Materials’ properties and the compatibility with different V-PAMs manufacturing.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"8812",leadTitle:null,fullTitle:"Contemporary Topics about Phosphorus in Biology and Materials",title:"Contemporary Topics about Phosphorus in Biology and Materials",subtitle:null,reviewType:"peer-reviewed",abstract:"This book addresses a diverse set of topics regarding phosphorus chemistry, namely phosphates and closely related chemical systems. Divided into two sections, chapters cover such topics as phosphate dynamics and phosphates in biomaterials. This volume is a useful reference for scholars and researchers and will inspire readers to make future discoveries in the field.",isbn:"978-1-78985-040-6",printIsbn:"978-1-78985-039-0",pdfIsbn:"978-1-83881-125-9",doi:"10.5772/intechopen.80727",price:119,priceEur:129,priceUsd:155,slug:"contemporary-topics-about-phosphorus-in-biology-and-materials",numberOfPages:214,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"86c427901f631db034a54b22dd765d6a",bookSignature:"David G. Churchill, Maja Dutour Sikirić, Božana Čolović and Helga Füredi Milhofer",publishedDate:"September 9th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8812.jpg",numberOfDownloads:7480,numberOfWosCitations:10,numberOfCrossrefCitations:23,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:37,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:70,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 7th 2019",dateEndSecondStepPublish:"March 6th 2019",dateEndThirdStepPublish:"May 5th 2019",dateEndFourthStepPublish:"July 24th 2019",dateEndFifthStepPublish:"September 22nd 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"219335",title:"Dr.",name:"David",middleName:"G.",surname:"Churchill",slug:"david-churchill",fullName:"David Churchill",profilePictureURL:"https://mts.intechopen.com/storage/users/219335/images/system/219335.jpg",biography:"David G. Churchill is a full professor in the Department of Chemistry at Korea Advanced Institute of Science and Technology (KAIST). He is an adjunct professor in the KAIST Institute for Health Sciences and serves as Head of the International Faculty Council at KAIST. His current research interests relate to main group synthetic chemistry and dementia research; his publications have recently focused on chemosensing and porphyrinoid chemistry. He has created and (co)organized the biannual International Symposium of Molecular Neurodegenerative Disease Research (ISMNDR) at KAIST (Korea, Daejeon), which was initiated in 2012. He has given seminars worldwide, published more than 120 articles in peer-reviewed journals, and has an H-index of 31. In 2017, he served as an associate visiting professor at IIT Technion in Haifa, Israel.",institutionString:"Korea Advanced Institute of Science and Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Korea Advanced Institute of Science and Technology",institutionURL:null,country:{name:"Korea, South"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"30822",title:"Dr.",name:"Maja",middleName:null,surname:"Dutour Sikiric",slug:"maja-dutour-sikiric",fullName:"Maja Dutour Sikiric",profilePictureURL:"https://mts.intechopen.com/storage/users/30822/images/system/30822.jpeg",biography:"Maja Dutour Sikirić received her doctorate from the Faculty of Sciences, University of Zagreb. During her studies she has acquired experience and developed an interest in organic - inorganic interactions in crystallization, as related to biomineralization, and physicochemical properties of novel gemini surfactants in solution and solid state. She joined Casali Institute of Applied Science, The Hebrew University of Jerusalem for Postdoctoral studies during which she was working on the development of organic-inorganic nanocomposites, to be used as coatings for metal prosthetic implants. After returning to Ruđer Bošković Institute she has continued her work on crystallization of calcium phosphates, nanocomposite biomaterials as well as using DLS for characterization of nanoparticles in different matrices. She is currently employed as Head of the Laboratory for biocolloids and interface chemistry, Division of Physical Chemistry.",institutionString:"Ruđer Bošković Institute",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Rudjer Boskovic Institute",institutionURL:null,country:{name:"Croatia"}}},coeditorTwo:{id:"285104",title:"Dr.",name:"Božana",middleName:null,surname:"Čolović",slug:"bozana-colovic",fullName:"Božana Čolović",profilePictureURL:"https://mts.intechopen.com/storage/users/285104/images/system/285104.jpeg",biography:"Božana Čolović graduated in 2007 and received her PhD degree in 2013, from the Faculty of Technology and Metallurgy, University of Belgrade. Since 2007 she has been employed at Vinča Institute for Nuclear Sciences. Her research is focused on development of biomaterials for application in bone tissue engineering and dentistry: synthesis of ceramics (hydroxyapatite, calcium silicate) and their modification with surface active substances to improve biocompatibility, as well as the deposition of bioactive coatingson the surface of metal implants to improve their mechanical and corrosion properties. So far, she has published 1 chapter in a book, 30 papers in international journals and 10 papers in national journals, presented 21 papers at international conferences and gave 3 invited lectures.",institutionString:"University of Belgrade",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:{id:"287710",title:"Dr.",name:"Helga",middleName:null,surname:"Füredi Milhofer",slug:"helga-furedi-milhofer",fullName:"Helga Füredi Milhofer",profilePictureURL:"https://mts.intechopen.com/storage/users/287710/images/system/287710.jpeg",biography:"Helga Füredi-Milhofer received PhD from the Faculty of Sciences, University of Zagreb in 1963. Subsequently she was postdoctoral researcher at Case Institute of Technology Cleveland Ohio, USA. In 1956. she joined Ruđer Bošković Institute, where she was the head of Laboratory for Precipitation Processes from 1976 – 1995. In the period 1990-991 she was visiting professor at the Weizman Institute of Science, Rehovot, Israel and from 1991-1992 at Casali Institute of Applied Chemistry, the Hebrew University of Jerusalem, Israel. In 1995 she returned to Casali Institute of Applied Chemistry where she was professor until retirement. Her research interests are i) nucleation, growth and phase transformation of ionic and molecular crystals ii) biological and pathological mineralization iii) 0rganic-inorganic nanocomposites based on amorphous and crystalline calcium phosphates.",institutionString:"The Hebrew University of Jerusalem",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorFour:null,coeditorFive:null,topics:[{id:"14",title:"Materials Science",slug:"materials-science"}],chapters:[{id:"72693",title:"Introductory Chapter: Phosphorus - Nature’s Versatile Pentavalent and Tetrahedral Covalent Building Block and Agent for Energy, Disease and Health",doi:"10.5772/intechopen.93009",slug:"introductory-chapter-phosphorus-nature-s-versatile-pentavalent-and-tetrahedral-covalent-building-blo",totalDownloads:377,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Woohyun Lee, Ariq Abdillah, Jaymee Palma and David G. Churchill",downloadPdfUrl:"/chapter/pdf-download/72693",previewPdfUrl:"/chapter/pdf-preview/72693",authors:[{id:"219335",title:"Dr.",name:"David",surname:"Churchill",slug:"david-churchill",fullName:"David Churchill"},{id:"222934",title:"BSc.",name:"Woo Hyun",surname:"Lee",slug:"woo-hyun-lee",fullName:"Woo Hyun Lee"},{id:"323130",title:"Dr.",name:"Ariq",surname:"Abdillah",slug:"ariq-abdillah",fullName:"Ariq Abdillah"},{id:"323131",title:"Dr.",name:"Jaymee",surname:"Palma",slug:"jaymee-palma",fullName:"Jaymee Palma"}],corrections:null},{id:"71223",title:"Phosphorus: A Boon or Curse for the Environment?",doi:"10.5772/intechopen.91250",slug:"phosphorus-a-boon-or-curse-for-the-environment-",totalDownloads:428,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Phosphorus, a limiting nutrient of biosphere, exists as dissolved inorganic phosphorus (DIP), dissolved organic phosphorus (DOP), particulate inorganic phosphorus (PIP) and particulate organic phosphorus (POP) in water of soil as well as ponds, lakes, etc. The only available phosphorus for plants are DIP, while the other forms need to be converted to DIP by the decomposing microorganisms of the soil. The heavy metals (such as arsenic and chromium), which are the menace of both terrestrial and aquatic environment, are taken up by the plants and animals causing toxicity at physiological level. However, the metal (Cr and As) toxicity can be mitigated competitively by phosphorus, since the latter is a structural analogue. Since, phosphorus is an essential nutrient, plants prefer it over Cr or As. At the same time, if excess of phosphorus is applied in the soil in the form of fertilisers, it gets discharged into the water bodies (ponds, lakes, etc.) through agricultural runoff, causing eutrophication followed by harming the health of the water bodies. This can be further mitigated by employing the phenomenon of luxury uptake by the aquatic plants such as Pistia stratiotes.",signatures:"D. Sayantan and Sumona Sanyal Das",downloadPdfUrl:"/chapter/pdf-download/71223",previewPdfUrl:"/chapter/pdf-preview/71223",authors:[{id:"313368",title:"Dr.",name:"Sayantan",surname:"D",slug:"sayantan-d",fullName:"Sayantan D"},{id:"317243",title:"Mrs.",name:"Sumona Sanyal",surname:"Das",slug:"sumona-sanyal-das",fullName:"Sumona Sanyal Das"}],corrections:null},{id:"71749",title:"Bone Mineralisation",doi:"10.5772/intechopen.92065",slug:"bone-mineralisation",totalDownloads:783,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The mineralisation term mentions the development of inorganic precipitation over an organic background. This process occurs in a life span of biological organism for the formation of bone, teeth, exoskeletons, egg shells, etc. So, basically bone mineralisation is defined as the process of deposition of minerals on the bone matrix for the development of bone. The human bone is made up of 60–70% minerals which include calcium phosphate in the form of hydroxyapatite followed by 20–40% organic matrix containing type I collagen fibres and less than 5% of water and lipids. During bone mineralisation process osteoblasts which are also known as bone forming cells, aids to the production of calcium phosphate crystals which are then aligned in the collagen based fibrous matrix. The bone mineralisation procedure also known as calcification is a lifelong activity of a human being.",signatures:"Pinki Dey",downloadPdfUrl:"/chapter/pdf-download/71749",previewPdfUrl:"/chapter/pdf-preview/71749",authors:[{id:"295348",title:"Ph.D.",name:"Pinki",surname:"Dey",slug:"pinki-dey",fullName:"Pinki Dey"}],corrections:null},{id:"67542",title:"Proteins in Calcium Phosphates Biomineralization",doi:"10.5772/intechopen.86718",slug:"proteins-in-calcium-phosphates-biomineralization",totalDownloads:998,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Biomineralization is a process of creating crystalline structures under biological control. The process takes place in hard tissues, such as bones, cartilages, and teeth. Biominerals are a combination of a crystal phase deposited onto an organic matrix. Inorganic components are mainly responsible for the biomineral hardness, while the organic matrix controls the shape, size, and polymorph of the crystals. Within the organic matrix, proteins exhibit a special biomineralization activity. Among them, one can distinguish insoluble collagen and soluble noncollagenous proteins. It is particularly noteworthy that noncollagenous proteins are intrinsically disordered proteins. High flexibility, acidic nature, and susceptibility to modifications make them especially adapted to the biomineralization control. This review paper is dedicated to the proteins which are involved in biomineralization of bones and teeth.",signatures:"Marta Kalka, Anna Zoglowek, Andrzej Ożyhar and Piotr Dobryczycki",downloadPdfUrl:"/chapter/pdf-download/67542",previewPdfUrl:"/chapter/pdf-preview/67542",authors:[{id:"292079",title:"Prof.",name:"Piotr",surname:"Dobryszycki",slug:"piotr-dobryszycki",fullName:"Piotr Dobryszycki"},{id:"301474",title:"MSc.",name:"Marta",surname:"Kalka",slug:"marta-kalka",fullName:"Marta Kalka"},{id:"301475",title:"Dr.",name:"Anna",surname:"Zoglowek",slug:"anna-zoglowek",fullName:"Anna Zoglowek"},{id:"301750",title:"Prof.",name:"Andrzej",surname:"Ożyhar",slug:"andrzej-ozyhar",fullName:"Andrzej Ożyhar"}],corrections:null},{id:"67902",title:"Inorganic Polyphosphates Are Important for Cell Survival and Motility of Human Skin Keratinocytes and Play a Role in Wound Healing",doi:"10.5772/intechopen.87183",slug:"inorganic-polyphosphates-are-important-for-cell-survival-and-motility-of-human-skin-keratinocytes-an",totalDownloads:790,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Inorganic polyphosphate (polyP) is a simple ancient polymer of linear chains of orthophosphate residues linked by high energy phospho-anhydride bonds ubiquitously found in all organisms. Despite its structural simplicity, it plays diverse functional roles. polyP is involved in myriad of processes including serving as microbial phosphagens, buffer against alkalis, Ca2+ storage, metal-chelating agents, pathogen virulence, cell viability and proliferation, structural component and chemical chaperones, and in the microbial stress response. In mammalian cells, polyP has been implicated in blood coagulation, inflammation, bone differentiation, cell bioenergetics, signal transduction, Ca2+-signaling, neuronal excitability, as a protein-stabilizing scaffold, and in wound healing, among others. This chapter will discuss (1) polyP metabolism and roles of polyP in prokaryotic and eukaryotic cells, (2) the contribution of polyP to survival, cell proliferation, and motility involved in wound healing in human skin keratinocytes, (3) the use of polyP-containing platelet-rich plasma (PRP) to promote wound healing in acute and chronic wounds, including burns, and (4) the use of polyP-containing PRP in excisional wound models to promote faster healing. While polyP shows promise as a therapeutic agent to accelerate healing for acute and chronic wounds, the molecular mechanisms as a potent modulator of the wound healing process remain to be elucidated.",signatures:"Cynthia M. Simbulan-Rosenthal, Bonnie C. Carney, Anirudh Gaur, Manish Moghe, Elliott Crooke, Lauren T. Moffatt, Jeffrey W. Shupp and Dean S. Rosenthal",downloadPdfUrl:"/chapter/pdf-download/67902",previewPdfUrl:"/chapter/pdf-preview/67902",authors:[{id:"182585",title:"Dr.",name:"Jeffrey W.",surname:"Shupp",slug:"jeffrey-w.-shupp",fullName:"Jeffrey W. Shupp"},{id:"297714",title:"Associate Prof.",name:"Dean",surname:"Rosenthal",slug:"dean-rosenthal",fullName:"Dean Rosenthal"},{id:"297716",title:"Prof.",name:"Cynthia",surname:"Simbulan-Rosenthal",slug:"cynthia-simbulan-rosenthal",fullName:"Cynthia Simbulan-Rosenthal"},{id:"297718",title:"BSc.",name:"Bonnie C.",surname:"Carney",slug:"bonnie-c.-carney",fullName:"Bonnie C. Carney"},{id:"297719",title:"Dr.",name:"Lauren",surname:"Moffat",slug:"lauren-moffat",fullName:"Lauren Moffat"},{id:"304095",title:"MSc.",name:"Manish",surname:"Moghe",slug:"manish-moghe",fullName:"Manish Moghe"},{id:"304096",title:"MSc.",name:"Anirudh",surname:"Gaur",slug:"anirudh-gaur",fullName:"Anirudh Gaur"},{id:"304097",title:"Prof.",name:"Elliott",surname:"Crooke",slug:"elliott-crooke",fullName:"Elliott Crooke"}],corrections:null},{id:"67886",title:"Phosphonates: Their Natural Occurrence and Physiological Role",doi:"10.5772/intechopen.87155",slug:"phosphonates-their-natural-occurrence-and-physiological-role",totalDownloads:1137,totalCrossrefCites:9,totalDimensionsCites:15,hasAltmetrics:0,abstract:"The first natural compound containing carbon-to-phosphorus bond—ciliatine was discovered 60 years ago, and for four decades, phosphonates were considered simply as a biological curiosity. Finding the importance of these compounds in biogeochemical phosphorus cycling, their role in methane production, as well as discovery of numerous phosphonates and phosphonopeptides of promising antibacterial and antifungal activities has stimulated the development of studies on this class of compounds, especially on their metabolism and biochemistry. These studies are driven by the use of 31P NMR and by a clever combination of genomics and innovative chemistry by using the method of selective labeling of metabolites. These studies revealed unusual and interesting chemistry of these compounds.",signatures:"Paweł Kafarski",downloadPdfUrl:"/chapter/pdf-download/67886",previewPdfUrl:"/chapter/pdf-preview/67886",authors:[{id:"71234",title:"Dr.",name:"Pawel",surname:"Kafarski",slug:"pawel-kafarski",fullName:"Pawel Kafarski"}],corrections:null},{id:"71445",title:"Calcium Phosphate Cements in Tissue Engineering",doi:"10.5772/intechopen.89131",slug:"calcium-phosphate-cements-in-tissue-engineering",totalDownloads:866,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Calcium phosphate cements (CPCs) consist of a combination of calcium phosphates and a liquid phase, allowing it to fit into the body where it was inserted. Several chemical compositions have been synthesized, promoting specific characteristics to the cements for applications such as bone augmentation and reinforcement and metal implant fixation. The hardening reaction mechanism is at low temperatures and makes it capable of incorporating different drugs and other biological molecules. In addition to the abovementioned advantages, CPCs have excellent bioactivity and osteoconductivity and the ability to form a bone bond. Its function as osteoconductor can be improved by insertion of growth factors. In addition, it is possible to functionalize it with silver ions and use it as a coating of implants, conferring antibacterial properties. In this chapter the physical, mechanical, chemical, and biological properties and the possibility of using these cements as drug carriers or biomolecules will be discussed.",signatures:"Manuel Pedro Fernandes Graça and Sílvia Rodrigues Gavinho",downloadPdfUrl:"/chapter/pdf-download/71445",previewPdfUrl:"/chapter/pdf-preview/71445",authors:[{id:"40763",title:"Prof.",name:"Manuel Pedro",surname:"Graça",slug:"manuel-pedro-graca",fullName:"Manuel Pedro Graça"},{id:"302803",title:"MSc.",name:"Sílvia",surname:"Gavinho",slug:"silvia-gavinho",fullName:"Sílvia Gavinho"}],corrections:null},{id:"67942",title:"Amorphous Calcium Phosphate as Bioactive Filler in Polymeric Dental Composites",doi:"10.5772/intechopen.86640",slug:"amorphous-calcium-phosphate-as-bioactive-filler-in-polymeric-dental-composites",totalDownloads:860,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:0,abstract:"As biocompatible and osteo-inductive precursor to biological apatite formation, amorphous calcium phosphate (ACP) resorbs at the rate that closely coincides with the rate of new bone formation and is more osteo-conductive than its crystalline counterpart. In addition, in the oral environment, ACP intrinsically provides a protracted supply of the remineralizing calcium and phosphate ions needed for regeneration of mineral lost to tooth decay. These features make ACP composites a strong remineralizing tool at the site of caries attack. Our group has been on the forefront of the research on bioactive, remineralizing, polymeric ACP-based dental materials for over two decades. This entry describes methods for filler, polymer, and composite fabrication and a battery of physicochemical and biological tests involved in evaluation of ACP-based restoratives. Also presented is our most recent design of ACP remineralizing composites with added antimicrobial capability that shows promise for extended dental and, potentially, wider biomedical applications.",signatures:"Diane R. Bienek, Anthony A. Giuseppetti and Drago Skrtic",downloadPdfUrl:"/chapter/pdf-download/67942",previewPdfUrl:"/chapter/pdf-preview/67942",authors:[{id:"297132",title:"Dr.",name:"Drago",surname:"Skrtic",slug:"drago-skrtic",fullName:"Drago Skrtic"},{id:"297135",title:"Dr.",name:"Diane",surname:"Bienek",slug:"diane-bienek",fullName:"Diane Bienek"},{id:"297137",title:"Mr.",name:"Anthony",surname:"Giuseppetti",slug:"anthony-giuseppetti",fullName:"Anthony Giuseppetti"}],corrections:null},{id:"68658",title:"Structural and Calorimetric Studies of Zinc, Magnesium and Manganese Based Phosphate and Phosphate-Silicate Glasses",doi:"10.5772/intechopen.88539",slug:"structural-and-calorimetric-studies-of-zinc-magnesium-and-manganese-based-phosphate-and-phosphate-si",totalDownloads:792,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Glasses of the (50-x/2)Na2O-xMO-(50-x/2)P2O5 (M = Zn, Mg or Mn) (0 ≤ x ≤ 33 mol%), (50-x)Na2O-xMO-50P2O5 (M = Zn, Mn) (0 ≤ x ≤ 33 mol%), and (0.9-x)NaPO3-xSiO2-0.1ZnO (0 ≤ x ≤ 0.1 mol) were prepared by the melt quenching technique. Samples were investigated by means of X-ray diffraction, Archimede’s method, ellipsometry, Fourier-transformed infrared (FTIR), Raman, 31P solid state magic angle spinning nuclear magnetic resonance (MAS-NMR), UV-visible spectroscopy and calorimetry. For zinc, manganese and magnesium phosphate glasses, the increase in density with the addition of MO oxide suggests the compactness of the vitreous network. For zinc phosphate silicate glasses, the variations of density and refractive index were attributed to the structural changes when SiO2 oxide is progressively introduced. The increase in the glass transition temperature (Tg) reflects an increase in the cross-link strength of the structure as MO and SiO2 oxides are gradually incorporated. For all glass composition, spectroscopic investigations revealed the depolymerization of metaphosphate chains (Q2) allowing the formation of phosphate dimers (Q1). Calorimetric dissolution shows that the dissolution is endothermic for lower MO content and become exothermic when x rises. For (50-x/2)Na2O-xZnO-(50-x/2)P2O5 (0 ≤ x ≤ 33 mol%) glasses, the formation enthalpy increases with the incorporation of ZnO oxide.",signatures:"Refka Oueslati Omrani, Mohamed Jemal, Ismail Khattech and Ahmed Hichem Hamzaoui",downloadPdfUrl:"/chapter/pdf-download/68658",previewPdfUrl:"/chapter/pdf-preview/68658",authors:[{id:"15449",title:"Dr.",name:"Mohamed",surname:"Jemal",slug:"mohamed-jemal",fullName:"Mohamed Jemal"},{id:"293256",title:"Prof.",name:"Khattech",surname:"Ismail",slug:"khattech-ismail",fullName:"Khattech Ismail"},{id:"293285",title:"Dr.",name:"Oueslati-Omrani",surname:"Refka",slug:"oueslati-omrani-refka",fullName:"Oueslati-Omrani Refka"},{id:"293291",title:"Prof.",name:"Ahmed Hichem",surname:"Hamzaoui",slug:"ahmed-hichem-hamzaoui",fullName:"Ahmed Hichem Hamzaoui"}],corrections:null},{id:"68130",title:"Temperature Influence on Inhibitory Efficiency of Three Phosphate Inhibitors by Mass Loss",doi:"10.5772/intechopen.88130",slug:"temperature-influence-on-inhibitory-efficiency-of-three-phosphate-inhibitors-by-mass-loss",totalDownloads:452,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The effect of temperature on steel samples immersed in concrete pore solutions contaminated by chlorides incorporating three inhibitors based on phosphate (Na3PO4, K2HPO4, and Na2PO3F) was studied by gravimetric measurements at several ranges: 298, 308, and 318 K. The results obtained for the use of these three products show that the inhibitory efficacy is lower at 318 K than that detected at 308 and 298 K of temperature. Also, we find that the best inhibitory efficiency at 298 K was detected for Na2PO3F (75.80% at 0.05 mol/l of concentration) followed by K2HPO4 (65.05% at 2.5 10−3 mol/l) and then Na3PO4 (61.48% at 7.5 10−3 mol/l).",signatures:"Latefa Sail",downloadPdfUrl:"/chapter/pdf-download/68130",previewPdfUrl:"/chapter/pdf-preview/68130",authors:[{id:"297226",title:"Dr.",name:"Latefa",surname:"Sail",slug:"latefa-sail",fullName:"Latefa Sail"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6320",title:"Advances in Glass Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6d0a32a0cf9806bccd04101a8b6e1b95",slug:"advances-in-glass-science-and-technology",bookSignature:"Vincenzo M. 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Patients not only experience physical and mental disabilities, but also impose a large financial burden that consumes an estimated over $60 billion in costs per year, including more than $20 billion in treatment in the United States of America alone.
\nSchizophrenic patients exhibit an array of clinical symptoms that consist of positive symptoms, negative symptoms, and cognitive impairments. Due to the heterogeneity in symptomatology, this disorder is difficult to diagnose and treat. Typically, the onset of symptoms occurs between adolescence and early adulthood, mostly within the age range of 16–30 years old, occurring in men (average 18) earlier than women (average 25). Cognitive and social deficits are the first symptoms to appear and exacerbate over time. Individuals display a lack of attention, short‐term and long‐term memory loss, as well as lack of executive functions that include disorganized thoughts and planning. In addition, patients have difficulties communicating ideas and notions, consequently leading to social withdrawal. As the individual gets older, negative symptoms appear, including a blunted affect of normal behavior and feelings. For instance, patients will express a lack in motivation and/or pleasure that often leads to depression and mood swings. Positive symptoms develop later and signify an escalated state of mind and altered reality, such as hallucinations, delusions, and false ideas. The amalgamation of these symptoms persist into adulthood and may perhaps lead to other comorbidities such as attention deficit hyperactive disorder (ADHD), depression, anxiety, aggression, and substance abuse [1].
\nUnfortunately, schizophrenia is challenging to diagnose due to the various signs and symptoms; however, neuroanatomical evidence displays structural aberrations in specific tissues that assist in characterizing the disorder. For instance, postmortem patients show an overall decrease in brain volume and more specifically reduced cortical gray matter in forebrain tissue, such as the dorsolateral prefrontal cortex (dlPFC), superior temporal gyrus, and limbic areas (i.e., hippocampal formation, anterior cingulate cortex). Other anatomical anomalies include enlarged cerebral ventricles, such as the lateral and third ventricles. Lastly, at the cellular level, there are reports of reduced neuronal number and dendritic spine densities in the hippocampus and dorsolateral prefrontal cortex [2, 3], although this observation appears to be controversial. Nevertheless, numerous studies have confirmed a significant decrease in pyramidal dendritic spines within superficial layers of the prefrontal cortex [2, 4].
\nThe neurophysiological changes are equally as detrimental as the structural changes observed in schizophrenic patients. For example, the most prevailing theories describing the etiology of schizophrenia is the “Dopamine hypothesis,” which predicts dopamine imbalances within the mesocortical and mesolimbic pathways underlie schizophrenia pathology. Specifically, dopamine deficiency from mesocortical projecting neurons to the prefrontal cortex results in “hypostimulation” of D1‐receptor neurons that contribute to the negative symptoms and cognitive impairments. In contrast, an excess of dopamine to the prefrontal cortex and striatum from mesolimbic dopamine pathways induces “hyperstimulation” of D2‐receptor neurons, responsible for the positive symptoms [5]. Therefore, current treatments target dopamine receptors, but leave other pathophysiological mechanisms untargeted. Typical and atypical antipsychotics, such as haloperidol and clozapine, respectively, block D2‐receptors to alleviate psychotic symptoms. However, dopamine‐specific targeted therapy is insufficient to relieve other aspects of the disease; therefore, additional neuronal systems are likely involved.
\nIn recent years, evidence has linked glutamatergic and GABAergic systems to the pathology of schizophrenia. An emerging hypothesis of schizophrenia suggests that N‐methyl‐D‐aspartate (NMDA) receptor hypofunction plays a major role in the dysregulation of GABAergic transmission, thereby contributing to the symptoms [6]. In this chapter, we discuss the structure and function of NMDA and gamma‐aminobutyric acid (GABA) receptors, including the effects of genetic abnormalities on them and their associated posttranslational modifications and signal transduction pathways. We will also include the reviewed literature describing the multiple neuronal subtypes and circuits involved in schizophrenia and potential therapeutic options.
Glutamate is an excitatory neurotransmitter that can act on four major classes of receptors, which are either metabotropic or ionotropic. Metabotropic receptors are G‐protein coupled receptors. Metabotropic glutamate receptors are composed of mGluR1‐8 subunits and have seven transmembrane segments that are connected to heterotrimeric G proteins. The remaining three classes are ionotropic receptors, or ion‐gated channels, that consist of NMDA, AMPA, and kainite receptors, which are readily distinguished by agonists, antagonists, kinetics, and permeability. Ionotropic glutamate receptors are composed of a tetramer of four subunits, with each representative monomer consisting of three transmembrane segments, a large extracellular glutamate‐binding domain, and a cytosolic loop that lines the channel pore (Figure 1).
Illustration of prototypic ionotropic receptor subunit. A subunit consists of a large extracellular N‐terminus domain, a membrane spanning segment (TM1), a segment that partially enters the membrane (TMII), a glutamate‐binding domain, two more membrane spanning segments, and an intracellular c‐terminus.
NMDA receptor hypofunction has long been proposed as one of the major hypothesis for the pathophysiology of schizophrenia [6]. NMDA receptors are highly abundant within the forebrain and are responsible for regulating a variety of neuronal pathways; theoretically, damage to the glutamatergic system could underlie many pathologies of the central nervous system. Accordingly, there is an overwhelming amount of evidence illustrating that NMDA receptor dysfunction contributes to the neurophysiology associated with schizophrenia [6, 7]. For instance, in postmortem subjects with schizophrenia, disruptive mutations of NMDA receptor subunits were revealed in the prefrontal cortex, hippocampus, and thalamus [8, 9]. Furthermore, it is well established that administering noncompetitive NMDA receptor antagonists such as phencyclidine (PCP), MK‐801 (also known as Dizocilpine), and ketamine can mimic the pathophysiology and behavioral attributes of schizophrenia [10–12]. Therefore, treatments that target to improve NMDA receptor function demonstrate an alleviation of schizophrenic symptoms [13, 14]. Finally, genes implicated in schizophrenia have strong associations with NMDA receptor regulation [15–17].
NMDA receptors are typically located on excitatory glutamatergic synapses, although present in many cell types (i.e., GABAergic neurons, dopaminergic neurons, etc.). NMDA receptors are responsible for synaptic plasticity and cortical development, as well as cognitive processes such as learning and working memory [18]. NMDA receptors are a heterotetrameric complex that consists of an obligatory homodimer of NR1 and homodimers or heterodimers of either combination of NR2A‐D or NR3A‐D subunits (Figure 2). The NMDA channel is voltage‐dependent and ligand‐gated, and highly permeable to Na+, K+, and Ca2+, causing depolarization of a cell and subsequent excitation and activation of intracellular signaling pathways. Although NR1 subunits are required for NMDA receptor function, NR2/NR3 subunits are specialized and critical for functional diversity such as calcium permeability, decay time, open channel time, and pharmacology sensitivity. In addition, NR1 and NR2 subunits contain distinct sites that bind glycine, PCP, and Mg2+ that modulate the activity of NMDA receptors (Figure 2).
Schematic diagram depicting a NMDA receptor complex. Glutamate binds at NR2/NR3 complex and co‐agonist glycine or D‐serine binds at NR1 complex. Upon depolarization, Mg2+ is removed. NMDA receptor permeates Na+ and Ca+ influx and K+ efflux upon activation. Binding sites for PCP, ketamine, and MK801 are included (Figure was modified from Snyder et al. [
Developmentally, there is an NR2B‐ to NR2A‐subunit switch that occurs from childhood‐to‐adulthood in most brain regions that facilitate synaptic maturation [19]. NR2B protein expression levels are highly abundant during early development and decline into adulthood; in contrast, NR2A levels begin low and rise in adult. Both subunits are essential for prefrontal synaptic plasticity and function; however, NR2B plays a more dominant role. For instance, in the prefrontal cortex, NR2B levels remain high into adulthood and are important for working memory function [20, 21]. NR2B‐containing NMDA receptors play a major role in calcium (Ca+) influx at the postsynaptic membrane, as NR2B receptors have slower kinetics, thus a slower decay time compared to NR2A‐containing NMDA receptors. This indicates that NR2B receptors conduct a large amount of Ca+ and Na+ due to the prolonged open channel state. Although NR2B is essential for cognition processes within the adult, an overabundance may be hazardous due to the significant increase in Ca+ conductance that could lead to excitotoxicity and neuronal death [21]. Therefore, NR2B/NR2A composition during development is extremely critical for normal synaptic maturation.
A major finding discovered by functional imaging studies was reduced activity in the dorsolateral prefrontal cortex (dlPFC) in patients with schizophrenia. The overall reduction in neuronal activity in the dlPFC could explain the cognitive deficits and negative symptoms. There is consensus that NMDA receptor hypofunction is strongly associated with the pathophysiology of schizophrenia. In human studies, single‐photon emission computed tomography (SPECT) shows “hypofrontality” patients suffering from schizophrenia [22]. Furthermore, there are genetic implications that show single‐nucleotide polymorphisms (SNPs) and a reduction in NR1 protein and mRNA in the dorsolateral prefrontal cortex in postmortem subjects of schizophrenia [9, 23]. Additionally, exome sequencing of patients with schizophrenia also displays disruptive mutations in genes that encode NMDAR subunits and NMDA receptor‐associate scaffolding proteins, such as PSD‐95 and SAP102 [24, 25]. These findings would suggest a lack of and/or function at the postsynaptic membrane of excitatory synapses that could be responsible for the cellular phenotypes of the disorder.
\nNoncompetitive NMDA receptor antagonists such as PCP, MK‐801, and ketamine have been extensively used to study the symptoms associated with schizophrenia in both human subjects and animal models [26]. Indeed, these studies have shown to mimic the effects of schizophrenia, corroborating the glutamatergic hypofunction hypothesis. Individually, PCP induces psychotic symptoms in healthy humans that resemble schizophrenic‐like behavior; MK‐801 elicits positive and negative symptoms; and lastly ketamine administration was shown to imitate the positive, negative, and cognitive deficits seen in schizophrenia [11]. In rats, NMDA receptor antagonists cause deficits in working memory, executive functions, and enhanced locomotor activity [27].
High‐risk genes associated with schizophrenia such as DISC1, dysbindin, neuregulin, COMT, and G72/G30 genes, responsible for neurodevelopment, neuronal growth, and migration, have all shown to be involved in NMDA dysfunction leading to schizophrenia [15]. The most prominent of the genes is
Environmental factors during development, such as infection, drug use, parental age, prenatal and early postnatal or childhood stress, have all been linked to the emergence of schizophrenia [33]. In addition, NMDA receptor function is susceptible to the latter environmental risk factors during adolescence, potentially contributing to the onset of the disorder [6, 33, 34]. This could be due to an alteration in NMDA receptor gene expression, as major transcriptional factors such as the cAMP response element binding protein (CREB) are extremely sensitive to environmental stimuli [35]. Previous studies describe that neurodevelopment in the prefrontal cortex is altered in patients with schizophrenia due to a substantial increase in synaptic elimination of glutamatergic excitatory synapses [36].
\nNMDA receptors are also influenced by posttranslational modifications such as ubiquitination, palmitoylation, and phosphorylation [34]. NMDA receptor phosphorylation is responsible for regulating receptor trafficking, stabilization, kinetics of the channel, and kinase activation. These processes are important for synaptic plasticity during neurodevelopment and if dysregulated could be highly responsible for the pathologies of schizophrenia [7]. NMDA receptor subunits are phosphorylated at serine/threonine and tyrosine residues, providing substrate sites for kinases such as Src family of kinases (SFK), casein kinase 2 (CK2), cAMP‐dependent protein kinase A (PKA), cyclin‐dependent kinase 5 (Cdk5), protein kinase C (PKC), and Ca2+/calmodulin‐dependent protein kinase II (CaMKII) [37–40].
\nOther modification processes such as palmitoylation and ubiquitination have also been directly linked to schizophrenia [41]. There is evidence of NMDA receptor dysregulation due to anomalous modifications that could potentially lead to neuropsychiatric disorders. Palmitoylation is a process that allows the covalent attachment of palmitate group to the cysteine residues of proteins that are facilitated via thioester bonds. Recently, it has shown to be involved in regulating NR2 subunit trafficking during neurodevelopment and synaptic plasticity [42] and is altered in a mouse model of 22q11.2 deletion syndrome. Ubiquitination is a process involved in the targeting and removal of proteins and is responsible for regulating NMDA receptors degradation during development. Specifically, subunits such as NR1 and NR2B undergo polyubiquitination at the synapse [41]. Nonetheless, palmitoylation and ubiquitination require further investigation in its role in NMDA receptor regulation and potential implication in schizophrenia.
Selective intracellular signal transduction pathways, such as the AKT‐GSK3β pathway, at excitatory glutamatergic synapses regulate NMDA receptor functions, and are associated with high‐risk genes involved in schizophrenia. AKT, also known as protein kinase B, is a serine/threonine kinase involved in neuronal plasticity, migration, protein synthesis, and cell death [43, 44]. Glycogen synthase kinase 3β (GSK3β) is also a serine/threonine kinase that is downstream of AKT and upstream of beta‐catenin [45]. Moreover, GSK3β knockdown leads to a reduction in NMDA receptor current [46]. AKT phosphorylation is a negative regulator of GSK3β activity; similarly, GSK3β phosphorylation induces beta‐catenin degradation. High‐risk genes such as DISC1, dysbindin and NRG1 are all modulators of the AKT‐GSK3β signaling pathway [34]. For instance, reduced DISC1 protein expression causes a decrease in AKT phosphorylation, and thus an increase in GSK3β activity [47]. In addition, reducing GSK3β activity can alleviate the behavioral impairments observed in DISC1 mouse models [48, 49]. These data suggest a link between high‐risk schizophrenia genes and intracellular pathways, such as the AKT‐GSK3B signaling pathway, that regulate neuronal plasticity. Theoretically, it can be assumed that the high‐risk schizophrenia genes would affect the AKT‐GSK3β signaling pathway, and thus cause NMDA receptor dysfunction, leading to aberrant neuronal systems that are responsible for the positive, negative, and cognitive symptoms observed in schizophrenia.
Typically, drug treatment for schizophrenia patients consists of antipsychotics, such as clozapine, that target D2 receptors to relieve the positive symptoms. However, a significant portion of schizophrenia subjects do not respond well to D2 antagonists; moreover, the negative and cognitive impairments are barely affected by treatment with antipsychotic drugs. As a result, medical professionals are testing new pharmacological agents that target NMDA receptors as a therapeutic option. Due to the observed glutamate hypofunction impairment in patients, investigative studies have focused on the enhancement of NMDA receptor function. Therefore, high doses of glycine agonists (60 g/day) that act upon the glycineB modulatory site are used to increase NMDA receptor function [13]. These agonists have been shown to modestly improve the negative and positive symptoms of schizophrenia and are currently being utilized as an adjunctive treatment to primary therapy with D2 antagonists. An alternative option is to target the glycine transporter‐1 (GlyT‐1) with the selective inhibitor, sarcosine, to increase glycine availability for NMDA receptor binding [14]. Sarcosine administered at 2 g/day have shown to improve negative and cognitive symptoms of schizophrenia. Other drugs include
It is theorized that NMDA dysfunction in neuronal subtypes of GABAergic and dopaminergic neurons collectively contribute to the neuropathologies of schizophrenia. More specifically, investigators speculate that NMDA receptor hypofunction occurs on GABA interneurons (see Figure 1 in [6]). Glutamatergic neurons have direct interaction with GABA interneurons, such as basket and chandelier cells, within the cortico‐limbic circuitry. These interneurons are responsible for suppressing output from glutamate‐releasing pyramidal cells, and due to recurrent collaterals from the two cell types, causes an inhibitory feedback loop. However, if GABAergic activity were suppressed, due to NMDAR dysfunction, it would lead to disinhibition of pyramidal neurons and excessive firing within the cortico‐limbic circuit. Physiologically, the excitotoxicity could have multiple effects on circuitry such as changes in membrane potential, receptor desensitization, or cell death. These results would have a twofold effect; first, the GABAergic downregulation would lead to negative symptoms and cognitive deficits. And second, the resulting excess glutamate release of cortico‐pyramidal neurons could activate dopaminergic systems that lead to positive symptoms and further cognitive impairments. The glutamate‐GABA systems in the forebrain, especially prefrontal cortex, are intertwined to produce prefrontal‐dependent cognitive function, as proposed in Figure 3. Still, how these two systems interact to induce phenotypes and symptoms in schizophrenia remains to be determined.
Cross‐connections between NMDA receptors, GABAergic neurotransmission, and PFC‐dependent cognition. PFC persistent neuronal firing is the foundation of working memory with NMDA receptor activity playing a substantial role in this process [
Cortical interneurons were first documented with Golgi staining by Santiago Ramón y Cajal and referred to as the “cells with short axons” [60]. Cortical interneurons are typically distinguished by four common attributes: locally projecting, aspiny or sparsely spiny dendrites, small cell soma, and GABAergic. Interneurons exhibit a large diversity and are categorized based on several features including morphology, connectivity, neurochemistry, and physiology [60–62] (Figure 4). Due to the heterogeneity of this neuronal population, interneurons can fall into more than one category, showing a great degree of overlap; therefore, interneurons fall more along a spectrum rather than into distinct subgroups. Although this group is very diverse, axonal arborization and the downstream target domain plays a major role in classification and can reveal a lot about a circuitry\'s function. Essentially, where and how an interneuron synapses onto a target cell ultimately effects neuronal output and therefore function [61], is an essential question for cortical function. Interneurons are crucial for synchronizing and shaping the excitatory activity of pyramidal cells to form a ‘task‐specific microcircuit’ for a particular brain region [61]; the prefrontal cortex contains this microcircuit specialized for working memory [62].
Cortical interneuron connectivity and firing patterns categorized by calcium‐binding neurochemical markers. Calretinin small bipolar cells target proximal dendrites and other GABAergic interneurons. Calbindin neurons, small basket cells, and Martinotti cells, target proximal dendrites/soma and distal dendrites. Parvalbumin interneurons are fast‐spiking and are further classified into large basket, nest basket, and chandelier (Ch) cells. Large basket cells target proximal dendrites and the soma. Nest basket cells target the cell soma and chandelier cells synapse on the axon initial segment (Modified from Lewis et al. [
Three common GABAergic neocortical interneurons that will be highlighted and addressed in this chapter are neurochemically defined based on the calcium‐binding proteins they express: calbindin (CB), calretinin (CR), and parvalbumin (PV) neurons. Calbindin interneurons (also referred to as somatostatin) makeup ~30% of the cortical interneuronal population and are generally characterized as having either small basket or Martinotti morphology. Commonly, small basket cells target proximal dendrites or the cell soma and electrophysiologically display regular‐spiking non‐pyramidal (RSNP) activity. Martinotti interneurons exhibit a burst‐spiking non‐pyramidal (BSNP) firing phenotype and target distal dendrites. Calretinin interneurons are the least prevalent (~15%) and stereotypically have small bipolar morphology. These interneurons target proximal dendrites and also other GABAergic interneurons having either RSNP or BSNP firing. Parvalbumin interneurons are fast‐spiking cells and neurochemically the largest group, making up half of the interneuronal population in the cortex. PV interneurons target all along a pyramidal cell, with large basket cells at the proximal dendrites/soma, nest cells at the soma, and chandelier cells targeting the axon initial segment. For the remainder of this section, we will focus on parvalbumin chandelier cells since these are the interneurons known to play a major role in prefrontal cortex‐dependent working memory and also have been implicated in the pathophysiology of neuropsychiatric disorders such as schizophrenia [60, 62].
GABA receptors respond to the ligand GABA, which is the main inhibitory neurotransmitter in the mammalian central nervous system. GABAergic neurons are therefore important for modulating neuronal activity throughout the brain and spinal cord [63–70]. The enzyme L‐glutamic acid decarboxylase (GAD) synthesizes GABA in presynaptic terminals through the conversion of glutamate to GABA. GABA is then stored in vesicles waiting for release following neuronal activation [67]. Extracellular GABA can bind to either postsynaptic or extrasynaptic receptors located on presynaptic neurons, leading to hyperpolarization of the target cell [69]. Postsynaptic receptor activation mediates phasic inhibition, whereas extrasynaptic activation mediates a tonic inhibitory state [65, 69]. To remove extracellular GABA in the synaptic cleft, GABA transporters located on the presynaptic terminal and glial cells regulate neurotransmitter uptake; this process is extremely important to retain a balanced circuitry and prevent over inhibition [67].
\nGABA receptors are classified into two groups, GABAA and GABAB, with GABAC receptors recently categorized as a subtype of GABAA rather than their own distinct class. Receptor characterization is based on structural, biochemical, modulatory, and physiological differences [67–70].
\nGABAA receptors are ionotropic chloride channels, conducting fast inhibitory neurotransmission, in which a ligand (i.e., GABA) binds and directly induces pore opening [67, 69]. GABAA receptors are members of a much larger group referred to as the Cys‐loop ligand‐gated ion channel superfamily, which also encompasses nicotinic acetylcholine receptors (nAChRs), glycine receptors, and 5‐hydroxytryptamine type‐3 (5‐HT3) receptors [65, 68–70]. The diverse pharmacology displayed by GABAA receptors sets them apart from the rest of the family and is clinically relevant targets for anticonvulsant, anxiolytic, and sedative drugs [65, 69]. Typically, GABAA receptors are heteropentameric structures composed of five different subunits (α1‐6, β1‐3, Υ1‐3 (Υ2S, Υ2L), ρ1‐3, δ, ε, θ, and π), each containing four transmembrane domains (TM1‐4) (Figures 5 and 6). Five out of twenty‐one available subunits comprise the complex, forming a pore from the TM2 segments [67–70]. The top three most common structural compositions in the brain are α1β2γ2, α2β3γ2, and α3β3γ2, with the likely stoichiometry of 2α:2β:1γ [65, 67, 69].
GABAA receptor structure and cross‐section. GABAA receptors contain five subunits, typically in the ratio of 2α:2β:1γ, with the transmembrane domain 2 (TM2) forming the chloride‐permeable pore. Each subunit consists of four hydrophobic transmembrane domains with the N‐ and C‐ terminus facing the extracellular side. The GABA binding site is located at the interface between α and β subunit, while the benzodiazepine (BZs) binding site sits at the junction between α and γ. GABA binding triggers channel opening, allowing inward chloride ion flux, whereas benzodiazepine binding potentiates the GABA‐induced chloride influx [
GABAA receptor transmembrane topology. Each subunit consists of four transmembrane domains. The N‐ and C‐terminus lie on the extracellular side, with the N‐terminus being the site of action for several drugs. A large intracellular domain exists between TM3 and TM4, providing a hub for a majority of the protein‐protein interactions as well as posttranslational modifications (palmitoylation, ubiquitination, phosphorylation) [
Benzodiazepines potentiate the inhibitory effects of GABA by allosterically altering the receptor and increasing its affinity for GABA [67]. Benzodiazepine‐insensitive receptors are formed when the γ subunit is replaced by δ, ε, or π [69]. Rho (ρ) subunits are unique because these subunits predominately co‐assemble together to form homo‐ and hetero‐oligomers. Previously, ρ oligomers were classified as GABAC receptors, but more recently are considered a subclass of GABAA receptors. Even though GABAA and GABAC receptors are structurally very similar to one another, these receptors formally fell into two different groups based on their differential pharmacology and physiology [69, 70]. A major difference between the A and C subtypes are that GABAA receptors are selectively blocked by bicuculline and modulated by benzodiazepines, steroids, and barbiturates. GABAC receptors are not sensitive to the same drugs, but rather are blocked by 1,2,5,6‐tetrahydropyridin‐4‐yl) methylphosphinic acid (TPMPA) and activated by Z‐4‐amniobut‐2‐enoic acid [cis‐aminocrotonic acid (CACA)]. Additionally, GABAC receptors exhibit a higher sensitivity to GABA, conduct less current, have longer channel opening times, and desensitize slower in the presence of an agonist. GABAC receptors, however, are no longer classified as a separate division, but are now considered a GABAA‐ρ subclass because they are exclusively constructed of ρ subunits [70].
\nGABAB receptors are metabotropic Ca2+ or K+ channels, conducting slow inhibitory neurotransmission, in which a ligand (i.e., GABA) binds and indirectly induces pore opening through G‐protein coupling activation and second messenger signaling [64, 67, 68] (Figure 7). Functional GABAB receptors exist as heterodimers composed of one GABAB(1) (1a‐g) and one GABAB subunit [70]. The GABAB(1) subunit binds to GABA and is mandatory for functional receptors, whereas the GABAB2 subunit is responsible for G‐protein coupling and signaling. The most prevalent GABAB isoforms are
GABAB receptor structure. GABAB receptors are heterodimers composed of either a 1a or 1b subunit and a mandatory 2 subunit. GABAB receptors are G‐protein coupled and are activated by the ligand GABA, which binds to the 1 subunit. Following GABA ligand binding, G‐protein activation induces opening of postsynaptic potassium channels and closing of presynaptic calcium channels, hyperpolarizing the target cell (Modified from Emson [
GABAA subunit expression has been well characterized in the rat brain [66]. Several subunits exhibit broad expression throughout the nervous system, fluctuating across development and regions. However, a few subunits demonstrate regional or cell‐type specificity. For example, α6 subunit is exclusively expressed in cerebellar granule cells and the ρ subunit is largely restricted to the retina. Peripheral expression of GABAA receptors has been demonstrated in the liver, smooth airway muscles, the lung, immune cells, and the intestines [68]. GABAB receptors are localized in the striatum, brainstem, thalamus, hippocampus, cerebellum, and cortex. The 1b subunit is the most prevalently expressed across all brains regions, except for the striatum in which the 1a subunit is the most abundant [64].
The prefrontal cortex (PFC) is the neuroanatomical hub for executive functions such as working memory, which can be metaphorically thought of as the brain\'s blackboard [21, 71]. Incoming stimuli are transiently stored, manipulated, updated, and guide goal‐directed behavior [72]. Working memory is dependent on prefrontal circuitry involving the unique balance between pyramidal Delay excitatory neurotransmission and GABAergic interneuronal inhibition [57, 62, 71]. Excitatory Delay cells become activated upon presentation of a salient cue and sustain neuronal activity throughout a delay period, essentially ‘remembering’ the cue, and allowing an appropriate response. For instance, Figure 8 represents an example of single unit prefrontal Delay cell activity in the primate dorsolateral prefrontal cortex (DLPFC) during an oculomotor delayed‐response task. In this working memory task, subjects are trained to fix their gaze at the center. A single cue is presented somewhere in the 360° perimeter, followed by a brief delay period in which the cue is absent. After the delay period, an appropriate response would be an eye saccade in the direction that the cue was first presented.
Single unit electrophysiological activity of a Delay cell in the primate DLPFC during a working memory task. The onset of Delay cell activity is triggered by the presence of relevant stimuli, or a cue. In the absence of a visual cue, Delay cells persistently fire during the delay period and allow for the generation of a goal‐directed response (e.g., saccade). The sustained neuronal firing during the delay period is hypothesized to be the neural correlate of working memory and depends on both excitatory pyramidal activity as well as fast‐spiking GABAergic interneurons in the DLPFC [
Working memory, the sustained neuronal activity that occurs during the delay, is not only dependent on prefrontal pyramidal cells, but also fast‐spiking GABAergic interneurons [57, 62, 71]. Pharmacological evidence supports the importance of fast‐spiking interneurons in the DLPFC for working memory function. Administration of a GABAAR antagonist, bicuculline, lead to impaired mnemonic tuning during an oculomotor delayed‐response task. Therefore, working memory, particularly sustained neuronal activity during the delay period, depends on GABAA receptors. Furthermore, GABAergic hypofunctioning in the DLPFC partly contributes to working memory deficits [62, 75]. GABAergic neuronal activity and its role in working memory function are also connected to gamma oscillations. Gamma oscillations, which fall in the band range between 30 and 60 Hz, are required for working memory function. A research study conducted in 2003 reported that gamma band oscillations increased proportionally with working memory load [57, 62, 76]. More specifically, fast‐spiking PV interneurons are a crucial input for gamma rhythm generation. Inhibition of PV interneurons attenuates gamma oscillations, whereas driving PV neuronal activity initiates gamma‐frequency rhythms [62]. Excitatory pyramidal output in the prefrontal cortex is modulated by inhibitory gamma oscillations, largely driven my PV‐interneurons, essentially fine‐tuning the circuit and allowing for proper working memory function. Conclusively, PFC‐dependent working memory involves a symbiotic balance between excitatory pyramidal output and fast inhibitory activity of PV‐interneurons, which shapes and fine‐tunes the circuit.
Schizophrenia is a debilitating neurodevelopmental disorder in which afflicted individuals suffer from cognitive impairments, working memory deficits being a core feature. Unfortunately, available medications poorly treat cognitive symptoms albeit cognitive performance most strongly determines functional outcomes. Working memory function requires fast and synchronous inhibition of pyramidal neuronal networks within the prefrontal cortex, which is regulated by GABAergic neurotransmission. Because individuals afflicted with schizophrenia display reduced frontal cortical gamma oscillatory power in the DLPFC during a working memory task and cognitive impairments are a core feature, disrupted GABAergic signaling is highly implicated in the pathology of this disorder [57, 62]. Glutamic acid decarboxylase (GAD), the enzyme that synthesizes GABA and PV prefrontal expression is reduced in schizophrenia, further demonstrating a GABA deficit in this neuroanatomical region [57, 62, 77–79].
\nNMDARs have been demonstrated to be vital throughout neurodevelopment, with NR2A specifically involved in the maturation and maintenance of GABAergic PV interneurons. A previous study showed that NR2A hypofunction leads to reduced GAD67 expression and PV immunoreactivity [59]. It is important to note that the reduction in parvalbumin is not due to density (i.e., interneuronal cell number), but rather a decrease in protein level expression. Researchers hypothesized that this suppressed expression in GAD67, and therefore PV, leads to GABAergic malfunctioning or hypofunctioning [57, 59, 62, 77]. Interestingly, GAD65, the other isoform, does not demonstrate such impairments. Cortical levels of GABA remained unaltered in animals without GAD65, thus demonstrated specificity to the GAD67 isoform [57, 62, 80]. Reductions in GAD67, however, are associated with decreased GAD enzymatic activity as well as GABA levels in the cortex [62, 81]. Individuals suffering from schizophrenia were also reported to have increases in the α2 subunit of GABAA receptors and decreased GABA transporter 1 (GAT1) levels. GAT1 are proteins important for the removal of GABA from the synaptic cleft, while the GABAA α2 subunit is highly concentrated at the axon initial segment of pyramidal neurons and mediate fast synaptic inhibitory neurotransmission (Figure 9). Therefore, this inverse correlation is speculated to act as a compensatory mechanism to increase the effect of GABA on postsynaptic cells and return the circuitry back to homeostatic conditions [57, 62, 82].
Comparison of normal and schizophrenia synaptic connection at the junction between a parvalbumin chandelier interneuron (PVCh) and a pyramidal axon initial segment. A core feature of schizophrenia is GABergic deficits; in the rebalanced circuitry, presynaptic expression of GABA transporter 1 (GAT1) on the axonal terminals of the GABAergic interneurons is decreased, while the expression of GABAAα2 receptors at the axon initial segments of pyramidal neurons is increased (Modified from Lewis et al. [
However, what remains to be unanswered is which proceeds which: NMDA receptor hypofunctioning or GABAergic deficits. In order to understand how cognitive impairments in schizophrenia emerge, we must first uncover the molecular underpinnings that lead to the root of these dysfunctions.
In individuals afflicted with schizophrenia, a compensatory mechanism to balance the circuit naturally gets set into motion. In order to offset the shift towards excitation, GAT1 is reduced presynaptically and GABAAα2 receptors are increased postsynaptically. These changes result in levels of GABA remaining in the synaptic cleft longer and more postsynaptic receptors available for activation. GABA Aα2 receptor agonists offer as a promising therapeutic to pharmacologically target the pathophysiological inhibitory deficit in the DLPFC [62]. GABAAα2 receptors are predominately located at the axon initial segment of pyramidal neurons and therefore should exhibit limited off‐target effects on other domains [83]. GABAAα2‐selective benzodiazepines are a likely candidate because these agents would only activate and potentiate GABAAα2 receptors in the presence of GABA, preventing dysregulated inhibition that would otherwise result from direct activation of these receptors. Treatment with GABAAα2‐selective benzodiazepines might also offer an additive benefit of reducing anxiety in patients, due to the anxiolytic effects that are mediated by GABAAα2 receptors [62, 84]. In aims to provide better treatment options, further research is warranted to elucidate the underlying mechanism of GABAergic hypofunctioning, which largely contribute to working memory deficits seen in schizophrenia.
Working memory is a key executive function that guides an organism\'s response by filtering out important information from the external environment and applying relevant details towards a goal‐directed behavior. This process requires the output of a specialized circuit localized within the prefrontal cortical circuits. The synchrony between excitatory pyramidal Delay cells, which produce the necessary persistent neuronal activity, and fast‐spiking GABAergic neurotransmission, which in turn shape and fine‐tunes the pyramidal cell output, underlies working memory. Both the excitatory and inhibitory components (such as NMDARs and GABAARs) are crucial in the maintenance of this delicate process, and dysregulation of either likely serves as a pathophysiological process in schizophrenia. Working memory deficits are a core feature of schizophrenia with NMDA and GABA hypofunctioning highly implicated in the etiology of the disease. Future research is warranted for further deciphering whether NMDA hypofunctioning precedes GABAergic deficits or vice versa.
This work was supported by NIH R01MH085666, R21MH110678, and NARSAR Independent Investigator Award 2016 from the Brain and Behavior Research Foundation to W.J. Gao.
In the recent past, Pneumatic Artificial Muscles (PAMs) have assumed a key role in the implementation of movement in soft robots. The strong research attention is due to their interesting mechanical characteristics for soft actuation (i.e., robustness, high pulling force, high-power to mass ratio, and high energy efficiency), compared to other mechanisms exploiting different actuation sources (i.e., electric motor or tendon driven [1, 2], piezoelectric actuators [3], dielectric elastomer actuators [4, 5], shape memory alloys [6, 7] or polymers [8], and ionic polymer-metal composite actuators [9], etc.). Many researchers and engineers have explored quite a few design principles for PAMs, and a wide range of robotic applications was introduced (i.e., industrial robots [10, 11], wearable [12, 13, 14], or medical devices [15, 16, 17], etc.) where some of the challenges that rigid-bodied robots cannot overcome were addressed [18, 19, 20, 21].
From the material point of view, PAMs are generally built from soft materials that can undergo large deformation under external forces. Softness may result from their intrinsic characteristics (i.e., chemistry) or because of a specific design of their structure [22], or both.
In the design phase, the mechanical performance of PAMs (i.e., deformation ratio and blocking force) can be tuned by optimizing some geometrical parameters to achieve specific morphologies. In particular, a tradeoff between deformability and stiffness should be met, depending on the desired mechanical performances. In the literature, different design principles have been used. As most of such designs show, radial strain is an important parameter given its main influence on the linear deformation ratio of the soft actuator.
Most soft pneumatic actuators operating with positive pressure (also called inflatable fluidic actuators) involve—(i) a section of the actuator that expands with pressure; or (ii) strain limiting components that guide the elastic expansion in the desired direction [23].
In the former case, topological and/or morphological approaches are undertaken to produce radial expansion/contraction by employing specific geometries, such as zigzag patterned pleats or convolutions. For instance, the Peano fluidic actuator consists of a set of tubes arranged side-by-side [24]. At null pressure (atmospheric pressure), the actuator remains completely flat. Once positive pressure is applied, each cylindrical tube is inflated, leading to a vertical contraction. Another example is to exploit a bellow that can reduce radial strain, and enlarge longitudinal strain. This design principle is quite useful since biaxial deformability (contraction and elongation) is enabled upon positive pressure and vacuum [25, 26]. In the latter case (ii) multi-material-based approaches were addressed, such as in McKibben actuators or pleated PAMs (PPAMs). A McKibben actuator generally consists of a cylindrical flexible rubber and/or silicone bladder, sheathed with an inextensible fiber network intersected at a certain angle [27, 28]. Different kinematic trajectories are enabled according to the intersection angle (e.g., extension at the intersection angle of more than 54.7 deg., otherwise contraction) [29, 30]. On the other hand, a PPAM generally consists of a membrane having many pleats, with high tensile stiffness (i.e., woven polyester cloth or Kevlar fabric) [31, 32]. This allows the actuators to contract with dramatic increases in diameter when positive pressure is applied. The pleats are arranged along the longitudinal direction, and as the skin begins to swell, the overall structure undergoes a radial shortening and expansion [33].
As mentioned above, desired mechanical performance for inflatable fluidic actuators can be achieved by adopting proper design principles. Nevertheless, the mechanisms exploiting volumetric expansion are commonly vulnerable, depending on material failures (i.e., delamination, fracture), resulting in degradation of the actuator, and poor reliability. Moreover, given the needed volumetric expansion and omnidirectional deformation, they are more likely to be applied where large spaces are available [23], Vacuum-powered pneumatic artificial muscles (or V-PAMs) represent a promising opportunity in soft actuation and solve some of the issues encountered by inflatable fluidic actuators. They rely on decreasing the volume with vacuum and, generally, they do not expand radially during movement. Rather, they can perform linear movements with a relatively low input vacuum pressure (within few hundred kPa) and avoid a stress concentration that could possibly incur along the overall structure at both local and global levels [34, 35]. These characteristics are pursued to achieve high reliability, and ensure a high bandwidth, allowing to saturate at the desired state with a fast response.
As with inflatable fluidic actuators, the constituting materials strongly influence performance, particularly the deformation ratio. Indeed, due to the incompressibility of the materials, the ratio of bulk modulus (K) to shear modulus (G) is extremely large or becomes almost infinite in case Poisson’s ratio is close to 0.5 [36]. Thus, only a slight shortening is achievable until internal walls contact, and collapse, and linear deformation hardly occurs, as shown in Figure 1. Moreover, the overall deformations generally include undesired kinematic trajectories (i.e., torsion or bending) due to structural instability (i.e., column squirm and/or buckling). For these reasons, V-PAMs need to be rigorously designed by taking into account geometry and/or morphology, structural stability for imposed deformation and/or load, etc.
Left, basic operating principles of pneumatic artificial muscles (PAMs). Right, a classification of vacuum-powered PAMs (V-PAMs) based on the different design approaches: morphological design [
Various design principles can be found for V-PAMs in the literature, however (to the authors’ knowledge), there are still no comprehensive articles on such an emerging topic, including design, fabrication, and materials. In this work, an overview of the developments of vacuum-powered actuators is provided and they are classified as based on morphological design, origami architecture, and structural instability. The fabrication protocols and soft materials involved are addressed, and their advantages and limitations are discussed and compared.
Soft pneumatic actuators can benefit from designs having zigzag patterns since they enable shear deformation, by enlarging deformations while avoiding structural instability. Typical designs consist of multiple convolutions or corrugations in series along the vertical or horizontal direction of the actuator. In this section, an overview of different types of morphological designs, including actuators with convoluted (or corrugated) skin and pleated skin, is provided by highlighting their pros and cons.
Convolution and/or corrugation in skin design includes a crumpled thin membrane. A bellow represents a unique structure made of multiple convolutions periodically arranged along the vertical direction of the structure, as shown in Figure 2a. In principle, its mechanical performance can be determined by geometrical parameters (i.e., number of convolutions, mean diameter, total length, etc.). The deformation can be defined as either positive or negative when subjected to extension or compression. In accordance with EJMA1 standard, the axial stiffness per convolution can be written as [41, 42]:
V-PAMs with morphological design. (a–c) schematic diagrams that show design parameters for a bellow actuator skin. (d) the 3D-printed linear soft vacuum actuator (L-SOVA). Reproduced with permission [
where
Given Hooke’s law (
where
Moreover, from Eqs. (1)–(3), it is worth mentioning that the axial stiffness of the bellow is strongly influenced by the skin thickness (
Based on such theoretical background, several examples can be found in the literature. Digumarti et al. presented a Hyper-Elastic Bellow (HEB) actuator capable of a euglenoid motion, where both axial and radial strains are enlarged [26]. The bellow, having a half angle of 38.66° with a total length of 50 mm and an outer diameter of 45 mm, was fabricated by using a soft elastomer (Dragon Skin™ 10 SLOW, Smooth-On). The HEB was capable of 40% contraction upon a small vacuum pressure of 8 kPa. More recently, by exploiting additive manufacturing, Tawk et al. presented a 3D-printed Linear Soft Vacuum Actuator (L-SOVA), capable of 51% contraction with a payload of 27.66 N. Another example is to exploit the integration of rigid parts (rings), periodically spaced along the actuator length. This way, Felt et al. showed that a bellow type PAM, made of a tubular thin membrane, can lift a high payload of 21.35 N at −5.52 kPa [47]. Such investigation on V-PAMs has demonstrated that this kind of actuation can enable a high contraction ratio and blocking force, opening the way to new PAM concepts. In refs. [38, 48], our group exploited rigid rings to improve axial stiffness and combined them with open-cell foam modules to build an Ultralight Hybrid PAM (UH-PAM) made of open-cell foam and elastomeric bellow skin (see Figure 2e). In this study, we investigated an optimal geometry of the skin and emphasized that even with a light weight of 20 g promising mechanical characteristics can be achieved. Due to the open-cell foam and rigid rings interfaced at each convolution, the axial stiffness of UH-PAM was enhanced, resulting in a high payload of 3 kgf and a high contraction ratio of 52%.
Furthermore, a bellow textile muscle (similar to the Peano fluidic muscle), made of fabric and multiple round discs along its edges and center, was developed to enlarge the deformation ratio [49]. Due to such inflatable and flexible material, the bellow’s textile muscle can be displaced to extremely flat (i.e., high contraction ratio of 89%) with a high payload of 32 N at −5 kPa. Recently, Yang et al. extended this work and presented a high-displacement PAM, converting the horizontal motion of the bellow actuator to a vertical motion, based on the contraction when subjected to positive air pressure [45]. Given that the contraction ratio of the bellow is strongly influenced by its thickness, exploiting textile for the skin enables to deform it to a completely flat configuration, upon vacuum pressure. On the other hand, the thin-walled structure could suffer from a lack of axial stiffness. Thus, the bellow structure does not sustain its own weight, which implies that the actuator cannot be set along the horizontal direction (e.g., beam orientation), and it should be placed along the gravity direction. Hence, for vacuum-powered bellow actuators, both enhancing the axial stiffness, and reducing the total weight remain open challenges.
A typical pleated airtight membrane creates chambers enabling a linear motion upon vacuum pressure, due to a similar morphological feature of the Robotic Muscle ACtuator (also called ROMAC muscle) [40], as shown in Figure 2f and g. While to the authors’ knowledge no vacuum-powered PAMs exploiting this principle can be found in the literature up to date, presumably mechanical benefits would be significant rather than contractile actuators operated by only positive pressure. Indeed, the created folds distributed along the circumference of the structure allow biaxial deformations. They can be depressurized until the internal walls touch. In principle, the compressibility of the air chamber enables radial contraction, resulting in elongation of the structure upon the vacuum pressure. On the other hand, the air chambers enable the overall structure to exhibit extension upon positive pressure due to significant radial expansion. Such biaxial deformability, mainly due to the deformation in the radial direction, could play a key role in keeping the volume constant during inflation/deflation (i.e., the muscular hydrostat principle [50]), and in enlarging a linear displacement, rather than uniaxial deformation that many PAMs have accomplished so far. Moreover, the tension force that the pleated PAM can produce is adjustable. From a theoretical point of view, the tension force (
where
Origami is a unique technique inspired by Japanese paper folding, which can be created by folding thin sheets along the predefined creases [52, 53, 54]. There are three identical crease patterns in the origami, which are the Yoshimura pattern, Miura-ori pattern, and Kresling (diagonal) pattern [55]. Depending on delivering motion, active or passive origami can be defined – the active origami exhibits movements through the embedded mechanism and/or structure itself. However, passive origami exhibits the motions derived from other actuation sources. Moreover, either supporting motions (i.e., structural stiffness enhancement) or achieving programmable motions can be achieved [56].
As regards the active origami, the deformability is commonly given by a function of a geometrical length (
Origami-inspired design approaches. (a) 2D crease pattern of the 4 x 6 Yoshimura-Ori (DoFs = 26, m = 4, n = 6). (b) an equilateral triangular shaped Origami-based vacuum PAM (OV-PAM) capable of contraction ratio up to 90% and blocking force up to 400 N. Reproduced with permission [
where
In the following, an overview of origami-inspired pneumatic actuators made of different crease patterns is provided, and their design principles allowing for linear motions upon vacuum pressure are introduced.
The Yoshimura pattern, enabling foldable and deployable 3D structure, was introduced in 1955 by a Japanese scientist who first observed a buckling at thin-walled cylinders upon axial compression [53]. The Yoshimura pattern consists of identical isosceles triangles symmetrically connected in each row [56]. This way, it generates a purely translational motion element with high axial stiffness. Due to these characteristics, the Yoshimura pattern can be exploited as, both, a passive origami to reinforce movements [61], and an active origami capable of axial movement [62].
Based on the Yoshimura patterns, Martienz et al. presented novel design principles for actuators to respond to pressurization with a wide range of motions (i.e., bending, extension, contraction, twisting, etc.) [62]. A bellow morphology made of 10 creases enabled high deformability, up to 361% at 17 kPa, and the lifting of high payloads, that is, 1 kgf being 120 times its own weight (8.3 g). This method (i.e., casting of elastomer and paper coating) is versatile and it allowed fabricating an active 3D origami structure capable of movements in different directions. Moreover, to achieve both linear movements and high actuation force upon vacuum pressure, Zaghloul et al. presented Origami-inspired Semi-soft Pneumatic Actuators (OSPAs) based on the accordion and Yoshimura patterns [63]. For the OSPA with the accordion patterns, a high contraction ratio of 36% and blocking force of 124 N were achieved at a vacuum pressure of −80 kPa. Unlike the conventional Yoshimura pattern, a new design principle was introduced by modifying the Yoshimura pattern [43]. The cross section has a unique configuration as an equilateral triangle, as shown in Figure 3b. These morphological features allowed not only the thin film to be folded in an even and ordered manner, but also the actuator to produce a large contraction ratio of up to 99.7%, with a high blocking force of 40 kgf at a vacuum pressure of 60 kPa.
In summary, the Yoshimura patterns enable active 3D origami actuators capable of high deformability and blocking force. These mechanical features are certainly useful to achieve highly versatile and robust soft machines. Moreover, also sensory integration has been investigated. Indeed, Shen et al. embedded optical sensing solution into the origami-inspired PAM (so-called Soft Origami Optical-Sensing Actuators (SOSAs)) and presented a hybrid underwater 3-DoFs manipulator [59].
The Miura-Ori pattern, introduced by Japanese Kogyo Miura, represents a folding technique consisting of congruent parallelograms forming a zigzag configuration in two directions [64, 65] (Figure 3c). The Miura folding enables high stiffness, compressibility, and extensibility [66]. Its geometry plays a key role in the mechanical properties of the folded metamaterial, exhibiting a negative Poisson’s ratio between the two planar degrees of freedom [67]. Due to such extraordinary mechanical characteristics, this folding pattern was employed for the packaging and deployment of large membranes in space, such as foldable maps or solar panel deployment [68, 69]. From the architecture point of view, two different approaches are available to achieve desired linear deformations—1) a single planar Miura-Ori sheet mainly due to in-plane kinematics; or 2) a 3D folding structure (i.e., bellow) mainly due to out-of-plane kinematics.
As regards in-plane kinematics, Li et al. presented a surface (2D) skeleton made of a standard Miura-Ori pattern and demonstrated its high compressibility of up to 92% upon vacuum pressure [57], as shown in Figure 3d. Moreover, by exploiting asymmetrical out-of-plane motions, a 2D Miura-Ori skeleton was capable of complex motions combining both torsion and contraction. For the 3D folding structures, Reid et al. explored the bistability of the bellow pattern with the Miura-Ori folds and presented a promising technique, enabling arbitrarily complicated bellows with finely tuned fold parameters [70]. To achieve a compressible 3D structure, each bend should be paired, and thus the number of bends was even. Another example is the monothetic foldable part composed of two Miura-Ori units combined up and down. Yu et al. introduced pneumatic foldable actuators (PFAs) capable of biaxial movements upon vacuum and positive pressures [66]. This way, the compression of up to 43% was achieved at −10 kPa. However, the extensibility was limited down to 19% at 10 kPa. It is noted that the movements were mainly dependent on the length change by the folding of the actuator at low vacuum pressure, rather than the volumetric changes by positive pressure.
The Kresling pattern consists of a series of parallel diagonal creases defined by triangular facets [71, 72] (see Figure 3e). Such triangulated cylinder pattern enables bistable movements (i.e., contraction and elongation) facilitated by the buckling of the thin wall [73] while ensuring the fully foldable structure. However, this approach could suffer from mechanical failures (i.e., unbalanced deployment), resulting in coupled longitudinal and rotational motions. In principle, the work (
Due to bistability, the actuators are generally capable of axial deformations together with coupled rotational motions
In origami-skeleton structures, zigzag patterned structure is exploited, as a skeleton made of minimally extensible materials, such as air-tight fabrics and polyethylene [57, 77]. In principle, these compressible skeletons incorporate collapsible structures inspired by origami and/or mechanical springs. Hence, although the skin enveloping the skeletal structure has no morphological features (i.e., bellow or pleated skin), the linear movement is mainly due to the compressible skeletons. More in detail, the vacuum pressure enables the volume inside the film pouch to be evacuated, and it induces a controlled collapse in the direction guided by the skeletal structure [78]. With these findings in mind, Li et al. introduced design principles that enable linear movements and presented Fluid-driven Origami-inspired Artificial Muscles (FOAMs) by exploiting symmetrical zigzag geometry [57]. They investigated the mechanical performance of the FOAMs based on different design parameters and concluded that the maximum contraction ratio can be achieved by exploiting thin zigzag skeletons. Indeed, for the nylon fabric pouches with 0.34 mm thickness, the actuator has shown 50% linear contraction with a blocking force of 201 N. In the case of a thinner film made of polyester material (0.038 mm, with a skeleton thickness of 0.254 mm), an ultralight FOAM (2.6 g) was capable of a blocking force of up to 3 kgf, as shown in Figure 3g. Based on these design principles, Oguntosin et al. developed artificial muscles completely made of soft silicone rubber without any rigid parts [79]. A maximum contractile strain of 67% was achieved upon null load and a vacuum pressure of 34.5 kPa.
Another approach consists in exploiting a mechanical compression spring. Kulasekera et al. presented a Low-Profile Vacuum Actuator (LPVAc) by low-profile spring encased within a polyethylene film pouch that contracts longitudinally when vacuum pressure is applied [80]. This study highlighted that actuation was strongly dependent on the mechanical characteristics of the low-profile spring, and a high force-to-weight ratio was achieved. Indeed, the LPVAc was only 14 g, yet a high contractile strain of 65% and blocking force of 2.2 kgf (that corresponds to 160 times its own weight) were achieved. The same research group extended further this work. An airtight pouch made of a TPU (thermoplastic polyurethane) coated fabric was interfaced with a helical spring skeleton. Hence, the overall weight was reduced down to 2 g, and a high-force-weight ratio (230) was obtained [81]. More recently, they proposed a Thin-walled Vacuum Actuator (ThinVAc) and developed a multi-filament actuator, allowing simple scaling of actuation force while retaining the ability to actuator during deformation [78]. Finally, the weight of the ThinVac was only 1 g and capable of 60% linear contraction and blocking force of 5.2 N upon null load. Thus, an extremely high force-to-weight ratio of 477 was achieved.
The research on these skin-skeleton designs, demonstrating that low weight and large force-to-weight ratio are achievable, led several researchers to develop them further for wearable applications. In particular, in the rehabilitation field of infants (of six months or younger), Mendoza et al. optimized the zigzag patterned skeleton. They presented a Low-Profile Vacuum-Powered Artificial Muscle (LP-VPAM) capable of a 61% linear contraction ratio, with a lifting force of 26.4 N at a low vacuum pressure of 40 kPa [77]. Similarly, the LPVAc has shown strong potential for exploiting them in Sit-To-Stand (STS) motion assistance [80, 82].
Mechanical instabilities in soft PAMs and V-PAMs induce a column squirm (also called buckling), which are considered as mechanical failures in rigid body structures, and result in sudden and significant geometric changes [48, 83, 84, 85]. However, in soft robotics structural instabilities can be fruitfully exploited, and this approach shows promising results enabling new functionalities [84, 86]. Indeed, it has been reported that a reversible buckling in assemblies of elastomeric beams or films can be exploited at a variety of soft robots’ applications, for example, stretchable soft electronics [87, 88], tunable metamaterials [89, 90, 91], or actuators [92]. More importantly, it is remarkable that a structure buckling allows instantaneously trigger large changes in internal pressure, deformation, shape, and exerted force [93].
In this view, it has been shown how a vacuum-driven actuator exploiting a structural instability can achieve an axial deformation due to reversible and cooperative buckling of the beams, enabling an anisotropic change in the shape of the structure [92]. More in detail, such Vacuum-Actuated Muscle-inspired Pneumatic structure (VAMP) was capable of a large longitudinal contraction (up to 40%) with a smaller horizontal deformation (5%), as shown in Figure 4a. Yang et al. expanded this work to develop a Shear Vacuum Actuated Machine (Shear-VAM) capable of a linear motion that works by converting the vacuum pressure, applied perpendicularly to its inextensible lateral surfaces, to a force parallel to them
(a) and (b) working principles of vacuum-powered Pneumatic Artificial Muscle (VAMP) exploiting a structural instability [
Another example is to exploit the characteristics of foams and elastomers. Roberston et al. presented a Vacuum-powered Soft Pneumatic Actuator (V-SPA) and developed 3-DoFs robotic platform [94]. A particular geometry (see Figure 4c) that allows inward compression and buckling of the side walls were employed to avoid possible interferences that could limit the actuator’s strokes. For a single module, the V-SPA was capable of generating a blocking force of 0.92 N upon vacuum pressure of 35 kPa [34].
The manufacturing process is an essential, yet delicate, step in the implementation of soft pneumatic actuators. However, from the manufacturing point of view, there are no significant differences among vacuum-powered or inflatable fluidic actuators.
Depending on the design principles, there are several approaches to fabricate V-PAMs, and an adequate fabrication protocol should ensure high reproducibility and repeatability. Due to the rapid development in additive manufacturing, modern techniques (e.g., stereolithography or multi-material 3D printing, etc.) are currently available, which enable the direct fabrication of the actuators with a good trade-off between material consumption and cost-effectiveness. Moreover, such additive manufacturing techniques are also widely used to fabricate molds and active elements typical of the hybrid manufacturing approach.
In this section, the fabrication approaches that are commonly used for implementing V-PAMs are overviewed (with mention to the employed materials), including molding manufacturing, additive manufacturing, and hybrid techniques. Their advantages and limitations are discussed and compared.
Molding manufacturing is defined as the process of shaping a liquid or a raw material using a rigid container called mold or matrix, which has a negative geometry of the desired shape. Due to the advent of 3D printing, laser cutting, and CNC milling, fabricating the mold has become affordable and relatively fast. Here, depending on the complexity of the object, different molding approaches need to be considered (i.e., casting, blow molding, injection molding, etc.), while only a few of them have been widely addressed to produce soft actuators. In literature, it is frequent to find examples of inflatable fluidic actuators [95, 96, 97, 98] and vacuum-powered actuators [44, 92, 99] mainly built
A correct design and construction of the mold is the first step to succeed in this process. A good practice is to design the mold to be reusable while simplifying the demolding phase and avoiding material waste due to sacrificial molds. This way the risk of damaging the samples during extraction is minimized. To this aim, materials used for the mold should be investigated, taking into account their compatibility with casting materials, and curing parameters. Given that soft actuators are generally built from silicon-rubber or urethane-based silicon, then Acrylonitrile butadiene styrene (ABS), PolyTetraFluoroEthylene (PTFE), PolyAmide (PA), and Chlorinated PolyEthylene (CPE) are good candidates for the molds. Alternatively, PolyLActide (PLA) could be used, while curing elastomers can be completed only at room temperature due to its thermomechanical characteristics (e.g., glass transition temperature Tg).
The second step is to pour the elastomers into the mold and to determine an adequate curing process with specific temperatures and timing. As shown in Figure 5a, based on the mold filling methodology, either casting (where the liquid material is driven by gravity in the mold cavities), or injection molding (where the material is forced into the mold by pressurization) can be used. Once the mold is filled, it must be placed in a vacuum chamber to remove air bubbles that would instead remain trapped in the cured material affecting the final mechanical characteristics of the same.
Different fabrication techniques. (a) shows different filling methodologies - Injection and casting molding, respectively. The hybrid fabrication processes combining two or more techniques - (b) encasing the foam core with the elastomer and smoothly merging each module by interfacing paper dividers. Reproduced with permission [
The last step is to extract the cured parts without any damage. Where proper mold design is insufficient to ensure a correct extraction, synthetic lubricants (e.g., Teflon coating) can help to avoid failures (e.g., delamination at boned layers). Finally, once all components are ready, the actuators are assembled in the desired configuration by using uncured materials or silicone adhesives.
With the aforementioned procedures in molding fabrication, Balak et al. developed a vacuum-powered omnidirectional soft robotic actuator (OSRA) [99]. A two-step molding process was employed. The core structure and cavities of the OSRA were first obtained by using three mold parts. Once the first part was cured, the actuator was completed by putting the cured part into a second mold to make the base seal. Similarly, in ref. [44], the authors employed the molding fabrication technique and could obtain a vacuum soft pneumatic twisting actuator (V-SPTA). First, the body and bottom parts of the V-SPTA were made by casting and, in a second step, attached through a silicone adhesive layer. The same two-step procedure was applied to fabricate the buckling actuators shown in refs. [44, 58, 79, 92, 99]. However, the silicone curing was performed in a controlled environment at 60°C for 10 minutes, reducing the fabrication time. Finally, Oguntosin and Akindele [79] show a remarkable example of a soft vacuum actuator fabricated entirely from silicon rubber. The approach followed the molding method, but unlike the previous examples [44, 79, 99], two different elastomeric materials were smoothly interfaced in one final structure.
Additive manufacturing (AM), also known as three-dimensional (3D) printing, encompasses several emerging techniques based on the same principle: starting from a 3D model, replicate the structure by sequentially adding layers of material until model completeness. In literature, different fabrication protocols have been investigated to obtain soft actuators operated by either positive [100, 101, 102, 103, 104] or negative pressure [37, 105, 106].
Table A2 (in the Appendix) summarizes different AM processes defined by ISO/ASTM 52900:2021. Of these, only Vat PhotoPolymerization (VPP), Material EXtrusion (MEX), and Material Jetting (MJT) have been widely used in the production of soft actuators [107]. In particular, Fused Filament Fabrication (FFF) is the most widely used MEX technology in soft robotics. In this process, a continuous filament of thermoplastic material is melted and extruded through a nozzle to form the horizontal
layers of the 3D structure [108, 109]. Using the same principle, in Direct Ink Writing (DIW), a liquid-phase ink is arranged along the horizontal path, defining the 3D structures layer by layer [110].
On the VPP side, Digital Light Processing (DLP) and Stereolithography (SLA) are commonly subjected. Both use photopolymer resin, differing curing methods [109, 111]. The DLP printer uses a digital light projector screen that flashes an image of the layer that defines the surface to be cured. In contrast, the SLA employs a laser to draw and cure the layer following the surface pattern. Unlike FFF, parts obtained with DLP and SLA need adequate post-processing to achieve optimal material properties. First, all components should be gently removed. Then, the excess resin is removed by using ethanol (bio) or isopropyl alcohol, preferably with ultrasound or under agitation. Once the supports are removed, the last step requires a post-curing step under high-power UV for a few minutes at about 65°C.
Finally, among MJT processes, PolyJet is the typical approach used. PolyJet relies on a sequential deposition of material droplets like an inkjet printer. First, photopolymer droplets are accumulated to form the layer, then instantaneous exposure to UV light cures the layer before a new one is deposited [112]. Stano et al. recently classified the AD approaches employed to fabricate soft robots in rapid mold manufacturing, hybrid, and total additive manufacturing [107].
In rapid mold manufacturing, the AM limits the production of the mold. The material used in this process does not define the properties of the actuator, which instead are linked to the casted material in a second phase, usually silicone or elastomer. The FFF is the standard technique used in this approach, and ABS and PLA filaments are the typical materials used. The resolution of the 3D printer plays an essential role in the presence of small details. Hence, even though there can be inherent shortcomings (e.g., the high cost of the printing system, the post-processing steps), professional 3D printers are preferred due to the higher resolution along the z-axis. Indeed, DLP or SLA techniques have been used, to implement complex structures that need to be fabricated with high precision.
Furthermore, the hybrid approach combines AM technologies with traditional manufacturing approaches. Unlike in molding, the elements printed with this approach are embedded in the final object and influence the kinematics of the actuators.
Total Additive Manufacturing (TAM) has attracted much interest in fabricating soft actuators. In this approach, only AD techniques are exploited. Depending on the actuator’s complexity, the TAM could follow either a modular or monolithic approach. For the former, all “modules” are printed separately and assembled into the final configuration only in a second step, whereas the latter involves TAM to obtain the actuator by a single printing cycle. Combined with multi-material 3D printing, monolithic TAM allows printing actuators made of two or more materials in a single cycle. The same approach permits embedding sensing elements in actuators, enhancing the mechanical synergy between sensing and movements. In parallel to selecting adequate printing methods among MEX, VPP, and MJT, the material properties need to be considered to accomplish desired mechanical performance. Otherwise, custom-made printers could be developed. Indeed, Byrne et al. proposed a custom setup to exploit the advantages of multi-material 3D printing [113]. Combining fused deposition modeling and a paste extrusion printer, they fabricated soft actuators capable of contracting, bending, or twisting in a single printing run. Similarly, by exploiting a commercial multi-material 3D printer (Ultimaker S3), Stano et al. presented a monolithic bending PneuNets made of TPU 80A and TPU 95A [114].
More recently, the TAM approach has been successfully applied to fabricate vacuum-driven actuators by using fused filament fabrication. In ref. [106], Tawk et al. proposed a bioinspired 3D printable Soft Vacuum Actuators (SOVAs). They showed the versatility functionalities of the AM fabrication by demonstrating various robotic applications (i.e., locomotion robots, grippers, and artificial muscles), by applying both monolithic and modular approaches. Similarly, they presented a Linear Soft Vacuum Actuator (LSOVA) fabricated in a single step using an open-source 3D printer and a commercial TPU filament NinjaFlex (NinjaTek, USA) [37], as shown in Figure 2d. While SOVA and L-SOVA are bellow-like and linear vacuum actuators, respectively, the solution proposed by Zhang et al. in [58] is a fully 3-D printed origami-inspired VPAM. Same as molding manufacturing, this demonstrates the versatility of the AM approach, which makes it suitable for different designs.
In summary, the success rate in fabrications exploiting AM is mainly dependent on determining adequate printing parameters. Indeed, an error that could occur at the beginning phase of printing significantly affects the entire process, resulting in printing failures. In particular, for FFF, the bed temperature should be identified to ensure proper layer adhesion without overheating the first layer. At the same time, the size of the first layer should be chosen to accomplish the best quality and airtightness. Avoiding high or low retraction values may help prevent under-extrusion or printed residue. Extrusion temperature, printing speed, and cooling speed deeply affect layer bonding, thus the quality and integrity of the printed part. Finally, an infill density related to the overall structure stiffness enables determining the strength of actuators.
Hybrid manufacturing combines two or more fabrication techniques. Typically, a tradeoff between 3D printing and other fabrication processes, such as molding manufacturing, is addressed. Qi et al. encapsulated 3D-printed elements made of custom material into a silicone structure obtained through mold fabrication [115]. Similarly, in ref. [116], a soft actuator with stiffness and shape modulation was obtained by embedding a 3D-printed Conductive PolyLactic Acid (CPLA) layer in a soft pneumatic actuator made of silicone. Robertson et al. in refs. [94, 117] fabricated a V-PAMs without employing molding and additive manufacturing, as shown in Figure 5b. First, by using a laser cutting machine, the foam chambers and rigid layers were cut. Then, by gluing them, the core structure of the actuator was assembled, manually coated, and sealed by using Elastosil M4601. Figure 5c shows the hybrid fabrication process proposed by the authors in order to develop the UH-PAM [48] (described in Section 2.1.1). Unlike previous examples, after patterning by laser cutting, the open-cell foams (Polyurethane) were integrated with Plexiglass©rigid rings, and with a silicone (Dragon Skin™ 30) skin having a bellow structure, previously molded by casting. Another example belongs to a completely hybrid concept compromising rigid and soft materials [78, 81]. In the V-PAM fabrication, a helical spring core was combined with a pouch, manually assembled from polyethylene (PE) film or TPU fabric. These studies show that hybrid manufacturing has a strong potential, to break down the barrier between rigid and soft materials and to allow them interfacing.
Despite the promising mechanical performance that the hybrid approach delivers to the soft actuators, it suffers from a decreased process controllability since a higher number of separate, and usually manual, fabrication steps are needed, resulting in reduced repeatability and reproducibility. For example, in refs. [78, 81], the repeatability, thus the homogeneity of two different actuators, cannot be ensured since both depend on the manual skills of the operator. Similarly, in ref. [94, 117] using a manual deposition of the core, the homogeneity of the silicone layer could be unevenly distributed.
In addition to exploring fabrication protocols, selecting adequate soft materials is a key enabler for soft robot bodies. Although the meaning of the term “soft” has been contentious, in literature soft robots are defined as systems composed of materials with Young’s modulus ranging from 10 kPa to 1 GPa, similar to soft biological materials (i.e., skin or muscle tissue) [118]. In this view, V-PAMs can consist of a wide range of materials (i.e., polymer, rubber-like silicone) that exhibit hyperelastic behavior with a large deformation ratio, or inextensible thin layered materials (i.e., paper, fabric) that could belong to both soft and rigid materials. In this section, some highlights to address an adequate selection of the materials are provided, referring to the main material candidates that are interesting for the fabrication of V-PAMs.
Given that soft materials strongly influence the actuator mechanical properties as well as its kinematic behavior, selecting adequate materials is mainly driven by the predicted deformations (and stresses) that are required along the overall structure. To this aim, for the linear motion, implicit (i.e., Finite element method (FEM)) or explicit numerical approaches (e.g., Euler beam theorem based) were employed to predict desired kinematic trajectories versus input vacuum pressure [119, 120, 121, 122]. Moreover, for a V-PAM to achieve high compliance, in addition to the skin material intrinsic compliance, air impermeability is necessary. From the material point of view, elastomeric polymers or silicones can withstand large deformations, in some cases like EcoFlex™ 00-30 up to 900%, without undergoing permanent plastic deformation. Moreover, both air impermeability and compliance can be obtained by exploiting compositions and depositions [123, 124].
As representative solutions, silicones and urethane-based rubbers can be used to realize V-PAMs where molding fabrication is employed. For those hyperelastic constitutive materials, two components (i.e., elastomers, catalyst, or hardener) are mixed at precise mixing ratios (typically 1:1) before degassing and curing. From the mechanical point of view, different elongation at break and Young’s modulus can be achievable, depending on materials. For example, platinum-catalyzed silicones (EcoFlex™, DragonSkin™, etc.) are commercially available and exhibit elongation at break ranging from 800% to 1,000% and Young’s modulus ranging from few hundreds kPa to 50 MPa; whereas the mechanical characteristics of Polydimethylsiloxane (PDMS, Sylgard184) can be tuned by using different elastomer/cross-linking agent ratio (e.g., 10:1, 20:1, 30:1).
As regards additive manufacturing, filaments of TPU, such as NinjaFlex® TPU or Ultimaker TPU, are the most used to fabricate soft actuators (including both inflatable fluidic actuators and V-PAMs) by the TAM approach. In general, TPU filaments are characterized by hardness in the 75–90 Shore A range, with an elongation at the break that could reach almost 700%. Alternatively, the Thermoplastic Polyether-Polyurethane elastomer, such as the Recreus FilaFlex, shows a similar characteristic, offering elongation at break up to 950% and hardness in the range 60–95 shore A.
Table 1 provides a brief overview of some of the most common materials used in the fabrication of V-PAMs. In terms of elongation at break, both silicone and filaments offer good performance, showing values that can range from 100% up to a maximum of 1000%. On the contrary, from the point of view of Young’s modulus, the V-PAM obtained with silicone shows values 10 times lower than the counterpart obtained with the TAM approach. This means that for the same structure, actuators obtained by casting are always softer than those obtained by 3D printing, which resulting more rigid require, an higher actuation power to achieve the same behavior. On the other hand, higher stiffness can lead to solutions that can support a higher payload. For this reason, the choice of material is a compromise between performance, feasibility of the concept and operating conditions. The latter point in particular makes it difficult to define a priori which material is best based on the design used alone, making careful analysis necessary in the design phase.
Young’s module [MPa] | Shore hardness [A] | Elongation at break [%] | Manufacturing | |||
---|---|---|---|---|---|---|
Molding | Additive | Hybrid | ||||
Silicones | ||||||
Ecoflex ™ 00-10 | 0.55 | 10 | 800 | • | • | |
Ecoflex ™ 00-20 | 0.55 | 20 | 845 | • | • | |
Ecoflex ™ 00-30 | 0.69 | 30 | 900 | • | • | |
DragonSkin™ 10, | 0.151 | 10 | 1,000 | • | • | |
DragonSkin™ 20, | 0.338 | 20 | 620 | • | • | |
DragonSkin™ 30, | 0.593 | 30 | 364 | • | • | |
Sylgard 184 (10:1) | 1.32 | 43 | 100 | • | • | |
Elastosil® M4601 | 0.262 | 28 | 700 | • | • | |
Filament (TAM) | ||||||
Ultimaker TPU | 26 | 95 | 580 | • | • | |
NinjaFlex© TPU | 12 | 85 | 660 | • | • | |
Chinchilla™ TPE | 34 | 75 | 600 | • | • | |
FilaFlex 60A (TPU) | 26 | 63 | 950 | • | • | |
FilaFlex 82A (TPU) | 22 | 82 | 650 | • | • | |
FilaFlex 70A (TPU) | 32 | 70 | 900 | • | • | |
Filament (molds) | ||||||
Ultimaker ABS | 1.618 | 76 | 90–105 | • | • | |
Ultimaker CPE+ | 1.128 | 75 | 90–110 | • | • | |
Ultimaker PLA | 2.346 | 83 | 55–65 | • | • | |
PolyLite™ ABS | 2.174 | — | 101 | • | • | |
PolyLite™ PLA | 2.636 | — | 63 | • | • |
Materials’ properties and the compatibility with different V-PAMs manufacturing.
This review introduces the promising potential of V-PAMs for implementing complex soft machines achieving robustness and fail-safe operation. In contrast to the inflatable fluidic actuators, given that vacuum pressure induces a volumetric contraction, the linear deformation is strongly influenced by the contraction in the radial direction. Thus, their structures and geometries can avoid stiffening and/or an increase in stress during movement, at the same time ensuring a good level of compactness and robustness. In particular, due to their reliability [37, 92, 106], the V-PAMs proposed to show a lifespan that varies from a minimum of 21,500 cycles of LSOVAs up to more than 1,000,000 cycles of VAMPs. Furthermore, being based on volumetric contraction, V-PAMs results suitable for operating in both large and limited spaces, oppositely to PAMs, which exploiting a volumetric expansion cannot properly work in confined environments.
Nevertheless, there are still several open challenges to be addressed. Indeed, new trade-offs among design principles and desired mechanical performance need to be found to enable energy efficiency in actuators with high power-to-weight ratio. Also, scalability remains barely impossible, mainly due to the square-cube law.
Given that upon vacuum pressure, the overall structure stiffness is mainly dependent on its bulk state, determining adequate materials is a key aspect to achieve the desired actuation force. Thus, exploiting different materials (multi-material) approaches that allow for enhancing the axial stiffness at a global level have been widely addressed [125, 126, 127, 128] by smoothly interfacing them with the structure. However, this approach could lead to an increase in the overall structure weight, as well as material failures (i.e., delamination). Thereby, there is the quest for new materials and/or investigation of novel design principles.
An interesting approach is to employ foam (like in the UH-PAM [38]) as a constituent material, or porous structures where the air-cells dimensions can be decided upon the desired stiffness. Notably, given the recent advances in foam-like sensing, (e.g., capacitive [129], inductive sensing [130], resistive sensing [131, 132], etc.), it can be construed that, in a near future, new designs should consider such transduction mechanisms embedded in V-PAMs. This approach seems promising to develop soft machines with embodied intelligence
Indeed, due to the rapid development in additive manufacturing, designing and fabricating 3D architectures made of metamaterials has been demonstrated [134, 135, 136, 137]. Hence, it can be expected for them to play a key role in the future development of soft actuation, allowing the soft machines to exhibit desired kinematic performance while reducing overall weight due to the tessellated topology and morphology. For this to happen, the quest is for materials that possess high extensibility (>500%), Young’s modulus in the range of tens of MPa, and high reliability and low hysteresis.
In conclusion, in any case, it will be important to address designs that exploit both positive and negative pressures, rather than choosing one of them. This way motions in different directions could be achieved with the same actuator, for example, elongation, contraction, bending, twisting, also inspiring from natural models. For example, this is the case of developing innovative continuum manipulators inspired from elephant trunks, like in the EU project PROBOSCIS [138], which aim is to develop “soft” yet “strong” perceptive soft machines.
This work has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 863212 (PROBOSCIS project).
The authors declare no conflict of interest.
Nomenclatures | Descriptions | Nomenclatures | Descriptions |
---|---|---|---|
D | Outer diameter | TPU | Thermoplastic polyurethane |
d | Inner diameter of the bellow | PDMS | Polydimethylsiloxane |
Dm | Mean diameter of the bellow | PE | Polyethene |
w | Convolution depth | AM | Additive Manufacturing |
Eb | Young’s modulus of the material used for the bellow | VPP | Vat Polymerization |
tp | Thickness of skin | MEX | Material Extrusion |
μ | Poisson’s ratio | MJT | Material Jetting |
n | Number of bellow plies (in case of multiple plies) | DLP | Digital Light Processing |
N | Number of convolutions | SLA | Stereolithography |
ABS | Acrylonitrile butadiene styrene | FFF | Fused Filament Fabrication |
PTFE | Polytetrafluoroethylene | DIW | Direct Ink Writing |
PA | Polyamide | TAM | Total additive manufacturing |
CPE | Chlorinated polyethylene | Tg | Glass transition temperature |
PLA | Polylactide |
Nomenclatures.
Process name | Operative principle |
---|---|
Binder Jetting (BJT) | A liquid bonding agent is selectively deposited to join powder materials |
Direct Energy Deposition (DED) | Focused thermal energy is used to fuse materials by melting as they are being deposited |
Material Extrusion (MEX) | Material is selectively dispensed through a nozzle or orifice |
Material Jetting (MJT) | Droplets of feedstock material are selectively deposited |
Powder Bed Fusion (PBF) | Thermal energy selectively fuses regions of a powder bed |
Sheet Lamination (SHL) | Sheets of material are bonded to form a part |
Vat Photopolymerization (VPP) | Liquid photopolymer in a vat is selectively cured by light-activated polymerization |
Binder Jetting (BJT) | A liquid bonding agent is selectively deposited to join powder materials |
Direct Energy Deposition (DED) | Focused thermal energy is used to fuse materials by melting as they are being deposited |
Material Extrusion (MEX) | Material is selectively dispensed through a nozzle or orifice |
Material Jetting (MJT) | Droplets of feedstock material are selectively deposited |
Powder Bed Fusion (PBF) | Thermal energy selectively fuses regions of a powder bed |
Sheet Lamination (SHL) | Sheets of material are bonded to form a part |
Vat Photopolymerization (VPP) | Liquid photopolymer in a vat is selectively cured by light-activated polymerization |
Different printing processes and their operation principles.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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While the Fourier transform creates a representation of the signal in the frequency domain, the wavelet transform creates a representation of the signal in both the time and frequency domain, thereby allowing efficient access of localized information about the signal.",book:{id:"10065",slug:"wavelet-theory",title:"Wavelet Theory",fullTitle:"Wavelet Theory"},signatures:"Karlton Wirsing",authors:[{id:"325178",title:"Dr.",name:"Karlton",middleName:null,surname:"Wirsing",slug:"karlton-wirsing",fullName:"Karlton Wirsing"}]},{id:"60864",title:"Statistical Methodology for Evaluating Business Cycles with the Conditions of Their Synchronization and Harmonization",slug:"statistical-methodology-for-evaluating-business-cycles-with-the-conditions-of-their-synchronization-",totalDownloads:1328,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The importance of the topic of business cycle research and their interaction is due to the fact that the cyclical nature of development is a universal feature of the market economy (regardless of the level of development of the country’s economy and the principles of its organization). In all cases, cyclical ups and downs depend not only on internal system cyclical processes and their factors in countries but also on the consequences of intercountry interaction. The ability to measure and predict business cycles, taking into account their mutual influence, is a prerequisite for the development of an adequate business policy of countries and their associations.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Elena Zarova",authors:null},{id:"54366",title:"Solution of Differential Equations with Applications to Engineering Problems",slug:"solution-of-differential-equations-with-applications-to-engineering-problems",totalDownloads:6815,totalCrossrefCites:5,totalDimensionsCites:7,abstract:"Over the last hundred years, many techniques have been developed for the solution of ordinary differential equations and partial differential equations. While quite a major portion of the techniques is only useful for academic purposes, there are some which are important in the solution of real problems arising from science and engineering. In this chapter, only very limited techniques for solving ordinary differential and partial differential equations are discussed, as it is impossible to cover all the available techniques even in a book form. The readers are then suggested to pursue further studies on this issue if necessary. After that, the readers are introduced to two major numerical methods commonly used by the engineers for the solution of real engineering problems.",book:{id:"5513",slug:"dynamical-systems-analytical-and-computational-techniques",title:"Dynamical Systems",fullTitle:"Dynamical Systems - Analytical and Computational Techniques"},signatures:"Cheng Yung Ming",authors:[{id:"191017",title:"Dr.",name:"Cheng",middleName:null,surname:"Y.M.",slug:"cheng-y.m.",fullName:"Cheng Y.M."}]},{id:"56538",title:"Stochastic Resonance and Related Topics",slug:"stochastic-resonance-and-related-topics",totalDownloads:1695,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The stochastic resonance (SR) is the phenomenon which can emerge in nonlinear dynamic systems. In general, it is related with a bistable nonlinear system of Duffing type under additive excitation combining deterministic periodic force and Gaussian white noise. It manifests as a stable quasiperiodic interwell hopping between both stable states with a small random perturbation. Classical definition and basic features of SR are regarded. The most important methods of investigation outlined are: analytical, semi-analytical, and numerical procedures of governing physical systems or relevant Fokker-Planck equation. Stochastic simulation is mentioned and experimental way of results verification is recommended. Some areas in Engineering Dynamics related with SR are presented together with a particular demonstration observed in the aeroelastic stability. Interaction of stationary and quasiperiodic parts of the response is discussed. Some nonconventional definitions are outlined concerning alternative operators and driving processes are highlighted. The chapter shows a large potential of specific basic, applied and industrial research in SR. This strategy enables to formulate new ideas for both development of nonconventional measures for vibration damping and employment of SR in branches, where it represents an operating mode of the system itself. Weaknesses and empty areas where the research effort of SR should be oriented are indicated.",book:{id:"6128",slug:"resonance",title:"Resonance",fullTitle:"Resonance"},signatures:"Jiří Náprstek and Cyril Fischer",authors:[{id:"207472",title:"Dr.",name:"Jiri",middleName:null,surname:"Naprstek",slug:"jiri-naprstek",fullName:"Jiri Naprstek"},{id:"213311",title:"Dr.",name:"Cyril",middleName:null,surname:"Fischer",slug:"cyril-fischer",fullName:"Cyril Fischer"}]}],onlineFirstChaptersFilter:{topicId:"15",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82378",title:"Covers and Properties of Families of Real Functions",slug:"covers-and-properties-of-families-of-real-functions",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.100555",abstract:"We present results on the relationships of the covering property GΦΨ for Φ,Ψ∈OΛΩΓ and G∈S1SfinUfin of a topological space and the selection property GΦ0Ψ0 of the corresponding family of real functions. The result already published are presented without a proof, however with a citation of the corresponding paper. We present a general Theorem that covers almost all the result of this kind. Some results about hereditary properties are enclosed. We also present Scheepers Diagram of considered covering properties for uncountable covers.",book:{id:"10677",title:"Advanced Topics of Topology",coverURL:"https://cdn.intechopen.com/books/images_new/10677.jpg"},signatures:"Lev Bukovský"},{id:"82356",title:"Geometric Properties of Classical Yang-Mills Theory on Differentiable Manifolds",slug:"geometric-properties-of-classical-yang-mills-theory-on-differentiable-manifolds",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105399",abstract:"Gauge theories make up a class of physical theories that attempt to describe the physics of particles at a fundamental level. The purpose here is to study Yang-Mills theory at the classical level in terms of the geometry of fiber bundles and differentiable manifolds. It is shown how fundamental particles of bosonic and fermionic nature can be described mathematically. The Lagrangian for the basic interactions is presented and then put together in a unified form. Finally, some basic theorems are proved for a Yang-Mills on compact four-dimensional manifolds.",book:{id:"11502",title:"Manifolds - Recent Developments and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11502.jpg"},signatures:"Paul Bracken"},{id:"82335",title:"Straight Rectangular Waveguide for Circular Dielectric Material in the Cross Section and for Complementary Shape of the Cross Section",slug:"straight-rectangular-waveguide-for-circular-dielectric-material-in-the-cross-section-and-for-complem",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.104815",abstract:"This chapter presents wave propagation along a straight rectangular waveguide for practical applications where there are two complementary shapes of the dielectric profile in the cross section. In the first case, the cross section consists of circular dielectric material in the center of the cross section. In the second case, the cross section consists of a circular hollow core in the center of the cross section. These examples show two discontinuous cross sections and complementary shapes that cannot be solved by analytical methods. We will explain in detail the special technique for calculating the dielectric profile for all cases. The method is based on Laplace and Fourier transforms and inverse Laplace and Fourier transform. In order to solve any inhomogeneous problem in the cross section, more than one technique can be proposed for the same mode-model method. We will explain in detail how and where the technique can be integrated into the proposed mode-model. The image method and periodic replication are needed for fulfilling the boundary condition of the metallic waveguide. The applications are useful for straight rectangular waveguides in millimeter regimes, where the circular dielectric material is located in the center of the cross section, and also for hollow waveguides, where the circular hollow core is located in the center of the cross section.",book:{id:"11150",title:"Recent Advances of Wavelet Transform and Their Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11150.jpg"},signatures:"Zion Menachem"},{id:"82204",title:"Some Solvability Problems of Differential Equations in Non-standard Sobolev Spaces",slug:"some-solvability-problems-of-differential-equations-in-non-standard-sobolev-spaces",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.104918",abstract:"In this chapter an m-th order elliptic equation is considered in Sobolev spaces generated by the norm of a grand Lebesgue space. Subspaces are determined in which the shift operator is continuous, and local solvability (in the strong sense) is established in these subspaces. It is established an interior and up-to boundary Schauder-type estimates with respect to these Sobolev spaces for m-th order elliptic operators, the trace of functions and trace operator are determined, the boundedness of trace operator and the extension theorem are proved, the properties of the Riesz potential are studied regarding these Sobolev spaces, etc. It is considered a second-order elliptic equation, and we study the Fredholmness of the Dirichlet problem in the Sobolev space generated by a separable subspace of the grand Lebesgue space. It is also considered one spectral problem for a discontinuous second-order differential operator and proved the theorem on the basicity of eigenfunctions of this operator in subspace of Morrey space, in which the infinitely differentiable functions with compact support are dense.",book:{id:"11149",title:"Differential Equations",coverURL:"https://cdn.intechopen.com/books/images_new/11149.jpg"},signatures:"Bilal Bilalov, Sabina Sadigova and Zaur Kasumov"},{id:"82011",title:"Spatial Statistics in Vector-Borne Diseases",slug:"spatial-statistics-in-vector-borne-diseases",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104953",abstract:"Vector-borne diseases are those caused by the bite of an infected arthropod, such as the Aedes aegypti mosquito, which can infect humans with dengue or Zika. Spatial statistics is an interesting tool that is currently implemented to predict and analyze the behavior of biological systems or natural phenomena. In this chapter, fundamental characteristics of spatial statistics are presented and its application in epidemiology is exemplified by presenting a study on the prediction of the dispersion of dengue disease in Chiapas, Mexico. A total of 573 confirmed dengue cases (CDCs) were studied over the period of January–August 2019. As part of the spatial modeling, the existence of spatial correlation in CDCs was verified with the Moran index (MI) and subsequently the spatial correlation structure was identified with the mean squarer normalized error (MSNE) criterion. A Generalized Linear Spatial Model (GLSM) was used to model the CDCs. CDCs were found to be spatially correlated, and this can be explained by a Matérn covariance function. Finally, the explanatory variables were maximum environmental temperature, altitude, average monthly rainfall, and patient age. The prediction model shows the importance of considering these variables for the prevention of future CDCs in vulnerable areas of Chiapas.",book:{id:"10678",title:"Biostatistics",coverURL:"https://cdn.intechopen.com/books/images_new/10678.jpg"},signatures:"Manuel Solís-Navarro, Susana G. Guzmán-Aquino, María Guzmán-Martínez and Jazmín García-Machorro"},{id:"81944",title:"The Basics of Structural Equations in Medicine and Health Sciences",slug:"the-basics-of-structural-equations-in-medicine-and-health-sciences",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.104957",abstract:"Structural Equation Models (SEM) are very useful and, with a wide range of practical applications in many fields of science, in medicine and health sciences, have increased interest in their usefulness. This chapter is divided into three sections. The first includes concepts, notation, and theoretical aspects of SEM, such as path diagrams, measurement model, confirmatory factor analysis, structural regression, and identification model. In addition, it includes some simple examples applied to health sciences. The second section deals with the estimation and evaluation of the model. On the first topic, the methods of Maximum Likelihood (ML), Generalized Least Squares, Unweighted Least Squares, and ML with robust standard errors are addressed, as well as alternative methods to the problem of violations of the multivariate normality assumption. On the second topic, some goodness of fit statistics of the estimated model are defined, such as the chi-square statistic, Root Mean Square Error of Approximation, Tucker-Lewis Index, Comparative Fit Index, Standardized Root Mean Square Residual, and Goodness of Fit Index. The last section deals with SEM example and its implementation using the lavaan library of R software.",book:{id:"10678",title:"Biostatistics",coverURL:"https://cdn.intechopen.com/books/images_new/10678.jpg"},signatures:"Ramón Reyes-Carreto, Flaviano Godinez-Jaimes and María Guzmán-Martínez"}],onlineFirstChaptersTotal:42},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:18,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\r\n\tSustainable development focuses on linking economic development with environmental protection and social development to ensure future prosperity for people and the planet. To tackle global challenges of development and environment, the United Nations General Assembly in 2015 adopted the 17 Sustainable Development Goals. SDGs emphasize that environmental sustainability should be strongly linked to socio-economic development, which should be decoupled from escalating resource use and environmental degradation for the purpose of reducing environmental stress, enhancing human welfare, and improving regional equity. Moreover, sustainable development seeks a balance between human development and decrease in ecological/environmental marginal benefits. Under the increasing stress of climate change, many environmental problems have emerged causing severe impacts at both global and local scales, driving ecosystem service reduction and biodiversity loss. Humanity’s relationship with resource exploitation and environment protection is a major global concern, as new threats to human and environmental security emerge in the Anthropocene. Currently, the world is facing significant challenges in environmental sustainability to protect global environments and to restore degraded ecosystems, while maintaining human development with regional equality. Thus, environmental sustainability with healthy natural ecosystems is critical to maintaining human prosperity in our warming planet.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/94.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11978,editor:{id:"61855",title:"Dr.",name:"Yixin",middleName:null,surname:"Zhang",slug:"yixin-zhang",fullName:"Yixin Zhang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYWJgQAO/Profile_Picture_2022-06-09T11:36:35.jpg",biography:"Professor Yixin Zhang is an aquatic ecologist with over 30 years of research and teaching experience in three continents (Asia, Europe, and North America) in Stream Ecology, Riparian Ecology, Urban Ecology, and Ecosystem Restoration and Aquatic Conservation, Human-Nature Interactions and Sustainability, Urbanization Impact on Aquatic Ecosystems. He got his Ph.D. in Animal Ecology at Umeå University in Sweden in 1998. He conducted postdoc research in stream ecology at the University of California at Santa Barbara in the USA. After that, he was a postdoc research fellow at the University of British Columbia in Canada to do research on large-scale stream experimental manipulation and watershed ecological survey in temperate rainforests of BC. He was a faculty member at the University of Hong Kong to run ecological research projects on aquatic insects, fishes, and newts in Tropical Asian streams. He also conducted research in streams, rivers, and caves in Texas, USA, to study the ecology of macroinvertebrates, big-claw river shrimp, fish, turtles, and bats. Current research interests include trophic flows across ecosystems; watershed impacts of land-use change on biodiversity and ecosystem functioning; ecological civilization and water resource management; urban ecology and urban/rural sustainable development.",institutionString:null,institution:{name:"Soochow University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null,series:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null},editorialBoard:null},onlineFirstChapters:{paginationCount:34,paginationItems:[{id:"81595",title:"Prosthetic Concepts in Dental Implantology",doi:"10.5772/intechopen.104725",signatures:"Ivica Pelivan",slug:"prosthetic-concepts-in-dental-implantology",totalDownloads:22,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Current Concepts in Dental Implantology - From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"80963",title:"Pain Perception in Patients Treated with Ligating/Self-Ligating Brackets versus Patients Treated with Aligners",doi:"10.5772/intechopen.102796",signatures:"Farid Bourzgui, Rania Fastani, Salwa Khairat, Samir Diouny, Mohamed El Had, Zineb Serhier and Mohamed Bennani Othmani",slug:"pain-perception-in-patients-treated-with-ligating-self-ligating-brackets-versus-patients-treated-wit",totalDownloads:21,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Current Trends in Orthodontics",coverURL:"https://cdn.intechopen.com/books/images_new/10780.jpg",subseries:{id:"2",title:"Prosthodontics and Implant Dentistry"}}},{id:"80500",title:"Novel Dental Implants with Herbal Composites: A Review",doi:"10.5772/intechopen.101489",signatures:"Gopathy Sridevi and Seshadri Srividya",slug:"novel-dental-implants-with-herbal-composites-a-review",totalDownloads:49,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Current Concepts in Dental Implantology - 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