the architecture of native extracellular matrices can be mimicked at the nanoscale level and therefore provide the primary base for the regeneration of new tissue [53]. Originally, a “top-down” approach was used as a tissue engineering method for scaffold fabrication. In this method, cells are seeded onto a biodegradable and biocompatible scaffold and are predicted to migrate and fill the scaffold hence creating their own matrix. By using this technique, several avascular tissues such as bladder [54] and skin [55] have been engineered effectively. However, due to the limited diffusion properties of these scaffolds, this technique faces several challenges for fabrication of more complex tissues such as heart and liver [56]. Therefore, “bottom-up” methods have been developed to overcome this problem [57]. Bottom-up approaches include cell-encapsulation with microscale hydrogels, cell aggregation by self-assembly, generation of cell sheets, and direct printing of cells [58]. These complex tissue blocks can be assembled using various methods including microfluidics [59], magnetic fields [60], acoustic fields [61], and surface tension [62]. These methods are relatively easy and have provided a solid foundation for the fabrication of scaffolds. However, as mentioned previously, these conventional methods suffer from several limitations including inadequate control over scaffold properties such as pore size, pore geometry, distribution of high levels of interconnectivity, and mechanical strength. As such, it is necessary to develop technologies with sufficient control so as to design more intricate tissue-specific scaffolds. In addition, scaffolds can be coated using surface modification techniques (such as introducing functional groups) to enhance cell migration, attachment and proliferation. Three-dimensional printing allows scaffolds to become more precisely fabricated (similar to that of the computer-aided design (CAD)) with higher flexibility in the type of materials used to make such scaffolds. Three-dimensional printing uses an additive manufacturing process where a structure is fabricated using a layer-by-layer process. Materials deposited for the formation of the scaffold may be cross-linked or polymerized through heat, ultraviolet light, or binder solutions. Using this technology, 3-D printed scaffolds can be prepared for optimized tissue engineering [52].
\nFor appropriate formation of tissue architecture, the seeding cells (often stem cells) require a 3-D environment/matrix similar to that of the ECM. The ECM acts as a medium to provide proteins and proteoglycans among other nutrients for cellular growth. The ECM also provides structural support to allow for cellular functionality such as regulating cellular communication, growth, and assembly [63]. With this in mind, scientists and engineers originally attempted to replicate the ECM through conventional techniques, which consequently established a framework for using more advanced techniques, such as 3-D printing, to yield higher quality scaffolds. The 3-D printing technique can create defined scaffold structures with controlled pore size and interconnectivity and the ability to support cell growth and tissue formation [64–66]. The current methods for 3-D printing involve a CAD, which is then relayed to each 3-D printing system to “print” the desired scaffold structure. Through various 3-D printing technologies, discussed below, researchers are trying to fabricate biocompatible scaffolds that efficiently support tissue formation (\nTable 3\n).
\nPrinting method | \nAdvantages | \nDisadvantages | \nPreclinical progress | \n
---|---|---|---|
Direct 3-D printing/inkjet | \n\n
| \n\n
| \n\n
| \n
W/electrospinning | \n\n | \n | \n
| \n
Bioplotting | \n\n
| \n\n
| \n\n
| \n
Fused deposition modeling | \n\n
| \n\n
| \n\n
| \n
Selective laser sintering | \n\n
| \n\n
| \n\n
| \n
Stereolithography | \n\n
| \n\n
| \n\n
| \n
Electrospinning | \n\n
| \n\n
| \n\n
| \n
Indirect 3-D printing | \n\n
| \n\n
| \n\n
| \n
Preclinical researches on various 3-D printing techniques for manufacturing scaffolds for tissue engineering [52].
The goal of tissue engineering is to create functional tissues and organs for regenerative therapies and ultimately organ transplantation/replacement. Trial and error was the long and tedious process mainly used to advance the field of regenerative medicine by clarifying the success of techniques.
\nResearchers needed to come up with a list of requirements in order to measure their successes or failures in tissue fabrication [48, 67]. This list was generated from the observations of natural human tissue.
\nAs gold standard of fabricated tissues is to be as similar as possible to natural tissues in the human body in different parameters, then these fabricated tissues must:
Be able to integrate with naturally occurring tissue, and attach via microsutures, glues [68], or through cell adhesion [69–71].
Be capable of essential functions in vivo [48].
Become fully vascularized in order to sustain its functionality [68, 71].
Also, the printers used for tissue fabrication required standardization as well [67, 69].
The bioprinting machines required set extreme sterilization methods to eliminate unwarranted contamination with previously used materials or foreign matter from the environment.
The conditions for printing must be ideal for tissue fabrication, so factors such as humidity and temperature must be closely monitored.
Nozzle size and methods of delivery affect the viability of the materials being printed; therefore, there must be set ideals for delivery methods in relation to the various printing materials.
As a result, researchers created a few methods of printing with the goal of finding a solution to the given problems for optimal tissue biofabrication [48, 68, 69]. Thermal inkjet bioprinting with bioink and direct-write bioprinting both make use of modified inkjet printers but with varied application techniques. Organ printing with tissue spheroids is the recent achievement of researches which seems promising to fabricate tissues directly. \nTable 4\n review advantages and disadvantages of all three common methods “Thermal Inkjet Bioprinting,” “Direct-Write Bioprinting,” and “Spheroid Organ Printing.” Organ printing, otherwise known as the biomedical application of rapid prototyping, may be defined as additive layer-by-layer biomanufacturing of cells. Advantages of organ printing include its automated approach offering a pathway for a scalable and reproducible mass production of tissue-engineered products. This also allows the precise simultaneous 3-D positioning of several cell types, hence enabling the creation of tissue with a high level of cell density. Organ printing may be used to solve the problem of vascularization in thick tissue constructs, and moreover, this technology may be done in situ. Therefore, this emerging transforming technology has potential for surpassing traditional solid scaffold-based tissue engineering [72].
\nType of bioprinting | \nMethod | \nTissue characteristics | \nNote | \n
---|---|---|---|
Thermal inkjet bioprinting | \n\n
| \n\n
| \n“Bioink,” which is a water-based liquid consisting of proteins, enzymes, and cells suspended in a media or saline. | \n
Direct-write bioprinting | \n\n
| \nPossibility of printing tissues with different compositions. | \n\n
| \n
Spheroid organ printing | \nSpheroids are punched into “biopaper” which is a sprayed layer of hydrogel. Each spheroid is made of living cells, thereby creating a ball of “living materials” capable of self-assembly and self-fusion. Alternatively, the spheroids can be digitally placed, undergo self-assembly, and fuse without the use of hydrogel. | \n\n
| \nResearchers fabricated three types of spheroids to create a vascular tree: solid or nonlumenized spheroids, spheroids with one big lumen (mono-lumenized spheroids), and microvascularized tissue spheroids. | \n
3-D bioprinting technique advantages and properties[67].
In order to create a complete and functional organ, the researchers must be able to create thick complex tissues with full vascularization containing lumens of various sizes, large vascular structures to microstructures, in order to sustain the surrounding organ tissue. The best way to achieve this type of vascularization is to fabricate the vascular system and tissue simultaneously, of which is easier said than done [48]. Thorough vascularization remains a common theme for current bioprinting limitations. Without a functional circulatory system, tissue constructs are limited to a means of diffusion for nutrition, which in itself is limited to just a few hundred microns [69].
\nCurrent methods of vascularization call for the infiltration of host microvessels into an implanted construct [67, 73, 74].
\nYet, this strategy is lacking in control and specificity for the developing microvessels. The invading microvessels have a limited penetration depth which prevents the successful incorporation of the microvessels into larger layered constructs. Additionally, the penetration of the vascular system itself may result in a distortion of the region penetrated or in the destruction of the fabricated tissue altogether. For these reasons, it would be ideal to construct tissues with direct vessel in-growth, or vascularization created within the tissue itself, all before implantation.
\nIn addition to vascularization, native tissues contain unique cellular combinations and organizations. There is a need to develop techniques that mimic the complexity of native tissues in order to drive tissue recovery and replacement for medical applications [69]. With the production of organs such as kidneys, for example, at least one million glomeruli and nephrons would need to be generated. Not only would the fabrication be a massive undertaking but also the fabricated tissue would need to be scalable. Scalability of biofabricated tissues is not presently a reality. Yet, spheroids have shown promise toward being scalable with further development. Finally, another major limitation for the development of natural-like, fully functioning fabricated human tissue is economic [68]. This challenge must definitely be overcome if biofabrication technology is to allow the creation of a functional living human organ.
\nIn this chapter, we have illustrated current guiding principles for 3-D bioprinting in tissue fabrication, as well as recent advances and technological developments. The speed at which our knowledge has advanced with additive manufacturing and automated printing systems shows a promise to expand our basic science and engineering capabilities toward addressing health care problems. One of the significant developments in 3-D bioprinting is to manufacture cell microenvironments from molecular to macroscopic scales, which are requested and suitable for tissue engineering and regenerative medicine. As novel methods and technologies introduced in recent years for 3-D printing of biomaterials, promising overview of future appears to manufacture scaffolds for tissue engineering that reach the gold standards and also better comprehensions of stem cells microenvironments and interactions. By aid of various novel technologies, such as microfluidic systems [75, 76], biopatterning [77], and layer-by-layer assembly [76, 78], researchers are now able to biomanufacture microtissue constructs within scaffolds and even also within scaffold-free environments. Considering the great and enormous improvements of biomaterial for tissue engineering, in contrast, there are still certain challenges and difficulties that need more attention. Vascularization is one of the limitations which receive most of attentions [79, 80] due to the fact that this challenge leads to hypoxia, apoptosis, and immediate cell death. For resolving this issue and providing sufficient space for vascularization, researchers attempts to fabricate porous scaffolds [81], to provide sufficient space for vascularization. However, this approach cannot overcome the vascularization challenge completely due to the diffusion of cells and other materials into these porous structures [82]. Forming interconnected, well-defined vascular structures during biomanufacturing process seems to lead to resolving this difficulty and providing better results during process. Other issues that have to be noticed are mechanical strength and stability in 3-D tissue engineering which is one of the key requirements [83]. To be clear in regeneration of hard (e.g., bone) and soft (e.g., vascular grafts) tissues, modulus of elasticity is a crucial parameter that desires improvement [84–86]. Furthermore, the development of a totally closed bioprinting system that integrates printing and post-printing processes such as in-vitro culture and maturation of tissue constructs continues to be a challenge.
\nWith advances in near future, which help finding solutions for the challenges mentioned above, bioprinting technologies will potentially help improvements of rapid clinical solutions and advances in medical implants. Further, we envision that the integration of cells and biomaterials through bioprinting with microfluidic technologies are likely to create unique microenvironments for various applications in cancer biology, tissue engineering, and regenerative medicine [87–91]. Additionally, developments on high-throughput biomanufacturing of 3-D architectures will pave the way for further advancements of in vitro screening and diagnostic applications, potentially enabling complex organ constructs. In the meantime, it is only the effective interplay of engineering concepts in combination with the well-established fundamentals of biology that will realize the true potential of this exciting area.
\nEpilepsy is a global health challenge, one that is responsible for a social and economic burden worldwide, it is estimated to be twice as common in low-income countries than that in the high-income countries, especially in a poor country like Sudan, resulting in unfair treatment, prejudice and stigma [1], and overwhelming decrease in quality of life [2]. People with epilepsy (PWE) in Sudan suffer from a collapsing and deficient health care system, and a community falling behind and lacking enough understanding towards their affliction, with a cultural heritage and misconceptions, and an educational system contributing to make it only that much more difficult for (PWE) to live a normal life, sometimes weighing them down and preventing them from seeking professional medical help altogether. The resultant treatment gab causes a mortality rate dwarfing that of first world countries [3]. On top of that, Sudan is lacking sufficient research and infrastructure to develop satisfying estimates about the situation on the ground, and recent data are scarce [3].
Sudan is the third largest country in Africa that occupies almost 728,000 square miles of northeast Africa. It sits along the sub-Saharan crossroads and along the cost of the red sea that runs through its east-northern borders. In addition to Egypt, Sudan shares borders with six other countries, which are Ethiopia, chad, Libya, Eritrea, Central African Republic, and lastly South Sudan that had its secession from Sudan by July 2011. Sudan is mainly formed of flat plains interspersed by mountain ranges, and due to its immense area, Sudan has different climates and several rivers coursing through the country, mainly the blue and white Niles that join together to form the river Nile in Khartoum the capital city of Sudan.
Although it’s an enormously sized country, it is sparsely populated compared to some of the African countries as it has an estimated census of 43 million people, the majority of which are rural in comparison to the urban population that is mainly centered in the capital.
Sudan is vastly enriched with different races, cultures and a blend of Arabic tribes that form the majority of the population and various African tribes and ethnicities, this enrichment may be contributing to its ever astounding cultural diversities and perhaps the fuel to political differences and the rather devastating civil wars that have crushed the country for ages, viciously affecting Sudan in every aspect possible. Sudanese people are still facing major challenges in everyday aspect of life duet to this overwhelming political instability through its history.
As a low middle-income country, Sudan is confronted with many brutal challenges, especially in health sector. Some of the challenges encountered are the poor assessment and execution of policies, lack of firm health informatics system, inadequate financial spending, centralized medical services and facilities in Khartoum and urban cities, and insufficient training for postgraduate doctors. To add more to the burden on medical care is the deficiency of preventive medicine application, poor referral system, problematic diaspora of physicians, lack of communities’ awareness leading to the fixed stigma and spiritual misconceptions of diseases that are causative of delayed medical seeking behaviors and use of folk medicine. These difficulties robustly affect the quality of health care and specifically the management of chronic diseases as epilepsy.
Neurology practice in Sudan is affected by the weakened health care system, Adult and child neurology is confronted by extreme challenges affecting people with neurological diseases. Up to the year 2005 there were only three practicing neurologists that were delivering medical care for an unconceivable ratio of one neurologist to 12 million people [4]. In addition to the enlarging population, this ratio could be attributed to lack of neurology training programs for postgraduate doctors which has begun in the past 10 years, in addition the shortage of neurology clinics in Sudan as today there are 3 tertiary neurology centers that provide adult neurology services, all of which are located in the capital which only aggravates the problem of the ability to seek neurology consultations and follow-ups especially for patients living outside Khartoum. Other major setbacks are the shortage of neuro-physiologists, neuro-imaging facilities and neuro-radiologists and the desperate need for neurology nursing and rehabilitation centers.
There is a lot of stigma and misconceptions that befall (PWE) in Sudan, where epilepsy is perceived as demonic possession, Satanic rituals, spells and witchcraft [3], some cultures have superstitions similar to that of Saudi tribes where they consider (PWE) as a presentiment of evil, a manifestation of envy and “Evil Eye” [5], while in some cultures (PWE) are considered a grace and bringers of god-bliss to their families [6]. However, others believe PWE are infectious, mentally ill, impotent and should neither get married nor have a job. Some people consider epilepsy an incurable disease, while others think the condition will pass on its’ own so they completely dismiss the therapeutic process as a futile endeavor. Some religious followers would resort to special forms of prayer involving rigorous movements to help alleviate the condition. Such beliefs direct people toward seeking traditional methods and healers, who antagonize demons, introduce herbs, ointments, cautery and prayers as standalone treatment for epilepsy.
A cross sectional study done in Sudan to evaluate the impact of spiritual and traditional believes of care givers on the management of children with epilepsy, it established that 80% of them were educated, one third of study population attributed epilepsy to supernatural causes. More than two thirds acknowledged use of both traditional and spiritual medicine, more than half used different religious methods to treat epilepsy. Almost half of participants believed that religious and or traditional treatment were truly effective in the management of epilepsy, and one third used herbs in the treatment of epilepsy [7].
In Sudan the number of centers where appropriate investigation tools has increased in the recent years, more cities are constructing new centers for neurology (like Madani neurology center, Aljazeera State), but it’s in no way comparable to the increase in patients and the services that need to be provided [8].
Despite the increase in number of medical faculties and doctors, the number of physicians with specialty training in neurology remains lacking. The overall condition of freedom and civil rights in the country along with the increased costs of living, which are all factors contributing to the mass immigration of doctors and other healthcare professionals to seek a respected income that enables them to live a decent life. It is worth mentioning that some doctors in Sudan live off salaries ranging anything from the equivalent of 15 to 300 dollars per month.
Currently, there are more than 25 licensed AEDs in clinical practice in the developed world, compared to few registered AEDS in Sudan, most of which are old generation AEDs, although older generation medications are still effective even in comparison to newer generation AEDs, the newer generation have less side effects and are more tolerable [9]. Tolerability and adverse effects are a major influence on compliance, and discontinuation of therapy, therefore increasing morbidity and mortality in people with epilepsy.
The use of AEDs is influenced by the pre-existing belief system that pushes people towards traditional herbals and local healers [3], with some believing the medication is useless while others consider s it to be undermining of the more trusted traditional methods. However, among those who would have access to proper medical help, and those who appreciate the need for medication, other factors further affect the treatment gap and challenge adherence to medication. Patients who are seizure free for a long duration or those taking more than one medication may fail to adhere to therapy or omit doses.
Descriptive analysis of cost-benefit for some patients indicates that their concern about the high price of the medication greatly outweighs the need for the drug, and would as a result seek free samples provided by charity organizations, while some patients fail to obtain the drug [10]. Antiepileptic drugs represent a tremendous economic burden on families of patients with epilepsy. The yearly cost of AEDs alone falls not less than 276 US dollars per patient per year, while visitations and consultations along with investigation could reach 51 dollars. Other indirect costs can include travel, for those who live far from the capital, reaching up to 90 dollars. Insurance rarely helps and patients find themselves forced to sell valuable assets like one’s cow or shop to cover the expenses, and many find themselves in debt. All of these factors need to be accounted for by the patient and caregivers and affect adherence negatively [11].
Access to AEDs like other medications in Sudan was subject to variations related to inflation and other complex geopolitical factors, resulting in fluctuating prices in the period from 2009 to 2013 (6 times change in pricing). And while the general market dynamics in the country were somewhat fluctuant, the general indicators of regional macroeconomics have been declining steadily (e.g. GDP in dollars) following factors like change in market policies, conflicts in the south leading to loss of big fractions of the country’s’ resources, up to the more recent financial crisis in the country in the period 2018-2020, where cash was virtually inaccessible to the public, making all medications into a luxury, and culminating in an event of pharmaceutical scarcity of drugs, despite the government’s best efforts to mitigate the impact of the economic situation [12]. Some policies had a relatively positive effect, like price liberalization privatization of the sector. And while reports and studies are yet to fully estimate the on-going catastrophe, the global status of lock-down and quarantine due to the COVID-19 pandemic certainly made it more challenging to get access to medical care or self-management for (PWE) in such a collapsing healthcare system [13].
Stigma is the social outspoken or perceived labeling of an individual or a group of people according to true or presumed different characteristics attributed to specific health related and non-health related conditions, rendering these individuals incapable of leading equal lives to their peers in society [14, 15].
Components of stigma include behavioral, emotional and cognitive elements that are portrayed in patients responses or attitudes and their interaction with society [16]. The burden of stigma unfolds in both active and passive manners, those who discriminate and those facing discrimination can inflict stigma after being subjected to it. This gives rise to the different entities of stigma and its effects on different life attributes of stigmatized individuals in society [15].
The manifestations and impact of stigma in the attitude form further branches it into perceived, anticipated, and internalized stigmas, while the social form of stigma includes the enacted or experienced stigma. Perceived stigma describes one’s thoughts or self-image perceived through the eyes of those surrounding one’s life regarding an acknowledged distinguishing characteristic [16]. Anticipated stigma refers to a presumed inappropriate response in the form of an act of discrimination or labeling in a social setting to one’s condition by others. Internalized stigma denotes self-inflicted discrediting and undermining due to awareness and acknowledgment of one’s difference. Experienced or felt stigma refers to consequences of an act of labeling or discrimination that was made intentionally to point out a stigmatizing characteristic [14, 16, 17].
Stigma is a major social determinant of health, attributing to disease morbidity, mortality and to the successfulness of healthcare services [18].
Elements that articulate the complex process of health conditions related stigma include illness nature, it’s course, and characteristics that represent origins of stigma; population related elements; treatment modalities and healthcare providers sought for consultation; reactions as well as coping mechanisms of stigmatized individuals to social acts of discrimination that may take a toll on their identity, social life, and economic thriving [17, 19, 20].
What is not so clearly defined however, is the relationship between stigma and healthcare outcomes, attributing to stigma being an entity that while having similar grounds in most health related conditions, its effects can be as illness specific as exclusive features of that illness, often referred to as the hidden burden of an illness, and this is an area that is deficient in research data [21, 22].
Health related stigma, can be visualized more clearly in communities where compensation of one’s health condition related disability is lacking. These compensations aim towards minimizing the gap between individuals with disabling health conditions and their peers in community. Communities where efforts to minimize this gap are lacking are mostly those of low-income economical index [20].
Stigma adversely affects individual health outcomes as well as related life chances, including educational opportunities, employment, housing, and social relationships. It has also been shown to negatively affect help- and treatment-seeking behaviors, compromising the ability to treat and prevent stigmatized health conditions. Masking of research on illness specific stigma under the generalization of its nature has limited the ability to understand the overall impact of stigma on individual wellbeing and the overall disease burden, restricting the ability to develop interventions addressing stigma, and this masking is amplified especially in low-income countries, because of the lacking resources available to healthcare research and services in general [20, 23].
Stigma affects caregivers of individuals being stigmatized, be it their families, relatives or close companions. Caregivers of patients in low-income countries suffer a heavier burden due to lacking national health agencies support, which widens the gap between illness-limited individuals and their peers in society, further enforcing stigma as well as worsening the financial burden. All these elements associated with stigma in low income countries develop a synergistic effect, in which each element contributes to the vicious cycle of further reducing the quality of life of stigmatized individuals [23].
The weight and burden associated with epilepsy in terms of stigma manifests with variable intensities and forms across different age groups and communities [6, 24].
Developmental aspects of one’s life including physical, mental and social development, and their bases of parenting by one’s family, education and an uninterrupted social learning experience, are affected differently with various onset age groups of epilepsy. For example, having a child with epilepsy puts tremendous pressure on the family and caregivers, especially in a low-income country where taking care of an illness free child can be troublesome. This leads to stressful parenting, creating many obstacles for a child who has epilepsy to develop at a normal rate. A child with epilepsy has a higher chance of academic underachievement, which would setback building of self-esteem and eventually in conjunction with other epilepsy related elements leads to enforcement of stigma and further disability and unsuccessful treatment, in contrast to adolescence onset of epilepsy which would have a different impact on their quality of life and would manifest in different aspects like social withdrawal despite being in a functional social and economic status. Adulthood onset of epilepsy and the manifestation of stigma associated with it could be less severe than childhood and adolescence onset and would affect one’s ability to be involved in certain elements of society, but could also be devastating in certain low-income regions with plummeting education and awareness levels, for example not being able to have a spouse in a low-income community where having epilepsy is thought to be of demonic possession [1, 6, 24].
Epilepsy in Sudan accounts for 1.6 annual mortality rates and 238.7 disability adjusted life years per 100,000. It is associated with notable stigma and social burdens. Patients with epilepsy suffer a tremendous burden of social discrimination adversely affecting their quality of life [6]. These patients are subject to being denied equal chances to a dignified life following neglect, isolation and lack of national healthcare support.
As studies in Sudan regarding epilepsy are primarily focused on clinical presentation of epilepsy, no in depth illustration or correlation between stigma of epilepsy and the outcome of epilepsy healthcare have been conducted.
However, some of the magnitude of epilepsy stigma in the Sudanese population has been captured across the different age groups of patients with epilepsy in urban and rural areas.
A study conducted by Taha et al. to identify epilepsy related stigma in the Sudanese community and to find correlation between penetrance of the type of stigma on patients through stigma degree scoring, have detected that approximately 16% of both men and women with epilepsy suffer from highly precipitated felt stigma. 12.5% of remaining patients of epilepsy who did not suffer from felt stigma have noted the common belief in their communities of the contagious nature of epilepsy while 56.2% declared their communities believed epilepsy was of demonic possession, 13% mentioned people were afraid from them when they were having seizures in public and hence they do not help them. The Sudanese community surrounding patients with epilepsy also showed poor respect to patients’ privacy evident with 77.4% of patients stating that despite not disclosing their condition, it was publicly known. Where expected least, Sudanese communities showed an alarming response to children with epilepsy from their teachers and mentors, as 22% of patients at primary school age mentioned that their teachers treated them badly. Two out of three patients with epilepsy were found to have either courtesy or coaching stigma, which represent enacted stigma of parents and guardians of patients with epilepsy, and this translates into a boosting effect for all forms of stigma being enforced in epileptic patients having their caregivers constantly reminding them of their condition. Patients who stated that their disease hindered their progress in life and those who expressed frustration and stress were found to be more than those who could cope with their condition, and this was significantly associated with a high seizure frequency. This shows that poor control of seizures inevitably diminishes the ability of patients to conceal their condition, leading to more discrimination and exacerbation of stigma [1].
An important implication of living in a resource-limited country is deficiencies that could be noted across all social services especially healthcare services. Muwada Bashir et al. portrayed a brilliant scope in their study of detecting the quality of life of Sudanese patients with epilepsy under the burden of inequalities of healthcare services, which showed that stigmatization, social discrimination and inadequate health services are major problems that Sudanese patients with epilepsy and their families confront in their daily life. The study concluded that stigma among other factors associated with epilepsy is worsening the burden on both patients and caregivers by crippling their healthcare services accessibility and by increasing efforts of coping with the disease in a society with a culture that is shaped by a low economic status [6].
Children constitute the main domain of people with epilepsy; this subpopulation faces many challenges. These challenges begin with the different etiologies of epilepsy in Sudan and Africa, of these etiologies central nervous system infectious agents (malaria, onchocerciasis), and perinatal insults constitute the main causes of epilepsy. Such causes could explain why the majority of people with epilepsy are in Africa. In addition, these causes along with other factors contribute to the poor outcome of epilepsy in the developing world.
Children with epilepsy have comorbidities including autism, intellectual disability that could be caused by perinatal insults and cerebral palsy; they are also more vulnerable to physical and sexual abuse. Studies from Sudan demonstrated that 10% of children with epilepsy have associated attention deficit hyperactivity disorder (ADHD) [25], one third had learning disabilities, and 10% had motor disabilities [26], theses comorbidities represent the difficulty in the management of these children, as a multidisciplinary approach is required in management, which is usually unavailable in Sudan and the developing world.
Since the 1950s, children with neurological disorders were seen in adult neurology clinics, as pediatric neurology training program in Sudan has recently been initiated, with a few pediatric neurologists available.
Currently there is one pediatric neurology tertiary center and four specialized child neurology clinics in Sudan, 3 of them are located in the capital, these 4 clinics serve the whole of Sudan, as well as referred patients from neighboring countries including: Chad, Eretria, and South Sudan where facilities for neurological investigations are limited. The shortage of pediatric neurologists and pediatric neurology centers and their location mainly in the capital, along with the high cost of transportation to the center, long waiting lists till evaluation by a specialist, further complicate the management of children with epilepsy [8].
It is important to review epilepsy status in school settings where children spend most of their time. Schools in Sudan rarely have dedicated clinics to accommodate children’s health needs, and while school teachers should act as caregivers, most of them are usually ill-informed or lacking appropriate knowledge about epilepsy, and none of them have had any sort of training to help in case of a seizure, so a considerable proportion does not know what to do when a child develops a seizure [27, 28]. Many teachers fall as victims of the communities’ misconceptions and could even play a passive role in the stigma, contributing to the child’s anxiety. Many had no idea about possible causes of epilepsy and guessed that parents would not sign up their children with epilepsy to school due to suspected mental sub-normality, stigma, or fear of unattended falls or attacks. On the other hand, figures demonstrated a significant amount of children ditch school altogether because of the illness. Other students do not mind having a classmate with epilepsy at school but they share their teachers’ beliefs and misconceptions, and would sometimes, as a result, engage in bullying and discriminatory behaviors against them. The condition is barely touched in school curriculums and students do not undergo any sort of training to help them act properly around their peers who have epilepsy.
Globally, 50% of women and girls with epilepsy are in the reproductive age range [29]. Epilepsy in the developing countries has a slight male predominance; this is likely due to underreporting of epilepsy in women due to negative attitudes and stigma facing them, that include difficulties in getting married, increased divorce rates, having children or even being abandoned by their families because of their illness, and harder chances of being employed. This underreporting of epilepsy in women leads to deficits in health care seeking behavior, hence contributing to the epilepsy treatment gap in women.
Apart from the aforementioned social difficulties, women with epilepsy are challenged with many issues that include the effect of epilepsy and AEDs on their sexual function, contraception, pregnancy, fetal abnormalities, childbirth, and breastfeeding [30, 31, 32, 33].
Due to the shortage of neurologists in Sudan, the majority of women with epilepsy are managed and counseled by non-specialized doctors. A study conducted in Sudan to assess doctors’ knowledge of women issues and epilepsy using standardized knowledge of women issues and epilepsy (KOWIE II) questionnaire concluded that the majority of Sudanese doctors’ knowledge was unsatisfactory. They were unaware of sexual dysfunction among women with epilepsy, that women with epilepsy should continue taking their AEDs when they are pregnant, and that women can safely breastfeed while taking AEDs [34].
Sudan has been a victim of war, poverty, substandard infrastructure, and a failing healthcare system. These factors along with epilepsy stigma, misconceptions and false believes represent major challenges in epilepsy management in Sudan.
All these challenges must be approached systematically to ensure the best management for patients with epilepsy. Such approaches include the need for a mass movement against epilepsy headed by individuals experienced in the field, and fundamental governmental partnership and aid to provide organizational efforts and funding for instituting and decentralizing neurology facilities outside Khartoum, and ensuring the availability and affordability of investigations and medications especially the new generation AEDs. Epidemiologic studies are needed to outline the treatment gap of epilepsy and guide nationwide strategies and efforts to increase the awareness of communities about epilepsy are needed especially in the rural areas to fight disease stigma, Special groups need further attention such as making efforts for prevention of infections leading to epilepsy in children, the involvement of other healthcare providers such as social workers, speech and language therapists, nutritionists, and special teachers in the management of children with epilepsy can never be overemphasized. Lastly, telemedicine should be implemented in the management of epilepsy in Sudan.
The authors declare no conflict of interest.
Ismat Babiker wrote the following sections: children with epilepsy, women with epilepsy, co-wrote AEDs in Sudan, and contributed in chapter editing.
Awab Saad wrote Sudan: background and population, healthcare system in Sudan, Neurology in Sudan, co-wrote epilepsy misconceptions in Sudan, and contributed in chapter editing.
Basil Ibrahim wrote stigma, health related stigma, manifestation of stigma in high vs. low-income countries, stigma in low-income countries and in Sudan, and contributed in chapter editing.
Mohamed Abdelsadig wrote the collapse of the healthcare system in Sudan, epilepsy in schools, scarce personnel and trained physicians, co-wrote AEDs in Sudan, epilepsy misconceptions in Sudan, and contributed in chapter editing.
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I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. 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I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. 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