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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\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:"5486",leadTitle:null,fullTitle:"Quality Control and Assurance - An Ancient Greek Term Re-Mastered",title:"Quality Control and Assurance",subtitle:"An Ancient Greek Term Re-Mastered",reviewType:"peer-reviewed",abstract:"Quality control and assurance cover a diverse area of modern life and play, undeniably, an important role. This book brings together a collection of international papers that showcase examples of current research and practice in industry and the medical profession. It is hoped that engineers, researchers and scientists will be assisted in their continuous quest for excelling in qualitative aspects. The Ancient Greek word arete means excellence or virtue and defines the highest qualitative state: a man’s effectiveness and skill in goodness (optimum potentiae). Indeed, Ancient Greeks believed that without quality control, specifications are useless and may result to illegitimacy, which in turn may become a threat to society itself.",isbn:"978-953-51-2922-6",printIsbn:"978-953-51-2921-9",pdfIsbn:"978-953-51-6696-2",doi:"10.5772/63135",price:119,priceEur:129,priceUsd:155,slug:"quality-control-and-assurance-an-ancient-greek-term-re-mastered",numberOfPages:228,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"549fefebffcb2f610fb669f6eb86c785",bookSignature:"Leo D. Kounis",publishedDate:"February 22nd 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5486.jpg",numberOfDownloads:19342,numberOfWosCitations:16,numberOfCrossrefCitations:14,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:26,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:56,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 26th 2016",dateEndSecondStepPublish:"May 17th 2016",dateEndThirdStepPublish:"August 21st 2016",dateEndFourthStepPublish:"November 19th 2016",dateEndFifthStepPublish:"December 19th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"111582",title:"Dr.",name:"Leo",middleName:"Dimitrios",surname:"Kounis",slug:"leo-kounis",fullName:"Leo Kounis",profilePictureURL:"https://mts.intechopen.com/storage/users/111582/images/system/111582.jpg",biography:"Leo D. Kounis is the Head of the Department of Communication and Informatics Battalion at the Hellenic Ministry of Defense, Hellenic National Defense General Staff. He obtained his BEng (Hons) degree in Manufacturing Systems Engineering, his MSc in Quality Engineering, and his PhD in Systems Reliability from the University of Hertfordshire, UK. Dr. Kounis has worked as a senior quality engineer in a number of private companies in Greece, and has acted as a part-time lecturer and scientific advisor in academia. His research interests are focused in the area of quality, transportation, and sustainable energy. He has published a number of scientific papers.",institutionString:"Hellenic National Defense General Staff",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"3",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"730",title:"Quality Control Management",slug:"engineering-control-engineering-quality-control-management"}],chapters:[{id:"53946",title:"The Evolution of Quality Concepts and the Related Quality Management",doi:"10.5772/67211",slug:"the-evolution-of-quality-concepts-and-the-related-quality-management",totalDownloads:4401,totalCrossrefCites:5,totalDimensionsCites:6,hasAltmetrics:1,abstract:"Enterprises usually adopt some quality practices to control the product quality during the manufacturing process in order to assure the delivery of qualitative good products to customers. The quality practices or quality management systems adopted by industries will further evolve due to the changes of quality concepts as time goes by. This chapter discusses the change of quality concepts and the related revolution of quality management systems in the past century. The quality concepts were gradually changed from the achievement of quality standards, satisfaction of customer needs, and expectations to customer delight. Since merely satisfying customers is not enough to ensure customer loyalty, the enterprises gradually focus on customers’ emotional responses and their delight in order to pursue their loyalty. The emotion of “delight” is composed of “joy” and “surprise,” which can be achieved as the customers’ latent requirements are satisfied. Thus, the concept of “customer delight” and the means to provide the innovative quality so as to meet the unsatisfied customers’ latent needs are elaborated on. Finally, a framework of innovation creation is developed that is based on the mining of customer's latent requirements. This outline will manifest the essential elements of the related operation steps.",signatures:"Ching-Chow Yang",downloadPdfUrl:"/chapter/pdf-download/53946",previewPdfUrl:"/chapter/pdf-preview/53946",authors:[{id:"11862",title:"Prof.",name:"Ching-Chow",surname:"Yang",slug:"ching-chow-yang",fullName:"Ching-Chow Yang"}],corrections:null},{id:"53024",title:"Key Aspects for Implementing ISO/IEC 17025 Quality Management Systems at Materials Science Laboratories",doi:"10.5772/66100",slug:"key-aspects-for-implementing-iso-iec-17025-quality-management-systems-at-materials-science-laborator",totalDownloads:2804,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Implementing a quality management system based on the requirements specified in ISO/IEC 17025 standard at materials science laboratories is challenging, mainly due to two main factors: (i) the high technical complexity degree of some tests used for materials characterization and (ii) the fact that most materials science laboratories provide materials characterization tests and also carry out research and development activities. In this context, this chapter presents key subjects while implementing a quality management system at materials science laboratories and some considerations on strategies for effectively implementing such systems.",signatures:"Rodrigo S. Neves, Daniel P. Da Silva, Carlos E. C. Galhardo, Erlon H.\nM. Ferreira, Rafael M. Trommer and Jailton C. Damasceno",downloadPdfUrl:"/chapter/pdf-download/53024",previewPdfUrl:"/chapter/pdf-preview/53024",authors:[{id:"20571",title:"Prof.",name:"Erlon H.",surname:"Martins Ferreira",slug:"erlon-h.-martins-ferreira",fullName:"Erlon H. Martins Ferreira"},{id:"145815",title:"Dr.",name:"Rodrigo",surname:"De Santis Neves",slug:"rodrigo-de-santis-neves",fullName:"Rodrigo De Santis Neves"},{id:"145816",title:"Dr.",name:"Carlos",surname:"Eduardo Cardoso Galhardo",slug:"carlos-eduardo-cardoso-galhardo",fullName:"Carlos Eduardo Cardoso Galhardo"},{id:"159056",title:"Dr.",name:"Jailton",surname:"Damasceno",slug:"jailton-damasceno",fullName:"Jailton Damasceno"},{id:"191863",title:"Dr.",name:"Daniel",surname:"Fernandes",slug:"daniel-fernandes",fullName:"Daniel Fernandes"},{id:"191865",title:"Dr.",name:"Rafael",surname:"Mello Trommer",slug:"rafael-mello-trommer",fullName:"Rafael Mello Trommer"}],corrections:null},{id:"53144",title:"Youden Two-Sample Method",doi:"10.5772/66397",slug:"youden-two-sample-method",totalDownloads:2398,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The results obtained when testing materials, equipment and procedures are not generally identical. Factors that influence the magnitude of the results are not fully controllable. As such, the interpretation and analysis of results must take into account the variations caused by numerous and random unavoidable causes. Intercomparison exercises are considered of being of importance, as they do allow the examination of the analytical process and their generated results. Youden plot is particularly aimed at interlaboratory comparisons. The raw results provided by the participating laboratories are treated by a statistical method applied by the centre performing the trial. In order to materialize this, two similar materials with small differences in the concentration of the characteristics are required. The advantage of Youden analysis is its ability to separate the random errors with a minimum effort by participants in the design from the point of view of the analytical requirement. This book chapter illustrates the method that has been applied to elaborate on data covering a diverse scientific field: polyunsaturated fatty acids in fat and oils, total blood cholesterol and aspirin in pharmaceutical preparations. Finally, liquid chromatography with tandem mass spectrometry detector has been applied to the determination of an emerging contaminant, methylparaben (MeP), in surface waters.",signatures:"Julia Martín, Nieves Velázquez and Agustin G. Asuero",downloadPdfUrl:"/chapter/pdf-download/53144",previewPdfUrl:"/chapter/pdf-preview/53144",authors:[{id:"190870",title:"Dr.",name:"Agustín G.",surname:"Asuero",slug:"agustin-g.-asuero",fullName:"Agustín G. Asuero"},{id:"190871",title:"Dr.",name:"Julia",surname:"Martín",slug:"julia-martin",fullName:"Julia Martín"},{id:"195055",title:"Dr.",name:"Nieves María",surname:"Velázquez",slug:"nieves-maria-velazquez",fullName:"Nieves María Velázquez"}],corrections:null},{id:"52915",title:"Using Lot Quality Assurance Sampling to Monitor the Prevalence of Abortions and the Quality of Reproductive Health Care in Armenia",doi:"10.5772/66092",slug:"using-lot-quality-assurance-sampling-to-monitor-the-prevalence-of-abortions-and-the-quality-of-repro",totalDownloads:1570,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Monitoring abortion prevalence is essential to plan control efforts. Lot Quality Assurance Sampling (LQAS) is an inexpensive, reliable method for monitoring abortion prevalence and access to quality reproductive health (RH) services. This chapter presents survey results from 2000 in three sites of Armenia (Gyumri, Gavar and Goris) using LQAS principles (i.e., 44%, 95% CI: ±6% of women had an induced abortion in their lifetime, a total abortion rate (TAR) of 2.0 abortions per woman). Modern contraceptive use was lowest in Goris (16%. 95% CI: ±7%) and highest in Gyumri (43%, 95% CI: ±11%). Only 37% (95% CI: ±9%) of women with an induced abortion received family planning information and 21% (95% CI: ±4%) of mothers were counselled about family planning after delivery. While limited access to family planning information and contraceptives is still an issue in Armenia, recently new reproductive health priorities—such as infertility, sex-selective abortions and abortions due to socio-economic difficulties—have become more common and can be investigated using LQAS in both community surveys and health facility assessments. This study demonstrates that measuring national abortion prevalence and access to services mask underlying variations; the awareness of which is essential for health program planning.",signatures:"Joseph J. Valadez and Lusine Mirzoyan",downloadPdfUrl:"/chapter/pdf-download/52915",previewPdfUrl:"/chapter/pdf-preview/52915",authors:[{id:"191876",title:"Prof.",name:"Joseph",surname:"Valadez",slug:"joseph-valadez",fullName:"Joseph Valadez"},{id:"195035",title:"Dr.",name:"Lusine",surname:"Mirzoyan",slug:"lusine-mirzoyan",fullName:"Lusine Mirzoyan"}],corrections:null},{id:"53019",title:"A Framework to Manage Quality of Enterprise Content Management Systems",doi:"10.5772/66199",slug:"a-framework-to-manage-quality-of-enterprise-content-management-systems",totalDownloads:1387,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:1,abstract:"There is a wide range of enterprise content management (ECM) systems which supports, among other things, document management processes, records management and Web content management. However, each of these systems has many features and some of them can meet organizational needs depending on the scale, sector and workflow of the organization. In addition, it is very common that organizations are unaware of what ECM system best fits their needs, since each company has its particular scope and strategic objectives. This chapter is contextualized within the real project called THOT designed for the Andalusian Public Administration in Spain. The aim of this project is to study in detail ECM systems and propose an objective method to compare them for the specific scope and strategic objective of organizations. Quality evaluation framework (QuEF) has been adapted for this purpose.",signatures:"José González Enríquez, Francisco José Domínguez Mayo, Julián\nAlberto García García, María José Escalona Cuaresma and Manuel\nMejías Risoto",downloadPdfUrl:"/chapter/pdf-download/53019",previewPdfUrl:"/chapter/pdf-preview/53019",authors:[{id:"104846",title:"Dr.",name:"Maria",surname:"Escalona",slug:"maria-escalona",fullName:"Maria Escalona"},{id:"191332",title:"Ph.D.",name:"José",surname:"González",slug:"jose-gonzalez",fullName:"José González"},{id:"191493",title:"Dr.",name:"F.J.",surname:"Domínguez-Mayo",slug:"f.j.-dominguez-mayo",fullName:"F.J. Domínguez-Mayo"},{id:"191494",title:"Dr.",name:"J.A.",surname:"García-García",slug:"j.a.-garcia-garcia",fullName:"J.A. García-García"},{id:"195075",title:"Dr.",name:"M.",surname:"Mejías",slug:"m.-mejias",fullName:"M. Mejías"}],corrections:null},{id:"53267",title:"Exploring the Relationship of Supply Chain Risk Management to Quality Management",doi:"10.5772/65847",slug:"exploring-the-relationship-of-supply-chain-risk-management-to-quality-management",totalDownloads:1524,totalCrossrefCites:4,totalDimensionsCites:4,hasAltmetrics:0,abstract:"This research explores the relationship between an organization's supply chain risk management (SCRM) maturity and quality maturity. SCRM maturity was measured using a survey questionnaire sent to organizations in the USA. Quality maturity was assessed via ISO 9001:2008 certification status as well as through a survey questionnaire of total quality management (TQM) practices for organizations in the USA. The results suggest that ISO 9001:2008 is not related to SCRM maturity, while TQM maturity is related to SCRM maturity. Organizations with more mature TQM programs appear to also have more mature SCRM programs.",signatures:"Tyler Florio",downloadPdfUrl:"/chapter/pdf-download/53267",previewPdfUrl:"/chapter/pdf-preview/53267",authors:[{id:"195084",title:"Mr.",name:"Tyler",surname:"Florio",slug:"tyler-florio",fullName:"Tyler Florio"}],corrections:null},{id:"52958",title:"ALAMEDA Ecosystem: Centering Efforts in Software Testing Development",doi:"10.5772/66043",slug:"alameda-ecosystem-centering-efforts-in-software-testing-development",totalDownloads:2074,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"One of the most important and critical aspects to improve the quality assurance in software is to improve the testing process by utilizing techniques and tools, which will enhance the software testing process, making it more effective and efficient. This chapter presents ALAMEDA ecosystem, a software package that centers its efforts in software testing development and is a result from a real-world project. ALAMEDA provides support to lifecycles focused on the generation, implementation, and testing organization from the earliest stages of software development. In addition, the ecosystem provides an environment of rating the degree of compliance of organizations with the International Standard for Testing ISO/IEC-29119. It is proposed as a tool to use during the various iterations that may occur in an agile software development process.",signatures:"José González Enríquez, Julián Alberto García-García, Francisco José\nDomínguez-Mayo and María José Escalona Cuaresma",downloadPdfUrl:"/chapter/pdf-download/52958",previewPdfUrl:"/chapter/pdf-preview/52958",authors:[{id:"104846",title:"Dr.",name:"Maria",surname:"Escalona",slug:"maria-escalona",fullName:"Maria Escalona"},{id:"191332",title:"Ph.D.",name:"José",surname:"González",slug:"jose-gonzalez",fullName:"José González"},{id:"191493",title:"Dr.",name:"F.J.",surname:"Domínguez-Mayo",slug:"f.j.-dominguez-mayo",fullName:"F.J. Domínguez-Mayo"},{id:"191494",title:"Dr.",name:"J.A.",surname:"García-García",slug:"j.a.-garcia-garcia",fullName:"J.A. García-García"}],corrections:null},{id:"53099",title:"Improving Quality Assurance in Multidisciplinary Engineering Environments with Semantic Technologies",doi:"10.5772/66222",slug:"improving-quality-assurance-in-multidisciplinary-engineering-environments-with-semantic-technologies",totalDownloads:1556,totalCrossrefCites:4,totalDimensionsCites:8,hasAltmetrics:0,abstract:"In multidisciplinary engineering (MDE) projects, for example, automation systems or manufacturing systems, stakeholders from various disciplines, for example, electrics, mechanics and software, have to collaborate. In industry practice, engineers apply individual and highly specialized tools with strong limitation regarding defect detection in early engineering phases. Experts typically execute reviews with limited tool support which make engineering projects defective and risky. Semantic Web Technologies (SWTs) can help to bridge the gap between heterogeneous sources as foundation for efficient and effective defect detection. Main questions focus on (a) how to bridge gaps between loosely coupled tools and incompatible data models and (b) how SWTs can help to support efficient and effective defect detection in context of engineering process improvement. This chapter describes success-critical requirements for defect detection in MDE and shows how SWTs can provide the foundation for early and efficient defect detection with an adapted review approach. The proposed defect detection framework (DDF) suggests different levels of SWT contributions as a roadmap for engineering process improvement. Two selected industry-related real-life cases show different levels of SWT involvement. Although SWTs have been successfully applied in real-life use cases, SWT applications can be risky if applied without good understanding of success factors and limitations.",signatures:"Dietmar Winkler, Marta Sabou and Stefan Biffl",downloadPdfUrl:"/chapter/pdf-download/53099",previewPdfUrl:"/chapter/pdf-preview/53099",authors:[{id:"95798",title:"Dr.",name:"Dietmar",surname:"Winkler",slug:"dietmar-winkler",fullName:"Dietmar Winkler"},{id:"135962",title:"Prof.",name:"Stefan",surname:"Biffl",slug:"stefan-biffl",fullName:"Stefan Biffl"},{id:"196030",title:"Dr.",name:"Marta",surname:"Sabou",slug:"marta-sabou",fullName:"Marta Sabou"}],corrections:null},{id:"53522",title:"The Use of Control Charts in the Study of Bitcoin’s Price Variability",doi:"10.5772/66360",slug:"the-use-of-control-charts-in-the-study-of-bitcoin-s-price-variability",totalDownloads:1638,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The focus of this research is bitcoin’s variability and its comparison with the variability of the EURO/USD exchange rate. Virtual currencies have been evolving in a dynamic way in the last few years. Under 600 different virtual currencies, the most successful was bitcoin. Its adherents saw in it an alternative to the traditional means of payments allowing the performance of real-time transactions at low costs. The accessibility, where no financial infrastructure is ensured or where either limited or no international agreements exist between financial and banking institutions was also an advantage. The opponents perceived this as a temporary curiosity with no future. Time confirmed that bitcoin has gained on popularity and the exchange rate to the main currencies rose in a dynamic way. The analysts, however, underline that the bitcoin is too volatile and unpredictable, so it cannot compete against the main currencies. The aim of this research is to compare the bitcoin (BTC) to US Dollar (USD) exchange rate and Euro to USD exchange rate volatility using control charts. 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Aleksic",slug:"radoslav-aleksic"}]},{id:"16722",title:"Composite Materials for Some Radiophysics Applications",slug:"composite-materials-for-some-radiophysics-applications",signatures:"Sergey Bibikov and Mikhail Prokof'Ev",authors:[{id:"30318",title:"Dr.",name:"Sergey",middleName:null,surname:"Bibikov",fullName:"Sergey Bibikov",slug:"sergey-bibikov"},{id:"92431",title:"Dr.",name:"Mikhail",middleName:null,surname:"Prokof'ev",fullName:"Mikhail Prokof'ev",slug:"mikhail-prokof'ev"}]},{id:"16723",title:"The Composite Materials for Localization of Volatile Radioactive Iodine Forms from Steam-Air Phase during Severe Accidents at NPPs",slug:"the-composite-materials-for-localization-of-volatile-radioactive-iodine-forms-from-steam-air-phase-d",signatures:"Sergey Kulyukhin, Lubov Mizina, Igor Rumer and Nikolai Mikheev",authors:[{id:"30586",title:"Prof.",name:"Sergey",middleName:null,surname:"Kulyukhin",fullName:"Sergey 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It combines the knowledge from different research areas including medicine, material science and engineering to develop engineered biological substitutes able to restore, maintain or improve tissue functions [1]. TE was introduced from the necessity of finding alternative methodologies to organ transplantations due to their increasing demand in clinical medicine. Furthermore, TE emerged as a promising approach to overcome the limitations of the conventional surgical approaches for the treatment of tissue damages caused by injuries, diseases and congenital disorders [2, 3]. These surgical procedures are based on replacing the injured tissues or organs with a healthy one harvested from the same patient (autograft), or a compatible donor (allograft). Although these approaches have been revolutionary and lifesaving, there are still some drawbacks that need to be addressed. The surgical procedures used to harvest both autografts and allografts are often invasive and painful. The risk of post-surgical limitations in the donor’s body due, for example, to infections and hematomas is, in fact, quite high. Moreover, when allografts are transplanted, the chance of inflammatory and immune responses in the patient body together with the transmission of diseases from the donor to the patient is significant [4].
TE aims at overcoming the complications associated with the conventional techniques used during organ transplantation by inducing the complete regeneration of the damaged tissues instead of replacing them [2, 3]. Several approaches to promote
Illustration of TE paradigm (figure created with
The scaffold plays an essential role in regulating the process of new tissue formation. An ideal scaffold should be biocompatible and should degrade with kinetics compatible with the rate of tissue regeneration. It should be highly porous (< 75% [7]) with adequate pore size to promote cell migration/scaffold colonization and nutrient transfer throughout the scaffold. A scaffold should mimic the features of biological tissues in terms of topological properties (e.g., shape, size), mechanical properties (e.g., stiffness), and the biochemical processes that control and regulate the functionalities of the tissues. Moreover, it should not alter the normal functions of cells, which should adhere, migrate and proliferate within the scaffold before producing new tissue [5, 6, 8, 9]. Depending on their applications, scaffolds with different shapes, compositions and properties have been developed so far.
The biomaterial formulations used to produce the scaffold strongly affect its properties [10, 11]. Thus, the selection of the proper biomaterial formulation is pivotal for inducing the regeneration of the tissue in a controlled manner avoiding any undesired side-effects (e.g., cytotoxicity, apoptosis, carcinogenicity). The most used biomaterial formulations in TE are mainly based on synthetic biopolymers, natural biopolymers and composites [12, 13]. Synthetic biopolymers, like polycaprolactone, can be produced on a large scale under controlled conditions with predictable and reproducible physicochemical properties (e.g., mechanical properties, biodegradability) [6, 14, 15]. However, many synthetic biopolymers that have been developed so far are mainly derived from petroleum and coal, which make them not compatible with the environment [16]. Natural biopolymers include animal-derived proteins (e.g., gelatin, hyaluronic acid, collagen, silk) and animal- and vegetal-derived polysaccharides (e.g., cellulose alginate, chitosan). One of the advantages of this class of biopolymers is their biological similarity to native tissues which is beneficial for supporting cell functionalities (e.g., cell adhesion). Nonetheless, the use of animal-derived biopolymers may be associated with a high risk of transmission of diseases from animal to patient [10, 17, 18]. Therefore, the use of naturally occurring biopolymers from vegetal sources represents an attractive alternative to overcome these limitations. Moreover, they represent an ecological alternative to synthetic biopolymers in the preparation of sustainable and green scaffolds.
In recent years particular attention has been paid to the adoption of methodologies to derive biopolymers from renewable sources, such as industrial by-products, such as pectin from fruit pomace produced from the fruit processing industry [19] and cellulose nanofibers obtained from paper waste [20]. The application of more ecologically viable biomaterials in TE may, in fact, strongly contribute to reduce the polluting impact of producing and using un-recyclable synthetic biopolymers. Among the renewable and natural biopolymers, pectin is gaining particular attention in TE for its advantageous properties including biocompatibility, biodegradability and non-toxicity [21, 22]. In addition, the versatility in processing pectin-based formulations allows to produce scaffolds with diverse properties and for different applications (Section 2).
This chapter aims at highlighting the applications of pectin as the building block of bidimensional (2D) and three-dimensional (3D) scaffolds for TE applications. With this aim, in Section 2 the properties of pectin as biomaterial are provided. Section 3 reports the most representative applications of pectin-based formulations for producing scaffolds for tissue regeneration in the shape of 2D films for wound healing and 3D scaffolds for tissue regeneration.
Pectin shows several remarkable properties as a biomaterial. It is biocompatible and biodegradable, and it is soluble in cytocompatible and non-toxic solvents (such as water). Pectin is a versatile biomaterial as its physical properties can be facilely tuned due to the presence of several functional groups (e.g., carboxylic groups) that can serve as binding sites for other functional groups, biomolecules and drugs [21, 22, 23]. It is a low-cost biomaterial due to its ubiquity in nature, and this can strongly reduce the costs associated with the development of engineered tissues.
Pectin can form hydrogel due to the ability of its macromolecules to absorb and retain large volumes of water. This unique property makes pectin a suitable candidate to produce a natural extracellular matrix, which naturally surrounds cells. Furthermore, due to the possibility to be processed under sterile and physiological conditions (i.e., the aqueous environment at 37°C), pectin enables to encapsulate cells within its matrix to produce cell-laden scaffolds [23, 24].
Pectin tends to dissolve under physiological conditions, therefore physicochemical approaches are required to stabilize pectin-based scaffolds. These are mainly based on the use of physicochemical crosslinking approaches which consist of the formation of a stable network of links among the pectin molecules. This network reduces the interactions of pectin molecules with water and prevents the disruption of pectin-based scaffolds. For example, the most employed approach to form water-insoluble scaffolds of low-methoxyl pectin is based on the use of divalent cations (e.g., Ca2+) that interact with the carboxylic groups of pectin forming the so-called ‘egg box’ structure [21]. Notably, the crosslinking treatments should also be cytocompatible (under specific conditions/concentrations), and should not interfere with the capability of pectin to encapsulate cells [25].
One of the major drawbacks that limit the application of pectin as a biomaterial for TE applications is its low cell adhesivity due to the lack of sites for cell adhesion (such as arg-gly-asp (RGD) sequences). Therefore, pectin is often combined/blended with other biopolymers or biomolecules to enhance its bioactivity [21, 26].
Pectin-based formulations have been processed through different fabrication approaches into scaffolds with various shapes for different applications. In particular, pectin has been mainly used for the production of 2D films for wound healing, and 3D scaffolds for tissue regeneration. Figure 2 provides a graphical overview of the main applications of pectin in TE.
Illustration of the application of pectin (derived from citrus fruits) for the production of scaffolds for TE applications (created with
One of the applications of pectin-based formulations is the preparation of 2D hydrogel patches for the treatment of wounds. These patches provide mechanical support to cells during the process of new tissue formation, and an antibacterial barrier preventing eventual infections. Moreover, the hydrophilic pectin molecules in the film can react with the fluids of the wound forming a soft gel. The presence of a gel allows to maintain a moist environment in the wound. This helps to remove or control secretions from the wounded tissue and in turn facilitates the healing process. The regeneration of the damaged tissue can be further promoted by the incorporation of bioactive molecules such as drugs (e.g., antibiotics) and/or growth factors within the pectin patches [21]. The controlled and prolonged release of these molecules directly in the damaged site can actively contribute to decreasing the risk of infections and accelerating the formation of new tissue. As mentioned in Section 2, pectin is often combined with other biopolymers to enhance its bioactivity and also to modulate the physical properties (e.g., tensile strength) of the final patch.
Pectin-based patches for wound healing reported in the literature so far are principally obtained in the shape of non-porous films and porous membranes, as detailed described in the following Sections 3.1.1 and 3.1.2, respectively.
Pectin-based films are generally 2D, non-porous and flexible substrates able to retain large volumes of water within their matrix. One of the approaches used to produce these films is the so-called ‘solvent casting’. In this approach, a pectin-based solution is initially poured into a mold, and the solvent is subsequently let to evaporate leaving a 2D non-porous film (Figure 3).
Illustration of the solvent casting approach (created with
Pectin-based patches produced with this approach support cell adhesion and proliferation and accelerate the processes occurring during the formation of new tissue [27, 28, 29, 30]. Moreover, films with high toughness and stretchability can be produced with solvent casting, and these can be potentially used as pectin-based patches for load-bearing tissues (e.g., cartilage, tendon) [28]. In addition, pectin-based patches for a controlled drug into the targeted tissue were also produced by incorporating drugs in the pectin matrix [30, 31].
Nanoporous membranes based on pectin have been mainly obtained through electrospinning. This approach allows to produce highly porous and flexible patches starting from pectin-based/polymer solutions subjected to an external electric field. A standard electrospinning apparatus is illustrated in Figure 4. It generally consists of (i) a syringe pump containing the polymer solution, (ii) a metallic needle through which the polymer solution is ejected, (iii) a high voltage power supply (in the range of tens of kVolts), and (iv) a grounded collector (usually a metal plate). When a drop of the polymer solution is extruded through the needle, the high electric forces in the space between the needle and the collector induce its stretching and the formation of fibers from a few nanometers to microns in diameters [32]. These fibers are therefore deposited and collected on the collector forming a non-woven fibrous membrane after complete evaporation of the solvent (Figure 4).
Illustration of an electrospinning setup with a magnification of the electrospun nanofibers on the collector (image obtained with scanning electron microscopy).
Pectin-based patches obtained by this approach show several advantageous properties for TE applications. The random organization of electrospun pectin fibers together with the hydrogel nature of pectin enables to mimic the nanoscale organization of the native extracellular matrix. Furthermore, the high porosity and high surface-to-volume ratio typical of electrospun patches promote cell migration and nutrient diffusion within the scaffold, which is beneficial for the process of new tissue formation [33]. Nevertheless, it is quite challenging to produce electrospun structures from pristine pectin due to some intrinsic molecular properties of pectin (such as insufficient chain entanglement) that disable the fiber formation [34]. Thus, to improve its electrospinning ability, pectin is often chemically modified [35, 36] and/or combined with other biodegradable biopolymers such as poly(ethylene oxide) [34], polyhydroxybutyrate [37] that work as carrier polymer to induce the formation of stable fibers.
Pectin-based nano-fibers find application for the preparation of films/structures that can be potentially used as patches for wound healing of soft tissues [35, 36, 37] (e.g., vascular tissue [35], retinal tissue [37]). In addition, drugs (such as antibiotics [38, 39]) and particles (such as argentum ions for antibacterial purposes [38]) can be successfully loaded in these structures obtaining patches for a local and controlled release of drugs directly into the wound.
Pectin-based formulations can be further processed to obtain 3D scaffolds able to mimic the complex architecture of biological tissues. 3D pectin-based scaffolds have been principally obtained in the shape of porous 3D sponges and 3D bioprinted scaffolds.
Sponges are comparable to foams with an interconnected network of pores. This type of architecture is beneficial for cell penetration and scaffold colonization, while ensuring adequate diffusion of nutrients to cells within the scaffold. Moreover, a highly porous scaffold with open and connected pores is of critical importance as it allows for the diffusion of nutrients and waste products through the scaffold [6, 7].
Pectin-based sponges are mainly obtained by freeze-drying, also known as lyophilization. This technique consists in freezing a polymer solution followed by the evaporation of the frozen solvent by sublimation. Thus, a solid polymer matrix with numerous and interconnected pores is obtained (Figure 5). Before freezing, polymer solutions are generally poured into molds to produce porous scaffolds with the desired shape.
Schematic of the process for obtaining cylindrical porous sponges was obtained by freeze-drying. Magnification of the porous sponges obtained by scanning electron microscopy (image created with
Pectin-based sponges have been principally used to produce scaffolds for wound healing and tissue regeneration. For example, sponges obtained with pectin-based formulations have been used as scaffolds for different types of tissues including cartilage [40, 41], skin [42], and bone [43]. The high hydrophilicity of pectin molecules and the interconnected porosity enables these sponges to entrap a large volume of water creating a 3D hydrogel-based environment that can mimic the natural extracellular matrix [40, 41]. Furthermore, this provides and stabilizes a moist environment for wounds that strongly contributes to accelerating the healing of the wounds [44].
Producing scaffolds with a customized architecture and by automated and high reproducible approaches is one of the main challenges of TE. The development of pectin-based scaffolds with patient-specific architecture may boost their clinical applications.
Pectin-based scaffolds with complex shapes have been principally obtained by extrusion-based bioprinting so far. Extrusion-based bioprinting is one of the most widely used technology in TE due to its simplicity and versatility in processing a large variety of biomaterials, cells and biomolecules. An extrusion-based bioprinter usually consists of a movable cartridge containing the biomaterial formulation (called ‘
Schematic of extrusion-based bioprinting.
The application of pectin-based inks in extrusion-based bioprinting is relatively recent compared to the other fabrication approaches described in the previous sections. Pectin solutions are often not suitable to be processed through extrusion-based bioprinting and structures with poor shape fidelity are often obtained. The first application of pectin as ink for extrusion-based bioprinting dates back to 2017. In this case, pectin was combined with another biopolymer (Pluronic F-127), and complex-shaped scaffolds were bioprinted [47, 48]. Cells were successfully loaded within this formulation and 3D bioprinted to produce living 3D constructs [24]. From that moment, other pectin-based inks have been developed and optimized to produce 3D scaffolds with high shape fidelity [49, 50, 51]. For example, pectin-based scaffolds with more complex shapes such as a human ear and nose shape for cartilage tissue regeneration were successfully obtained (Figure 6) [41].
TE represents an alternative approach to conventional surgical techniques used to treat damaged, injured or diseased tissues or organs. This approach is based on the use of tissue-mimicking and biodegradable constructs, based on the so-called ‘scaffolds’, able to restore, maintain or improve tissue functions. The physicochemical properties of the final scaffold play a key role in the process of new tissue formation. The selection of the proper biomaterial formulation is therefore essential. Recently, renewable biomaterials derived from industrial by-products are finding increasing application in TE as an alternative to petroleum-derived and unrecyclable polymers. In this regard, pectin, a polysaccharide commercially derived from citrus peel and apple pomace (both by-products of the food processing industry), is gaining attention in TE due to its biocompatibility, biodegradability and non-cytotoxicity. Diverse pectin-based formulations have been developed and employed for the fabrication of functional scaffolds for TE applications.
This chapter presented the most representative applications of pectin-based formulations for the fabrication of scaffolds for TE applications. In particular, by properly processing these formulations through specific fabrication techniques is possible to produce pectin-based scaffolds with different features: from 2D non-porous films (obtained by solvent casting) to 3D scaffolds with patient-specific shape (obtained by extrusion-based bioprinting). Although pectin shows diverse advantageous properties as biomaterial, its application in clinical practice is still under investigation. The increasing number of studies on the preparation of biocompatible pectin-based formulations may strongly boost the employment of this polysaccharide in the fabrication of sustainable scaffolds for future TE applications.
The authors wish to acknowledge the Crosslab Additive Manufacturing of the Department of Information Engineering of the University of Pisa.
The authors declare no conflict of interest.
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All published Book Chapters are licensed under a Creative Commons Attribution 3.0 Unported License. Monographs are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others. Our Copyright Policy aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. IntechOpen upholds a flexible Copyright Policy meaning that there is no copyright transfer to the publisher and Authors hold exclusive copyright to their work.
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