",isbn:"978-1-80356-951-2",printIsbn:"978-1-80356-950-5",pdfIsbn:"978-1-80356-952-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"bb6fc82b35ad2c63618a9bc15aeb61ce",bookSignature:"Dr. Kim Ho Yeap and Dr. Magdalene Goh Wan Ching",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11948.jpg",keywords:"MOSFET, CMOS, OFET, JFET, FinFET, Integrated Circuit (IC), Oxidation, Metallization, Semiconductor, Silicon (Si), Gallium Arsenide (GaAs), Silicon Carbide (SiC)",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 7th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"9 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A researcher in the fields of microelectronics and electromagnetics. Member of IEEE, IET, IEM.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"24699",title:"Dr.",name:"Kim Ho",middleName:null,surname:"Yeap",slug:"kim-ho-yeap",fullName:"Kim Ho Yeap",profilePictureURL:"https://mts.intechopen.com/storage/users/24699/images/system/24699.jpg",biography:"Kim Ho Yeap is an Associate Professor at Universiti Tunku Abdul Rahman, Malaysia. He is an IEEE senior member, a Professional Engineer registered with the Board of Engineers, Malaysia,a Chartered Engineer registered with the UK Engineering Council, and an ASEAN Chartered Professional Engineer (ACPE). He received his BEng (Hons) Electrical and Electronics Engineering from Universiti Teknologi Petronas in 2004, his MSc in microelectronics from Universiti Kebangsaan Malaysia in 2005, and his PhD from Universiti Tunku Abdul Rahman in 2011. In 2008 and 2015, respectively, Dr. Yeap underwent research attachment at the University of Oxford (UK) and Nippon Institute of Technology (Japan). Dr. Yeap is the external examiner and external course assessor of Wawasan Open University. He is also the Editor in Chief of the i-manager’s Journal on Digital Signal Processing. He has also been a guest editor for the Journal of Applied Environmental and Biological Sciences and Journal of Fundamental and Applied Sciences. Dr. Yeap has been given the university teaching excellence award, and 22 research grants. He has published more than 100 research articles (including refereed journal papers, conference proceedings, books, and book chapters). Prior to joining the academic industry, Dr. Yeap worked in Intel corporation in the pre-silicon validation group. He was awarded 4 Kudos awards by Intel for his contributions in the design and verification of the microchip’s design for testability (DFT) features.",institutionString:"Universiti Tunku Abdul Rahman",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Universiti Tunku Abdul Rahman",institutionURL:null,country:{name:"Malaysia"}}}],coeditorOne:{id:"454196",title:"Dr.",name:"Magdalene",middleName:null,surname:"Goh Wan Ching",slug:"magdalene-goh-wan-ching",fullName:"Magdalene Goh Wan Ching",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Dr Magdalene Goh Wan Ching\r\nDesignation: Senior lecturer\r\nQualifications: Diploma in Electrical & Electronics Engineering (Inti College), BEng in Electrical\r\nEngineering & Electronics (University of Liverpool, UK), PhD in Solid State\r\nDevice Physics & RF Transistors Design (University of Liverpool, UK)\r\n\r\nProfessional Body\r\nMemberships:\r\n\r\nInaugural Senior Member, International Engineering & Technology Institute\r\n(IETI), Hong Kong\r\n\r\nBiodata: Dr. Magdalene Goh obtained her Diploma in Electrical & Electronics Engineering\r\nfrom Inti College before leaving for the UK to pursue her BEng in Electrical\r\nEngineering & Electronics and later on, her PhD. Prior to joining the academia,\r\nshe has worked for a few years in the industry in the areas of semiconductor\r\nprocess technology, silicon wafer characterizations, mask layout design,\r\nanalogue circuits design and design for testability (DFT). While in the academic,\r\nshe had served as a judge for Innovate Malaysia undergraduate final year\r\nprojects competition from 2012 - 2015. She had served as an external examiner\r\nfor a PhD candidate from VIT University, India in 2013, and an external examiner\r\nfor SEGi College Penang from 2014 – 2018. She has been actively involved with\r\nthe Penang Science Cluster in their radio telescope team since 2014, where she\r\nworks with a team of volunteers (from both academia and the industry in\r\nPenang) to create curricula in radio astronomy, for the purpose of introducing the\r\nconcepts of radio astronomy and radio telescopes to both school pupils and\r\ncollege students. She has been a member of the Astronomical Society of\r\nPenang since 2016.\r\n\r\nCourse Development\r\nExperience:\r\n\r\nSince joining WOU, Dr. Goh has developed eight courses, namely Control\r\nSystems, Microprocessors, Digital Communications, Microelectronics, VLSI\r\nDesign, Process Control & Instrumentation, Power Electronics & Drives and\r\nElectrical Power & Drives.\r\n\r\nResearch Interest: Dr. Goh’s research interests are in the areas of semiconductor physics and\r\nelectromagnetics. She also has strong interest in the field of astronomy and is\r\nworking with a group of volunteers to promote astronomy education in the\r\nsecondary schools in Penang. She had also worked with some interns on the\r\nradio telescope project at the Penang Science Cluster.\r\n\r\nResearch Projects and\r\nConsultancy Work:\r\nSelected Publications: Design of Radio Frequency Metal-Insulator-Metal (MIM) Capacitors. \r\n\r\nExperimental Investigation on Thermoelectric Generator for Battery - Charger\r\nBased Oven.\r\nAnalyzing the Physics of Radio Telescopes and Radio Astronomy (book\r\nchapters).\r\n\r\nConferences,\r\nSeminars and\r\nWorkshops:\r\n\r\nDr. Goh was appointed as one of the Technical Committee Member for the\r\nVirtual Conference on Electronics and Communication: Loading Intelligence on\r\nFuture Electronics (October 2020).\r\n\r\nHonorary\r\nAppointments and\r\nAwards:\r\n\r\nDr. Goh is a reviewer of the following journals:-\r\n1. Microwave and Optical Technology Letters.\r\n2. Journal of Electrical Engineering.\r\n3. Journal on Digital Signal Processing.\r\n\r\nOfficial\r\n\r\nDr. Magdalene Goh Wan Ching\r\nSenior Lecturer & Programme Coordinator of Bachelor of Technology in\r\n\r\nCorrespondence\r\nAddress:\r\n\r\nElectronics,\r\nSchool of Science & Technology\r\nWawasan Open University\r\n54, Jalan Sultan Ahmad Shah,\r\n10050 Penang\r\n\r\nEmail Address: magdalenegoh@wou.edu.my\r\nPersonal Homepage\r\n(optional):\r\n\r\nBTEL facebook page:\r\nhttps://www.facebook.com/groups/238200129533176/",institutionString:"Technology Wawasan Open University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444312",firstName:"Sara",lastName:"Tikel",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/444312/images/20015_n.jpg",email:"sara.t@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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1. Introduction
Enzymes are biological catalysts that are believed to be the cornerstones of life. They assure metabolic needs of cells and assist in a great range of life-sustaining biochemical reactions. The majority of natural enzymes are highly efficient and can increase the rate of biotransformation up to 1017 fold [1]. Enzymes can carry their functions at ambient temperatures and pressures, with a minimum of by-products and waste, leading to the specific product of interest in a single catalyzed step, whereas synthesis of the same product with the means of organic chemistry may require many steps and produce a mixture of undesired isomeric, epimeric, or rearranged compounds [2]. The field of biotechnology strives to exploit isolated enzymes and whole cell cultures as biocatalysts capable of accelerating and refining complex chemical transformations of organic compounds for industrial and synthetic use [3]. Well known examples of such biocatalysts include microbial lipases that are used to synthesize cost-effective biopolymers, biodiesel, pharmaceuticals, and agrochemicals from renewable natural sources, b-glycosidases employed in industrial plant biomass saccharification [4, 5] and fungal oxidoreductases that have a potential to become biocatalysts in a bio-based (circular) economy by converting biomass into renewable building blocks for manufacturing biodegradable materials [6]. Unfortunately, the scope of natural enzymes is limited, and certain challenges have to be overcome before we can rely on biocatalysts for efficient, low-cost industrial transformations and greener synthetic chemistry. Such challenges include instability of enzymes in vitro (denaturation in high temperatures or extreme pH), low selectivity, product and substrate inhibition, and low reaction yield in non-aqueous solvents [2, 7]. Four general approaches exist to address the above mentioned limitations: additive approach, chemical modification, enzyme immobilization, and protein engineering [8]. While protein engineering is concerned with modifying functional properties of the enzyme at the genetic level, the other three approaches are focused on physico-chemical alterations of the media, enzymatic surface residues, or support material for biocatalyst stability [9].
Using Figure 1 as a guide, we will review both physico-chemical and functional modification strategies for enzyme improvement, starting with the earliest methods to address solvent-dependent limitations and leading to the most recent technologies, like de novo and computational enzyme design [10, 11] (Figure 1).
Figure 1.
Enzyme stabilization methods available for improvement of physico-chemical (yellow) and functional (blue) properties of biocatalysts.
2. Improving biocatalysis in organic solvents by additive approach
Enzymes may be remarkable catalysts in biological systems where water is ubiquitous, but they are less suited for biotechnology where organic solvents are largely employed for chemical transformations. For example, the activity of intestinal proteases subtilisin and a-chymotrypsin is reduced 104–105 times if the enzymes are transferred from aqueous to anhydrous octane media [12]. Knowing that water is essential for structural integrity of many biomolecules and seeing vast experimental evidence of decreased catalytic activity in non-aqueous solvents, scientists have been skeptical about using enzymes as industrial biocatalysts or about using water as a solvent for industrial applications due to undesired hydrolytic side-reactions [3]. However, these challenges were proved to be surmountable when new, improved properties of the enzymes in organic and ionic solvents were discovered several decades ago. In many cases, enzymes that had been stripped of their folded structure in a non-aqueous solution not only became more thermostable and easier to store (due to higher melting points), but also became capable of catalyzing new reactions, impossible in aqueous media. For instance, hydrolases, such as subtilisin, routinely accelerate hydrolysis in aqueous conditions, but in anhydrous solvent, they are capable of catalyzing transesterification reactions [12]. The possibility of using novel, industrially favored substrates as well as the possibility of controlling enzymatic activity and selectivity by finely tuned modifications of the solvent lead to the discovery of numerous approaches to stabilize the enzyme in a non-aqueous solvent [3]. Early trial and error experiments with lyophilized (freeze dried) enzyme powders and solvent additives resulted in the development of empirical strategies like addition of water or water-mimicking solvents and addition of salts for stabilizing biocatalysts. The additive approach currently employs the addition of wide variety of lyophilized chemical substances, also known as lyoprotectants, to the media and still appeals to scientists, as it incorporates the simplicity of use and high efficiency [13, 14].
2.1 Addition of water
The lubricating effects of water on biocatalyst flexibility in organic systems were highlighted in multiple studies [12, 15, 16, 17, 18, 19]. For instance, in chymotrypsin activity trials, the amount of residual water retained on the enzyme after the addition of organic component correlated with the catalytic activity of the enzyme [12]. It was later determined that the addition of trace amounts of water, even if the enzyme have been unfolded in organic media, can remediate some of the activity loss: in the experiments with subtilisin Carlsberg suspended in organic solvents, increase in water content from 0 to 1% resulted in the increase of reaction rate 11-fold in isooctane and 50-fold in THF [18]. Moreover, hydration of organic solvent does not prevent the enzyme from acquiring novel properties valuable for synthetic and industrial applications. For example, adding 1% water to glycerol helped to retain the secondary structure of a-chymotrypsin similar to that in aqueous solvent, however, the enzyme stability at high pH was still much greater in 99% organic solvent over that in water [19]. More importantly, while the enzyme suspended in water was fully denatured after 1 min at 100°C, a-chymotrypsin in 99% glycerol retained 80% of its catalytic activity after incubation at 100°C for 10 h [19].
In recent years, water addition strategy has benefitted many promiscuous biocatalyzed synthesis reactions, such as Henry reaction, Michael addition, Mannich reaction, asymmetric aldol reactions, and others [14]. You can refer to the excellent review by Liang and Lin for the empirical data on yield increase in these reactions due to hydration.
It is important to note that while too few water molecules may be not enough to activate biocatalyst in organic solvent, too many water molecules may result in reduced substrate solubility or hydrolytic reactions side product [14].
2.2 Addition of water mimics and lyoprotectants
Just like water that is thought to lubricate the enzyme enhancing protein flexibility with its multiple hydrogen bonds, water-mimicking substances, such as glycerol, formamide, ethylene glycol and formic acid can provide similar hydrogen bonding, while avoiding unintended hydrolysis product [14, 20]. One of the early water mimic studies concluded that adding 0.1% ethylene glycol to the solvents with optimal water content of 0.2% can increase the activity and stereo-selectivity of Candida cylindracea lipase [21].
Since enzymes often have to be freeze-dried, it is important to ensure their stability during the long-term storage or temperature changes associated with thawing. The most common lyoprotectant up to date is trehalose sugar that helps to preserve enzyme structure and allows for industrial storage of biocatalysts [18].
Most recent reviews also list organic bases, crown ethers, surfactants, and salts as possible additives used to improve catalytic activity of enzymes in chemical synthesis [14]. For the purpose of this section, we will only cover the addition of salts and the role of ionic interactions in biocatalyst enhancement.
2.3 Addition of salt
In 1994, Khmelnitsky et al. discovered that lyophilization of an enzyme in a salty matrix prior to its suspension in organic media lead to a dramatic enhancement in the rate of catalyzed reaction [22]. In this study, 3750-fold increase in activity of subtilisin Carlsberg was documented when 98% w/w KCl-containing lyophilized enzyme powder was added to hexane, as opposed to salt-less enzyme preparation [22]. The authors explained this phenomenon by the protective ability of the salt that was able to prevent direct contact between enzyme molecules and the organic solvent; however, more recent findings using electron spin resonance spectroscopy suggest that salt-induced ionization stabilizes the charged transition state and thus, increases the polarity of the active site [23]. It is also known that while adding certain ions to enzyme preparation or sometimes directly into the solvent can improve both the reaction rate and enantioselectivity, other ions improve only the rate of the reaction or have no effect on the catalysis [14]. Empirical evidence suggests that only kosmotropic (increasing viscosity of water) salts can stabilize catalysts due to preferential hydration effect that addition of Ca ions is more activating than the addition of Ba, Sr, or Mg divalent metal salts [24, 25], and that by using aqueous solutions of smaller alkali metals or alkaline earth metals rather than hydrating the enzyme with water alone we can markedly increase enantioselectivity of the reaction [26].
Even though additive approach for biocatalysis improvement has offered many successful results, several disadvantages limit its use and call for exploring other methods of enzyme stabilization. Such disadvantages include the fact that the effect of molecular additives varies widely from case to case, depending on the enzymes used, desired substrates and reactions. Since the majority of successful additive methods were discovered by accident, there are no general protocols developed for this approach, and only few stabilizing additives are researched enough for us to clearly understand the molecular mechanisms behind their role in catalysis [14].
3. Chemical modifications to stabilize enzymes
Chemical modification of enzymes is a very common stabilization strategy. In fact, covalent modification by the cross-linking with glutaraldehyde reagent can stabilize almost any enzyme, protecting it from denaturing and other effects of the new solvent [27]. This finding led to the development of carrier-free enzyme immobilization methods (to be discussed in detail in Section 4).
Another popular chemical method involves covalent conjugation with an amphiphilic polymer polyethylene glycol (PEG) and is often referred to as enzyme PEGylation [28]. PEGylating permits binding of specific polymeric functional groups to the free amino groups on the enzyme, creating PEGylated biocatalyst soluble in organic solvents [19]. This method is especially useful for preparation of biopharmaceuticals with high stability and low antigenicity [29]. Additionally, reagent methoxymethyl-PEG (mPEG) bound to the enzyme horseradish peroxidase (HRP) can protect the protein from pH extremes and high temperatures, making HRP particularly useful in industrial and clinical biosensors [30].
Chemical alterations of the enzyme can introduce a new functional group for a covalent attachment or modify one of the reactive side chains. For instance, the treatment of Candida rugosa lipase with diethyl p-nitrophenyl phosphate modified one of the two reactive functionalities and resulted in a more selective lipase catalyzing a single reaction [31].
Chemical modification makes it possible to introduce and attach a new cofactor, which can in turn induce novel enzyme functions [32]. Lastly, some post-translational enzyme modifications either in vivo or in vitro have been linked to an enhanced stability of enzymes [33]. For example, when DNA ligase from Thermus scotoductus was chemically adenylated, new irreversible covalent binding of the cofactor resulted in structural changes within the active site and overall protein compaction. As the result of this cofactor-induced conformational change, the enzyme gained increased resistance to thermoinactivation [34, 35].
As strategies for enzyme improvement continue to evolve, chemical modification has been rediscovered to become a robust complimentary approach to both protein engineering and immobilization [36].
4. Enzyme immobilization
It is clear that while additive or chemical approaches represent a simple and attractive route for a small-scale chemical synthesis, they have to be supplemented or substituted with other enzyme-stabilizing approaches when applied to complex enzyme systems or whole-cell catalysts in biotechnology.
Much like in a living organism, where enzymes are associated with a membrane or a cell structure that ensures their stability, in industrial setting, it is often necessary to anchor the enzyme to a certain area of a reactor in order to stabilize and reuse the same catalytic device over and over [8]. Enzyme immobilization approach usually achieves this goal by constraining enzymes to a more stable support (a carrier), thus, creating insoluble heterogeneous catalyst of native conformation with reduced flexibility [37]. Not only immobilized catalyst is less likely to be deactivated in organic solvent, is not perturbed by lyophilization [38], is more resistant to sheer stress and high temperatures [39, 40], but it is also less costly, as it is recycled in a continuous fixed-bed process and allows for an efficient enzyme purification and recovery with the help of selective adsorbents [41, 42].
Biocompatible carrier can be chosen from almost any organic polymer or inorganic material that is inert [43]. The requirements to the ideal carrier also include: affordability (the cost of the enzyme and the carrier should not be more than a few percent of the total production cost), stability, physical strength, regeneration ability, as well as the ability to aid in catalytic functions [38, 44], promoting enzyme specificity and reducing product inhibition and non-specific interactions [45]. Moreover, the carrier has to match certain surface properties of the enzyme (e.g. polar groups of amino acids or apolar surface areas), have high superficial density of reactive groups [46], and have a large surface area (e.g. contain high number of small-sized particles or large dimensional pores) [47]. In some cases, where stronger covalent binding with the enzyme is desired, reactive functional groups have to be chemically introduced as monomers in a polymeric carrier matrix [48]. All the above requirements for the carrier are not easy to meet, and sometimes carrier-less approach is used, where enzyme molecules are cross-linked to each other, providing support [38]. Fundamental strategies of biocatalyst immobilization include adsorption, covalent binding, cross-linking, and entrapment/encapsulation [8, 47, 49] (Figure 2). In this section, we will review these approaches and their successful combinations, as well as some promising “smart” enzyme immobilization techniques with possible applications.
Figure 2.
Fundamental methods of enzyme immobilization.
4.1 Adsorption
More than a century ago, it was empirically proven that invertase enzyme can be adsorbed onto a solid support like charcoal or aluminum hydroxide with its catalytic activity remaining similar to that in its free soluble state [50]. Since then, the methods of adsorption of enzymes onto carriers may have evolved, but the principle has remained the same: intermolecular forces between the enzyme and support result in protein accumulation on a solid surface [8]. Adsorption forces are rather mild and generally involve non-specific van der Waals, hydrophobic, hydrogen bond (H-bond) and ionic interactions [42]; however, high coverage and stronger adherence can be achieved by choosing the right carrier based on enzyme’s surface charge and polarity [51]. For instance, a hydrophobic carrier will work well with the enzyme of large lipophilic surface area due to entropy and hydrophobic effect [47]. Alternatively, H-bonding to hydrophilic carriers (e.g. cellulose, porous glass, silica gel, Avicel, or Celite) is used if the enzyme has hydrophilic surface residues, especially, if the enzyme is glycosylated [47].
The main advantage of adsorption method is its simplicity and low cost [52, 53]. The enzyme can be simply added to the active adsorbent’s surface [43], or deposited onto the carrier via evaporation of aqueous phase [54], there is no need to previously modify the ligand [55], or to wash off the enzyme that has not been adsorbed [43]. Typically, mild, reversible interactions of physical adsorption are preferred for immobilization, since they do not change the native structure of the catalyst and do not disturb its active enzymatic sites [53]. The disadvantages of adsorption include the fact that it only proceeds in organic solvents due to intrinsic solubility of enzymes in such media; otherwise, enzyme leaching is unavoidable either as a result of H-bonds with water or due to ion exchange for the enzymes immobilized by ionic forces [47]. Apart from enzyme leaching as a function of time [8], in a physical process such as adsorption, active site blockage due to nonspecific interaction with the carrier can greatly reduce the activity of immobilized catalyst, especially if the substrate is large [49, 56].
In order to improve the stability and activity outcomes of non-specific adsorption, multiple specific adsorption methods were proposed in recent years, including biospecific adsorption that involves immobilized antibodies, affinity adsorption that uses carrier-bound immobilized dyes as ligands, coordination adsorption where immobilized transition metal ions interact with amino acid residues on the enzyme, and others [57].
4.2 Covalent binding
It was discovered in 1960s that certain pre-functionalized carriers covalently bound to the enzyme (native or modified) can act as a scaffold for enzyme stabilization, while substantially improving its performance as a biocatalyst [42]. Covalent forces between the functional groups of the support matrix (whether it is an inner wall of a bioreactor, or a packed-bed industrial reactor filled with glass or biopolymeric beads [8] and reactive active amino acid residues on the enzyme surface can create extremely strong linkages [58]. For example, pre-treatment of glucose oxidase from Aspergillus niger with periodic acid helped to activate its carbohydrate residues for new covalent linkages to a hydrophobic polymer p-aminostyrene. As a result, immobilized glucose oxidase retained its full activity and even gained higher thermostability at 60°C compared to that of a native soluble enzyme [59]. Unlike adsorption, covalent binding can be performed in any solvent; however, it is a method of choice for immobilizing enzymes in aqueous solvents or under denaturing conditions [47]. The rigid covalent binding prevents enzyme leaching caused by non-specific interactions with water and locks the enzyme in its native conformation, resisting thermoinactivation [60]. Similar to physical adsorption, both hydrophilic and hydrophobic carriers can be used for immobilization [47]. Carrier activation may also require long or short spacer molecules between the carrier and the enzyme, in order to provide more accessible catalytic sites and to attach desired reactive groups to the matrix [55]. Most commonly introduced reactive groups include aldehydes or epoxides to be attacked by nucleophilic amino groups on the protein, which is followed by instant reduction of the product and irreversible attachment of the enzyme to the carrier [42, 48]. Nevertheless, such chemical modifications can be harsh for the three-dimensional protein structure, especially, if chemical microenvironment of the enzyme (including possible storage additives) is interfering. The main disadvantages of immobilization by covalent binding include non-uniform attachment if the bond density is too low [61], or, if the bond density is too high, the risk of immobilized catalyst being irreversibly deactivated and rendered unusable [37].
4.3 Entrapment and encapsulation
Entrapment and encapsulation within the polymeric matrix are immobilization techniques that, similar to physical adsorption, employ non-covalent interactions [49]. Unlike in surface adsorption, the support matrix is not pre-fabricated but is synthesized at the same time as the enzyme is being entrapped or encapsulated in situ [38].
In the entrapment method, a catalyst (soluble or insoluble) is dispersed in a solution of a monomer or polymer of low molecular weight, and later becomes entrapped in a matrix formed by hydrolytic polymerization [42]. Inside the polymer lattice, almost every side chain on the enzyme surface physically interacts with the support material around it, while allowing small substrate product molecules move in and out of the complex through the pores [43]. As an attempt to modulate the porosity and diffusion pattern, silica sol–gels of varying densities (e.g. xerogels, ambigels, aquagels, or aerogels) with additives to create hydrophilic or hydrophobic surfaces are commonly used [62]. When xerogels of high density entrap one or more enzymes by hydrolytic polymerization, the substrate selectivity of the extremely small pores can be particularly useful for the development of biosensors [63, 64]. Entrapment matrices with hydrophobic surfaces can activate lipases, the most used enzymes in synthetic organic chemistry [65]. Moreover, catalytic activity of Candida antarctica lipase entrapped in a hydrophobic sol-gel can be improved 2–8-fold compared to that of non-immobilized freeze-dried lipase powder [66]. Nonetheless, the practical application of entrapment is limited because of the requirements, like small substrate size and delicate balance between physical properties of the matrix and enzymatic activity [43]. Insufficient substrate interaction and leakage of enzymes due to continuous use are major disadvantages of the entrapment method [67].
Alternatively, enzymes can be encapsulated within a semi-permeable polymeric membrane [43]. Immobilization by encapsulation occurs when microcapsule walls are formed around enzymes as a result of polymer desolvation [68]. The capsule can provide desired chemical microenvironment for a specific enzyme in terms of pH, temperature and solvent stability, very similar to the microenvironment in the living cell [69]. Depending on the material used, the membrane can be permanent or non-permanent. Non-permanent membranes can be formed by liquid surfactants, while permanent membranes are often made of polystyrene, cellulose, gliadin, nylon, and other materials used to encapsulate pharmaceuticals, food, cosmetics, and chemicals [68, 70].
Although high enzyme concentrations and large surface areas of encapsulated biocatalyst can ensure faster reaction rates [71], similar to enzyme entrapment, traditional method of microencapsulation can only be applied to a limited number of enzymes with small substrates [62]. In recent years, the structure of microcapsule from a hollow bead evolved to a complex multilevel three-dimensional sphere. Such biomimetic capsule design often allows to adjust permeability in favor of mass transfer of substrate and product, while dramatically improving catalytic activity of encapsulated enzymes [72].
4.4 Carrier-free immobilization by cross-linking
Carrier-free immobilization method was developed as a way to address the issue of inevitable activity drop associated with the carrier attachment. The non-catalytic part often represents 90–99% of the immobilized catalyst [37], and although it provides the catalytic element with enhanced stability and longer half-life, it is also responsible for unwanted mass-transfer effects, low product yields and higher production cost [73].
It was first reported by Yale scientists in 1964 that di-functional reagent glutaraldehyde, normally used as a fixative for electron microscopy slide preparation, can form irreversible covalent linkages between enzyme molecules. When carboxypeptidase-a enzyme crystals treated with glutaraldehyde were tested by diffraction techniques, cell dimensions of the enzyme remained very similar to that of its native state, even after mechanical stress and changing the solvent; moreover, the enzyme tested retained most of its catalytic activity [27]. Therefore, pure enzyme in almost any form (solubilized, crystallized, aggregated or atomized) now can be chemically modified to act as its own carrier [74]. The mechanism of this reaction involves the formation of Schiff’s bases between carbonyls on the cross-linker and free amino groups on the enzyme’s lysine residues together with a pH-dependent Michael 1,4-addition to a,b-unsaturated aldehydes [75].
Two most popular carrier-less preparations that can be used in industrial and pharmaceutical synthesis are cross-linked enzyme crystals (CLEC) and aggregates (CLEA) [76]. CLECs, obtained by crystallization of the pure enzyme prior to cross-linking [77], according to the patent of 1997, are able to retain at least 91% of enzyme’s initial catalytic activity if incubated with a protease for 3 h, compared to unmodified enzyme that loses at least 94% of the activity under the analogous conditions [78]. Resistance to proteases also allows to administer CLEC biocatalyst orally as a longer-acting drug [79]. As for the industrial uses, advantages of CLECs, like possibility of indefinite storage at room temperature, their near-maximum catalytic activity in harsh conditions, and high tolerance to organic solvents [80], allow for various potential applications, including microporous phase for chromatography and environmental toxicity biosensors [81, 82]. And yet, CLEC method requires highly purified enzyme for crystallization, which translates into higher expense and renders CLEC superseded by closely related technique CLEA [37].
CLEAs, first described in 2000, are prepared by aggregating enzymes with precipitants, like acetone, ethanol, or ammonium sulfate, and then by cross-linking the aggregates with glutaraldehyde or dextran polyaldehyde [38, 83]. After the protein is cross-linked with the reagent, sometimes protective reagents and other additives can be used to create a “tailor-made” biocatalyst [47]. For instance, knowing that surfactants, amines, and crown ethers can activate lipases, one study prepared CLEAs of seven microbial lipases by co-precipitation with different additives. As a result, two of the lipases were hyper-activated (had 2–3 times higher activity than that of a native enzyme) in the presence of SDS surfactant, demonstrating that precipitation with the right additive can lock the catalyst in the preferred conformation [84].
Apart from broad applicability, high stability, and possibility of catalytic hyper-activation by chemical optimization, the CLEA technology eliminates laborious enzyme purification and crystallization steps required for CLECs as well as the expense of using a carrier required for other immobilization methods [85]. This makes CLEA protocols reproducible in almost any lab that has a relatively crude enzyme sample [49]. Interestingly, crude samples containing several enzymes can be used to make combi-CLEAs that recreate multistep, multi-enzyme cascade processes for biotechnological or clinical applications [85].
4.5 Combinatory physicochemical approaches
Rational combinations of immobilization methods described above together with chemical enzyme modifications (see Section 3) often have synergistic effect [33]. Therefore, combinatory approaches have been increasingly applied with the goal of designing an improved, robust catalyst from the native enzyme by physicochemical means at a low cost. For instance, physical adsorption, a simple and less expensive immobilization technique [52], would be more commercially viable if it could avoid desorption of enzyme immobilized by weak, non-specific forces. It was reported that entrapment of Candida lipase prior to its co-adsorption with lipase-activating chemical additives not only protected the enzyme from desorption, but also was a cheaper and more efficient method of biodiesel production from waste cooking oil, compared to immobilization methods described in previous studies [57]. Combination of enzyme cross-linking prior to entrapment in sol–gel beads was determined to be a viable technique for stabilizing enzymes in glucose biosensors [67]. In some cases, filtration-enabled reusability of CLEAs may be problematic due to similar size of the particles and the substrate. To ensure easy enzyme separation, it was proposed to encapsulate the enzyme solution in a soft porous membrane and thus, create particles of desired size prior to their aggregation and cross-linking [44].
With a number of successful techniques available and so many variables involved in the trade-off between stability and activity of immobilized enzyme, choosing the most efficient approach for a less-studied enzyme can be a problem. In this case, combination of computational analysis with experimental methods, known as structure-based immobilization, can be of assistance [47]. For instance, GRID computational analysis of the functional groups on the enzyme can help to locate nucleophilic amino groups on the lysine residues that would be involved in the covalent binding. If such groups are present in the close proximity of the active site, non-covalent techniques, like adsorption, entrapment, or encapsulation should be considered. Additionally, hydrophobic and hydrophilic surfaces of the enzyme can be established in order to choose the appropriate support material [86].
According to bibliometric analysis of 2019, new trends in enzyme immobilization research can be seen from the top-50 author-keywords list, based on the works published globally in the last 5 years. The top directive terms included: gold nanoparticles, meso-porous silica, magnetic nanoparticles, response surface methodology, glucose biosensor, and cross-linked enzyme aggregates (CLEAs) [74]. It is evident, that immobilization on nano-particles, nano-fibers, and nano-gels is a field of special interest, due to high adaptability, high retention of activity, and effortless enzyme separation and recycling [49, 87]. The main advantage of nano-structures is their high surface to volume ratio, where decreasing size of the carrier allows progressive exposure of the enzyme to reaction media, making nano-immobilization a method of choice for development of powerful enzyme-based fuel cells [88]. Magnetic nanoparticles (e.g. mCLEA) that can be functionalized for enzyme isolation by magnetic decantation or used in magnetically stabilized reactor beds are part of a new, promising approach, known as “smart” enzyme immobilization [89]. Finally, there is a possible turn of interest to a matrix algebra- and statistics-based response surface method (RSM) that can be used for optimizing operational conditions of immobilized biocatalysts [90].
5. Enzyme engineering
“What I cannot create, I do not understand”
Richard Feynman
Enzyme engineering approach originated as an ultimate challenge to test our understanding of protein structure and function in early 1980s [91]. Since then, the field of biocatalysis have been revolutionized by the advances of recombinant DNA technology, use of computational tools, and modern bioengineering. Alterations of the primary protein structure can be tailored not only to stabilize the enzyme, but also to broaden the substrate range, optimize catalytic performance, and obtain products of high value for various biotechnological applications. Enzyme designers can modify or develop a novel biocatalyst with a new primary function [3] by using one of the following approaches: rational redesign (RR), directed evolution (DE), semi-rational redesign (SR), or de-novo enzyme design (DN) [92]. Enzyme engineering methods are laborious and all have the following pre-requisites in common: enzyme encoding gene of interest, microbial or yeast expression system, and sensible screening tools for mutant detection [93]. In this section, we will briefly review these methods and their possible applications in fine chemical synthesis.
5.1 Rational redesign (RR)
RR strategies for enzyme improvement genetically modify the existing biocatalyst based on known structural criteria. To begin with, different pieces of data, like protein structure obtained by X-ray diffraction techniques, molecular models based on computational algorithms, and biochemical specifics, like locations of interacting ligand residues obtained by NMR-analysis, must be evaluated to propose rational genetic alterations [94]. The method of choice for introducing specific alterations is site-directed mutagenesis (SDM) [2]. Most commonly, beneficial mutations are induced with the goal of changing catalytic mechanism, reinforcing the promiscuous reaction, altering substrate/cofactor specificity and improving the overall stability of the biocatalyst [93]. To ensure the specificity of mutations, the majority of RR techniques employ polymerase chain reaction (PCR) with the primers (short sequences of synthetic DNA complementary to the template gene) that have been modified using a known mutant codon or codons [2].
Two common methods of inserting/deleting specific amino acids into/from the target gene by SDM are overlap extension and whole plasmid single round PCR [10]. The former method uses two pairs of primers with one of the primers in each pair containing a modified (mutant) codon, which results in a PCR-produced heteroduplex plasmid with overlapping breaks. The later method is simplified by using a “QuikChange Site-Directed Mutagenesis Kit” patented by Stratagene and adding two primers with desired mutations that are complementary to the opposite strands of the DNA template. The mutant plasmid obtained by PCR is then nicked by a specific restriction enzyme to be repaired upon transformation into competent cells [95]. A more efficient one-step version of QuikChange method suitable for single or multiple-site insertions and deletions was described in [96]. Successful applications of SDM include the induction of acid-resistance and 16.7-fold higher catalytic activity in a-amylase used for industrial sugar and detergent production [97], thermostability enhancement in sucrose isomerase producing a non-cariogenic, nutritional sugar isomaltulose that slows down the rate of insulin release in diabetes management [98], and even attempts to design high efficiency H2-producing cyanobacterial cells to make biofuels [94]. At the same time, numerous attempts of RR fail due to insufficient knowledge of mechanisms responsible for the specific structure–function relationships. The process of SDM is often too tedious and expensive, requiring mutant enzyme confirmation by sequencing and purification [99].
5.2 Directed evolution (DE)
In contrast to RR, the methods of DE can be applied to the enzymes even in the absence of existing structural and mechanistic data. DE relies on accelerating Darwinian evolution in laboratory with the means of mutation and random recombination, followed by multiple rounds of selective “molecular breeding” [100]. Three steps common for all DE methods are: (1) construction of mutant library by the means of random mutagenesis or in-vitro recombination, (2) screening/selection of mutants with the desired properties via high throughput assays, and (3) improved protein gene isolation [49, 92]. Initial generation of molecular diversity can be achieved by methods like chemical mutagenesis, error-prone PCR (epPCR), gene site saturation mutagenesis, and DNA shuffling [2, 49].
Chemical mutagenesis is used extensively for a “food grade” enzyme improvement: avoiding the introduction of heterologous DNA, it applies chemical agents like ethyl methyl sulfonate or nitrous acid to bacterial strains lacking DNA repair mechanisms, generating random mutations [101].
EpPCR method introduces random changes in a catalyst encoding gene by using error-prone Taq DNA polymerase for the PCR process. Unlike in chemical mutagenesis, the rate of mutation can be controlled by modifying PCR conditions. For instance, it is possible to introduce an average of one amino acid substitution per PCR cycle, and 3–7 cycles are usually enough to improve the thermostability and enantioselectivity of the enzyme [2, 102].
DNA shuffling method relies on in vitro DNA recombination of closely related parental genes either obtained from different organisms or produced by epPCR [92]. The genes are digested with DNaseI or with a mixture of restriction endonucleases to yield random, small fragments that will be purified and reassembled by epPCR, where fragments cross-prime each other [95]. Therefore, genes from multiple parents, including different species, can be shuffled in a single step, sometimes resulting in a hybrid DNA with unique, novel traits not expressed in either parent [103]. Nevertheless, DNA shuffling cannot induce drastic functional changes, as these are known to require considerable evolutionary changes in polypeptide backbone [99].
The technique known as gene site saturation mutagenesis can be used for the replacement of each amino acid of a protein with each of the other 19 amino acids occurring in nature [2]. For instance, PCR amplification with a mixture of 64 different forward and 64 different reverse primers would be necessary to randomize one codon in the enzyme gene (based on 4 letters of genetic alphabet and 3 nucleotides in one codon), but one could eliminate stop codons by restricting the third nucleotide to G or C and use a mixture of 32 forward and reverse degenerate primers. Statistically, the size of the mutant library obtained by this method can be calculated as 20n, where n is the number of amino acid residues in the protein of interest [2]. Hence, the biggest limitation of DE methods is the requirement of an efficient high throughput screening process for the mutant libraries that even with millions of variants, still sample only a very small fraction of the enzyme sequence [104]. Nevertheless, the field of DE is actively developing, and recent publications report achievements, such as induction of pH-, temperature- and oxidation-tolerance in a catalyst [105, 106], including the development of a novel enzyme structure as a result of a new function acquired by DE [107].
5.3 Semi-rational (SR) and de novo (DN) design approaches
Addressing major limitations of both DE and RR, SR design creates smaller, manageable mutant libraries based on the structural/biochemical data or computational predictive algorithms [104]. In other words, if the 3-D structure of an enzyme is available, random mutagenesis can be focused on a specific site (usually within the active site) in the protein sequence, leading to higher probability of identifying the key amino acids, randomly replacing them or reinforcing them via cumulative effects [3].
Site saturation mutagenesis rationally applied to a specific codon or codons is an example of a semi-rational approach. In the method known as CASTing (combinatorial active site saturation test) several amino acids of the active site are targeted and mutated one by one or in combination [108]. Combinatorial saturation of residues can produce mutants improved by synergistic effects. However, these vast multiple-site saturation libraries are almost impossible to screen with traditional DE means. In this case, computational algorithms are used to virtually screen the library, eliminating the mutants that have been misfolded due to unfavorable amino acid interactions [109].
“Region specific random mutagenesis” is another semi-rational method that employs SDM performed with 64 different forward and reverse primers targeting a single codon to be randomized based on its importance for enzyme structure and function [95].
There is no doubt that the fine-tuning of engineered enzymes benefits from the use of combinatorial approaches. SR design has a great potential to create specialized biocatalysts for the industrial use. For example, improved uronate dehydrogenase enzyme of high thermostability can be used to catalyze the production of glycaric acids (top-value chemical precursors for greener and less expensive biofuel synthesis) [110]. Nevertheless, even with reduced mutant libraries, SR approaches are not straight forward. Sometimes, molecular interactions and cascade effects far away from the active site are responsible for certain catalytic effects [3].
In cases when enzyme structures do not appear to be optimized for a specific chemical transformation, synthesizing enzyme of a completely different structure de novo may be the most reasonable solution. In 2008, DN engineering of artificial enzyme Kemp eliminase from scratch provided the evidence that it is possible to create a new functional enzyme using a multi-level approach that involves quantum mechanical (QM) calculation, computational algorithms, and directed evolution [111]. Generalized DN workflow starts with the engineering of a minimal ideal active site containing catalytic machinery and interaction residues, optimized by QM into a model structure called “theozyme”. The theozyme is then matched to a pre-existing protein scaffold by a hashing algorithm. After the scaffold-theozyme structure is stabilized, the enzyme is ranked in silico based on its geometry and binding energy and can be empirically tested. If tested active, but inefficient, the catalytic activity can be improved by several rounds of DE [11]. DN development would not have been possible without computational tools, like METAL SEARCH, DEZYMER, ORBIT, ROSETTA match, ROSETTA design, and MODELER (see [49, 109] for details).
Although it is able to provide predictive frameworks for rational in silico engineering and generate more focused, “smart” libraries, computational enzymology is still in its infancy. Combinatorial strategy where directed evolution is integrated with rational optimization remains a method of choice for protein engineering [104].
6. Conclusions
While enzymes have been involved in commercial production processes for centuries, their vast potential for a large scale chemical synthesis and industrial applications was not fully realized until better empirical models and methods of biocatalyst stabilization were developed using a trial and error approach. In this chapter, we reviewed fundamental strategies for enzyme improvement, such as chemical modification, additive approach, enzyme immobilization, and protein engineering. It appears that enzyme immobilization is currently considered to be the most promising strategy for obtaining industrial biocatalysts with controlled, more specific substrate interactions, resistance to denaturation, and high product yield at low cost [74]. At the same time, enzyme engineering methods recently made numerous successful advances to redesign existing enzymes on the level of their primary structure using targeted random mutagenesis, in vitro recombination, and various computational tools. Although there is high demand for such specialized, robust biocatalysts, they are generally produced as soluble enzymes, not reusable in the industrial synthesis. Therefore, integration of physico-chemical methods and protein engineering is possibly the most efficient strategy for creating a powerful, recyclable biocatalyst fit for the real-world biotechnological processes.
Conflict of interest
To our knowledge, there has been no conflict of interest.
Notes/thanks/other declarations
We would like to thank our families for the support and encouragement.
\n',keywords:"biocatalysis, enzymes, additive approach, PEGylation, enzyme immobilization, adsorption, entrapment, encapsulation, cross-linking, CLECs, CLEAs, nano-biocatalysis, enzyme engineering, rational redesign, site directed mutagenesis directed evolution, DNA shuffling, error prone PCR, saturation mutagenesis, CASTing, de novo enzyme design",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/66503.pdf",chapterXML:"https://mts.intechopen.com/source/xml/66503.xml",downloadPdfUrl:"/chapter/pdf-download/66503",previewPdfUrl:"/chapter/pdf-preview/66503",totalDownloads:1545,totalViews:0,totalCrossrefCites:5,totalDimensionsCites:12,totalAltmetricsMentions:0,impactScore:4,impactScorePercentile:89,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"December 20th 2018",dateReviewed:"February 7th 2019",datePrePublished:"April 1st 2019",datePublished:"February 19th 2020",dateFinished:"April 1st 2019",readingETA:"0",abstract:"Biotransformation with the help of enzymes can greatly improve the rate and stereospecificity of reactions in organic chemistry. However, the use of organic solvents and harsh conditions in biotechnological applications often correlates with enzyme deactivation or a dramatic drop in catalytic activity. Detailed molecular understanding of the protein structure and conformational dynamics allows us to address such limitations and to finely tune catalytic activity by modifying the solvent, the support, or the active site of the enzyme. Along with physico-chemical methods of enzyme stabilization, such as additive approach, chemical modification, and immobilization of enzymes, approaches of enzyme engineering based on DNA recombination can be used to enhance the performance of biocatalysts. Since successful synthetic and industrial applications of biocatalysts require systems that are not only stable and active, but can also be reused in a continuous flow process reducing the production cost, the goal of this chapter is to introduce the reader to the vast scope of techniques available for enzyme improvement, highlighting their opportunities and limitations for the real-world technological processes.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/66503",risUrl:"/chapter/ris/66503",book:{id:"6897",slug:"biophysical-chemistry-advance-applications"},signatures:"Yauheniya Osbon and Manish Kumar",authors:[{id:"290106",title:"Dr.",name:"Manish",middleName:null,surname:"Kumar",fullName:"Manish Kumar",slug:"manish-kumar",email:"m_k135@txstate.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Texas State University",institutionURL:null,country:{name:"United States of America"}}},{id:"292602",title:"Ms.",name:"Yauheniya",middleName:null,surname:"Osbon",fullName:"Yauheniya Osbon",slug:"yauheniya-osbon",email:"eugenia0@txstate.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Improving biocatalysis in organic solvents by additive approach",level:"1"},{id:"sec_2_2",title:"2.1 Addition of water",level:"2"},{id:"sec_3_2",title:"2.2 Addition of water mimics and lyoprotectants",level:"2"},{id:"sec_4_2",title:"2.3 Addition of salt",level:"2"},{id:"sec_6",title:"3. Chemical modifications to stabilize enzymes",level:"1"},{id:"sec_7",title:"4. Enzyme immobilization",level:"1"},{id:"sec_7_2",title:"4.1 Adsorption",level:"2"},{id:"sec_8_2",title:"4.2 Covalent binding",level:"2"},{id:"sec_9_2",title:"4.3 Entrapment and encapsulation",level:"2"},{id:"sec_10_2",title:"4.4 Carrier-free immobilization by cross-linking",level:"2"},{id:"sec_11_2",title:"4.5 Combinatory physicochemical approaches",level:"2"},{id:"sec_13",title:"5. Enzyme engineering",level:"1"},{id:"sec_13_2",title:"5.1 Rational redesign (RR)",level:"2"},{id:"sec_14_2",title:"5.2 Directed evolution (DE)",level:"2"},{id:"sec_15_2",title:"5.3 Semi-rational (SR) and de novo (DN) design approaches",level:"2"},{id:"sec_17",title:"6. Conclusions",level:"1"},{id:"sec_21",title:"Conflict of interest",level:"1"},{id:"sec_18",title:"Notes/thanks/other declarations",level:"1"}],chapterReferences:[{id:"B1",body:'Benkovic S, Hammes-Schiffer S. A perspective on enzyme catalysis. Science. 2003;301(5637):1196-1202. DOI: 10.1126/science.1085515'},{id:"B2",body:'Glazer AN, Nikaido H. Microbial Biotechnology : Fundamentals of Applied Microbiology [Internet]. Cambridge; New York: Cambridge University Press; 2007. pp. 398-429. DOI: 10.1017/CBO9780511811227.012'},{id:"B3",body:'Tunon I, Moliner V. Simulating Enzyme Reactivity: Computational Methods in Enzyme Catalysis, RSC Theoretical & Computational Chemistry Series. England: Royal Society of Chemistry; 2017. 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1. Introduction
During the past few years, business leaders have been faced with the confluence of multiple challenges, the likes of which they had never seen before: the Covid-19 pandemic, systemic racism and the continued escalation of the climate crisis. These challenges forced companies to search for new ways to create value for their investors and other stakeholders; these challenges forced business leaders to think differently about the role that their companies play in the broader society.
Of course, corporations will have an enormous impact on what happens in the broader society in the days ahead. The past few years have been very chaotic - but they are in the past. The business opportunities we experienced in the past may or may not be the same opportunities we see in the future. Companies need to develop systems and strategies that are capable of creating economic value in the future, regardless of the societal opportunities and challenges that come their way. Companies need to move beyond seeing social dynamics as short-term opportunities and incorporate them into long-term strategies.
Business leaders are paid to ensure that their companies survive in the short-term while attempting to thrive over the long-term. But getting this balance right, especially in times with enormous social turbulence, is never easy. As we think about how business leaders balance these short-term opportunities and long-term strategies, it is critical that they realize that he level of social responsibility expected by society has risen significantly in recent years. Some companies used to pursue corporate social opportunity (CSO) thinking about how companies engage with significant social shocks over the short-term. These actions are symbolic and empty gestures. The key to creating long-term economic value will be thinking beyond these short-term opportunities and developing strategies that align with what matters to stakeholders. In this study, we offer 6 rules for moving forward and for turning short-term social opportunities into long-term strategic value creation.
Milton Friedman [1] famously said that the only corporate social responsibility any business has is to maximize profits. But how does any business maximize profits? Alex Edmans [2] shows that profits are maximized but connecting a strategy with a what stakeholders are willing to pay for. Bielak et al. [3] show that employees are the stakeholder group that has the greatest influence on how a firm engages with social shocks and societal expectations. Other research, including Schiller [4] and Dai et al. [5], focus on the role that customers play in forcing firms to have more sustainable and socially responsible supply chain. Stakeholders matter, over both the short term and the long term. Anat Admati [6] warns that stakeholder influence can be muted if government regulations and social structures are not conducive to firms addressing such social shocks. And, Gillan et al. [7] provide empirical evidence that firms which have more embedded corporate social responsibility and ESG cultures have lower costs of capital, suggesting that investors and other stakeholders see the value in firms investing in environmental, social and governance imperatives. The challenge for firms is to get the balance right between short-term social opportunities – which may lead to fleeting profitability – and long-term responsibilities – which should lead to long-term and sustainable economic value creation.
This is a conceptual study aimed to help business leaders better understand their role in the decision-making process and what they need to do to ensure their business can survive in the short-term and thrive in the long-term. Doing so requires their business offering products, services and relationships that help their stakeholders improve their lives. We also connect various research streams - from stakeholder theory to resource dependency theory to Milton Friedman’s perspective on social responsibility - to show how academics can think about their own research and where it fits in the broader literatures on social responsibility and value-creation. In doing this, we rely on both academic studies and case studies to show how moving beyond corporate social opportunity and towards value creation through social responsibility is the key to long-term corporate success.
2. Corporate social opportunity vs. corporate social responsibility
Where does economic value come from? That’s not a rhetorical question; but it is a question that we – as both academics and business leaders – frequently take for granted. Yet, through the social and economic tumult of 2020, many business leaders were forced to try to answer that question. The Covid-19 pandemic and related shutdowns put many companies out of business and left many others scrambling for a strategy to survive through the crisis. At the same time, business leaders were working to design strategies to address the Black Lives Matter and other social justice movements around the world, while also dealing with the short-term and long-term effects of a worsening global Climate Crisis. The historic economic shocks of 2020 shed a bright light on where economic value comes from: economic value is created by people working to create a better life, greater wellbeing and greater opportunity for themselves and their loved ones. More simply, economic value is created by people.
Economic and social shocks can present business leaders with short-term opportunities to connect with people and to create economic value. Companies that are agile and able to adapt to these new opportunities will benefit the most. For entrepreneurs, agility and adaptability – or organizational improvisation – can be extremely valuable in being able to quickly turn a short-term shock into the start-up’s long-term strategy [8]. The same mentality applies to companies of all sizes. And when the shocks are so intense, such as the pandemic-related shocks of 2020, business leaders feel like they have to capitalize on every fleeting opportunity. But what if these opportunities do not align with their missions, strategies and resources? What if the businesses cannot strategically improvise? Should the companies still pursue them because they seem good opportunities?
A recent study by the U.S. Federal Reserve studied business closures during the Covid-19 pandemic [9]. In an average year 7.5% of all businesses close. During the first year of the pandemic, business closures were approximately one-quarter to one-third higher than normal. This increase was dominated by “Other Services” (barber shops and yoga studios) and “Leisure & Hospitality.” However, there were some industries that experienced lower than typical closure rates during the pandemic, including grocery stores, take-out restaurants, electronics stores and arts, entertainment and leisure. Why? What did companies in these industries do differently? Perhaps it was as simple as being essential and providing both needs and wants in safe and efficient ways. But maybe it’s not that simple.
We present an approach that business leaders can use to think beyond these short-term opportunities and stay committed to their long-term missions and strategies – which is especially useful in times of turbulence and uncertainty. Since the beginning of 2020, business leaders have seen many chances to take advantage of these windows of opportunity and (perhaps) realize some short-term profits; we know that the time perspective regarding windows of opportunity is particularly critical for entrepreneurs and small businesses [10]. But what happens when those windows close? What happens if the company does not have the resources to effectively leverage those opportunities?
Corporate social responsibility is generally thought of as creating value in ways that satisfy legal obligations and society’s prevailing conventions [11]; we use the term “corporate social opportunity” to refer to these windows where business leaders think they can follow a social movement to create economic value. Corporate social opportunity is distinct from corporate social responsibility because it has a short-term focus and may be disconnected from the strategic intent of any corporate actions. Corporate social opportunities are frequently symbolic and empty gestures, aimed at following moments of economic and social chaos, but are not part of longer-term strategy or movement.
During the summer of 2020, as the Black Lives Matter and anti-racism movements were growing around the world, many businesses announced new initiatives and positions focused on diversity, equity and inclusion. But what has been done since then? The concern, obviously, is not with business leaders wanting to address systemic racism, both within their companies and within society. The concern is with the authenticity of these initiatives [12]. Business leaders know there is a lot to do in this area; but are they genuinely intent on building the infrastructure and developing the strategies necessary to address racism over the long-term [13]? Are they willing the make the necessary financial investments; or are they looking capitalize on short-term emotions? A similar analogy can be made about corporate initiatives to buy carbon offsets, rather than to actually reduce carbon emissions, in order to (appear to) address the Climate Crisis. In environmental circles, we have referred to such actions as greenwashing for decades; our term “corporate social opportunity” includes greenwashing, but also includes empty gestures about fighting racism, investing in essential employees, caring about employees and their mental health and any other fleeting words that do not have the necessary financial and strategic investments behind them.
In scholarly research, we frequently separate financial and strategic investments, even though we innately appreciate how interconnected they are. We explicitly connect financial, strategic, corporate social responsibility, leadership and entrepreneurship perspectives in order to provide more relevant policy and practical lessons. We use the foundations of stakeholder theory to consider the decisions that individuals are constantly making regarding short-term costs and long-term benefits as they work to create better lives. But then we expand on that to show how an inclusive stakeholder theory perspective can help business leaders understand their role in decision-making and what they need to do to ensure their business can survive in the short-term and thrive in the long-term. Where does economic value come from? Economic value comes from people working to improve their lives; for businesses, economic value comes from offering products, services and relationships that help their stakeholders improve their lives.
3. Strategies for creating economic value
In the words of Larry Fink, CEO of BlackRock, one of the world’s largest investment managers, “climate risk is investment risk” [14]. We could say the same about other macro risks: social risk is investment risk, governance risk is investment risk and leadership risk is investment risk. This connects directly to our central argument: that corporate managers need to move beyond capitalizing on short-term corporate social opportunities and focus on embracing their stakeholders’ values and working to create strategies that lead to long-term economic value creation [15]. Financial and economic value are only created when leaders realize the benefits that come from managing climate, social, leadership and other macro risks.
But how do we do that? What are some strategies and best practices that we can employ? We offer the following 6 rules for moving forward and for turning short-term social opportunities into long-term strategic value creations.
Create Positive Externalities – Economists frequently talk about externalities in only negative ways, such as the pollution imposed on a community by one single factory; the entire community pays the costs for the factory’s benefits. But positive externalities exist, too. If I invest $1,000 in my home’s front garden, it may increase the value of my home and of my neighbors’ homes by much more than that initial $1,000. Businesses can create positive externalities, too. Think of Starbucks paying for its associates to attend college; think of UPS drivers only making right turns. These are (relatively tiny) short-term investments that can have (relatively large) long-term benefits.
Embrace New Stakeholders –At any given time, no company will ever know if they are maximizing economic value. They think they know who their stakeholders are and what their profits are; but could the profits be higher? Can we embrace new stakeholders who will create even greater profits for us? In the United States, fewer than 20% of corporate directors are women and fewer than 5% of CEOs are women. Given that 40–60% of most companies’ stakeholders may be women, what do these leadership demographics say about inclusion and representation? Do the female customers and employees feel respected? Many companies have increased the number of women serving as directors and many companies have created Director of Diversity positions in recent years. These are necessary but not sufficient investments for embracing new stakeholders. The real test will be whether those new stakeholders are integrated with the strategies and operations of the firm over the long-term, instead of extracting value from certain stakeholders.
Ignore Sunk Costs – The investments we made in the past are in the past. As we decide what strategies and investments to make for the future, we only care about the incremental, future cash flows associated with any investment. Maybe we have to pay $1 million to shut down a project in order to move forward with a project that will create $5 million. The corollary to ignoring sunk costs is to focus on opportunity costs. What opportunities are we sacrificing by not moving forward? Think of ExxonMobil being one of the last global energy producers to begin investing in non-fossil fuel source of energy. Think of Ford and General Motors ignoring investing in hybrid technology during the early 2000s. Think of any automobile manufacturer not going all-in with electric technology during the 2010s and 2020s as Tesla has. The opportunity costs of avoiding the future can be quite significant.
In Business, Nothing is Intangible – In business, everything has economic and financial value. We are either creating value or we are destroying value. Leadership, communication and organizational design may seem intangible but, they all have a significant impact on a company’s finances. So do many other seemingly intangible aspects of business that directly affect that how employees perform their work: morale, respect, trust and culture. Every decision has economic and financial impact and it’s up to each organization’s leadership to ensure that all decisions move the organization towards its mission. Thinking any business issue is intangible is myopic and dangerous.
Culture Matters – Culture can be a very powerful positive externality. In business, culture can be defined as programmed behavior. Culture can be influenced and managed (McNulty, 2016). Sometimes this programming is active, sometimes it is passive (e.g., one company may have an explicit dress code, whereas another may not have a dress code but all employees choose to wear a similar outfit anyway). Culture is a function of the people, systems and institutions within any organization or community. The behavior that becomes programmed within any organization is a function of the choices made by the leadership of the organization. And it is the behavior of an organization’s people that will determine how effectively and efficiently it achieves its mission, creates social welfare and maximizes economic value. Economic value is created by culture. And all too often, economic value is destroyed by culture.
Profits Only Happen Because of People and the Planet – For years, people, planet and profit have been referred to as “the 3 Ps” that determine a company’s success; these are the three factors we see in triple-bottom line accounting. People and the planet are inputs, resources essential for the company’s operations; profits are the result of how effectively and efficiently the company employs human and natural resources in its operations. No company has ever made a profit without people or the planet. We learned this in 2020: without customers and employees, and with limited ability to employ natural resources during the pandemic lockdowns, many companies lost their profits and had to rely on loans and government subsidies to survive, thus borrowing on a future that may or may not come. The year 2020 gave us a painful reminder that we get to decide how we embrace people and the planet as we move into the future.
The foundation for creating positive externalities and embracing new shareholders represent the company’s impact and operations. These tactics will be closely aligned with the company’s underlying mission. The foundation for ignoring sunk costs and knowing that all investments and actions have tangible economic impact is the firm’s strategy. A SWOT analysis or similar strategic plan can identify the internal resources and external factors that will dictate the cash flows and economic impact of the company’s actions into the future, independent of what may have happened in the past. And the foundation for appreciating that culture matters and that profits happen because of people and the planet is the company’s authenticity [16]. Culture is an evolving dynamic, framed by leadership, that influences stakeholders’ actions; a company’s people and relationship with the environment determine the company’s profits [17]. Myopic greenwashing, propaganda and riding social opportunities are empty gestures that will destroy firm value in the long-term; being authentic with communication, incentives and investments is the only way to align corporate mission with economic value-creation [18].
4. Inspiration for value-creation
4.1 Literature & history: Milton Friedman debates
It may be cliché to have a discussion around corporate social responsibility and aligning strategy with purpose by addressing Milton Friedman’s 1970 position that a company’s only corporate social responsibility is to maximize profits [1]. But, given the multiple economic and social challenges of 2020 – not to mention the 50-year anniversary of Friedman’s article – this perspective needs to be understood. Friedman wrote his article in response to the many calls for businesses to focus on social issues – and not just profits – following the social and environmental challenges that erupted during the 1960s. Friedman contends, that in open and free markets, shareholders can invest in philanthropic or social causes that are important to them individually, but it is not a CEO’s role to make such investment on behalf of the shareholders. Importantly, Friedman does explain that it is perfectly appropriate – or, responsible – for CEOs to make such investments if the shareholders demand such and doing so maximizes profits.
We do not mention Friedman to agree with him or to disagree with him; many brilliant people have disagreed on the appropriateness of Friedman’s perspective over the years. Alex Edmans has generally defended Friedman’s perspective as suggesting that “it is legitimate for a company to focus on increasing profits because the only way it can do so, at least in the long term, is if it treats stakeholders seriously” [2]. Anat Admati argues that allegiance to Friedman’s perspective can produce enormous damage to society because it is built on assumptions that do not exist in reality and Friedman’s rules of the game “become meaningless without effective enforcement, with the ultimate outcomes reflecting little if any ‘social responsibility’” [3].
We will not settle this debate here. We mention Friedman to lay out the foundation for how we believe corporations should address social opportunities and strategies. Directly or indirectly, Friedman’s perspective is a foundation of the agency theory [19]. Agency theory recognizes both the separation of control and the conflicts of interest that arise when principals hire agents to serve the principals’ interests. The key to a successful principal-agent relationship is aligning the interests of the agents with the objectives of the principles. Many critics of agency theory argue that the focus on agents serving the myopic needs of the principals overemphasizes short-term profits at the expense of long-term value creation, because doing so maximizes the rational self-interest of the agents. Hart and Zingales [20] advocate moving from shareholder wealth maximization towards the more shareholder welfare maximization because shareholders are pro-social humans who (may) care about more than just money. In the short-term, there can be a significant difference between shareholder wealth and shareholder welfare, as markets may be slow (or unable) to accurately price-in both the positive and negative externalities that result from corporate actions.
We know that small businesses and entrepreneurs have much higher business failure rates than larger businesses do [9]. On average, approximately 15% of businesses with fewer than 5 employees fail in a given year; the rate is closer to 30% for such small firms that opened during 2020–2021. Many of these firms do not suffer from principal-agent conflicts, as the managers are frequently also the owners. But small businesses are particularly vulnerable to economic whims and may be tempted to capitalize on short-term opportunities. If those opportunities align with their mission, strategy and resources, then those short-term social opportunities can become long-term purpose and profits. But what if they are not so aligned? What is the company sacrificing by chasing fleeting social opportunities? What happens when the current window of opportunity closes and a new issue arises? Resources – human, financial and natural – are limited and using limited resources to chase a fleeting moment is likely to have long-term, negative consequences. The key to turning short-term opportunities into long-term profits is to authentically align their investments in these new opportunities with their long-term mission and strategies [21].
4.2 Examples from the early 2020s
The Covid-19 pandemic obviously created many challenges for businesses of all sizes. We saw the disastrous consequences most vividly with start-ups and small businesses; while some entrepreneurs saw the social and economic shocks as opportunities to create a new venture, creating a sustainable business was particularly challenging during 2020 [22]. But, during 2020 and 2021, we know that business leaders were faced with the confluence of multiple challenges, the likes of which they had never seen before: the Covid-19 pandemic, systemic racism and the continued escalation of the Climate Crisis. As 2021 progresses, we know that the business opportunities we experienced in the recent past may or may not be the same opportunities we see in the future. Companies need to ignore sunk costs. Companies need to develop systems and strategies that are capable of creating economic value in the future, regardless of the societal opportunities and challenges that come their way.
Businesses exist to create economic value. Of course, there are many ways to define economic value. Some companies may view economic value in purely financial terms; some may view economic value as relating to broader social welfare; others may view economic value in more specific and personal terms, such as a third-generation family business owner wanting to pass the business down to the fourth and fifth generations. In competitive markets, the dynamics that lead to financial value, to broader social welfare and to family business succession become the same. Those dynamics relate to people and resources; economics is the science of allocating resources to be used by people. However, many companies are not focused on how to use social dynamics to create value for people. Companies that fail to focus on the social dimension are failing to focus on their future.
For many people around the world, the dominant economic event of 2020 was the Covid-19 pandemic and how it affected health, wealth and relationships. For others, the Black Lives Matter movement and devastating climate crisis were the dominant economic and social events of 2020. These events combined to make 2020 a most unique year. And a unique example can help us understand how these different social issues may be more connected than they at first seem. During the year 2020, American electric vehicle-maker Tesla saw its stock price increase by 743%. Tesla’s market capitalization was more than double the combined market value of Ford, General Motors, Toyota and Honda. Why?
Of course, nobody knows why. But we do know (or assume) that stock prices represent the present value of expected future cash flows and value-creation. Stock prices are a bet on the future of a company. Tesla’s corporate mission is “to accelerate the world’s transition to sustainable energy.” Since becoming a listed company in mid-2010, 2020 was Tesla’s only profitable year; and 2020 gave the company 4 of its 10 profitable quarters since mid-2010. Maybe Tesla’s stock price performance in 2020 was a result of newfound profitability and investors updating their forecasts and narratives about the company’s future.
But perhaps the 743% stock price appreciation was directly a result of the economic, social, governance and environmental challenges the world faced in 2020. Perhaps these events illuminated Tesla’s unique strategies and competitive advantages – and those are the factors that investors were updating in their forecasts and narratives. If we accept that that the Covid-19 pandemic was (at least indirectly) a result of our increasingly globalized business worlds and lifestyles, the narrative of business success in the future may include the costs and benefits of our business relationship with the natural environment. As business encroaches on the natural world, we increase the probability of the natural world fighting back and presenting us with ever more challenges we were not prepared to deal with. In order to prevent another Covid-19 and another 2020, we may need to change our preparedness for dealing with another deadly virus or our relationship with nature. Thus, an investment in Tesla might represent a bet on us changing our relationship with the natural world and how we use our natural resources.
We are not pretending that Tesla’s 2020 stock price appreciation was entirely driven by Covid-19 related enlightened expectations of a changing world. There are many other factors that could have driven investors towards the stock: more effective leadership, more efficient production, greater access to recharging stations. We know that Tesla’s mercurial CEO, Elon Musk, has the potential to affect the company’s stock price negatively or positively with a simple tweet or interview.
But what may have changed in 2020 is investors gaining a greater appreciation for the role that environmental, social, leadership and strategic factors play in each company’s success. During 2020, these factors each became significantly more important to individual stakeholders and the societal institutions entrusted to serve individuals’ values. And some investors expect Tesla to deliver on aligning our values with the world we want in the future. Investors like to talk about ESG investing, looking at the ways that Environmental, Social and Governance issues; but we generally only consider one of the 3 letters at a time when we analyze each company. We rarely consider a company’s combined E, S and G dimensions. Tesla, however, may be one of the few companies and investments where we really see the E, the S and the G in ESG being integrated.
5. Frameworks for value-creation
5.1 ESG principles
As discussed above with respect to Tesla, the events of 2020 increased investors’ focus on ESG – or environmental, social and governance – factors that drive corporate value. The term ESG has been part of the business vernacular for nearly two decades; it was introduced in 2004, in a report titled “Who Cares Wins” by the United Nations’ Global Compact and the International Finance Corporation as an investment strategy for asset managers [23]. Since then, it has evolved from being a filter for investors to being a focal point for corporate strategy, as corporate leaders have worked to integrate the tenets of ESG into their long-term visions. But what does this really mean? And how have ESG principles been put into practice?
The “Who Cares Wins” report stated that its purpose was to “better integrate environmental, social and governance issues” into both investment and corporate strategies. However, this integration has never happened. Investors, managers and leaders see the terms environmental, social, governance as independent ideals. They focus on one at a time. Managers do regularly account for E, S and G issues in their investment decisions, but full integration of the relationships and synergies between the ideals has never happened [24]. Many of us have been expecting a paradigm shift in how leaders think about and invest in ESG, but there is still a long way to go before businesses fully scale and integrate the interconnected elements of ESG to create economic value [25].
The 2000s were the decade of the G in ESG. Following the corporate governance scandals of Enron, Parmalat, WorldCom and others, corporations focused on increasing the transparency and independence of their governance structures. In the U.S., two major pieces of regulatory reform – Sarbanes-Oxley in 2002 and Dodd-Frank in 2010 – provided guidance on improving the G in ESG. And markets responded. The number of independent directors on boards increased considerably (from just over 50% in 2000 to nearly 80% by 2020) and shareholders felt they had greater ability to monitor and influence corporate decisions (such as through “Say on Pay” votes, encouraged by Dodd-Frank).
The 2010s were arguably the decade of the E in ESG. Following the Global Financial Crisis, many governments realized that they needed to envision new drivers of innovation and growth. In the U.S., the American Recovery and Reinvestment Act of 2009 provided substantial subsidies for businesses to invest in renewable energy programs and infrastructure. For this first time since the U.S. government began subsidizing energy in the early 1900s, renewable energy investments were incentivized more than fossil fuel investments. And the markets responded. Walmart became one of the world’s largest buyers of photovoltaic systems. Tesla and its mission “to accelerate the world’s transition to sustainable energy” grew out of this legislation. And companies around the world – including Unilever, Nike, ING, Nestle, Danone and others – became missionaries for connecting customers’ environmental values to corporate profits.
While it is still early in the decade, the multiple challenges of 2020 and 2021 suggest that the 2020s may be the decade of the S in ESG. The Covid-19 outbreak and the many, divergent attitudes that arose regarding how best to address the pandemic, the continued impact of Black Lives Matter, the resurgence of MeToo, the mental health, data privacy, and relationship issues of a locked-down society and many other potential social issues suggest that we will continue to face new and more complex challenges than we have ever seen before. Companies need to find ways understand how social factors drive value-creation.
The challenge is that this idea can quickly become abstract when trying to quantify social value. Estimating the return on investment on the installation of solar panels or understanding how investors value transparency can be measurable aspects of ESG; understanding how respect, empowerment, equity and inclusion create value is far more complicated. But we know that investing in empowerment, equity and inclusion can lead to greater representation, stronger commitment and higher productivity, all examples of positive externalities that lead to improved cash flows and profits.
But that complexity does not mean that corporate leaders should ignore it. Nothing a business does is intangible; everything has economic impact. As we see the social dimension become more prominent in business strategy, we may begin to see the three ESG factors become integrated. Covid-19 has had disproportionate impacts on certain populations – elderly, immuno-compromised, front-line workers – as a result of the G and the S interacting. The climate crisis around the world has exposed inequities, vulnerabilities and environmental racism that has existed for centuries, as a result of the E and S interacting. These dynamics are not going to moderate until we integrate the E, S and G into corporate strategies that extend beyond the current opportunity. People, the S, will always be the source of revenue for every business and will always be the source of executing any corporate strategy. One key to integrating these seemingly disparate dynamics may be to effectively create novel partnerships between stakeholders rather than traditional business transactions [25, 26]. Short-term partnerships can become long-term relationships if the businesses are able to authentically integrate stakeholders’ values into the strategic plans [27]. So far, the 2020s have made it clear that integrating the broader social dynamics with corporate strategy for their unique stakeholders is more essential now than ever.
5.2 Social responsibility & stakeholder welfare
In theory, economic value-creation and financial profits come from the same place, making it unnecessary to settle any debates about the accuracy of Milton Friedman’s arguments. But where do profits come from? Simply, profits are the result of revenue increasing or relative costs decreasing. Revenues come from customers; costs are paid to employees, suppliers, governments, partners and investors. Let us assume that all of these people are rational and they only engage with a business because such engagement makes their life better, however they choose to define ‘better’. Revenues only increase when the company provides products and services that customers choose to buy; costs only decrease because the employees, suppliers, investors or others choose to charge the company less, presumably because the company is making their life better in some way independent of the cash compensation that shows up on the income statement.
Would customers be willing to pay more for a seemingly inferior product that comes with superior customer service?
Would suppliers accept less cash in exchange for a long-term contract?
Would employees accept lower wages in exchange for on-site childcare?
We know the answers to all of these questions: they might. Questions such as these fit within the realm of stakeholder theory (or even social identity theory). Stakeholder theory never attempts to identify which stakeholders are most important; it merely suggests that all stakeholders are important and it’s up to managers to determine which stakeholders create the most value for each firm [28]. Shareholders are certainly important stakeholders; they provide financial capital so the firm can invest in people, projects and growth. If the return on their investment is less than what they require, they will take their money elsewhere; if the return on their investment is greater than what they require, they will invest more. Shareholder capital is a critical resource that can be used to increase profits, which will only happen if the company is improving stakeholder welfare.
Hart and Zingales [20] argue that corporations can scale social investments in ways that individual investors cannot and corporations can be more effective at pursuing pro-social objectives than government entities, in part because corporations are more immediately affected by individuals’ preferences. Where corporate managers may be expert in designing marketing strategy or financial policy, many issues of ethics or social policy are a matter of individual shareholder well-being and not managerial expertise. Zingales and Hart [20] do not address stakeholders other than shareholders, but it’s easy to extend their argument to all other stakeholders. Do managers, directors and owners incorporate the welfare of all stakeholders when setting corporate policy? Of course, they do this all the time. For example, any marketing professional will tell you that their job is to “create customer value.” Could any company maximize shareholder welfare without creating customer value? In the same sense, no company can maximize profits without also optimizing its relationships with people and the planet; all of these dimensions are interconnected and interdependent.
5.3 Stakeholders: The creators of economic value
One lesson that business leaders were reminded of during 2020 is that all stakeholders matter. Many hospitality firms, restaurants and other entertainment companies went bankrupt as their customers stopped giving them money. Employees were classified as “essential” if their work was immediately required for the short-term execution of the company’s business. And the importance of efficient supply chains came into full view as we all worried that we may never have another opportunity to buy toilet paper, hand sanitizer or disinfectant. Amazon’s stock price increased by 117% during 2020. Can we infer that this means Amazon’s stockholders benefited more than Amazon’s customers, employees or suppliers? No, we cannot. What would have happened to these non-shareholder stakeholders if Amazon had not done its job throughout the year? Where would customers have gotten our toilet paper, hand sanitizer and disinfectant? The 117% stock price appreciate was the result of Amazon creating economic value for all stakeholders, not just the measure of creating financial value for shareholders. For Amazon, and many other companies, embracing new stakeholders was the key to their ability to survive and thrive and 2020.
In the context of CSR or CSO, maximizing profits is only possible if companies satisfy the values and needs of their stakeholders. Society’s values represent the economic decisions that individuals make based on what they value, on what is important to them. Government institutions are responsible for taking care of the most basic of these values; but governments can be slow, inefficient and too easily influenced [18]. During 2020, the role that businesses served in helping individuals satisfy their values and needs became ever more important. Companies in certain industries, such as travel and hospitality, were devastated by the pandemic and related restrictions. Others that were able to satisfy our most basic values (like Amazon), our needs (like Zoom) and our wants (Etsy) created enormous amounts of financial value – because they created enormous amounts of value for individual people. Amazon’s stock price rose 117% during 2020; Zoom’s stock price rose 396% during 2020; Etsy’s stock price rose 302% during 2020. Are these examples of companies capitalizing on short-term social opportunities created by the pandemic? Perhaps. But, while they aren’t perfect, stock prices should be forward-looking. Stock prices should not reflect what any company was able to do in the past, but rather they should reflect what the companies are expected to do in the future. Stock prices will always ignore sunk costs; business leaders need to do the same.
6. Creating economic value
6.1 The business case for integrating the E, the S and the G in ESG
The 6 strategies provided in Section 2 above provide some general perspective on turning short-term social opportunities into long-term strategic value creation. Each of these rules or perspectives can be incorporated into the aforementioned ESG framework for deriving value through environmental, social and governance dimensions. But frameworks and ideals may not be enough to convince your CFO and investors that investing in ESG will improve firm value. The story you tell and how you justify investing in ESG is critical. We have identified 6 drivers of economic value that may help corporate leaders make the business case for investing in environmental, social and governance initiatives.
Market Access – Clearly identifying new product, geographic or labor markets that can generate new revenues or lead to lower relative expenses.
Operating Efficiency – Making investments that can lower operating expenses is perhaps the most quantifiable driver of the business case for ESG. But investing in people and culture can also lower turnover, increase inclusion and increase productivity.
Innovation – How can we utilize new technologies to create economic value? Can we create those new technologies ourselves? External forces and evolving stakeholder preferences will always present opportunities to innovate; businesses must have the courage to invest in those opportunities.
Risk Management – People, safety and other risk management tools can be enormous sources of value creation through ESG. Think of opportunity costs: what are the costs of not making certain investments? Avoiding many costs creates economic value.
Regulatory Mandate – In 2020, we saw the devastating confluence of public health, social inclusion and environmental factors. In response, we have seen, and may continue to see, increased regulatory pressures on companies to invest in ESG. This is not new (such as quotas on the number of women serving on boards of directors, incentivized investments in renewable energy, and adopting the United Nations’ Sustainable Development Goals as country-specific goals). Companies that align their strategies with such regulatory initiatives are likely to benefit the most over the long-term.
Reputation Enhancement – As customer and stakeholder preferences evolve, they will look to businesses to provide value in different ways. Companies that align strategies with stakeholder preferences will improve their brand and reputations the most. When Walmart invests in solar energy, is cost reduction the only goal? Surely these investments improve many people’s perception of Walmart’s values as a company – which can directly create economic value for Walmart. And there’s nothing wrong with that.
These 6 drivers of economic value are key to turning a short-term opportunity into a long-term movement. The examples in Table 1 show how we can use these business case drivers to tell the economic story of the social events that dominated 2020 – and will continue to dominate economic growth throughout the 2020s.
#BLM black live matter & social justice
#MeToo gender inclusion & gender equity
#ClimateAction natural resources & the environment
Market access
Selling products and services in communities and regions that you have previously ignored; inclusive leadership teams provide innovative vision and perspectives; new investors; flexible work arrangements.
Selling products and services in communities and regions that you have previously ignored; inclusive leadership teams provide innovative vision and perspectives; new investors; flexible work arrangements; on-site childcare.
Creating products and platforms that will shape the future of natural resource relationships; new partnerships lead to new product and geographic markets; new investors.
Operating efficiency
Broader and more inclusive supply chains lead to lower costs; enhanced corporate culture decreases employee turnover costs and improves productivity.
Broader and more inclusive supply chains lead to lower costs; enhanced corporate culture decreases employee turnover costs and improves productivity.
Natural resource scarcity will increase energy costs from traditional sources; pivoting to innovation and renewables lowers costs over the long-term; enhanced corporate culture decreases employee turnover costs and improves productivity.
Innovation
New products, services, marketing, partnerships, leadership & corporate culture.
Diverse representation in management and leadership builds long-term trust; long-term trust among all stakeholders grows brand, revenues and opportunity.
Diverse representation in management and leadership builds long-term trust; long-term trust among all stakeholders grows brand, revenues and opportunity.
Visionary leadership & diverse investments build long-term trust; long-term trust among all stakeholders grows brand, revenues and opportunity.
Example companies
Lowe’s, Apple, Nike
Nestle, Danone, Natura
Unilever, ING, Tesla, Ford, Firmenich
Table 1.
This table shows how the six business case drivers can be applied to three of the most significant social movements. Guidance is provided as to how managers can implement these drivers and how other stakeholders can benefit from these drivers. Examples of companies using these drivers to address these social movements are provided.
6.2 Economics, wellbeing and 2020
It is worth remembering that “economics” is not about money; economics is about resources and allocating society’s natural and human resources in optimal ways. Money is merely a currency that helps us to establish an exchange rate for trading different resources. Having 100 luxury vehicles does not matter if we cannot trade them for dinner, housing or some type of utility. We like money because it enables acquiring resources that are important to us; but it should be those resources that we ultimately want, not the pile of money.
When Covid-19 became a pandemic in early-2020, many societies around the world went into lockdown to limit the possible spread of the virus. And when the societies went into lockdown, much economic activity stopped. For a few months, most developed economies were in an odd stage of suspension; we were not producing much, individually or collectively. We had become completely dependent on integrated economies that relied on trading resources with others to meet our daily needs. Economic growth, or an increase in the resources we have to allocate among society’s citizens, depends on coordination between different people to trade resources. But economic growth also depends on production that utilizes natural and human resources to create more valuable and useful resources. All of this stopped when Covid-19 hit. And, just over a year since Covid-19 first changed our lives, societies are still trying to figure out how to adjust our actions to best grow our micro- and macroeconomies.
When should schools re-open? How should schools re-open?
Will work-from-anywhere become permanent? Is it safe to return to the office?
When can I travel again? When can I see my family again?
Figuring out how businesses proceed involves an assessment of the short-term and long-term benefits and consequences of any decision. This is the implicit decision everyone makes every time they make a personal or business decision. When we buy milk or eggs at the market, we are implicitly saying that having those items makes our lives better more than having the money we needed to buy them (and, similarly, more than the labor, effort or other resources we gave up acquiring the money needed for the milk and eggs). This discussion of trade and resource allocation is simple because we think we know the precise costs of such decisions and we know how much we benefit from those decisions. But most decisions in life – especially those involving communities of people – are rarely this simple and easily understandable. We do not want our children and teachers to get sick (or worse), but what is the loss to society over the next 20+ years if we sacrifice 10–20% of our children’s education today? Nobody knows the answer to this question.
Yet this question is typical of the types of economic decisions that business, community and government leaders will be forced to make in the future. Is this an issue of corporate social responsibility? Is this an issue of increasing profits? Is this an issue of creating economic value? Of course, it is all of the above. Every decision any business ever makes is all about people, society, prosperity, well-being and money. Businesses choosing to strategically invest in people and society will continue to determine the prosperity and well-being that we see in the future, just as it always has.
7. From corporate social opportunity to corporate social responsibility
The turmoil of 2020 presented many challenges for companies as they tried to create economic value; but the events of 2020 also presented many corporations with social opportunities that might lead to economic value creation. We refer to this as corporate social opportunity, or how companies respond to economic and social shocks in the short-term. Examples of corporate social opportunity include adding women to a board of directors in response to the #MeToo movement, creating a new Chief Diversity Officer in response to Black Lives Matter or football teams around the world paying respect to health care workers who led the fight against Covid-19, without a long-term strategy that integrates those actions.
To be sure, capitalizing on corporate social opportunities is not necessarily wrong or bad; that’s not the issue. The issue is more about authenticity, strategy and impact. Do the female directors have the same power, authority and ownership as the longer-serving males or do they just meet a quota? Is the Chief Diversity Officer granted all of the power and resources she needs to exert true change and leadership or is the creation of the position just for public relations? And what message are those football players if, a few hours after paying respects at the beginning of a match, they are posting photos of a house party that is clearly violating all of the Covid-19 protocols that the health care workers want us to follow? What is the message they send when they stop kneeling before matches?
From a strategic perspective, corporate leaders need to anticipate and plan for what they will do when the next social moment impacts their business models. Will they abandon these previous efforts and choose to ride the momentum of this window of opportunity? Doing so may create very short-term profits, but potentially at the expense of long-term strategy and at the expense of many valuable stakeholder relationships. Corporate social opportunity is a more expansive application of greenwashing to a broader universe of environmental, social and governance issues – and it can destroy enormous economic value.
CSO views opportunities through a short-term narrow window, while CSR is more embedded into a company’s long-term strategy, culture and operations. Thus, the crux of our argument is that while it may be tempting for companies to capitalize on short-term opportunities instigated by social shocks, true and sustainable economic value is created over the long-term through a company’s strategy, culture and operations.
Thinking and acting beyond corporate social opportunity is important for all firms, but it most critical for entrepreneurs and small businesses who have severely constrained resources and limited time – where being successful in the short term may be the difference between success and failure of the business. The costs of wasting resources to chase fleeting moments are magnified for small businesses. But so are the benefits of authentically integrating the dynamics of stakeholders and mission into strategic plans. What will these businesses lose if they do not authentically develop strategic plans that integrate the needs and desires of all stakeholders into their strategies? For too long, businesses have ignored the S in ESG as a unique creator of economic value. But we know that all economic value comes from people and how businesses enhance their lives and their wellbeing. Focusing on creating value for stakeholders will continue to be the secret to surviving future economic shocks that arise from social movements.
8. Discussion and conclusion
Corporate social responsibility is not a choice. All economic value ever created by any firm has been generated through its stakeholders. These stakeholders – people – all have individual preferences and values. These stakeholders, including customers, employees, investors and suppliers, only choose to work with any firm because that firm creates value for them or makes their life better. When enormous shocks to the social landscape occur, such as Covid-19, Black Lives Matter or MeToo, every firm is forced to rethink how it engages with stakeholders and how it will create value.
Some business leaders will view these shocks as opportunities to capitalize and extract rents. This is very dangerous; these windows of opportunity will soon close. Business leaders need to focus on long-term strategy and not just short-term opportunity in order to survive, thrive and maximize value. Peloton is the perfect example of a company struggling to see beyond the short-term Covid-19 opportunity; Tesla is an example of a company incorporating the confluence of environmental, social and governance issues into its long-term strategy.
In this chapter, we have offered practical solutions for business leaders to use to develop such a long-term strategy. We have provided six rules that all leaders should follow move beyond short-term opportunities towards long-term social responsibility: ignore sunk costs, embrace new stakeholders, nothing is intangible, culture always matters, focus on creating positive externalities and profit only happens because of people and the planet. To help operationalize these rules, we have provided 6 drivers to the business case for investing long-term that can be directly connect to the firm’s income statement and cash flows: investing in CSR and ESG can create new market access, can improve operating efficiency, can help mitigate cash flow risk, can address regulatory mandate, can lead to innovation and can enhance the firm’s brand and reputation. Following these 6 rules and building a strategy around these business case drivers will be the key to creating value through social dynamics.
So far, the decade of the 2020s has been the decade of the S in ESG; as the Social component of an ESG philosophy becomes more and more important, business leaders will need to think more creatively about how to create value in the future. The key to success will be to focus on the long-term and not be infatuated with short-term windows of opportunities. When these windows close, profits will cease and economic value will go away. By following the frameworks, rules and business case drivers outlined in this chapter, business leaders can move beyond a view of short-term corporate social opportunity and towards a strategy of long-term corporate social responsibility.
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These challenges forced companies to search for new ways to create value for their investors and other stakeholders; these challenges forced business leaders to think differently about the role that their companies play in the broader society. As we think about how business leaders balance these short-term opportunities and long-term strategies, it is critical that they realize that he level of social responsibility expected by society has risen significantly in recent years. Companies need to move beyond seeing social dynamics as short-term opportunities and incorporate them into long-term strategies. In this study, we offer 6 rules for moving forward and for turning short-term social opportunities into long-term strategic value creations. Business leaders need to focus on offering products, services and relationships that help their stakeholders improve their lives. 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Introduction",level:"1"},{id:"sec_2",title:"2. Corporate social opportunity vs. corporate social responsibility",level:"1"},{id:"sec_3",title:"3. Strategies for creating economic value",level:"1"},{id:"sec_4",title:"4. Inspiration for value-creation",level:"1"},{id:"sec_4_2",title:"4.1 Literature & history: Milton Friedman debates",level:"2"},{id:"sec_5_2",title:"4.2 Examples from the early 2020s",level:"2"},{id:"sec_7",title:"5. Frameworks for value-creation",level:"1"},{id:"sec_7_2",title:"5.1 ESG principles",level:"2"},{id:"sec_8_2",title:"5.2 Social responsibility & stakeholder welfare",level:"2"},{id:"sec_9_2",title:"5.3 Stakeholders: The creators of economic value",level:"2"},{id:"sec_11",title:"6. Creating economic value",level:"1"},{id:"sec_11_2",title:"6.1 The business case for integrating the E, the S and the G in ESG",level:"2"},{id:"sec_12_2",title:"6.2 Economics, wellbeing and 2020",level:"2"},{id:"sec_14",title:"7. From corporate social opportunity to corporate social responsibility",level:"1"},{id:"sec_15",title:"8. Discussion and conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Friedman M. A Friedman Doctrine: The social responsibility of business is to increase profits, The New York Times, 1970'},{id:"B2",body:'Edmans A. What Stakeholder Capitalism Can Learn From Milton Friedman. University of Oxford Business Law Blog; London, England, United Kingdom; 2020. Available online: https://www.law.ox.ac.uk/business-law-blog/blog/2020/11/what-stakeholder-capitalism-can-learn-milton-friedman'},{id:"B3",body:'Bielak D, Bonini S, Oppenheim J. CEOs on Strategy and Social Issues. The McKinsey Quarterly, McKinsey & Company; 2007'},{id:"B4",body:'Schiller C. Global Supply-Chain Networks and Corporate Social Responsibility. Arizona State University Tuscon, Arizona United States of America: Arizona University; 2018'},{id:"B5",body:'Dai R, Liang H, Ng L. Socially responsible corporate customers. Journal of Financial Economics. 2021;142:2'},{id:"B6",body:'Gillan S, Koch A, Starks L. Firms and social responsibility: A review of ESG and CSR research in corporate finance. Journal of Corporate Finance. 2021;66. DOI: 10.1016/j.jcorpfin.2021.101889'},{id:"B7",body:'Admati A. Anat Admati on Milton Friedman and Justice. Stanford Graduate School of Business; Palo Alto, California United States of America; 2020. Available online: https://www.gsb.stanford.edu/insights/anat-admati-milton-friedman-justice'},{id:"B8",body:'Fultz A, Hmieleski K. The art of discovering and exploiting unexpected opportunities: The roles of organizational improvisation and serendipity in new venture performance. Journal of Business Venturing. 2021;36:4'},{id:"B9",body:'Crane L, Decker R, Flaaen A, Hamins-Puertolas A, Kurz C. Business Exit During the COVID-19 Pandemic: Non-Traditional Measures in Historical Context. In: Federal Finance and Economics Discussion Series 2020-089r1. Washington: Board of Governors of the Federal Reserve System working paper; 2021'},{id:"B10",body:'Tang J, Levasseur L, Karami M, Busenitz L. Being alert to new opportunities: It’s a matter of time. Journal of Business Venturing Insights. 2021;15. DOI: 10.1016/j.jbvi.2021.e00232'},{id:"B11",body:'Falck O, Heblink S. Corporate social responsibility: Doing well by doing good. Business Horizons. 2007;50(3):247-254'},{id:"B12",body:'Mallick M. Do you know why your business needs a chief diversity officer? Harvard Business Review. 2020;11. Available online: https://hbr.org/2020/09/do-you-know-why-your-company-needs-a-chief-diversity-officer'},{id:"B13",body:'Pedulla D. Diversity and inclusion efforts that really work. Harvard Business Review. 2020. Available online: https://hbr.org/2020/05/diversity-and-inclusion-efforts-that-really-work'},{id:"B14",body:'Fink L. Larry Fink’s 2021 Letter to CEOs. BlackRock; 2021'},{id:"B15",body:'Chatterjee I, Cornelissen J, Wincent J. Social entrepreneurship and values work: The role of practices in shaping values and negotiating change. Journal of Business Venturing. 2021;36:1'},{id:"B16",body:'O’Leary M, Valdmanis W. An ESG reckoning is coming. Harvard Business Review. 2021;4:2021. Available online: https://hbr.org/2021/03/an-esg-reckoning-is-coming'},{id:"B17",body:'Warrick DD. What leaders need to know about organizational culture. Business Horizons. 2017;60(3):395-404'},{id:"B18",body:'Capelle-Blancard G, Petit A. Every little helps? ESG news and stock market reaction. Journal of Business Ethics;157:543-565'},{id:"B19",body:'Jensen M, Meckling W. Theory of the firm: Managerial behavior, agency costs and ownership structure. Journal of Financial Economics. 1976;3(4):305-360'},{id:"B20",body:'Hart O, Zingales L. Companies should maximize shareholder welfare not market value. Journal of Law, Finance and Accounting. 2017;2:247-274'},{id:"B21",body:'Kromer T. The question index for real startups. Journal of Business Venturing Insights. 2019;11. DOI: 10.1016/j.jbvi.2019.e00116'},{id:"B22",body:'Kuckertz A, Brändle L, Gaudig A, Hinderer S, Reyes CAM, Prochotta A, et al. Startups in times of crisis – A rapid response to the COVID-19 pandemic. Journal of Business Venturing Insights. 2020;13. DOI: 10.1016/j.jbvi.2020.e00169'},{id:"B23",body:'United Nations. Who Cares Wins Conference Report: Investing for Long-Term Value, 2005'},{id:"B24",body:'van Duuren E, Plantinga A, Scholtens B. ESG integration and the investment management process: Fundamental investing reinvented. Journal of Business Ethics. 2016;138:525-533'},{id:"B25",body:'Benninger S, Francis JNP. Resources for business resilience in a Covid-19 World: A community-centric approach. Business Horizons. 2021:65(2):227-238'},{id:"B26",body:'Karami M, Read S. Co-creative entrepreneurship. Journal of Business Venturing. 2021;36:4'},{id:"B27",body:'Plachy R, Smunt T. Rethinking managership, leadership, followership, and partnership. Business Horizons. 2021. DOI: 10.1016/j.bushor.2021.04.004'},{id:"B28",body:'Freeman RE. Strategic Management: A Stakeholder Perspective. Cambridge, MA: Cambridge University Press; 1984'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Brian Bolton",address:"brian.bolton@louisiana.edu",affiliation:'
Moody College of Business, University of Louisiana at Lafayette, United States of America
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Publishing with IntechOpen means that your scientific publications already meet these basic requirements. It also means that through our utilization of open licensing, our publications are also able to be copied, shared, searched, linked, crawled, and mined for text and data, optimizing our authors' compliance as suggested by the European Commission.
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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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Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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