\r\n\tThe protection of biodiversity is a major target of the European Union Marine Strategy Framework Directive, requiring an assessment of the status of biodiversity on the level of species, habitats, and ecosystems including genetic diversity and the role of biodiversity in food web structure and functioning. The restoration of marine ecosystems can support the productivity and reliability of goods and services that the ocean provides to humankind, to maintain ecosystem integrity and stability. Some of the goods produced by the marine ecosystem services are fish harvests, wild plant and animal resources, water, some of the services provided recreation, tourism, breeding and nursery habitats, water transport, carbon sequestration, erosion control, and habitat provision.
",isbn:"978-1-83968-460-9",printIsbn:"978-1-83968-459-3",pdfIsbn:"978-1-83968-544-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"727e7eb3d4ba529ec5eb4f150e078523",bookSignature:"Dr. Ana M.M. Marta Gonçalves",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10845.jpg",keywords:"Non-indigenous Species, Dynamics, Ecosystem Maturation, Ecological Succession, Water Quality, Recovery, Biodiversity, Environmental Status, Ecosystem Services, Goods Production, Carbohydrates, Carrageenan",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 14th 2022",dateEndSecondStepPublish:"June 22nd 2022",dateEndThirdStepPublish:"August 21st 2022",dateEndFourthStepPublish:"November 9th 2022",dateEndFifthStepPublish:"January 8th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Ana Marta Gonçalves (h-index 19) holds a Ph.D. in Biology, from the University of Coimbra, Portugal, in collaboration with Ghent University, in 2011. During her research career obtained several grants is highly international competitive calls, including the MARS award for young scientists funded by The Royal Netherlands Institute for Sea Research (NIOZ) and the Foundation for Science and Technology (FCT, Portugal) grants.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"320124",title:"Dr.",name:"Ana M.M.",middleName:"Marta",surname:"Gonçalves",slug:"ana-m.m.-goncalves",fullName:"Ana M.M. Gonçalves",profilePictureURL:"https://mts.intechopen.com/storage/users/320124/images/system/320124.jpg",biography:"Ana Marta Gonçalves obtained a Ph.D. in Biology with a specialization in Ecology from the University of Coimbra, Portugal, in collaboration with Ghent University, Belgium, in 2011. Currently, she is an auxiliary researcher at the Marine and Environmental Sciences Center (MARE), Portugal, where she is also a member of the Directive Board. Since 2016, she has been a member of the Scientific Council of the Institute for Interdisciplinary Research, University of Coimbra (IIIUC). Dr. Gonçalves holds various administrative and management positions in international networks, societies (e.g., Society of Environmental Toxicology and Chemistry, AIL), and associations (e.g., PROAQUA). She is an editorial board member and reviewer for several indexed journals. She has published more than 70 journal articles, 50 book chapters, and 165 communications in international scientific events. She participated as a member and/or coordinator in more than twenty-five national and international projects and is currently the coordinator of four research projects. She has supervised more than ninety-five national and international undergraduate and graduate students. She has experience as a teacher of university courses and in accredited training sessions for teachers. Additionally, she has coordinated several ocean literacy and environmental education activities for kindergarten and school students. During her research career, Dr. Gonçalves obtained several grants and a MARS award for young scientists funded by The Royal Netherlands Institute for Sea Research (NIOZ).\n\nShe has expertise in biosafety, biochemical pathways, and impacts of stressors in aquatic species. Her research focus is on the valorization of marine resources and their applications in the industrial sector, such as the food and pharmaceutical industries. Her studies also highlight the application of biomarker tools for monitoring and managing aquatic systems",institutionString:"University of Coimbra",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Coimbra",institutionURL:null,country:{name:"Portugal"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"12",title:"Environmental Sciences",slug:"environmental-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"278926",firstName:"Ivana",lastName:"Barac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/278926/images/8058_n.jpg",email:"ivana.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],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:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"117",title:"Artificial Neural Networks",subtitle:"Methodological Advances and Biomedical Applications",isOpenForSubmission:!1,hash:null,slug:"artificial-neural-networks-methodological-advances-and-biomedical-applications",bookSignature:"Kenji Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/117.jpg",editedByType:"Edited by",editors:[{id:"3095",title:"Prof.",name:"Kenji",surname:"Suzuki",slug:"kenji-suzuki",fullName:"Kenji Suzuki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3828",title:"Application of Nanotechnology in Drug Delivery",subtitle:null,isOpenForSubmission:!1,hash:"51a27e7adbfafcfedb6e9683f209cba4",slug:"application-of-nanotechnology-in-drug-delivery",bookSignature:"Ali Demir Sezer",coverURL:"https://cdn.intechopen.com/books/images_new/3828.jpg",editedByType:"Edited by",editors:[{id:"62389",title:"PhD.",name:"Ali Demir",surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"872",title:"Organic Pollutants Ten Years After the Stockholm Convention",subtitle:"Environmental and Analytical Update",isOpenForSubmission:!1,hash:"f01dc7077e1d23f3d8f5454985cafa0a",slug:"organic-pollutants-ten-years-after-the-stockholm-convention-environmental-and-analytical-update",bookSignature:"Tomasz Puzyn and Aleksandra Mostrag-Szlichtyng",coverURL:"https://cdn.intechopen.com/books/images_new/872.jpg",editedByType:"Edited by",editors:[{id:"84887",title:"Dr.",name:"Tomasz",surname:"Puzyn",slug:"tomasz-puzyn",fullName:"Tomasz Puzyn"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3569",title:"Biodegradation",subtitle:"Life of Science",isOpenForSubmission:!1,hash:"bb737eb528a53e5106c7e218d5f12ec6",slug:"biodegradation-life-of-science",bookSignature:"Rolando Chamy and Francisca Rosenkranz",coverURL:"https://cdn.intechopen.com/books/images_new/3569.jpg",editedByType:"Edited by",editors:[{id:"165784",title:"Dr.",name:"Rolando",surname:"Chamy",slug:"rolando-chamy",fullName:"Rolando Chamy"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"69080",title:"Concepts for Designing Tailored Thin Film Surfaces with Potential Biological Applications",doi:"10.5772/intechopen.89092",slug:"concepts-for-designing-tailored-thin-film-surfaces-with-potential-biological-applications",body:'\nThe interfacial region of a real system interacting with the environment determines many of its properties [1]. The control of the structure, topography, composition, charge density and distribution, wettability, and the viscoelastic properties at the interface plays a key role in determining the ultimate characteristics of a material interacting with a biological system [2]. Thus, thin films and coatings can be used to obtain tailored interfaces with nanoscale controlled properties with the aim of generating systems with different complexity and specific functionalities of biological interest. This issue is of particular interest for engineering material surfaces with potential biomedical applications as implants or medical devices, or platforms for fundamental studies at the cell level [3, 4, 5, 6].
\nBiological entities, such as proteins, prokaryote, or eukaryote cells, are expected to interact with a material when the material is in contact with biological fluids or tissues. In the case of the interaction of cells with an interface, the triggered biochemical signals that generate spatial and temporal changes in the interaction process should be considered [7]. Cells appear to be smart macromolecular systems that trigger cooperative phenomena upon interaction with a substrate with particular physicochemical and biochemical properties.
\nDepending on its specific applications, a proposed biocompatible material is required to enhance or inhibit protein and cell adhesion. For instance, interfacial properties of materials for implants should promote tissue-material integration [8] and avoid bacterial infections [9]. Moreover, for many medical devices to act as barriers, antiadherence and antifouling characteristics are needed [10, 11].
\nIn recent years, the combination of new and improved techniques for patterning a substrate [12, 13], spatially controlling the deposition of a material [14], supramolecular synthesis [15], as well as new assembling procedures to fabricate tunable films at the nanoscale [16, 17], has allowed the introduction and control of spatial and temporal, physicochemical and biological cues. It has been possible to wisely design materials to (i) modulate and study cell behavior and fate [18, 19, 20, 21], (ii) deliver, release and sense bioactive molecules [22, 23, 24, 25], and (iii) increase the biocompatibility and functionalities of materials and devices [26, 27]. In many situations, the tailored system properties depend on both the characteristics of the pristine substrate and those of the coating. Typical examples (Figure 1) are presented to show some design strategies, without pretending to be complete, as a large number of systems are possible: (a) a thin film is coated onto a rigid substrate to improve biocompatibility; (b) the thin film can be used to modulate the viscoelastic properties of the system; (c) a rigid substrate is modified by a coating containing species that can be internalized by cells or are released to the medium; (d) the thin film controls the release of molecules from a solid substrate underneath; (e) the thin film is a porous material capable of releasing drugs encapsulated in the pores; (f) the thin film is tailored with species interacting specifically with a target; (g) either an underneath or an upper thin film bearing actuator moieties are responsive under external stimuli that trigger a change in the properties of the system; and (h) nanotopographic characteristics with spatial control can be introduced in the substrate surface. The topographic features can be combined with a thin film, and physicochemical properties such as specific moieties, stiffness, charge, and wettability can be tuned.
\nDifferent strategies of thin film biological applications. (a) Organic and inorganic thin films that modify the interfacial properties toward cell behavior. (b) Stiffness modulation by organic thin films. (c) Thin film as cargo systems. (d) Thin film to control biomolecule release from a porous substrate. (e) Porous organic thin film for biomolecule release. (f) Thin film for “target” delivery. (g) Responsible thin films under either a direct or indirect stimulus. (h) Morphological features that can be incorporated by a thin film.
In the next sections, we will first give a brief comment about the desired biocompatibility of new proposed materials and survey some materials to fabricate thin films for biological applications. Then, we will depict the material properties that affect cell behavior and conclude with some examples of thin films to modulate cell behavior.
\nThin films with potential applications in biology need to be biocompatible. There are many definitions for biocompatibility, but generally it is meant to refer to a material that is expected to carry out a suitable response in the host biological environment without producing any undesirable effects [28]. Different assays are performed to test the biocompatibility of a material, including in vitro experiments of cell proliferation and adhesion, interaction with biological fluids, and in vivo performance evaluation of the material function in model animals and its inflammatory response [29].
\nMany of the thin film materials presented in this chapter have potential applications but require further research for good biocompatibility.
\nA wide variety of inorganic thin films and coatings have been proposed to be used in biology, including pure metals, alloys, metallic compounds, carbon-based thin films, oxide layers, and ceramic materials [3].
\nTitanium and its alloys are the most important materials for biomedical applications, particularly as bulk metal with proper surface modifications. Titanium oxide (TiO2) and titanium nitride (TiN) coatings are very appealing as they form bioinert layers, protect substrates from corrosion and promote desirable biological functionalities, such as osteoblast adhesion and proliferation and apatite formation.
\nMesoporous titania surfaces and nanotubular titania layers are appealing for biomedical applications since both titanium and titania exhibit good biocompatibility and are commonly utilized for biomedical devices and implants. Pores in the mesoporous titania can be designed for the encapsulation of drugs for delivery, growth factors, and antibiotics that can either facilitate cell material interaction or inhibit the presence of bacteria.
\nGold and platinum metallic coatings are also used as microelectrodes to monitor signals from neurons and evaluate the electrophysiological activity of the neuronal network. Platinum-based thin films are also employed for pacemakers, implanted defibrillators, stents, and hearing assist devices, due to their good electrical conduction and biocompatibility.
\nBioceramic thin films are used for coating implants and prostheses, as they exhibit good corrosion resistance and better bioactivity than the metal substrate. Bioceramic thin films deposited on Ti prostheses yield better integration and bone growth in comparison with the bare metal. Some bioceramics utilized in patients are bioinert, for example, oxide and silicon ceramics. Other ceramics are resorbable, as is the case of calcium phosphates, and others are bioactive, such as bioglasses and hydroxyapatite.
\nCarbon-based materials, that is, diamond-like and carbon nitride thin films are potential materials for coating substrates for biological applications as biomedical devices. Diamond-like carbon shows lower platelet adhesion than carbon nitride. Despite this, carbon nitride thin films are able to yield harder coatings.
\nUnlike diamond-like and carbon nitride thin films that are amorphous carbon materials, nanocrystalline diamond thin films allow the tuning of their crystalline structure and can mimic the surface roughness of bone. These films also provide high chemical and corrosion resistance, making them very appealing for biological applications.
\nCarbon nanotubes and graphene sheets are promising materials for biomedical applications [30], presenting new opportunities due to their unique mechanical, electrical, and optical properties. Furthermore, carbon-based nanomaterials can mimic the microenvironment provided by the biological extracellular matrix [30]. These systems have been extensively studied as drug/gene delivery vehicles for anticancer treatments.
\nIt has also been reported that graphene can favor the osteoblast linage of mesenchymal stem cells (MSCs) [31] and increases the rate of human MSCs osteogenic differentiation by a similar magnitude to bone morphogenic protein, BMP-2 [32].
\nOrganic thin films, particularly those of natural origin, are very appealing for creating a biocompatible interface and are potentially suitable for biological applications. The drawback of these materials is their poor mechanical properties, as they resemble soft biological tissues. Soft materials are characterized by a limited cell adherence. Thus, they are often modified to fulfill the requirements of their intended application.
\nExamples of polymers used for thin film fabrication include the following:
Extracellular matrix components. For instance, collagen, fibronectin and laminin, growth factors and glycosaminoglycans, among others.
Zwitterionic polymers, which display an equal number of cationic and anionic groups making them hydrophilic and antifouling.
Polyethylene glycol-modified polymers (PEGylated polymers) and hyperbranched polymers with oligosaccharide surfactant hydrophilic moieties, which result in antifouling coatings.
Thermoresistive polymers derived from poly(N-isopropyl acrylamide) (PNIPAM) [33].
Polymers employed in the fabrication of devices (such as biosensors), used to prevent nonspecific adhesion of biological materials forming hydrophilic/hydrophobic layers, namely polydimethylsiloxane (PDMS), polyethylene (PE), perfluoropolyethylene (PFPE), polyimide (PI), parylene C, polyetheretherketone (PEEK), cyclic olefin/copolymer, poly(methyl methacrylate) (PMMA), polypropylene (PP), and polystyrene (PS) [34].
Polyelectrolyte multilayers (PEMs) of either synthetic or natural polyelectrolytes assembled by the versatile layer-by-layer (LbL) techniques driven by different molecular forces, that is, electrostatic or hydrogen bonding. The LbL technique allows the combination of different materials as building blocks and a wide variety of substrates can be coated.
Hybrid nature-inspired inorganic/organic materials have been fabricated, that is, layered systems can include metallic nanoparticles and nanotubes, mesoporous materials with organic moieties, hydrogels with in situ synthesized nanoparticles, etc. These systems can benefit from the multiple functionalities that can be carried by the nanomaterials to enhance gene delivery [35], imaging [36], and alternative disease treatments [37]. Furthermore, meso- and nanostructured titanium-based materials can be used to fabricate hybrid static and dynamic systems that include bioactive molecules as well as polymeric films to increase the material functionalities [21]. This approach is suitable to tackle the important issue of the miniaturization of medical devices.
\nA scheme of the classification of materials utilized to fabricate thin films of biological interest is depicted in Figure 2.
\nClassification of materials for thin film coatings and applications.
Living cells in an organism are sensitive to the environmental properties defined by neighboring cells and the extracellular matrix (ECM) [38]. Proteins play a key role in the cell sensing process of the microenvironment characteristics. For instance, cells are able to sense the viscoelastic and topographic properties of the environment through transmembrane proteins such as integrins [39]. Furthermore, growth factors, hormones, antibodies, vitamins, and other bioactive molecules can interact with specific cell receptors and induce a certain cell phenotype [40].
\nIn general, cells in contact with a substrate interact with it through proteins deposited on the substrate. These proteins come from biological fluids or are produced by the cell itself upon interaction with the substrate [41]. Furthermore, in most of the experimental conditions employed for cell/material interaction studies, cells are cultured in medium supplemented with fetal bovine serum, and therefore, serum proteins interact with the substrate moieties. Among these proteins, bovine serum albumin (BSA) and fibronectin (FN) are usually considered as an example of nonadherent and adherent protein models, respectively.
\nCell adhesion is the first step of many physiological and pathological processes such as wound healing, bacterial infections, and tumor progression. Eukaryote cell adhesion is possible if the intracellular forces exerted by stress fibers are balanced by the substrate stiffness [42]. The effect of the substrate stiffness is cell-type dependent, while adhesion of some cell lines is sensitive to changes in the substrate mechanical properties, other cells are less influenced [43]. Cells are able to sense the forces exerted by the environment and transduce them into biochemical signals; the study of this process is relatively recent and can profit from new actuator microdevices such as microelectromechanical systems (MEMs) constructed with new biomaterials and methods to avoid toxicity [44].
\nOn the other hand, cells can sense the stiffness of objects that are not in direct contact, depending on the compliant polymer thickness and its physicochemical properties [45]. Thus, cell adhesion can be modulated by depositing a compliant soft polymer upon a stiff support with controlled topography and by varying the thickness of the soft polymer [46]. Cells sense the stiffness that is the result of the combination of the stiffness of both the upper soft polymer and the rigid substrate underneath, namely “complex stiffness.”
\nThe cell adhesion characteristics and subsequent cell functionalities will depend strongly on the physicochemical properties of the biomaterial surface. In the next paragraphs, a brief survey of these properties will be given.
\nFor highly hydrophobic surfaces, the amount of adsorbed protein is relatively large, but the intra-protein interaction and the protein/substrate interaction are high and may produce denaturing or hamper remodeling from cells.
\nOn more polar hydrophilic surfaces, proteins adsorb in relatively low concentrations diminishing inter-protein interactions and preserving their native state. However, it has been observed that on highly hydrophilic surfaces, cell adhesion is limited and even completely unviable. In this case, the adhesion proteins are labile as relatively weak forces take place. This would cause the detachment of cells particularly when the monolayer density is high [2].
\nIt has been reported that for UV-irradiated polytetrafluoroethylene in a NH3 atmosphere, the generated positive charge interacts synergistically with oxygen-containing groups, and the adhesion of mouse 3T3 fibroblast, human umbilical vein endothelial cells, and human embryonic kidney cells is stimulated [47, 48, 49].
\nOther works reported that the presence of carboxylate groups added to a copolymer of poly(dl-lactic acid) and poly(ethylene oxide) enhances rat aortic smooth muscle cells in comparison to a noncarboxylated surface [50]. The carboxylate groups may not only bring negative charge to the interface but they also increase its wettability to values suitable for cell adhesion [51].
\nIt has been observed that bovine aortic endothelial cells adhere with a larger spreading area when the modified substrate bears a larger number of positively charged amine groups than negative carboxylate ones, both attached to self-assembled monolayers of alkanethiols [52]. In this work, the authors reported that the amount of osteopontin proteins adsorbed on both modified surfaces was very similar, thus they suggested that the orientation and geometrical conformation of osteopontin was more suitable for cell adhesion to the amino group-containing positive surface.
\nCell adhesion is insensitive to the macroroughness as cells are able to adhere to or between the surface irregularities that are larger than cells.
\nThe micro-/submicroroughness significantly affects cell behavior as reviewed elsewhere [7]. Some studies have reported a positive influence of surface microroughness on cell adhesion, whereas in other studies, its influence has been shown to be negative. For instance, rat osteoblasts on microporous surface of titanium dental implants exhibited an increased average cell spreading area in comparison with flat surfaces [53]. Similarly, human osteoblast-like MG-63 cells cultured on Ti substrates with microroughness showed a more differentiated phenotype as a large expression of alkaline phosphatase (ALP), osteocalcin, and the faster production of an osteogenic environment were observed [54].
\nIn contrast, a Ti-based alloy with microroughness exhibited poorer adhesion characteristics and decreased proliferation of MG-63 cells than flat surfaces [54].
\nThese contradictory results are partially caused by the lack of systematic research work on the effect of micro-/submicroroughness, in part due to the ambiguity of the parameters used to characterize the surface roughness.
\nFinally, the nanoroughness of a biomaterial surface has been reported to have a beneficial influence on cell adhesion in a large number of papers. This fact occurs because nanoroughness resembles many aspects of the ECM morphological features. It appears that the proteins that induce cell adhesion adsorb on the biomaterial surface with the appropriate conformation for presenting specific sites, that is, Arg-Gly-Asp, to cell membrane receptors [2].
\nSynthetic polymers such as polyacrylamide (PA) with modified stiffness have been utilized to study MSC differentiation. These cells differentiate into neurons on soft PA gels, myoblast on gels of intermediate stiffness and bone cells on stiffer gels [57].
\nPEM mechanical properties can be improved by adding layers of “hard” polyelectrolytes [58], properly changing the pH and the ionic strength during assembling [59], by cross-linking the layers [60], or incorporating nano-objects into the multilayer structure [20, 61]. In these cases, some of the reagents employed may be toxic and add additional synthesis steps.
\nIn recent papers, we reported about the effect of thermal annealing of PEMs on the adhesion of different cell lines [62]. We employed polycationic terminated PEMs made up of 15 layers, (polycation/polyanion)7polycation: poly-l-lysine (PLL)/alginate (Alg); PLL/dextran sulfate (DEX) and chitosane (Chi)/hyaluronic acid (HA). By treating PLL/Alg and PLL/Dex PEMs at 37°C for 1–3 days, we reported an enhancement of cell adhesion. The cytoplasm spreading area of A549 and C2C12 cells on unannealed PLL/Alg films is poor, while cells seeded on annealed (PLL/Alg)7PLL PEMs present an extended cytoplasm with well-defined focal contacts and large actin fibers, like cells seeded on glass. In contrast, annealed Chi/HA PEMs exhibit a hampered adhesion of A549, C2C12, BHK, and MC-3T3 cells [26]. The advantage of this strategy is the absence of toxic substances and the simplicity of the procedure.
\nRecently, a well-characterized PEM based on poly(4-styrenesulfonic acid) (PSS) and poly(diallyl dimethyl ammonium chloride) (PDADMAC) has been employed to demonstrate the dynamic nature of the interface interacting with cells and the key role played by the strength of the interaction of proteins with the substrate [63]. Cells are able to sense the stiffness of the substrate provided they attach to adhesion proteins that are adsorbed on the interface with sufficiently high interaction energy. In this work, the authors measured an abrupt change in cell adhesion by varying the number of deposited layers (PEM thickness) rather slightly but maintaining its roughness constant, pointing out that the stiffness of the substrate was not an important property in the observed adhesion behavior, but rather the competition of proteins from the culture medium with preadsorbed ones. For these experiments, the authors used PEMs with variable surface charge and protein radiolabeling.
\nThermal annealing results in the reorganization of PEMs, the polyelectrolytes rearrange in the multilayers from a stratified organization to molecular complexes of polycations and polyanions, where the interaction between oppositely charged polyelectrolytes is maximized [64]. For the case of PLL/Alg PEMs (Figure 3a and c), thermal annealing increases the stiffness of the film, increases the contact angle to about 90°, augments the negative charge, and renders a relatively flatter surface. Nevertheless, for both preadsorbed FN from a solution of FN alone and from a solution of FN and BSA, thermal annealing of PLL/Alg PEMs increases the stability of adsorbed FN as demonstrated by gamma counting of radiolabeled proteins and protein exchange assays. Furthermore, circular dichroism studies indicated that upon annealing, there is likely a larger number of arginine-glycine-aspartate (RGD) groups from FN that are able to interact with cell membrane integrins to favor cell adhesion [65].
\nCell adhesion modulation on unannealed and annealed (PLL/Alg)7PLL and (Chi/HA)7Chi PEMs. (a) Contrast phase images of A549 cells adhered to unannealed and annealed (PLL/Alg)7PLL. The respective atomic force microimages are included. (b) Cell adhesion and atomic force images for unannealed and annealed (Chi/HA)7Chi PEMs. (c) Physicochemical and fibronectin (FN) adsorption properties of unannealed and annealed (PLL/Alg)7PLL and (Chi/HA)7Chi PEMs.
In the case of Chi/HA PEMs (Figure 3b and c), the changes in physicochemical properties are significantly smaller after annealing than for unannealed PLL/Alg PEMs. The interface remains hydrophilic, the contact angle decreases from 30 to 21°, the charge becomes slightly more negative, and the stiffness remains unchanged. Contrarily, there is a significant change in the root mean square (RMS) roughness for annealed Chi/HA PEMs compared with unannealed Chi/HA PEMs: the RMS roughness decreases to half the value measured for unannealed films. This topographic change is expected to cause different interactions of the PEM surface with cells after annealing, increasing the antiadherent properties. For Chi/HA PEMs, we also conclude that thermal annealing reduces the interactions between adhesion proteins and the PEM interface, the reverse effect of that observed for PLL/Alg PEMs.
\nOne of our goals in this work was to relate the changes in cell adhesion upon annealing of PEMs to the deposition and stability of adhesion and nonadhesion proteins and rationalize the effect of the changes in the physicochemical properties of PEMs on cell adhesion.
\nCells are able to expand due to proper forces applied to the substrate for increasing cell cytoplasm tension. Thus, cells sense the increase in the Young’s modulus of PLL/Alg films upon annealing provided adhesion proteins interact tightly with the PEM surface (Figure 4a). Upon annealing, both BSA and FN exhibit an increased interaction with the substrate. Moreover, FN adsorbed on annealed PLL/Alg adopts an elongated tertiary structure, favoring the exposure of RGD adhesive groups that enhance cell adhesion. For Chi/HA PEMs, results indicate a combined effect of a larger deposition of BSA (nonadhesive protein), and lower deposition of FN, the latter with an increased exchangeability, which renders the PEM surface unfavorable for stable interactions with integrins from the cell membrane (Figure 4b).
\nScheme of cell interaction with protein adsorbed on unannealed (top) and annealed (bottom) (PLL/Alg)7PLL (a) and (Chi/HA)7Chi PEMs (b).
Biologically inspired materials play a key role in the design of realistic platforms to modulate cell function. We proposed a novel biologically inspired supramolecular coating generated via one-step dip coating of the substrate in an aqueous solution of polyallylamine and phosphate anions [66]. We found selective cell adhesion, following the order in adhesion C2C12 myoblast > HeLa cells > MC-3 T3 preosteoblast, by varying the deposition time, that is, the thickness of the film from 20 to 120 nm (Figure 5) due to changes in the “complex stiffness”. The proposed platform supports a cell-type dependent exponential proliferation rate, with viability tested during a month.
\nSelective cell adhesion modulation on Pi/PAH-coated coverslips and the effect of thermal annealing at 37°C for 2–3 days. (a) Phase contrast images of HeLa, C2C12, and MC-3T3 cells seeded on unannealed Pi/PAH-coated substrates with tD = 40 and 90 min, as indicated in the figure. (b) Contrast phase images of cells adhered to annealed Pi/PAH-coated substrates with tD = 120 min. For C2C12 myoblasts and MC-3T3 preosteoblasts, cell adhesion characteristics improve in comparison with unannealed samples. (c) Stiffness (distribution of Young’s modulus, E) for unannealed Pi/PAH samples with tD = 40 min (black bars), tD = 120 min (gray bars) and annealed Pi/PAH samples (red bars). (d) Some physicochemical properties of unannealed and annealed Pi/PAH-coated coverslips.
This phosphate-polyamine film can be used to coat either adherent or nonadherent substrates and perhaps even more interesting, relatively thick films (≈100 nm) that exhibit poor cell adhesion properties, irrespective of the cell line, recover their adhesive properties toward eukaryote cells upon annealing at 37° for 2–3 days (Figure 5). This effect was mainly explained by the increase in the film stiffness due to partial irreversible dehydration accompanied with an increase in the film roughness. Upon thermal annealing, the contact angle increases approaching about 70°, the surface charge remains negative, and the mass of FN adsorbed accessed by quartz crystal microbalance remains constant (Figure 5d).
\nCell behavior is markedly affected by the spatial distribution of mechanical and biochemical cues at the cell microenvironment. The overall cooperative result impacts on either physiological or pathological processes.
\nThe fabrication of films with a gradual change in their swelling behavior has been obtained by gradual immersion of assembled PSS/PDADMAC multilayers into NaCl solutions [67]. In this work, the migration of smooth muscle cells (SMCs) at an appropriate cell density, in the direction of lowering hydration (relatively low swelling) has been observed. Furthermore, by time-controlled immersion in a solution of natural cross-linkers, a stable stiffness gradient on either free standing PEMs or assembled on silica substrates presenting differential cell adhesion has been reported [68].
\nA multilayer composed of poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH) grafted with photosensitive benzophenone was employed to generate stiffness gradient (55–140 MPa) by illuminating the assembled films with a gradient density filter that regulates the amount of UV light deposited onto the films [69]. Here, SMCs and MC-3T3 cells adhere and spread better on stiffer regions.
\nOther systems that include stiffness gradients [70] and concentration gradients of cell adhesive peptides or growth factors have been reported [71]. These concentration gradients are usually developed by microfluidic devices, allowing a spatially controlled surface arrangement of biological cues that are combined with physical ones to modulate cell fate.
\nWe have recently reported on the post-assembly treatment of PLL/Alg PEMs with a temperature gradient between 10 and 50°C in samples 2 cm in length [19]. The resulting temperature gradient appears to be linear with the distance between sources at fixed temperature. A continuous change in the physicochemical properties appears to set in along the substrate upon the application of a thermal gradient. For the substrate region held at the highest temperature, C2C12 cell adhesion was roughly close to that observed on glass. In contrast, at the coldest region, cell adhesion was very poor. The most significant changes in the average cell spreading area were observed between 30 and 22°C (Figure 6). The application of a thermal gradient to locally modify the physicochemical properties of films as well as the adhesion characteristics toward different cell lines can be extended to other polymeric systems to increase the versatility of new materials for rapid testing of cell functionalities.
\nThermal gradient applied to (PLL/Alg)7PLL PEM. (a) Scheme of the experimental setup for applying a thermal gradient. (b) Contact angle variation in the sample. (c) Spatial variation of cell adhesion characteristics.
The design of hybrid systems is motivated by the aim of profiting from the properties of the different materials composing them. For example, metal- and metallic oxide-derived thin films combined with polymeric layers that eventually contain bioactive molecules are useful to obtain multifunctionality.
\nTi, its oxides, and alloys are widely used materials for biomedical applications. A detailed knowledge of the surface characteristics of Ti-based materials is needed for understanding the relation with their reactivity and biological performance [72]. Titanium oxide surfaces can be treated by chemical etching, sonochemical modifications or electrochemical treatment, to obtain hierarchically micro-/nanostructured porous surfaces [21]. These treatments enhance the photoactivity of the oxide layer. And, besides the inherent effect of the modified micro-/nanotopography on cell functions, for instance, the appropriate size of topographic features to efficiently promote integrin clustering, the porous materials can be loaded with bioactive molecules that promote prokaryote cell-material interaction [73].
\nBy combining metallic surfaces with stimuli-responsive polyelectrolyte/polymer multilayers and supramolecular interacting systems, eukaryote and prokaryote cell behavior modulation has been achieved. A review of the application of these concepts is given in [21].
\nAn example in relation to cell modulation behavior by a hybrid multifunctional system is provided in this section. The system is built up with a photocatalytically active TiO2 film sonochemically nanostructured. Upon illumination, a photohole and a photoelectron are formed on the oxide surface as well as both H+ and HO−, one species prevailing over the other according to the composition of the interface. Thus, upon illumination for a certain time, a change in the pH at the interface is obtained. The system also includes a pH-sensitive high-amplitude actuating polymer, a linear triblock terpolymer consisting of polybutadiene (B), poly(methacrylic acid) (MAA), and quaternized poly[2-(dimethylamino)ethyl methacrylate] (Dq) [74]. In aqueous solution, the system (BMAADq) forms self-assembled micelles (BCM) with a hydrophobic core and a pH-sensitive MAA shell, and a strong Dq corona. BCMs are positively charged and are assembled with PAA to fabricate the pH sensitive coating. The resulting TiO2/BCM/PAA/BCM/PAA architecture is switched in response to the local changes in pH induced by the photocatalytic reactions on the oxide surface, resulting in a layer of variable thickness and stiffness. Thus, the authors achieve an efficient and controllable strategy to convert energy of electromagnetic illumination into a local pH variation that triggers the reversible response of the soft polymer. The same authors reported that the MC-3T3 cell migration is modulated in the proposed system. By local illumination of the film, cells are induced to migrate from softer to stiffer regions [75].
\nThe strategy briefly commented above shows the capability of hybrid smart systems to modulate cell behavior by spatial and temporal control of physicochemical cues.
\nIn this chapter, a number of materials and strategies employed to obtain inorganic, organic, and hybrid thin film functional systems with actual and potential applications in biosciences have been presented. We have depicted some materials of natural and synthetic origin employed to fabricate thin films to be used as platforms for fundamental cellular studies and potential applications. The system properties that affect cell functions and modulate its behavior and fate in a context approaching real situations have been also pointed out.
\nFurthermore, we briefly comment on some of our research works in relation to biocompatible materials based on polyelectrolyte assembly and post-assembly treatments to change the performance toward cell adhesion and proliferation.
\nThe biocompatibility of these materials determines the ultimate success of a developed material. Despite the large number of wisely designed systems with tunable spatial and temporal properties, even at the nanoscale, the challenge to bring these advances to the clinic is a central issue and requires the convergence of basic and applied sciences as well as commercial and social considerations.
\nS.E.M. thanks the MAT2017-88752-R and the CTQ2017-87637-R Retos projects from the Spanish Ministry of Science. N.E.M., M.A.P., and O.A. thank the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina) (Grant No. PIP 0602).
\nThe management of individuals with orofacial clefts extends from infancy till adulthood. Taking impressions of the dental arches is a frequently needed procedure, that can be utilized for recording, measuring and planning. However, conventional impression is considered a technique-sensitive procedure and prone to some complications and limitations, such as dimensional changes and patients’ intolerability, especially in patients with orofacial clefts. Moreover, storage and maintenance of the poured models is a continuous challenge to clinicians. The last decade has witnessed a digital revolution that led to the introduction of digital intraoral scanners for dentistry. Since then, the number of IOS devices as well as their technology are tremendously growing to offer accurate and comfortable replacement for the traditional impression techniques. This chapter summarizes the different IOS technologies, advantages, clinical considerations, and applications in the craniofacial field.
The very first intraoral scanner was introduced in the 1980 [1] and incorporated into the CEREC® by Sirona Dental Systems LLC (Charlotte, NC) system for restorative dentistry. Later after that, many manufacturers introduced multipurpose IOS to the market including the orthodontic purposes. IOS adopt non-optical technologies to provide an intraoral three-dimensional map where data points are captured by either a scanning unit or handheld wand and fed back to a workstation and can be viewed on a monitor. These technologies include confocal imaging, triangulation, and 3D in motion video [2].
Acquisition is briefly based on capturing of in-focus (confocal) images and deflecting any defocused images which increases the scan accuracy [3]. Trios IOS AND iTero Element are examples of the majority of the IOS that adopt the confocal imaging. Both offer systems where the teeth are not necessarily powder coated before scanning, thus shorten the scanning time and enhance the color capture [4]. They have a wide use in implant and restorative dentistry, and the orthodontic field.
This technology allows for capturing high-speed data in recording undesirable or inaccessible areas. It uses either a lens or a light source, and a sensor that is sensitive to light for image formation. The is based upon Pythagoras theorem, where by knowing the position and angle of two points of a triangle, we can easily calculate the position of the third point (object). Single detector “prism shaped” or two detectors are used to detect the two different points in the exact time. Cerec (Dentsply Sirona, USA) adopts this technology. Bluecam Cerec requires a reflective powder coating for scanning while Omnicam Cerec can provide a powderless scan [2].
his technology generates a true replica of the oral anatomy using a high-resolution video camera. It captures 3D data in a video sequence and models the data in real time. IOS that adopt this technology require a powder coating. However, it is lighter than that used with IOS with triangulation technology [2]. 3 M ESPE IOS adopt this technology.
The capability of directly recording the patient’s dental arch and creating a digital 3D model alleviates the need for conventional impression techniques which may cause patient discomfort or inconvenience by either the material itself or the impression tray [5, 6, 7]. Neonates, Children, and patients with gag reflex cannot tolerate the conventional procedure, that’s why the intraoral scanning process is much appreciated [8, 9, 10]. It is reported by the literature that patients prefer intraoral scanning process over the traditional impression techniques [11].
Intraoral scanners are proven to save working time in comparison with the conventional techniques [12, 13]. Although IOS do not appear to significantly save time in full arch scans (take less than 3 minutes) when compared to the conventional techniques that take from 3 to 5 minutes. However, they save time afterwards where the following steps of cast pouring, direct communication can be done with the laboratory by emailing the 3D digital model rather than courier delivery or using regular mail [12, 14, 15, 16]. Consequently, IOS can save throughout the working year a considerable amount of money and time [11, 14, 15, 17, 18, 19, 20].
Communication between dentist and dental technician can be simplified, strengthened, and improved by being offered a real time assessment of the optical impression quality [15, 20, 21]. In addition to that, IOS can serve as an effective tool for patient education as well as communication which amplifies the psychological involvement that positively affect the overall treatment journey. Also, IOS can be considered as a powerful marketing tool as patients are becoming more interested in technology and digitally equipped dental offices and mention that to their circle of communication [22]. Intraoral scanning leads to digital models which can be saved as an STL file, the clinical and logistic merits of digital models include easy data archival, smart and effective storage, durability with maintaining model integrity and diagnostic versatility [23].
Orofacial cleft is considered as one of the most common congenital disorders. Cleft lip and/or cleft palate (CL/P) is the most common craniofacial condition. Orofacial clefts have a significant influence on the development and quality of life not only on of the affected patients but on their families as well. A systematic review and meta-analysis conducted by Kadir et al. reported that 1 child in every 730 births will be born with CL/P (whether associated with syndrome/condition or not) [24].
Palatoplasty for patients with cleft palate is delayed till approximately from 9 to 10 months to avoid any maxillary growth limitation [25, 26]. At this age, the preoperative evaluation of the palate is very challenging because of its small size, not to mention that even in adults it is a very difficult structure to record [27]. Different attempts were conducted for the preoperative evaluation of the anatomy of the palate, yet it was very difficult because of limited accessibility and dynamic movements. Some surgeons depended on clinical examination by eyeballing (looking directly into patients’ mouth while open) [27]. This method of assessment is very subjective and provide insufficient diagnostic information. That’s why, alternative methods as diagnostic plaster models, CBCT scanning of the patient to provide a 3-dimensional anatomy of the palate, and Magnetic resonance scanning have been used to overcome the limitations of the physical examination method [28, 29, 30].
Plaster models have been considered as the gold standard in recording the dental arches [31]. Although plaster casts may record accurately the anatomy of the hard palate, yet it is fails to provide a detailed recording of the soft palate [32]. Despite the presence of alternative radiographic methods as CBCT, high radiation exposure particularly in pediatric patients can be a limitation, in addition to possible images overlap and inaccurate recording of borders of soft tissue structures [33]. Also, studies reported that MRI may provide a gap between the radiographic and clinical case severity, so it cannot be used solely to evaluate patients with cleft palate and should be combined with clinical examination to provide an appropriate treatment plan [34].
The evolution of digital intraoral scanning is considered by most of the orthodontists especially the craniofacial ones as an absolute innovation, literature has reported many studies that validate their use in terms of accuracy in the orthodontic field [35, 36]. Also, recent studies began to validate the use of IOS in recording the palatal tissue and reported intraoral scanning as a reliable method [37, 38]. Among the reported challenges of using IOS to record the soft palate or the palatal area in general is the accessibility as well as recording the posterior part of the soft palate as a smooth surface without any corrugations [32]. There are now intraoral scanners with smaller and thinner scanning tips - thanks to the developing scanning technologies – which significantly improved the accessibility and reduced any discomfort particularly in infant and neonate patients.
Three-dimensional analysis of the records captured by IOS (Figure 1) can offer a diagnostic opportunity that allows for accurate measurements between marked points on the palate. This facilitates the treatment planning part for the care providers where they can accurately record the various occlusal indices required to evaluate the inter-arch relationships [39].
Digital models of a patient with unilateral cleft lip and palate on the right side, which can be used for detailed diagnosis and tailored treatment planning.
Presurgical infant orthopedics, known as (PSIO) started its popularity in the 1950s and was validated later by Matuso in 1988 who noticed that the newborn’s cartilage is soft and non-elastic thus, can be molded [40]. The PSIO is advisable to start as early as from birth up to 4 months due to the high estrogen and hyaluronic acid levels which inhibit the crosslinking of the cartilage matrix and allow for proper cartilage molding [40, 41]. In 1950, Grayson initiated the technique that is widely used till now and named it “presurgical naso-alveolar molding (NAM), this technique allows passive molding that aims mainly for repositioning the deformed alveolar process, nasal cartilage and lengthening of the columella. The Grayson technique itself then went through further modifications aiming for preferable outcomes and more comfort to the patients and their caregivers [42, 43, 44].
The concept of clear orthodontic appliances was first introduced in 1946 by Kesling to align the teeth in better positions [45]. Later after that, the clear aligner treatment (CAT) was introduced by Align Technology (Santa Clara, California). CAT was very acceptable for adult patients [46]. However, it was not that popular for pediatric patients in craniofacial orthopedics and orthodontics, this was related to the possible discomfort, allergy, and respiratory obstruction from impression material in newborns with cleft palate [47]. The introduction of a digital workflow that includes IOS instead of conventional impression techniques then designing and 3D printing of clear aligner for nasoalveolar molding has paved the way to a more friendly yet accurate method of reducing the cleft defect before surgery [48].
The scanning process is usually done using a small-sized scanning tip, the newborn/infant’s head is advised to be stabilized gently with the parent’s hand while keeping the infant seated in the parent’s lap. The overall intraoral scanning process should take less than 3 minutes, an exact reported average of 1 minute 30 seconds up to 2 minutes has been reported in literature [48].
It is worth mentioning that the IOS software is accustomed to record continuous dental arches and interpret any discontinuous surface as a redundant or spurious surface that should be removed [47]. Hence, the most challenging part to be scanned was the cleft gap. However, the orthodontists’ experience in the scanning process plays a significant role (Figure 2). On another hand, the scanning speed is recommended to support up to 3000 images per second with the rationale of reducing any errors that may result from any movement between the scanning tip and the surrounding oral structures [47].
Intraoral scan of an infant with unilateral cleft lip and palate. The digital impression can be used to assess the maxillary arch/segment dimensions and to fabricate a nasoalveolar molding (NAM) aligners.
Fully digital workflow can be implemented to successfully design and manufacture palatal plates for patients with cleft palate or any functional disorder. Applying this workflow in orthodontics requires the synchronization between different technologies to be able to finally create appliances, it is now possible to create palatal plates based on digital intraoral scanning [49].
Xepapadeas AB et al. [50], reported a detailed technique for scanning the patients with Trisomy 21 syndrome for the aim of manufacturing palatal plates. They advised that the orthodontist should make sure to record all the intraoral structures that can crucially affect the fit of the plate as the maxillary tuberosity, labial frenulum, and vestibule. Also, another important tip is to always define a reference point to mark the start of the scan - usually it is the incisive papilla - so that if the scanning position is lost, the papilla or the last scanned area can be taken as a starting point. The scanned data represents the digital working model. At first, adjusting the scan orientation is done then defining the outer borders of the scan to determine the final dimensions of the orthodontic model. The final step includes removing any undercuts or irregularities resulting from registration errors, this is usually done using the free form tool. In patients with cleft palate, it is advised to virtually block the cleft to ensure that all the anatomic structures are recorded rather than being removed and considered as redundant images. Thereby, the digital model is ready to be exported as Standard Tessellation Language (STL) file for the design of the palatal plate.
In the craniofacial field, accurate diagnostic information, precise understanding of the anatomy, and practice are the key for any successful surgery. Palatoplasty simulation on a 3D printed cleft palate model based on data from intraoral scanner is now a growing viable option. This simulation offers a training opportunity to the medical students and residents to increase their expertise [27].
The 3D filed is rapidly and favorably developing. This includes 3D imaging, scanning and printing. Following the promising development of the 3D filed, it was about time for software creators to incorporate three-dimensional surgical modules into various software programs. Utilizing different 3D technologies together paved the road for virtual surgical planning (VSP) to accessible and widely spread.
Two fundamental elements are needed for VSP; 3D radiographic imaging (CT or CBCT) and intraoral digital impression. The intraoral scan of a patient’s mouth is done in order to obtain a STL file, that will be accurately placed overlaying the dentition on the patient’s CT or CBCT volume. This merging will provide an accurate representation of the patient’s skeleton, dentition and facial soft tissues; i.e. creating a “virtual patient” [51]. Utilizing specific software programs, VSP can be performed with a step-by-step guidance. First, the boundaries of the maxilla, mandible and dentition are identified through landmark identification. Then, the surgical movements of one jaw or both are decided in all dimensions (anteroposterior, lateral, vertical, yaw, pitch and roll) depending on the surgical plan (Figure 3). 3D surgical guide(s) and Inter-mediate or/and final splint(s) can be created virtually and then 3D printed (Figures 4 and 5).
Virtual surgical planning (VSP) showing double-jaw surgery with final splint is in place.
The surgical guides are virtually designed. Screw holes are accurately distributed to avoid any injury to the adjacent structures (such as teeth and nerves). Note that in figure (B), numbers represent the predetermined length of the screws, while screw (*) indicates the need to used angular screw.
The surgical guides for the maxilla and mandible are virtually designed then 3D printed. A, right side of the maxilla; B, left side of the maxilla; C, right side of the mandible; D, left side of the mandible.
The VSP allows for accurate osteotomy cuts, better predictability of the outcomes and significant reduction in the amount of time spent in the operating room [52, 53, 54]. With the current and upcoming advanced in the 3D filed, it is only logical to consider VSP not only as a viable option, but as an upgraded alternative to traditional surgeries.
Digital intraoral scanners can be considered as an accurate novel diagnostic tool in the craniofacial field as well as a safe alternative to the traditional impression techniques especially for infants with craniofacial conditions. They allow for 3D evaluation of the scanned data; this can be very beneficial for infants/newborns with cleft palate by facilitating the treatment plan formulation based on accurate 3D measurements and analysis. Furthermore, IOS can enable the manufacture of craniofacial appliances when combined with a proper digital workflow. Finally, the with the marriage of IOS and 3D printing technology, surgical models can be easily fabricated for surgical training purposes.
The authors declared that there is no conflict of interest.
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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:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{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. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. 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Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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