Biological factors in bone regeneration.
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
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\r\n\tApoptosis or programmed cell death is an essential biochemical process that mediates cell turnover, immune system, embryonic development, and induced cell death. Malfunction in the apoptotic mechanism leads to various human diseases, including but not limited to neurodegenerative diseases, cancer, and immune disorders. Therefore, physiology and pathology of apoptosis are under intensive investigation to reveal therapeutic potential out of these correlations. Cell cycle machinery and signaling pathways are the focus of the biochemical process to understand cell cycle arrest and apoptosis control mechanism. Although most components of this energy-dependent pathway have been identified, physiology and pathology of the initiation as well as inhibitors-activators have been under investigation. Apoptotic machinery is an important part of health and disease and this book provides recent insights into novel research that may influence therapeutic interventions.
\r\n\r\n\tThe first part of the book will spotlight signaling pathways, physiology, and pathology of the apoptosis, while the second part of the book will elaborate mathematical modeling of the apoptosis, instrumental assays, and clinical applications. The book will compile a comprehensive review of the current literature. Therefore, it will not be interesting only to early-career scientists, but also to the experienced researchers who want to link relevant research to their analysis.
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He obtained his MSc and Ph.D. degrees at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and National Institutes of Health (NIH/NIDDK), USA. Dr. Tutar’s research is mainly focused on biochemistry, biophysics, genetics, and molecular biology with a specialization in the fields of prion, drug design, cancer, protein structure-function, protein folding, microRNA, pseudogenes, molecular cancer, proteomics, genomics, and protein expression and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"3",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"6",title:"Biochemistry, Genetics and Molecular Biology",slug:"biochemistry-genetics-and-molecular-biology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"259492",firstName:"Sara",lastName:"Gojević-Zrnić",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/259492/images/7469_n.png",email:"sara.p@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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by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander 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Regeneration",doi:"10.5772/62523",slug:"regenerative-medicine-a-new-paradigm-in-bone-regeneration",body:'\nThe regeneration of bone tissue remains an important challenge in the field of orthopedic and maxillofacial surgery. Bone defects produced by trauma, tumors, infectious diseases, biochemical disorders, congenital disorders or abnormal skeletal development are the major causes of functional disability, and esthetic and psychological trauma for patients.
\nOne of the goals of treating a bone defect is to restore the normal morphology and function of the affected structure. Specific surgical techniques such as distraction osteogenesis, implantation of biomaterials (bone substitutes) and implants of bone grafting have been developed to reach bone regeneration [1, 2]. Demand for bone grafts is considerable and represents the second most common procedure after blood transplants, with more than 2.2 million bone grafts performed annually worldwide in orthopedics and dentistry [3].
\nDespite advances in bone regeneration and the availability of many treatments, most clinicians and researchers continue to come to the same conclusion: autologous bone grafting remains the “gold standard,” compared to other reconstructive procedures [4–9]. Bone from the same patient lacks immunogenicity and contains all the elements necessary to effectively induce tissue regeneration. It has osteoprogenitor cells which go directly to the implant site, cytokines and extracellular matrix [5], providing the three classic elements of an ideal bone graft: osteogenesis, osteoconduction and osteoinduction [5–7, 9, 10]. However, autologous bone grafts have several important limitations, including high risk of morbidity in the donor site [5, 6, 11], with disadvantages in terms of costs, time of surgical procedure, discomfort for the patient and possible complications.
\nAdditionally, many times the volume of tissue available for the procedure is not sufficient to fill or cover a defect, given the limited availability of autologous tissue [4, 10], and the quality of the autograft is highly variable and is influenced by age and metabolic abnormalities of the patient [7]. To overcome these limitations, a variety of exogenous substitutes, including allografts, xenografts and alloplastic materials, have been introduced into clinical practice in the past three decades [4]. However, these substitutes have less osteogenic and osteoinductive properties [6, 12] and a greater possibility of transmission of infectious diseases [6, 8], restricting their use [8].
\nIn order to successfully overcome the shortcomings of current approaches for bone regeneration, tissue engineering emerged as a discipline that provides the necessary tools for bone regeneration and restoration. The presence of cell populations that orchestrate the release of growth factors, the maintenance of a stable matrix and the stimulation of angiogenesis are key factors to successful regeneration of bone tissue, because they play a decisive role in the healing process [13, 14]. The technologies developed recently based on tissue engineering, such as gene therapy, stem cell therapy and the application of osteoinductive growth factors, looking for the control of the dynamics of these elements to enable more predictable bone regeneration surge as a significant promise in clinical practice [15].
\nCell-based therapy for the regeneration of bone tissue has been extensively investigated. Several cell types have been used as alternatives for the reconstruction of bone tissue, including osteoblasts, embryonic stem cells, periostium derived-progenitor cells (a specialized cell type that covers bone surfaces and have the potential to differentiate into multiple mesenchymal tissues, including bone) and mesenchymal stem cells, also known as multipotential stromal cells (MSC) [16].
\nMSC has become one of the best alternatives in cell therapy and specifically in bone regeneration. MSCs can be isolated from virtually all vascularized tissue and they are able to differentiate into various mesenchymal tissues such as bone, cartilage, muscle, tendon, adipose tissue and hematopoiesis-supporting stroma. However, a growing number of recent reports in the literature have revealed that even if a therapeutic effect can be documented, the implanted MSC cells do not differentiate and do not survive for a long time [17, 18].
\nThe use of MSCs in the treatment of musculoskeletal injuries was initially based on their ability to differentiate into various cell types [1, 7, 8]. The rationale was that after implantation or MSC injection, the cells would be able to colonize the injured site and differentiate into the appropriate lineages. This mechanism has now been challenged by a new paradigm to extend it to an alternative mechanism called paracrine effect, where MSCs secrete biologically active molecules which have beneficial effects on the injured tissues [9] by inhibiting fibrosis, apoptosis and inflammation [10, 11] and promoting angiogenesis and tissue regeneration [19–21].
\nFor the development of new therapeutic tools for restoring bone defects exceeding the critical size, it is necessary to look at the prototype model of physiological bone regeneration. This process, involving a coordinated interaction of cells, growth factors and extracellular matrix, consists of multiple and well-orchestrated stages that start immediately after the injury occurs, with a local inflammatory response followed by the mobilization of hematopoietic and mesenchymal stem cells to the site of injury to form new vascular networks, soft tissue matrix, cartilage and/or bone and finally inducing mature bone formation [22–24]. All four components involved in the site of injury, including cortical bone, periosteum, bone marrow and external soft tissue, contribute to a different extent in the healing process, depending on various parameters such as growth factors, hormones and nutrients, pH, oxygen tension, the electrical environment and mechanical stability [25].
\nImmediately after bone trauma, damage of the local vasculature at the site of injury is responsible for producing a blood clot or hematoma [24, 26, 27]. This hematoma is a localized collection of blood products, including platelets, leukocytes, macrophages, fibrin, soluble growth factors and cytokines, which in turn provides a matrix that allows the migration of inflammatory cells, endothelial cells and fibroblasts [24] (Figure 1).
\nThis first stage of fracture healing is the beginning of the so-called inflammatory phase, which begins within the first 12 to 14 hours, has its peak during the first 24 hours and is completed around 7 days after the injury. It is characterized by a destructive phase, with a local acute inflammatory response and hypoxia. The first cells to arrive at the site of injury are neutrophils, and subsequently macrophages and lymphocytes. Macrophages not only phagocyte necrotic tissue but also release a number of growth factors and cytokines that initiate the healing process of bone wound [26] (Figure 1).
\nTemporal progression of bone healing. The healing response to bone injury is characterized by overlapping biological processes: immediately after bone injury, hematoma formation and inflammatory response permits the release of pro-inflammatory cytokines and growth factors that initiate the process of wound healing. Between days 1–7, MSCs proliferate and differentiate into the osteogenic or chondrogenic lineages and increase the production of blood vessels from pre-existing vessels. New bone formation occurs through intramembranous or endochondral ossification that is finally mineralized, forming a mature bone that is continuously remodeled through the rest of his life.
The factors secreted by platelets, macrophages and bone cells include transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), interleukins 1 and 6 (IL-1 and IL-6), tumor necrosis growth factor alpha (TNF-α), bone morphogenetic proteins (BMPs) [26, 27], fibroblast growth factor (FGF) and insulin-like growth factors I and II (IGF-I and IGF-II) [26]. These factors stimulate the migration of multipotent stem cells, probably originated from the periosteum, bone marrow, blood vessels and the surrounding soft tissue and induce the differentiation of cells to different mesenchymal cell types including angioblasts, fibroblasts, chondroblasts and osteoblasts [26].
\nDuring the following days, the construction phase starts. This phase is characterized by the formation of new blood vessels [17], and the thrombus reorganization into granulation tissue, which is then condensed in a soft callus providing an osteoid and/or cartilage scaffold, which acts as a stabilization structure and a template for subsequent mineralization [26] (Figure 1).
\nDepending on the type of bone, the type of bone lesion, the morphology and structure of the tissue and the fixation method, bone healing can take two forms: primary healing, where osteoblasts secrete an osteoid matrix for future mineralization (intramembranous ossification); and secondary healing, which occurs through the formation of a cartilage matrix produced by chondrocytes, which is then replaced by an osteoid matrix with subsequent mineralization (endochondral ossification) [24–27]. Most common growth factors related to bone healing, osteoinduction and osteoconduction are: PDGF, BMPs [15, 28, 29], IGFs [28, 30], TGF-β [15, 28], FGF [24, 29] and VEGF [15, 24, 29].
\nLocal vascularization at the site of injury has been identified as one of the most important parameters that influence the healing process [14, 31, 32]. Bone formation can only proceed successfully if the tissue is adequately vascularized [15]; therefore, angiogenesis is a key component in bone repair. The new blood vessels carry oxygen and nutrients to the metabolically active callus, allowing gas exchange and the output of waste products and serve as a route for inflammatory cells, and cartilage and bone precursor cells [33, 34], and also provide the gateway of systemically circulating factors that can modify the bone healing process [34]. Vascularization is needed for both the formation of intramembranous and endochondral bone. During the formation of endochondral bone, cartilage avascular environment is invaded by blood vessels that allow the osteoblastic, chondroblastic and progenitor cells, to deposit new bone on the surface of the islands of cartilage. During intramembranous ossification, vascularization is also needed to allow the arrival of osteoblast precursor cells [34].
\nAngiogenesis and migration of vascular endothelial cells are stimulated by pro-angiogenic factors such as VEGF, BMPs, TGF-β, FGF and angiopoietins (especially angiopoyectina I and II) [26].
\nFinally, over the course of months to years, the third stage, the remodeling phase of bone healing occurs, whose main objective is to reshape the bone in order to restore its original structure and strength. During this phase, osteoclasts reabsorb recently formed bone tissue, due to the stimulation of growth factors and cytokines that promote osteoclastogenesis as TNF-α, TGF and BMPs. Osteoblasts deposit more osteoid and calcium phosphate in the newly regenerated bone, increasing the density of mineralized matrix. Therefore, the transverse diameter of the bone decreases but the density of internal structure increases, closer and closer to the architecture of the intact bone. As this stage keeps going, cellularity is gradually reduced and bone density is enhanced [26].
\nDuring the process of bone regeneration, the release of growth factors occurs as a series of highly time-space regulated biological events. These soluble molecules are able to regulate signaling cascades that specifically influence cellular responses such as differentiation and proliferation [28].
\nBiological signaling molecules function effectively by a limited window of time to get a proper result in the target cell. Therefore, it is necessary to have a precise understanding of the temporal pathways for natural bone regeneration. Biological signaling agents can be classified into the following categories: pro-inflammatory cytokines, growth and differentiation factors and angiogenic factors. Pro-inflammatory cytokines are activated immediately after bone injury and establish and maintain the acidic and hypoxic environment for the initial destruction phase. Growth and differentiation factors function during the constructive and destructive phases, while angiogenic factors are focal points for the revascularization of the wounded area [25, 26, 35] (Table 1).
\nSignaling Molecules | \nExpression Pattern | \nSource | \nTarget cells | \nfunction | \n
---|---|---|---|---|
Cytokines (IL-1,IL-6, TNF-α) | \nIncreased levels from days 1 to 3 and during bone remodeling | \nMacrophages Inflammatory cells Cells of mesenchymal origin | \nMesenchymal and inflammatory cells | \nChemotactic effect on other inflammatory cells Stimulation of extracellular matrix synthesis, angiogenesis, recruitment of endogenous fibrogenic cells to the injury site and at later stages bone resorption | \n
TGF-β | \nExpressed from very early stages throughout fracture healing | \nDegranulating platelets Inflammatory cells endothelium, extracellular matrix, chondrocytes, osteoblasts | \nMSCs, osteoprogenitor cells, osteoblasts, chondrocytes | \nPotent mitogenic and chemotactic for bone-forming cells, chemotactic for macrophages | \n
PDGF | \nReleased at very early stages of fracture healing | \nDegranulating platelets, macrophages, monocytes (during the granulation stage) and endothelial cells, osteoblasts (at later stages) | \nMesenchymal and inflammatory cells, osteoblasts | \nMitogenic for mesenchymal cells and osteoblasts, chemotactic for inflammatory and mesenchymal cells | \n
BMPs | \nVarious temporal expression patterns | \nOsteoprogenitors and mesenchymal cells, osteoblasts, bone extracellular matrix and chondrocytes | \nMesenchymal and osteoprogenitor cells, osteoblasts | \nDifferentiation of undifferentiated mesenchymal cells into chondrocytes and osteoblasts and osteoprogenitors into osteoblasts | \n
FGFs | \nExpressed from the early stages until osteoblasts formation | \nMonocytes, macrophages, mesenchymal cells, osteoblasts, chondrocytes | \nMesenchymal and epithelial cells, osteoblasts and chondrocytes | \nAngiogenic and mitogenic for mesenchymal and epithelial cells, osteoblasts, chondrocytes α-FGF mainly effects chondrocyte proliferation β-FGF (more potent) involved in chondrocytes maturation and bone resorption | \n
IGFs | \nExpressed throughout fracture healing and endochondral ossification | \nBone matrix, endothelial and mesenchymal cells (in granulation stage) and osteoblasts and non-hypertrophic chondrocytes (in bone and cartilage formation) | \nMSCs, endothelial cells, osteoblasts, chondrocytes | \nIGF-I: mesenchymal and osteoprogenitor cells recruitment and proliferation IGF-II: cell proliferation and protein synthesis | \n
VEGFs | \nExpressed during endochondral and bone formation | \nBone matrix, endothelial and mesenchymal cells | \nEndothelial progenitor cells | \nPotent stimulators of endothelial cell proliferation | \n
Angiopoietin (I and II) | \nExpressed from the early stages throughout fracture healing | \nExtravascular tissue cells | \nEndothelial progenitor cells | \nFormation of larger vessel structures, development of co-lateral branches from existing vessels | \n
Biological factors in bone regeneration.
Essential signaling molecules in bone regeneration: their time of expression, source, target cells and their major functions (Adapted with the permission from Dimitriou et al. [25]. Copyright© 2005).
In the next section, we will list some of the common molecules associated with the bone regeneration process, and describe their biological significance.
\nMembers of the TGF-β are the most widely studied growth factors in recent years. This family includes, among others, five isoforms of TGF-β (1–5), bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs), which participate in a complex series of molecular events that lead to mesenchymal precursors during bone morphogenesis [25, 29, 33, 36]. They originate from high molecular weight precursors and are activated by proteolytic enzymes. They act on serine/threonine kinase membrane receptor on target cells. This ligand-receptor interaction activates intracellular signaling pathways which ultimately affects gene expression in the nucleus [25].
\nThe BMPs are a unique family of proteins within the TGF-β superfamily that play an essential role in regulating the formation, maintenance and bone repair [30]. To date, about 20 different proteins have been termed BMPs, but not all of them have osteogenic potential [37]. Among the BMPs with osteogenic potential we have, BMPs-2, -3 (osteogenin), -4, -6, -7 (also known as osteogenic protein-1 [OP-1]), -12 (also known as growth/differentiation factor 7 [GDF-7]) and -14 (also known as GDF-5, or cartilage-derived morphogenetic protein-1 [CDMP-1]). These proteins have been evaluated for healing and bone regeneration in clinical and preclinical models showing enhanced and accelerated bone formation [30]. In bone tissue, BMPs are produced by osteoprogenitor cells, osteoblasts, chondrocytes and platelets. Their regulatory effects depend on the target cell, stage of differentiation, local concentration, as well as interactions with other secreted proteins. BMPs induce a sequential cascade of events leading to chondrogenesis, osteogenesis, controlled angiogenesis and extracellular matrix synthesis [37]. Large number of preclinical studies has shown that BMPs are capable of inducing bone formation at ectopic sites and induce critical size defects healing [29]. It has been shown that BMPs 2, 4 and 7 play an important role in determining, migration, condensation, proliferation and apoptosis of skeletal cells. It has also been reported that BMP-4 and BMP-7 are responsible for inducing the cells of the neural crest, while BMP-2 is involved in the condensation of mesenchymal cells appearing before formation of immature bone structures during both endochondral and intramembranous ossification [33]. BMP-4 is predominantly active from days 1–5 after injury, with a peak closer to day 5. The BMP-2 is active during the bone regeneration process, culminating the bone remodeling to lamellar and haversian bone tissue, while BMP-7 is active after 14 days [23]. Target cells of BMPs include MSC, bone marrow cells, osteoblasts, myoblasts, prefibroblast and neuronal cells. The general effects on osteoblasts and cells of the periosteum involve an increase in the activity of DNA synthesis and transcription of genes involved in the synthesis of bone matrix proteins [23].
\nScientific evidence of the role of BMPs in bone regeneration is overwhelming. There are a number of publications confirming that the delivery of BMP at the site of injury promotes bone regeneration in animal and human models [38–40].
\nBMP-2 and BMP-7 have been extensively evaluated in clinical studies of nonunion, bone defects, open tibial fractures and spinal fusion, demonstrating their efficacy in the acceleration of bone regeneration and healing of fractures [29]. In order to be used in the clinical practice, a local and controlled delivery of BMPs is required; so, it is important to consider its short half-life time. Various delivery systems have been developed to overcome this limitation [37]. Currently, there are several forms of the human recombinant proteins commercially available. For example, for rh-BMP2: InductOs® (United Kingdom) and InFUSE (United States), (Medtronic Sofamor Danek, Inc., Minneapolis, MN), which are supplied in a bovine collagen sponge allowing slow release over time, and for rhBMP-7, Osigraft® (United Kingdom) and OP-1™ (United States) (Stryker Biotech, Hop-kinton, MA), in a bovine collagen granular form [34, 36, 37].
\nThe five isoforms of TGF-β regulate cellular functions such as proliferation, apoptosis, differentiation and cell migration. TGF-β is produced by osteoblasts and chondrocytes, and is stored in the bone matrix [25, 41]. TGF-β is also released by platelets and TGF-β1 indeed, was the first member of the family to be described in human platelets, as a 25 kDa protein with a possible role in the healing process [42]. During the initial phase of inflammation resulting from a bone injury, platelets release TGF-β and therefore this factor seems to be involved in the initial callus formation stage [25, 41].
\nTGF-β is a multifunctional, secreted protein, with different functions in the cell, such as control of cell growth and proliferation, differentiation and apoptosis. TGF-β induces the proliferation of MSCs, pre-osteoblasts, osteoblasts and chondrocytes and stimulates the extracellular production of proteins such as collagen, proteoglycans, osteopontin, osteonectin and alkaline phosphatase [25, 41]. It is also a potent chemotactic agent for MSCs. During chondrogenesis and endochondral bone formation, it induces the synthesis of BMP by osteoprogenitor cells, and it inhibits the activation and promotes osteoclast apoptosis [41].
\nThis polypeptide growth factor has potent chemotactic and mitogenic stimulatory effects on MSCs [30], plays an important role in the differentiation of pre-osteoblasts to osteoblasts [43] with the ability to promote angiogenesis during wound healing [30]. The PDGF family includes four isoforms: PDGF-A, PDGF-B, the more recently discovered PDGF-C and PDGF-D [44]. PDGF-A and B form homodimers (AA or BB) and a heterodimer (AB) [30]. PDGF-AB and PDGF-BB are variants circulating in alpha platelet granules and are released when platelets bind to the site of injury. The PDGF-BB variant has an active role in mitogenesis and chemotaxis of cells in the injured area [15] and plays a key role in bone regeneration [23]. After bone injury, PDGF is released by macrophages and platelets and acts as a potent chemo-attractant and mitogenic factor for cells of mesenchymal lineage, recruit fibroblasts, endothelial cells, osteoblasts and cells of the immune system. PDGF is active during the first 72 hours after injury, and as a promoter of angiogenesis plays a role in revascularization of bone defects [23].
\nThey constitute a family of structurally related polypeptides with a potent mitogenic effect on osteoprogenitor cells [29]. They are humoral factors originally identified by their ability to stimulate cell proliferation [33]. During bone healing, they can be secreted by monocytes, macrophages, mesenchymal cells, osteoblasts and chondrocytes in the early stages of bone fractures healing [33]. Members of the FGF family are present at the site of the wound for up to three weeks and its main activity is to stimulate endothelial cell migration and subsequent angiogenesis and mesenchymal cell mitogenesis [25, 34]. α-FGF mainly affects chondrocyte proliferation and is probably important for chondrocyte maturation, while β-FGF is expressed by osteoblasts and is generally more potent than α-FGF [45].
\nTwo separate pathways are involved in the regulation of angiogenesis during bone healing: a VEGF dependent pathway and the angiopoietin-dependent pathway [31]. VEGF is a potent angiogenic [29, 43] and vasculogenic [23] factor that not only increases the differentiation and proliferation of endothelial cells but also increases the tubular formation and mobilization and recruitment of endothelial progenitor cells [34]. VEGF is increased in response to hypoxia, ischemia and during healing of bone tissue [15, 34]. It has been shown that VEGF works synergistically with BMPs. VEGF by itself does not promote bone regeneration, but rather acts in coordination with BMPs to increase the recruitment of MSCs to the defect site and induce active differentiation of osteoblasts [46]. VEGF is expressed predominantly 14 to 21 days after the injury; and therefore, it is a candidate for early in situ application to promote mineralization and bone regeneration remodeling [23].
\nIGF-1 and -2 play a critical role in stimulation of organogenesis and growth during the first stages of embryogenesis as well as in regulating the functions of specific tissues and organs in later stages of development [47]. The sources of IGF-1 and IGF-2 are the bone matrix, endothelial cells, osteoblasts and chondrocytes [25]. IGF-1 promotes bone matrix formation (type I collagen and non-collagenous matrix proteins) by fully differentiated osteoblasts and is more potent than IGF-2 [45]. IGF-2 acts at a later stage of endochondral bone formation and stimulates type I collagen production, cartilage matrix synthesis and cellular proliferation [25].
\nClinical failure of bone tissue is defined as a discontinuity of the integrity of bone resulting from trauma, congenital malformation or surgical recession. Particularly, bone deficiency “critical size” is the bone defect that cannot regenerate spontaneously during the lifespan of the patient and, therefore, requires a surgical intervention for recovery [23].
\nThe processes that drive the biology and biomechanics of bone regeneration remain largely unknown. During regeneration of bone tissue, many highly complex interactions between multiple cell types are mediated by soluble and insoluble factors and they have not been sufficiently characterized. The challenge for tissue engineering and regenerative medicine is to rebuild the regenerative healing process of bone tissue and then join the components to produce osteoangiogenic and, therefore, osteoregenerative therapies that fulfill the biomechanical parameters for the healing of a bone defect that exceeds the critical size.
\nWe must remember that the bone has an inherent capacity for regeneration, so it is important to not only design therapies that do not interfere with the natural regenerative processes but also complement them and work synergistically with the endogenous bone healing process.
\nRegenerative therapy of bone tissue should include the three essential elements of bone regeneration: osteogenesis, osteoinduction and osteoconduction. Osteogenesis refers to the ability to produce new bone by bone-forming cells. Osteoinduction is the process whereby the presence of biological mediators stimulates the recruitment of mesenchymal stem cells to the wound site and their subsequent differentiation into mature bone cells, and osteoconduction is the physical property of providing a matrix facilitating the invasion of blood vessels and the new bone formation [48, 49].
\nBased on these fundamental principles, the main goal of regenerative medicine in clinical treatment is to reduce surgical morbidity by applying biological signals or cellular components that allow the reconstruction and restoration of lost tissue without autologous tissue transfer.
\nBone cell-based therapies seek to create viable tissue equivalents, providing live and metabolically active cells to repair the site of injury by continuous synthesis of bone matrix [50]. Mesenchymal stem cells are the center of a multitude of clinical studies currently underway (http://clinicaltrials.gov) [51]. Scientific evidence shows that they are one of the best choices in cell therapy, because of their ease of access and isolation, great potential of expansion in culture, immunosuppressive properties, paracrine effect and ability to migrate to injured tissues [52]. Moreover, their great therapeutic potential has been documented in the repair and regeneration of injured tissues in nearly every organ of the body, including the heart [53], immune system [54], liver [55], kidneys [56] and bone and cartilage tissue [57].
\nMesenchymal stem cells are defined as pluripotent cells capable of self-renewal and differentiation into various specialized types of mesenchymal cells, such as osteoblasts, chondrocytes, adipocytes, myocytes, fibroblasts [52, 58–61]. MSCs are a group cells that have been isolated from virtually every vascularized tissue [62]. MSCs are a group cells that have been isolated from virtually every vascularized tissue [52]; however, recent reports have documented that they can also be isolated from other sources as umbilical cord [62], peripheral blood [63], adipose tissue [64–67], hair follicle [68], periodontal ligament [69–72], gingival tissue [73] and dental pulp [74, 75], among others.
\nMSCs, for its ability to differentiate to multiple lineages, specifically, their osteogenic potential and their immunomodulatory, anti-inflammatory and anti-apoptotic properties, have become a major tool in cell therapy for the regenerative treatment of pathologies affecting functionally bone tissue [76–79]. In vitro analyzes show that MSCs induced by osteogenic differentiation medium increase the expression of osteogenic differentiation markers such as alkaline phosphatase, osteocalcin, osteopontin, bone sialoprotein and calcium deposits in the extracellular matrix. The progress in the study of the biology of bone tissue and the isolation and in vitro cultivation of MSCs opened the possibility of studying the molecular and biological mechanisms of bone regeneration, making significant progress, as evidenced by the more two thousand publications of experimental reports on the application of MSCs in bone defects in animal models promoting bone regeneration, and the more than five hundred clinical trials currently registered on the NIH clinical trials website (http://clinicaltrials.gov) [51].
\nThe mechanisms through which MSCs enhance the bone tissue repair process are complex, since they can participate in the three phases of bone healing: inflammation, proliferation and remodeling [80]. The in vivo identity and location of MSC have been difficult to establish. However, various reports, especially the work of Crisan et al., presented evidence of a relationship between MSCs and perivascular pericytes. Irrespective of their tissue origin, perivascular cells exhibit osteogenic, chondrogenic and adipogenic potentials and express MSC markers [81]. Based on these reports, Caplan suggests that all MSCs are pericytes, which would explain the presence of MSC in all vascularized tissues. When an injury disrupts the normal architecture of the blood vessels, pericytes are activated giving rise to MSCs that then contribute to tissue repair by secreting trophic factors that can control the endogenous inflammatory reaction, promote angiogenesis and stimulate the proliferation and differentiation of progenitor cells [82] (Figure 2).
\nSchematic model of the MSCs’ paracrine effect on tissue regeneration.
As mentioned before, a growing number of recent reports in the literature have revealed that even if a therapeutic effect can be observed, the implanted MSC cells do not differentiate and do not survive for a long time. For example, in an animal model of acute myocardial infarction, it was established that the MSCs implanted do not survive, and only 4.4% of grafted MSC could be found 1–2 weeks after transplantation [17], and MSC transplantation in a model of spinal cord injury in rats revealed that MSCs implanted disappeared from the host after 1–2 weeks [18]. It has been also reported that human adipose tissue-derived MSCs effectively induce bone regeneration in rabbit jaws, but they do not differentiate and do not survive more than 12 days in the site of implantation [21]. Recent reports have demonstrated that many of the therapeutic effects of MSCs can be mediated by the secretion of trophic factors, opening the possibility that direct administration of these mediators may replace the use of the cells in some instances [57]. This implies a shift from a paradigm centered on cell differentiation to a new vision where the MSCs can have a therapeutic effect even if they are not grafted or differentiated into specific tissue cells, which significantly increases the options of MSC therapeutic applications. According to this concept, Caplan has proposed that the most important feature of the MSC which determines its therapeutic potential is not their stemness but the ability to secrete a large number of trophic factors, and he has proposed that their name to be changed to medicinal signaling cells, keeping the same MSC acronym [83].
\nCaplan also proposes a model whereby MSCs exert their therapeutic action at the site of the injury by two different activities: from the front of the cells, away from the area of injury, MSCs create a curtain, by the production of bioactive molecules that control local inflammation and prevent autoimmune reactions. From the back of the MSC, they produce molecules that: (1) stop scar formation, (2) inhibit cell apoptosis due to ischemia, (3) stimulate the formation and stabilization of blood vessels and (4) secrete trophic factors that induce the replication of endogenous tissue progenitors [84] (Figure 3).
\nSchematic diagram illustrating the concept of application of MSC conditioned media in bone injuries. The MSC secretome, containing chemokines and growth factors, promote the recruitment of endogenous osteogenic cells and stimulate their migration to injured sites, inducing their differentiation and bone formation.
The broad spectrum of factors secreted by the different types of MSCs is generally referred as MSC secretome. Recent data demonstrate that MSC secretome factors, collected as conditioned media (CM), are sufficient to exert the MSC therapeutic effects.
\nPrevious studies have reported many growth factors and cytokines derived from the CM of various stem cells [19–21, 85–89], which could be responsible for the paracrine protective effects of stem cells against several diseases. Consequently, the use of stem cells CM instead of direct implantation of stem cells may be a feasible approach to overcome the limitations of current cell-based therapy. In addition, because CM is not a cell, but a conjugate of many growth factors, the administration of CM has no ethics concerns related with cell therapies.
\nHowever, secretomic signatures of the various types of MSC are not completely known, and the qualitative and quantitative characterization of MSC secretomes and their functions in secretome-mediated repair will contribute to the development of new regenerative therapies that will not require cell transplants [90].
\nRecently, the great potential of tissue engineering and regenerative medicine strategies for bone augmentation has been demonstrated, and the feasibility of using CM from MSC as an osteoinductive agent for future clinical use is becoming more evident. CM from bone marrow-MSC increased the migration and proliferation of MSCs, vascularization and the early bone regeneration in rabbit sinus model, showing CM as a promising novel therapeutic agent to promote bone regeneration after maxillary sinus floor elevation [91]. It has been shown that CM can have stronger effects than MSCs, accelerating the mobilization of endogenous endothelial and MSC cells for bone regeneration in rat calvarial bone defect model [92]. Intravenous administration of MSC-CM provided the protection of osteoblasts and osteoclasts, induced angiogenesis, anti-apoptotic and anti-inflammatory effects in a rat bisphosphonate-related osteonecrosis of the jaw-like model [93]. It has also been reported that the use of MSC-CM may be an alternative therapy for periodontal tissue regeneration [94]. CM from human MSC accelerates the formation of new bone callus, shortening the time period required for distraction osteogenesis treatment in a mouse model by recruiting endogenous mouse bone marrow stem cells (mBMSCs) and EC/EPCs via MCP-1/-3 and IL-3/-6 signaling [95].
\nWe have also reported that human Ad-MSCs and their CM induce bone regeneration in a jaw rabbit model, and that morphometric, radiographic and histological analysis demonstrate that the amount and quality of neoformed bone, repaired area, bone density, arrangement of collagen fibers, maturation and inorganic matrix calcification are very similar between Ad-MSC and CM-treated groups [21] (Figure 3).
\nAll the scientific evidence on the paracrine effect of MSC provide the opportunity to exploit the therapeutic potential of MSC-CM and opens up scenarios for the identification of new candidate molecules for tissue repair via proteomic analysis of the MSC secretome. MSC-CM delivers osteoinductive growth factors and cytokines that modulate the behavior of endogenous cells contributing to the formation of new tissue. Furthermore, the use of MC allows us to avoid some of the limiting factors associated with the clinical application of stem cells, such as the risk of tumorigenesis and transmission of infectious diseases [80], immunological incompatibility, costs and waiting time for cell ex vivo expansion [80].
\nThe use of MSC-CM as a novel therapeutic strategy has several practical advantages. CM storage and transportation procedures are not as complex as they are for MSC. CM production can be less expensive, enabling access to disadvantaged populations and reducing costs for health systems.
\nDespite the advantages of its use, CM application may not always supersede the use of MSC, and it is possible that for some type of disorders MSC could be a more effective alternative. The number of known molecules mediating the paracrine effect of MSC grows every day, and significantly increases the potential range of their therapeutic applications.
\nBuildings have become the major energy consumers over the world as they consume around 40% of total end-use energy [1]. In Europe, the Directive on Energy Performance of Buildings establishes a “nearly Net Zero Energy buildings” (NZEBs) as the aim for all new buildings from 2020 [2]. In recent literature, more and more studies consider nZEBs as part of a smart grid or a micro-grid (MG) and identify trends on energy management techniques and technological solutions for electric power system management. The main advantages of nZEBs have been identified to be the integration of renewable energy sources; the integration of energy storage mechanisms such as plug-in electric vehicles and the implementation of zero-energy concepts such as net zero source energy, net zero energy costs and net zero emissions.
The renewable energy exploitation is one of the most important aspects of NZEBs. Renewable Energy Sources (RES) are those sources of energy that can be derived from natural processes and thus can be replenished continuously such as solar energy, wind energy, biomass, hydropower etc. The wind and solar energies are mostly used in green buildings modeling and design [3] but they come with a number of issues that have to be taken into consideration. The wind energy systems may not be technically feasible at all sites due to the low wind speeds and/or to high unpredictability with respect to solar energy. In addition, the availability of a specific resource depends each time on the corresponding season and may also vary during the day [4]. NZEBs, either as standalone or as parts of a Net Zero Energy District, could help improving the energy performance of an electrical grid by shifting loads and reducing peak demands. Buildings, as one of the most important contributors involved in a smart grid, can deliver useful information such as energy behaviors, power demand and the corresponding load shifting potentials for grid control and optimization [5].
A microgrid is an electric system of limited extent, typically the suburban/district level, that includes distributed generation (i.e., solar, wind, cogeneration, electric vehicles, etc.), consumers and storage facilities, and operates by intelligently managing its own costs and production capacity to ensure a level of quality service. It is connected to the global grid but is designed to operate independently if necessary (islanded mode). Microgrid can be understood as a case of a more general concept called ‘Smart grid’, collecting a set of technological solutions for electric power system management. Its localized nature allows responding efficiently and accurately the energy needs and ensuring adequate levels of quality, safety, security, reliability, and availability. It is able of being disconnected from the global network for several hours without loss of service while ensuring voltage and frequency stability. In addition, the proximity of the sources of production to the consumption allows reducing energy transmission losses. Thus, the use of such a system (mainly decentralized) has as an aim to gain flexibility and adaptability with respect to the classical centralized power system model.
The development and the extensive utilization of building automation systems, Information and Communication Technologies (ICT) and grid energy management system facilitates the bidirectional communication between buildings and a grid which can be widely established and therefore be used for interacting and optimizing the power supply and the demand. This chapter attempts to address the major issues that are related to the design and optimization of grid-connected nearly and/or net zero energy buildings as parts of a smart grid and on which several scholars/researchers have been working the last years.
In this work, a microgrid with a certain number of DER components connected to an office building (in a university campus) provided with electricity by a utility company is considered. These components include a PV installation, a Storage Energy System (ESS), a small Combined Heat and Power (CHP) unit, and a fleet of electric vehicles (EVs) used for work-related trips. The mobility behavior of the EVs fleet is modeled considering deterministic realizations of the probabilistic distributions used for the arrival/departure and the time EVs remain parked. PV production and electric load are modeled under uncertainty. We use actual data from smart meters to formulate the scenarios. We also assume that each DER element can, through an EMS controller, to communicate and control the power exchange from and towards this component. We also consider that two-way communication with the utility company can be achieved via aggregators using advanced metering infrastructure. The energy generated by the DERs can be sold to the grid by the microgrid building-manager, and/or it can be stored for future utilization. The recommended EMS configuration is shown in Figure 1.
Energy management and system configuration.
To classify PV and electric load production, yearly data-measurements from smart meters installed in Walloon region, Belgium, have been used. The smart meters communicate with the utility company server every 15-min providing the updated PV and load measurements. The 15-min datasets were merged to formulate 8760 hourly readings (365 24-hour PV generation and load profiles). The total PV capacity is 50 kVA. The original datasets are shown in Figure 2.
The 365 original profiles for (a) PV production, and (b) electric load demand.
We use the scenario reduction technique introduced in [6] to construct the scenarios. A script developed in Matlab based on [6] is utilized to aggregate the two sources of uncertainty into one. That is, a discrete probability has been assigned to each one of the generated scenarios. Every scenario comprises two 24-hour vectors where each vector corresponds to a specific profile (one vector for PV production and one for load demand). Moreover, this scenario construction technique considers the potential correlation within the data. The latter is very important as, for example, a sunny day with increased PV production is expected to affect the load demand downwards and vice-versa. Moreover, one may notice that the PV profiles of Figure 2a look asymmetric and seem to have been shifted towards the left side of the time axis. This is due to the minimum cut-in voltage level required from the power electronics of the inverter to start being operational.
It is important that the final number of generated scenarios retain most of the relevant information on the stochastic process contained in the original scenario sets, while significantly reducing its cardinality. A very large number of scenarios may result in a computationally intractable associated stochastic programming problem which would require both increased time and computational resources to be solved. On the other hand, a small number of scenarios might not be representative of the original data sets. Thus, in order to decide the appropriate number of scenarios we take into consideration the total expected system cost (TESC), its standard deviation (SD), and the total computational time, as shown in Table 1. Simulations take place on an Intel Core i7-5500U CPU @ 2.4 GHz with 16 GB memory.
Numb of scenarios | 6 scen. | 12 scen. | 24 scen. | 48 scen. |
---|---|---|---|---|
TESC ($) | 26.06 | 20.07 | 16.68 | 15.64 |
SD ($) | 23.22 | 24.33 | 24.35 | 24.45 |
Elapsed time (s) | 0.09 | 0.11 | 0.23 | 0.42 |
Parameters related with the number of scenarios.
We can see in Table 1 that the TESC decreases considerably from the 6 to 12 scenarios, and from 12 to 24. On the other hand, the cost reduction from the 24 to 48 scenarios is smaller. The standard deviation of the TESC increases somehow from the 6 to 12 scenarios, but it remains relatively constant in the rest scenario cases. Finally, one may notice that the computational time needed to obtain the optimal solution is increased around 100% in both cases, from the 12 to 24 and from 24 to 48 scenarios. Considering all the information above, the case of 24 scenarios provides a favorable trade-off between a satisfactory scenario representation and a computationally tractable problem. One should also note that the constructed scenarios are not equiprobable, but probability weighted. The 24 scenarios for PV generation and load demand are illustrated in Figure 3.
The 24 representative scenarios for (a) PV production, and (b) electric load demand.
For the deterministic approach, we used the average yearly profiles (obtained from the original datasets in Figure 2) for both PV production and the electric load demand. These profiles are illustrated in Figure 4.
The average yearly profiles for (a) PV production, and (b) electric load demand.
When connected to the microgrid, the charging and discharging behaviors of the EVs make them considered as either power supplies (when discharging) or power loads (when charging). Here, the EVs selected for the fleet are used for work-related trips and it is also assumed that the mobility behavior with the EVs remains similar as with conventional vehicles.
In this work, the mobility behavior profiles for a fleet of 30 EVs are generated. In Belgium, 82% of the population has fixed working hours and shifts [7]. Usual working hours are considered from 8 am to 6 pm but they are not binding. The arrival time distribution is fitted in the form of chi-square distribution [8] with its probability density function given by:
To simulate the thermal performance of a building, engineers developed, among other tools, the thermal network method. Thermal networks have been used to study the internal mass effects [10], appliances, indoor air temperature and heating load [11] for different buildings. In addition, they represent a comprehensible idea about the heat transfer phenomena in buildings with a simple systematic formulation of the problem. In the thermal network method, the whole mass of the system is accumulated in finite number of nodes, which are connected to thermal capacitances. The heat transfer between two nodes occurs through thermal resistances. It has been shown, that the functionality of control systems can be improved by the implementation of the thermal network method and the system identification approach [12].
System identification is an approach to construct mathematical models of dynamic systems by means of measurements of the system’s input and output signals. The system identification needs the measured input and output signals from the system, a model structure, and an estimation method to estimate values for the adjustable parameters in the selected model structure. In a dynamic system, the output signal depends on both the instantaneous values of its input signals and on the initial conditions. In fact, a model is a mathematical relationship between a system’s input and output variables. Differential or difference equations, transfer functions, and state-space equations are common methods to describe a dynamic system. The RC model method describes the system with ordinary differential equations that can be easily represented with the state space method.
Obtaining a good model of the system depends on how well the measured data reflects the behavior of the system. For this purpose, the measured data must capture the dynamics of the system. It is necessary to measure the right variables with enough accuracy and duration to capture the dynamics of interest. In general, to supply an appropriate dataset, the following inputs that excite the system dynamics are important: data duration to capture the important time constants, a detailed analysis of signal-to-noise ratio, and finally measuring the outputs at appropriate sampling intervals [13].
The use of the RC model method provides the structure of the model, but not the numerical values of its parameters. Afterwards, it is possible to represent the system with a state-space model and estimate the values of its parameters from the data. This approach is known as gray-box modeling. The system identification approach refers to methods and algorithms that estimate the model parameters by minimizing the error function (cost function -- the mean square error), as shown below between the model output and the measured data.
where L is the number of data samples,
The MATLAB® system identification toolbox is used in this work to minimize the cost function of Eq. 2 and to estimate the model parameters. MATLAB uses various minimization algorithms to perform the optimization. In our case, the ‘auto’ algorithm is used for the search method to minimize the cost function and to estimate model parameters, as it determines the optimized trajectory among different techniques at each iteration.
The simplified thermal model presented in [14] is used in this study to obtain the thermal load for the university building. The building is simulated using TRNSYS software utilizing weather data from the Uccle meteonorm file (Belgium). It has a heavy structured envelope and the buildings material properties are presented in [14]. Here a 4R2C model is proposed and used to simulate the thermal performance of the building. The corresponding proposed thermal network is represented in Figure 5.
The proposed thermal network.
To determine the parameters in the thermal network, the system identification approach has been used. Data from TRNSYS have been used as the information matrix for the model to be trained. To identify the model’s parameters, the Matlab system identification toolbox is utilized. The information matrix contains one-month data. The model identification determines the values of each resistance and capacitance to achieve the highest fitness between the thermal network and the information matrix. Then, the identified model can predict the thermal performance of the building for a predetermined period of days.
To formulate a daily thermal load profile, so as it can be used by the EMS for its 24-hours scheduling horizon, the average heating load of the predicted working days is calculated. The calculated thermal load offers a temperature approximately around 22°C during working hours (from 9 am to 6 pm). The daily thermal load prediction is illustrated in Figure 6.
Daily thermal load prediction.
The thermal load is low during the night and the early morning hours and starts increasing around 8 am. This is necessary, so as the targeted thermal comfort level to be achieved in the office building during the working hours. The thermal load is covered by CHP’s thermal production.
The mathematical formulation of the EMS is presented in this Section. The objective function which minimizes the total expected system cost is given by Eq. (3) below:
where
The expected cost function (3) is a probability-weighted mean of all the scenarios considered. It minimizes the power requested from the grid
Finally, the third term of Eq. (3) introduces a prioritization mechanism in the form of a penalty factor. Parameters
Eq. (4) enables the actual power generated by the PV to be utilized in three different directions. A portion can be sold directly to the grid
The ESS operation is characterized by Eq. (5)–(10). The actual power provided by the ESS when discharges can be either sold back to the grid
The EVs operation is described in Eq. (12)–(18). Eq. (12) ensures that the discharge power of the EVs is either injected back to the grid
The utilization of small-sized CHP turbines is typical for covering thermal load demand and has been often proposed in literature as a distributed energy resource [16]. The equations that describe the operation of the CHP microturbine are presented in Eqs. (19)-(24) below.
Constraint (19) states that the total power
The total power injected to the grid is described in Eq. (25). The total power injected to the grid at time t and for each scenario
The power balance equation is defined in Eq. (26) below.
Constraint (26) forces the balance between the input and the output electric power of the EMS in each time interval. More specifically, it is stated in Eq. (26) that the total load consisting of the office-building electric load demand, the charging needs of the ESS and the sum of the charging needs for the EVs is covered by the power requested from the grid and/or by the combined procurement of power provided by the PV, the ESS, the sum of discharging power of the EVs, and the CHP.
Finally, Eq. (27) and Eq. (28) realize the logic of power exchange.
When the EMS needs to draw power from the grid, power is not allowed to be injected into the grid at the same time, and vice versa. The limitations in power exchange are imposed by parameter L which corresponds to the local line capacity. To avoid the installation of extra power facility infrastructure for the EMS, the potential limits of the university-building dedicated medium-voltage to low-voltage (MV/LV) transformer are used. The apparent power of the transformer is 160 kVA with MV input 10.5 kV and LV output 400 V. Assuming a whole building’s power factor of 0.9, the actual (useful) power that can be drawn from the grid at any time is 144 kW. This constraint can be also time-dependent and be imposed to lower values, for example, by an aggregator responsible for coordinating multiple microgrids owning EMS or by the utility company itself responsible for the smooth operation of electrification in the area.
To examine the effectiveness of the proposed EMS algorithm, the impact of different case studies on total system cost is evaluated. The proposed EMS framework is a mixed integer linear problem modeled in GAMS v.24.7.1 and solved by the IBM CPLEX Optimizer v.12.6. The time required to find the optimal solution varies from a few seconds to several minutes, depending on the model. The optimality gas has been set at 1.0E-04.
The electric load demand and PV scenarios are given in Section 2.1 along with the deterministic day-ahead (DA) forecasts. The thermal load demand prediction is shown in Section 2.3. It should be noted that as the PV generation data came from actual smart metering measurements, no study regarding the positioning and the installation of the PV panels was performed.
The bidirectional energy flows between the utility company and the end-user (the building-microgrid manager in this case) assume the utilization of smart-metering approach. The day-ahead time-varying price signal which represents the electricity cost at each time interval t is depicted in Figure 7. A time-varying rate has also been applied for the energy sold back to the grid. This rate is 20% lower than the aforementioned time-varying price signal, based on the assumption that the utility company would not buy energy at a more expensive rate than it would sell it. In this study, no other incentive-based scheme (e.g., selling green certificates for renewables) apart from the utility company price signal is applied.
Day-ahead electricity price forecast.
The ESS consists of a battery group with a total capacity of 80 kWh. The maximum charging/discharging rate is 40 kW with corresponding power electronics efficiency of 0.88. The minimum allowed state-of-energy of the ESS has been set to 10 kWh (12.5% of max ESS capacity) to prevent deep battery discharging. The initial state-of-energy of the ESS is 40kWh.
The thermal efficiency
As mentioned earlier, a bidirectional energy flow concept for EVs and their potential V2B and V2G capabilities could significantly reshape the current perception of power systems. The first step is their integration into the smart grid (or microgrid). The EVs are equipped with constantly bigger battery capacities increasing thus their potential contribution as DERs. The EVs could either be granted to (University’s or a company’s) personnel for commuting purposes under the form of a third-party contract and/or they could be privately owned. In both cases, it would make sense to assume that the EV users would be willing to allow the building-microgrid operators to use their batteries’ capacity but they would not prefer to have a lower state-of-energy upon departure compared to their arrival. In addition, in the case of self-owned EVs, possible monetary benefits for the EV owners may be needed for motivating them to opt-in the EMS scheme.
In our base case study, the first business model is considered, namely the EVs are provided to the personnel and, in exchange, the EVs’ users have to participate in the EMS framework. It is considered here that the final state-of-energy of the EVs should be at least equal to their initial one. We have also considered
First, we consider the total system cost (TSC), as shown in Table 2.
Case | Description | Total system cost |
---|---|---|
1 | No EMS in operation (average of all historical data) | 59.47 |
2 | With EMS in operation (average of all historical data) | 13.51 |
3 | Expected mean of all 24 scenarios | 16.68 |
4 | Most probable scenario of the 24 (prob. 9.3%) | 58.11 |
Total system cost across all case [$].
The first case corresponds to an operation of the microgrid without the presence of an EMS and thus, no optimization takes place. That is, the loads cannot be shifted and are always met. In addition, as the EVs should depart at least having the same battery state of energy as the one they had when arrived, charging/discharging of the EVs are not activated. The ESS operation is also omitted, as its charging /discharging cannot be coordinated due to the absence of an EMS. Finally, when there is a net energy consumption at time t, electricity is bought at price
Total system cost distribution for the 24 scenarios.
The importance of considering an EMS in microgrid’s operation is depicted in the TSC results across all cases, as shown in Table 2. First, the total system cost of case 1, where no EMS is assumed, is 340% higher compared to case 2, where an EMS is present coordinating the microgrid operation (from $13.51 to $59.47). The expected TSC for case 3 is 23% higher compared to case 2 due to the impact of some extreme scenarios on the final result. Moreover, the total cost distribution across all the different scenarios (Figure 8) implies that the final total system payoff for the majority of the scenarios is positive in terms of cost (a positive value declares a cost, while a negative one declares a profit). Finally, one may notice that the TSC for the most probable scenario, as seen in case 4, is much higher compared to the other two cases (case 2 and 3) in which an EMS is also present on microgrid’s operation. The reason is that for this particular scenario, the PV generation and the building load demand are very different compared to the corresponding annual average values, as these are considered for case 2 (Figure 4). More specifically, the projected PV generation in the most probable scenario is much lower than the yearly average, as presented in case 2. On the contrary, the building load demand is higher than the average. Therefore, the results presented in this Section should be interpreted taking this context into account.
To analyze a few more aspects of the optimization results and examine the individual scheduling of each DER, as it is decided by the EMS, we compare the microgrid’s operation under two different case studies: case 2, which from now on will be referred to as simply the deterministic case, and case 4, which will be referred to as the most probable scenario. (Figure 9).
Most probable scenario for (a) PV production, and (b) electric load demand.
Figure 10 presents the total power requested by the EMS from the grid and injected back to it for the deterministic approach and the most probable scenario.
Power requested from and injected to the grid for the most probable scenario and the deterministic approach.
There are many observations one might make regarding Figure 10. First, notice that the power requested from the grid is zero during the whole 24-hour time horizon for the deterministic approach. This implies that the microgrid can fully cover its electric load demand using its own distributed energy resources. In addition, it is able to inject a great portion of its produced energy back to the grid. From 1 pm to 4 pm though, the microgrid neither requests nor injects power back to the grid. This means that the produced energy is entirely used to cover the local microgrid load demand.
On the other hand, we can see that during the most probable scenario, the microgrid draws power from the grid from around 9 am to 5 pm which indicates that the microgrid’s distributed energy resources cannot fully cover the load demand during that period. This is mostly due to the limited daily PV production assumed in this scenario in combination with a higher than average electric load demand. In addition, one may notice that the total power injected back to the grid is much lower in the most probable scenario.
To better understand how EMS coordinates the operation of the microgrid’s components, Figure 11 presents the decomposition of the total power injected to the grid for the involved DERs (PV, ESS, CHP, and EVs).
Decomposition of power injected to the grid for the (a) deterministic approach, and (b) the most probable scenario.
In both the deterministic and the most probable scenario, CHP is the DER that injects most of the power back to the grid. We can see that in the deterministic case PV also contributes, especially during the noon hours. The ESS is more active in the case of the most probable scenario, while one might notice that the EVs are not used at all as a potential source for energy to be injected to the grid. This happens mainly due to the lowest prioritization factor EVs have for selling energy back to the grid as described earlier, but also due to the penalty that has been set to prevent EVs battery degradation. Finally, we can observe that in both the deterministic and the most probable scenario, the EMS tries to inject most of the power back to the grid during the peaks of electricity price (around 7 am and 6 pm as shown in Figure 7) to maximize the reward.
Figure 12 shows the decomposition of the projected PV generation for the deterministic approach and the most probable scenario.
Decomposition of PV production for the (a) deterministic approach, and (b) the most probable scenario.
In the deterministic case study, PV production is mostly sold to the grid (early and noon hours) or stored in the ESS for future exploitation (afternoon hours). Only a small portion at 1 pm is used to cover the building’s load demand. On the contrary, in the most probable scenario, all the produced PV energy is used to meet the building’s load demand.
Figure 13 shows how the electric power produced by the CHP is divided among the grid, the ESS, and the local building load. Like the PV, most of the CHP electric production in the most probable scenario is used to cover the building’s load. Moreover, we can see that the EMS tries to inject most of the CHP’s produced energy back to the grid, during the electricity price peak hours. Finally, in both cases a smaller amount of the CHP’s produced energy is stored in the ESS for future implementation. The thermal load demand parameter
Decomposition of CHP electric produced power for the (a) deterministic approach, and (b) the most probable scenario.
Storage is an important distributed energy resource for the system. As stated in Eqs. (9)-(10), the ESS can either be charged from the grid, the PV, and the CHP. When discharging, its energy can be either injected into the grid and/or cover a portion in building’s load demand. Figure 14 shows the decomposition of the ESS available energy for the deterministic approach, as well as for the most probable scenario.
Decomposition of ESS provided power for the (a) deterministic approach, and (b) the most probable scenario.
Figure 14 can be better analyzed taking into account Figure 15, which demonstrates the evolution of the ESS state of energy for the two aforementioned case studies.
State of energy for the ESS for the (a) deterministic approach, and (b) the most probable scenario.
We can see that in both deterministic and most probable scenario cases, the ESS is mainly active during two distinct period of times, in the morning (between 7 am and 8 am), and in the afternoon (between 5 pm and 7 pm). There are two main observations one may make regarding the ESS operation. First, the ESS uses two discharge cycles in the deterministic approach, while it only discharges once in the most probable scenario. The relatively high PV generation considered in the deterministic scenario is responsible for this second cycle of charge/discharge. Looking at Figure 12, we notice that PV production during the afternoon hours is mostly directed to the ESS. Second, the ESS covers mainly the building’s load demand in the deterministic case, while in the most probable scenario the ESS injects most of its energy back to the grid.
EVs constitute the third available DER in the microgrid but contrary to the rest DERs (PV, ESS, and CHP), they are not actively involved in microgrid’s energy exchange. The EVs battery degradation cost on the one hand, and the lowest energy prioritization factor that has been assigned to them on the other hand, do not make the an attractive alternative power source for the EMS (in terms of cost). Nevertheless, the EVs can always be used as a back-up ancillary power source in case of an emergency situation.
Sensitivity analysis is used to study the robustness of the solution to a linear programming model. If there is cause for concern regarding the accuracy of the data used, sensitivity analysis is undertaken to determine the way the solution might change if the data were different. When the solution does not change (or when the nature of the solution does not change, as when the basis remains optimal), one may assume that the proposed solution is appropriate.
Dual variables, also known as shadow prices, are of great interest in the solution of a linear optimization problem. A dual variable is reported for each constraint. The dual variable is only positive when a constraint is binding. The dual price can be defined as “the improvement in the objective function value if the constraint is relaxed by one unit”. In the case of a less-than-or-equal constraint, such as a resource constraint, the dual variable gives the value of having one more unit of the resource represented by that constraint. In the case of a greater-than-or-equal constraint, such as a minimum production level constraint, the dual variable gives the cost of meeting the last unit of the minimum production target. The units of the dual prices are the units of the objective function divided by the units of the constraint. To obtain the values of the dual variables, we first solve the MILP to find the optimal allocation. Next, we remove the integrality constraints and insert equality constraints that force the integer variables to assume their optimal values in the resulting linear program [17].
The following example presents how the dual variable of a constraint can be used for the sensitivity analysis. Figure 16 shows the dual prices of constraint Eq. (4) for the 24 hours of the daily time horizon. One should recall that this is a resource constraint, and specifically it bounds the actual power generated by the PV to be less-than-or-equal-to the maximum PV generation, as this is defined by parameter
Value of sensitivity factor: Dual variable corresponding to the upper bound of constraint (4) [$/kWh].
This value implies the sensitivity of the system cost with respect to the actual PV power utilized by the system. Note that the positive value for this dual variable means that the total system cost decreases with the additional availability of PV power. More specifically, it indicates the decrease in the total system cost that corresponds to the increase of the available PV generation by 1 kWh. The fact that the value of the dual variable is positive during the whole day implies that additional PV potential has always positive impact on the total system cost, regardless the time of the day. However, one might also notice that there some time periods (7 am, from 5 pm to 9 pm), where the extra PV power would be more beneficial for the system compared to the rest time periods. In a similar way, one could evaluate the impact of the relaxation of the rest important resources to the total system cost.
The transition to the new “smart” era requires the utilization of smart technology through comprehensive and efficient energy management functions. We propose in this study, a two-way communication energy management framework for a microgrid in a university campus including local renewable energy sources, a storage system, a combined heat and power small turbine, and a fleet of EVs used for work-related trips. Two-way energy exchange is allowed using net metering technology. The developed MILP framework incorporates an optimizer which decides the power exchange among the DER components of the microgrid and the grid, exploiting the V2B and V2G capabilities of the distributed energy resources. It also provides a specific level of thermal comfort to the building’s occupants by meeting the predicted heating load. The formulation of an EMS model which takes into account the PV and load variability is very important if we want to consider the impact of planning for one scenario, and having another scenario occurs. To overcome this challenge, actual smart metering data for a period of one year have been used to construct a number of potential scenarios. The PV and load demand data are classified using a scenario construction technique, leading to the formulation of 24 different PV and electric load scenarios, each one represented by a designated probability. The importance of considering an EMS in microgrid’s operation is depicted in the total system cost across all cases. Results confirm that the EMS substantially decreases the total system cost by optimally coordinating and scheduling the microgrid operation. An additional significant remark is that the majority of the total daily system’s cost is due to the natural gas expenses required for the operation of the CHP microturbine. Finally, we compare the optimal scheduling of the microgrid’s DERs under the deterministic case and the most probable scenario. The most probable scenario assumes a lower PV production and a higher building electric load demand than the average values considered in the deterministic case, resulting in a substantially different energy scheduling for the DERs. It is worth noting that under the deterministic approach and the current design, the microgrid seems to be self-sufficient in terms of covering its energy demand. However, this is not the case under the most probable scenario approach, where the microgrid relies also on grid energy to meet its load demand, on top of the energy production of its own DERs. Suggestions for future work include the introduction of additional stochasticity parameters (e.g., electricity price) and the integration of power flow constraints into the optimization problem.
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\n\nRead more about Open Access in Horizon 2020 here.
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