Summary of the glass and glass-ceramic scaffolds reported in literature produced via the foam replica method.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
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She became a Teacher of Mathematics at the Berzsenyi Dániel Teacher Training College in 1988. Dr. Lányi obtained the Dr. Univ. degree at the University of Veszprém, Hungary in Physical-chemistry (1993), and the Ph.D. degree at the University of Veszprém, Hungary in Computer Science (2000). She has worked as a software engineer and as an associate professor for program languages at the University of Pannonia.\nCurrently, she is focused on virtual reality and its application, user interface design, computer graphics for informatics engineering students and using multimedia in the education for teacher training courses. Ph.D. and Masters’ supervision has an emphasis on multimedia/ virtual reality for the rehabilitation of children with disabilities and patients with mental health issues. She has supervised altogether 180 BSc and MSc thesis works from 1997. Her students received numerous awards.\nDr. Lányi received several awards, the most important ones are: “Master teacher” award of the Hungarian Ministry of Education (2001), the \\"Kalmar\\" award from the John von Neumann Computer Society (2016), the “Hungarian Higher Education Plague” of the Ministry of Human Capacities (2016), the “Diamond-Award from the Association for the Advancement of Assistive Technology in Europe (2015), which is a personal recognition, granted for outstanding work in advancing assistive technology in Europe and the “King Salman Award for Disability Research” of the King Salman Center for Disability Research (2018).\nShe was the secretariat manager of EDeAN in 2009 and the representative of Hungary in IFIP Technical Committee 13: Human-Computer Interaction (TC13) in the period of 2008-2018. 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With the ageing and continuous growth of the population, surgeons face an increasing number of operations aiming to replace and/or repair tissue that has been damaged through disease and trauma [1]. According to the International Osteoporosis Foundation, incidence of fracture, for example, is anticipated to increase by 240% in women and 310% in men by 2050 [http://www.mdbuyline.com/research-library/articles/bone-graft-substitutes-bone-matrix-cost/, visited last April 2016]. This factor is expected to drive the rise in the global bone graft market. Bone regeneration market was evaluated at USD 2.35 billion in 2014 and is expected to rise to USD 3.48 billion by 2023, as reported in transparency market research [http://www.transparencymarketresearch.com/pressrelease/bone-grafts-substitutes-market.htm, visited June 2017]. The gold standard in bone grafts is, at present, the use of allograft. An allograft is a tissue received from a donor which is demineralised before use, thus, genetically different than an autograft (where tissue comes from the patient itself). However, a risk of infection is associated with such practices. To overcome the infection risk, the allograft tissue must be pre-treated. Techniques used are tissue freezing, freeze drying and sterilization. The average cost per procedure was estimated to be USD 3154.
\nBioceramics, pertaining to their excellent biocompatibility and higher mechanical properties compared to polymers or metals, have always been regarded as the most promising biomaterials for hard tissue repair. The advantage of bioceramics lies in their wide tissue/implant response: from being nearly inert to bioactive depending on their composition. A subset of bioceramics which have expanded at a tremendous rate in the past decade are bioactive glasses. These materials support not only osteoconduction (growth of bony tissue at the surface of the implant) but also osteoinduction (acceleration of new bone formation by chemical means) [2]. Bioactive glasses have, now, been used widely clinically especially in dental and bone repair applications.
\nFor the repair and regeneration of bone defects, tissue engineering strives to produce 3D constructs that can support mechanical load and provide a template in which cells can migrate and colonized. The optimum attribute of a 3D scaffolds are summarized as follow:
\nThe biomaterials should not only be biocompatible but must support cell adhesion and proliferation. The material should be at minimum osteoconductive but ideally osteoinductive.
The biomaterials should resorb over time. The resorption rate of the implant should match as closely as possible the regrowth of the new tissue.
The implant should be porous with an open interconnect structure to allow fluid penetration, angiogenesis and cell proliferation. In general, interconnected pores of at least 100 μm and an open porosity of over 50% is considered the minimum requirement for tissue ingrowth [3–5]. Optimally, it is reported that the construct should have pores within 100–500 μm and an overall porosity of over 90%. However an increase of porosity comes at the expense of mechanical strength [6].
The mechanical properties, which is mainly function of the porosity and the pores organisation, should be tailored to the site of implantation, i.e. similar to cancellous bone in non-load bearing applications and similar to cortical bone in load-bearing applications. In all case, the mechanical properties should be maintained throughout the bone reconstruction.
Porogen processing is a method in which glass powders are mixed with a polymer bead used as a ‘space holder’, and packed into a mould. The polymer is then burnt away in a two stage sintering process to create porous scaffold. This process relies on using a combustable polymer and sufficient oxygen flow to gain complete burn out during sintering, if complete burn out is not achieved it can result in inhomogeneous scaffolds being formed with a porosity gradient. The scaffolds tend to have limited porosity of up to 50% [7].
\nFreeze casting is a traditional ceramic foam processing method, which is based upon the formation of an aqueous slurry where ice crystals are formed in the direction of freezing. Under vacuum, the ice crystals are then sublimated to leave a porous green body which is then sintered [8]. This was initially developed in 2011 for use with hydroxyapatite, but has since been used with various glass and glass-ceramic compositions [9–11]. The scaffolds produced tend to have small pores (up to 100 μm) with low levels of interconnection, with consequently high strengths. Due to the small pores, they have not been significantly investigated in either the glass or glass-ceramic field for bone repair.
\nThe foam replica process employs a polymeric foam, commonly made of polyurethane, to act as a template for a glass slurry to create scaffolds with a foamed morphology. The foam is soaked in a glass suspension, and dried. By completing multiple cycles of infiltration and drying the wall thickness of the scaffolds can be increased, however, the shape obtained is still dependent upon the foam itself. The sintering process is then completed in two stages, firstly to burn out the polymer foam, and secondly to sinter the particles to form a continuous construct. The foam template is key within this process, its pore shape, size, and distribution all control the outcome of the scaffolds produced. The mechanical properties of the scaffolds produced via this technique are predominately dependent upon the particle distribution within the foam prior to burnout, which is controlled by the stability and concentration of the suspension used.
\nThe process was first adopted to produce glass ceramics from the 45S5 composition in 2006. Scaffolds were produced from 45S5 glass powder, then sintered at 1000°C for 1 hour, forming fine crystals of Na2Ca2Si3O [12]. It was then adapted by Fu et al. [13] using the 13-93 glass composition which were kept amorphous post sintering (54.6 SiO2, 22.4 CaO, 6 Na2O, 1.7 P2O5, 7.9 K2O, 7.7 MgO in mol%). The scaffolds met many of the requirements for bone regeneration, with a reported porosity of 85 ± 2%, interconnected pores between 100 and 500 μm, and compressive strengths of 11 ± 1 MPa. These values are similar to those of human trabecular bone and outperformed other glass-ceramic foams reported in literature at the time [13]. This could be attributed to their optimisation of glass loading within the slurry. Their particle size distribution (modal size of 2 μm) allowed for good particle packing within the green body enhancing sintering. Combining this with the sintering window provided by the 13-93 composition allowing viscous flow without crystallisation during sintering, leads to the formation of dense struts with limited distortion of the foams morphology.
\nTable 1 summarises the variety of glass and glass ceramics that have been produced via this method; as shown there are large differences between the properties obtained but it highlights the flexibility of the processing method. A limitation of the foam replica process is that excess slurry can become trapped inside the sacrificial polymer foam after infiltration, which can be difficult to remove prior to burnout and sintering. It has to be squeezed out and if excess slurry remains, the structure produced will be heterogeneous with a porosity gradient being formed. Even with optimum processing, the foam replica method can leave struts with hollow centres which reduce the mechanical properties and performance of the scaffolds [14].
\nComposition name | \nComposition used/mol % | \nPore size/μm | \nPorosity/% | \nCompressive strength/MPa | \nReported bioactivity | \n
---|---|---|---|---|---|
Glass-ceramics | \n|||||
CEL2 [17] | \n45% SiO2, 3% P2O5, 26% CaO, 7% MgO, 15% Na2O, 4% K2O | \n100–300 | \n75 | \n1 ± 0.4 | \nHA reported after 1 week | \n
Borosilicate® [18] | \nP2O5–Na2O–CaO–SiO2 | \n200–500 | \n95 | \n0.06 ± 0.01 | \nHA reported after with 72 hours | \n
[19] | \n57SiO2–34CaO–6Na2O–3Al2O3 crystal formation: CaSiO3 | \nMean: 240 | \n56 ± 6 | \n18 | \nNot reported | \n
45S5 [12] | \nCrystallised phase: Na2Ca2Si3O9 | \n510–720 | \n89–92 | \n0.27–0.42 | \nHA reported after 3 days | \n
45S5 [20] | \nCrystallised phase: Na2Ca2Si3O9 | \nNot reported | \n90 | \n0.4 | \nNot tested | \n
45S5 [21] | \nNa6Ca3Si6O18 and Na2Ca4(PO4)2SiO4 | \n25–600 | \n61 ± 3 | \n13.78 ± 2.43 | \nHA reported after 7 days | \n
Glass | \n|||||
Zn-doped borosilicate [22] | \n6Na2O, 8K2O, 8MgO, 22CaO, 36B2O3, 18SiO2, 2P2O5; Zn substitution at 1.5, 5 and 10 wt.% ZnO | \n200–400 | \n80–92 ± 7 | \nNot reported | \nHA reported after 90 days,8 weeks in a rat calvarial defects, glass doped with 5% Zn enhanced bone formation | \n
13-93 doped with copper [23] | \n6Na2O, 8K2O, 8MgO, 22CaO, 36B2O3, 18SiO2, and 2P2O3 (mol%) Copper doping at 0, 1 and 3 wt.% | \n100–300 | \n85 ± 3 | \nNot reported | \nHA reported after 90 days | \n
13-93 doped with cobalt [14] | \nwt.%: 53SiO2, 6Na2O, 12K2O, 5MgO, 20CaO, and 4P2O5 Cobalt doping at 0 wt.%, 1 wt.% and 5 wt.% CoO | \n200–400 | \n89–91 | \n2.3–4.2 | \nHA reported after 3 days | \n
13-93 [13] | \n53SiO2, 6Na2O, 12K2O, 5MgO, CaO, 4P2O5 wt.% | \n100–500 | \n85 ± 2 | \n11 ± 1 | \nWithin 7 days | \n
13-93B1 [24] | \n6% Na2O, 8% K2O, 8% MgO, 22% CaO, 18% B2O3, 36% SiO2, 2% P2O5 | \nMean 500 | \n78 | \n5.1 ± 1.7 | \nHCA within 30 days, to non critical osseous defect model in a rabbit, one in the femoral head, one in radius bone supported regrowth | \n
[25] | \n22 CaO, 6 Na2O, 8 MgO, 8 K2O, 18 SiO2, 36 B2O3, and 2 P2O5 | \n250–500 | \n72 ± 3 | \n6.4 ± 0.1 | \nHA reported after 7 days | \n
Summary of the glass and glass-ceramic scaffolds reported in literature produced via the foam replica method.
Sepulveda and Binner [15] first used gel-cast foaming to create porous ceramics. Rather than using a foam template, as used within the foam replica process, the ceramic slurry was foamed under vigorous agitation with the aid of a surfactant. The process used in-situ polymerisation of an organic monomer, such as methacrylamide, to form a gel and stabilise the foam. The polymer was then burnt out during the sintering cycle. Wu et al. [16] adapted this gel-casting process to manufacture scaffolds using the composition ICIE16 (49.46% SiO2, 36.27% CaO, 6.6% Na2O, 1.07% P2O5 and 6.6% K2O, in mol%). The process was based upon in situ polymerisation of acrylamide by using a cross-linker, surfactant and initiator. Although this alternative processing method avoided the ‘hollow strut’ issues associated with the foam replica process it was limited in its ability to be scaled up to higher volume manufacture due to the small gelation window of the polymer used, it was also shown to precipitate sulphur rich crystals upon the glass surface. The scaffolds produced by Wu et al. [16] had porosities of 79%, with modal pore diameters of 379 μm and compressive strength of 1.9 MPa. These values were a factor of 10 lower than those reported by Fu et al. for foam replica scaffolds manufactured from 13-93 [13].
\nThe gel-casting process was later adapted by Nommeots-Nomm et al. by using the thermally controlled gelation of gelatin to increase the processability of the system and stop unwanted sulphur byproducts. Amorphous scaffolds with foam morphologies were produced with porosities of 75% with modal pore interconnects between 100 and 150 μm. Scaffolds were produced from three glass compositions ICIE16, PSrBG (44.5 SiO2, 17.8 CaO, 4 Na2O, 4.5 P2O5, 4 K2O, 7.5 MgO and 17.8 SrO mol%) and 13-93 with compressive strengths of 3.4 ± 0.3, 8.4 ± 0.8 and 15.3 ± 1.8 MPa respectively, higher than values presented in literature for equivalent foamed scaffolds.
This process has also been adapted for the production of glass ceramics and more recently glass ceramics from pre-ceramic polymers. Fiocco et al. used pre-ceramic polymers to produce wollastonite diopside scaffolds with 77% open porosity and compressive strengths of 1.8 ± 0.3 MPa [27].
\nSelective laser sintering (SLS) is a layer-by-layer additive manufacture technique capable of manufacturing green bodies. Glass particles are most commonly mixed with a thermoplastic binder after which, a laser locally heats the areas of interest creating a layered green body, the powder bed then drops down and another layer of particulate is dispersed and then selectively bound. Unbound particles are removed and the green body is sintered using a two stage process to remove the binder and merge the particles together. As with most powder based 3D printing technique, its advantages are that complex or challenging geometries can be manufactured. However, it is limited by the accuracy of the laser, the size of construct that can be produced, the detail of the features that can be formed, and the ability to completely burn out the binder without leaving residual porosity [28].
\nOne study utilising SLS by Velez et al. reports scaffolds of 13-93 glass, with particles of sizes up to 75 μm, using stearic acid as a binding agent. The scaffold with 50% porosity had strengths of 40 ± 10 MPa post-sintering [29]. Work by Kolan et al. [28] reported mechanical properties within the same range as Velez et al. [29] of 41 MPa for 50% porosity. Their work looked at optimising the process by reducing the binder concentration and particle size, and increasing the laser power to increase processing speed. However, the time to produce scaffolds compared with competing 3D printing techniques, such as direct ink writing was still much longer.
\nStereolithography is a slurry-based 3D printing technique; a bed is flooded with a homogenous dispersed slurry of particles containing a photocurable polymer. A laser is then used to cure the polymer locally to build a layer of the desired design. The bed is then dropped down and flood again with the slurry, and a second layer is cured into place. The stereolithography process offers the freedom to design and fabricate very complex shapes, but again as with selective laser sintering the processing times are slow.
\n45S5 glass-ceramic scaffolds have been successfully printed into a variety of pore design and geometries [30]. They found that, for a diamond-like structure, reducing the pore size from 700 to 400 μm while maintaining the same overall porosity (~60 vol%) increased the mechanical strength from 3.5 to 6.7 MPa respectively.
\nRobocasting is another ‘3D printing’ method being used to manufacture porous scaffolds from bioactive glasses. Originally developed in 1998 by Cesarano et al., it can be described as a solution based extrusion process controlled by computer aided design [31]. The robocasting technique relies on the formulation of glass loaded inks which can be extruded through fine diameter nozzles. An example of the scaffolds produced is shown in Figure 1. The first development of this technique relied on manipulating the interparticle forces within particle loaded suspensions to create inks with the correct rheological properties for printing [31]. Now binder ‘inks’ are formulated with the correct rheological properties to act as a carrier of the particles which bind them together prior to sintering. An ideal ink would be easy to mix, allow for high glass powder loadings while maintaining a printable viscosity, have pseudo-plastic rheological properties, and yield strength and storage modulus high enough to be able to withstand the weight of multiple layers of scaffolds and the spanning distance.
\nAn example of robocast scaffolds produced from ICIE16 bioactive glass (authors own).
Robocasting is the most commonly used 3D printing technique for bioactive glasses. This is for a number of reasons: the speed of fabrication; the ease at which inks can be produced; and the capability and accessibility of the machines. This enables the printing of inks with high glass loading, which produce scaffolds with low strut porosity, enhancing their mechanical properties.
\nThe first robocasting paper published from a bioactive glass was by Fu et al. using 13-93 glass and Pluronic F-127 surfactant as a carrier ink [32]. Pluronic F-127 is a block co-polymer surfactant with thermally reversing rheological behaviour, made up of poly(ethylene oxide)-poly(propylene oxide)-poly(ethyleneoxide) tri-blocks (PEO-PPO-PEO) (HO(C2H4O)a(C3H6O)b(C2H4O)c). Pluronic F-127 can be dissolved in water, forming a stable suspension via steric repulsion of the –OH groups [33–35]. Due to its thermally reversible properties it enables easy mixing of glass particle at low temperatures while enabling the formation of high modulus, and high stiffness pseudoplastic inks at room temperature. Since Fu’s initial work, groups have worked with a variety of different glass and binder chemistries, summarised in Table 2.
\nGlass used | \nMax glass loading/vol % | \nInk chemistry and (dispersant) | \nStrut size/μm | \nPore size/μm | \nPorosity/% | \nCompressive strengths/MPa | \n
---|---|---|---|---|---|---|
6P53B [32] | \n30 | \nF-127 (water) | \n100 | \n500 | \n60 | \n136 ± 22 | \n
13-93B3 13-93 [38] | \n45 | \nEthyl cellulose/PEG (ethanol) | \n300 ± 20 | \n420 ± 30 | \n48 ± 3 | \n65 ± 11 142 ± 20 | \n
13-93 [39] | \n40 | \nF-127 (water) | \n330 | \n300 | \n47 | \n86.9 ± 9 | \n
45S5 [40, 41]* | \n45 | \nCarboxymethyl cellulose (water) | \n250–300** | \nNot available | \n63 ± 3 | \n13 ± 1 | \n
Summary of current literature on scaffolds produced via direct ink writing.
Not amorphous post sintering.
Values not reported, therefore, measured using imageJ from the published SEM images available.
The homogeneity of the ink, particle packing, sintering process, strut size and spacing all contribute to the scaffolds overall mechanical properties. Due to the periodically arrange structure the strengths achieved are substantially higher than other scaffold processing methods, offering strengths in the range of cortical bone instead of cancellous [36].
\nGlass-ceramic scaffolds have also been produced via this technique. Roohani-Esfahani et al. produced scaffolds of various designs from a heat treated sol-gel Sr doped Ca2ZnSi2O7 (HT) composition. They reported high strengths in excess of 100 MPa with high fatigue and crack resistance created by the multiphase composition [37].
\nOne point, that all scaffold processing technique have in common, is the necessity for a sintering step. Sintering is a thermally induced phenomenon where, initially, the particles will undergo viscous flow. Viscous flow will ultimately lead to reorientation of the glass particles and neck growth. At a later stage, the contact between particles will grow and the pores will shrink resulting in a dense body where, usually, some closed pores will become trapped. Trapped pores are characteristically in the sub-micron range. However, in the case of glass and more particularly bioactive glasses, the heating process may induce crystallization.
\nThe crystallization of the two most used and FDA approved glass, i.e. 45S5 and S53P4, has been studied in details by Massera et al. [42]. In this study, the activation energy for viscous flow as well as the activation energy for crystallization was quantify for fine (<45 μm) and coarse (300–500 μm) glass particles. As expected, the activation energy for viscous flow was independent of the glass particle size and ranged between 750 and 800 kJ/mol. On the other hand, the activation energy (Ec) for crystallization was found to be constant with respect to glass particles size, for the glass S53P4 with a value around 300 kJ/mol. In the case of the glass 45S5, Ec was found to decrease, from 338 to 230 kJ/mol, with increasing particles size. This is typically an indication of a change in the crystallization dimensionality with respect to the crystal size. The Jonhson-Mehl-Avrami exponent, which gives an indication of the dimensionality of the primary crystal phase, was calculated. While a value of ~1 was constantly derived for the glass S53P4, independently of the technique used (Augis and Bennett equation, Ozawa and isochronal method), the value was found to change from 0.8 to 2.8 when using the Augis and Bennett equation. Not only the ‘n’ exponent was found to change as a function of particles size but it also varied depending on the method employed. Such variation in the JMA exponent calls for questioning the Johnson-Mehl-Avrami crystallization model. The JMA model validity was tested using the methods proposed by Malek and Mitsuhashi [43]. While the JMA model was validated for the glass S53P4, the JMA model was found to be unsuitable to the crystallization of glass 45S5. Overall, both glass S53P4 and 45S5 were found to be fragile glass, i.e. a small change in temperature leads to a significant change in viscosity. The activation energy for viscous flow is high indicating that sintering or fibre drawing at moderate temperature will be virtually impossible. Crystallization is surface initiated (n ~ 1) for the glass S53P4. Figure 2a presents a SEM image of the glass surface after a heat treatment at 730°C for 2 hours and Figure 2b presents the crystallized layer thickness as a function of heat treatment time.
\nSEM image of a glass S53P4 heat treated for 2 hours at 730°C (a) and layer thickness as a function of heat treatment time at 730°C (b) (authors own).
As shown in the SEM image the crystallization initiates at the glass surface with a growth rate of about 3.5 μm/min. Such crystallization kinetic will prevent proper sintering of the glass particles. Furthermore, one should keep in mind that during scaffolds processing, it is generally accepted, that small particles size should be used. Decreasing the particles size leads in an increase in the surface area and therefore an increase in nucleation sites. Therefore, this glass may not be suited for the sintering of amorphous scaffolds.
\nThe crystallization of the glass 45S5, described in [42] seemed to be initiated within the bulk. However, it appears that the glass becomes phase separated, with one amorphous phase crystallizing at lower temperatures than the secondary phase. Upon increasing the duration of the heat treatment the crystals grew via surface controlled crystallization thereby the elements of the secondary phase, at the interface with the crystals, ‘feeds’ the crystal. The formation of large pores was also evident during sintering of this glass composition.
\nThe kinetics driving the crystallization of the two most known and clinically used bioactive glasses does not permit complete sintering of scaffolds without formation of crystallites.
\nThe impact of crystallization on the bioactivity or, more precisely, on the ability of the glass to precipitate a HA layer, has been first studied by Peitl Filho et al. [44]. Their conclusion was that below 60% crystallinity the ability of the glass 45S5 to precipitate a reactive layer was not impaired whereas above 60% crystallinity the reactive layer precipitated at a slower rate. This was then confirmed with glass S53P4 by Fagerlund et al. [45]. They demonstrated that when the glass particles were heat treated at temperature to maintain the glass fully amorphous a clear formation of Si-rich layer, a mixed layer and a Ca–P with a Ca/P = 1.6–1.7 was formed. When the glass started to crystallize, the precipitated reactive layer was much thinner and disappeared with an increase in heat treatment temperature. Interestingly, at temperature above 750°C a secondary crystal phase was formed. Upon immersion in simulated body fluid the primary crystal phase, belonging to the combeite composition dissolved, leading to the formation of thick mixed-layer. However, no Ca–P reactive layer precipitated at the surface of the particles. Furthermore, the secondary phase was found insoluble in simulated body fluid. Therefore, it can be concluded that while the bioactivity is not fully suppressed in this silicate-bioactive glasses a clear decease in the ability of the glass to form a HA layer was greatly slowed down. One should keep in mind that the precipitation of such layer is only a small contribution of the glass towards the bioactivity and, as such, is not sufficient to make firm conclusion regarding the bioactivity of the materials
Other well-known and promising bioactive glasses for bone regeneration belongs to the phosphate composition. Ahmed et al. [46] Neel et al. [47], as well as Massera et al. [48–50], have developed phosphate glass composition that not only can promote cell attachment and proliferation but that can also be shaped into fibres. Nevertheless, a thorough understanding of the glass crystallization is necessary in order to understand the possibilities and limitations of these glasses. Massera et al., developed a glass within the 50P2O5–(40–x)CaO–xSrO–10Na2O that can promote the activity of human gingival fibroblasts [49]. The crystallization kinetics of these glasses along with the
SEM micrograph of glass with composition 50P2O5–20CaO–20SrO–10Na2O heat treated at 40°C below the crystallization temperature Tp (from DTA) for 30 min and immersed for 72 hours in simulated body fluid (reproduced from Massera et al. [
It appears clear on the SEM micrographs that the precipitation of the reactive layer is not suppressed. However, the reactive layer is only visible at the amorphous surface. This indicates that fully crystallized phosphate glasses will not support the precipitation of reactive layer.
\nA fully crystallized phosphate glass (50P2O5–40CaO–10Na2O) was also immersed in simulated body fluids. No reactive layer could be detected at the surface of the glass particles. The phosphate and calcium ions released within the solution were quantified by ICP and are presented in Figure 4.
\n[P] (a) and [Ca] (b) concentration in the simulated body fluid when the glass and the corresponding crystallized are immersed for various times (authors own).
As expected the amorphous glass released phosphate ions and consume the calcium. This is attributed to the congruent dissolution of the phosphate glass and subsequent precipitation of a calcium phosphate reactive layer with a Ca/P ratio of 1. The crystallized glass, however, released a greater amount of P whereas the Ca remained constant within the accuracy of the measurements. From XRD the fully crystallized glass is composed of NaCa(PO3)3 crystals and Ca(PO3)2. The NaCa(PO3)3 crystals which is the primary crystal phase is more soluble than the secondary phase. The large release of phosphorus ions leads to a drastic decrease in the pH, which suppress the precipitation of the reactive layer [50].
\nTherefore, one can say that the impact of crystallization on the
Alternative composition, which can be processed into amorphous porous scaffolds, are available. One example, among others, is the glass 13-93 [51]. This glass has been found to be bioactive and to have a wide hot forming window and a viscosity/temperature relationship enabling sintering prior to the crystallization. More recently, another family of glass composition which is gaining interest are borosilicate. Fu et al., taken as an example, processed 13-93 glass composition were the SiO2 was partially to fully replaced by B2O3 [52]. They demonstrated that the precipitation of the hydroxyapatite was accelerated with the presence of boron. However, the cell proliferation,
The current need for an off the shelf bone repair product is evident, and due to the current ageing demographic that need is growing. Literature presents a wide variety of bioactive glass and glass-ceramic compositions with tailored bioactivity and therapeutic effects suitable for bone repair. A huge wealth of different scaffold processing methods have been employed in the last 10 years, offering different morphologies, porosities and mechanical strengths. Previously these materials have been limited by their mechanical strength - porosity relationships. However, since 2011, with the growth of 3D printing, scaffolds with compressive strengths in the range of cortical bone have now been developed.
\nThe common point of all scaffolds processing technique is the need for a sintering step at medium to elevated temperature. Sintering of bioactive glass is known to often lead to glass crystallization. Understanding the relationship between crystallization and bioactivity of bioactive glasses is of paramount importance. The available results demonstrate that the impact of the crystallization can have various effect on bioactivity depending upon the glass composition in question. While partial to full crystallization of the most known and widely used silicate bioactive glasses (S53P4 and 45S5) leads to a decrease in the bioactivity. Metaphosphate bioactive glasses have been shown only to precipitate HA on remaining amorphous surfaces.
\nRegardless of the glass composition, partial to full crystallization leads to drastic change in the ions releasing rate and the dissolution mechanism. The dissolution behaviour of the crystallized phases is then different to that of the original glass. The crystallization of bioactive glasses is difficult to control, therefore leading to large variation from samples to sample disabling full prediction of the materials degradation.
\nThe impact of glass crystallization on the bioactivity is dependent upon the crystals composition, size and density. Therefore, a better understanding of the crystallization mechanism of these glasses may allow for predictable ion release and enhanced mechanical properties.
\nOrthodontic developments, especially during the last years, have been accompanied by a significant increase in the esthetic demands of the patients [1]. With the significant recent improvements in computer-aided design/computer-aid-ed manufacturing (CAD/CAM) and dental materials, there has been an increase in the demand for plastic systems [2]. Clear aligners provide an esthetic and comfortable treatment experience, facilitate oral hygiene, cause less pain as compared to fixed orthodontic appliances, and reduce the number and duration of appointments [3, 4, 5]. The aligner therapy also involves a lower incidence of demineralization, enamel abrasion, periodontal lesions, and mucosal irritations [6].
The concept of clear aligners was introduced by Kesling in 1946 with a tooth positioner fabricated by thermoplastic material molding technology and designed for minor tooth movements during the finishing stages of orthodontic treatment. In 1993, Sheridan and colleagues developed a technique of giving new clear retainers to the patient at each visit, incorporating interproximal reduction to provide the necessary space for tooth movement [3, 7]. With further advancement in orthodontic technology, Align Technology introduce the clear aligner treatment (CAT) rendering Kesling’s concept a feasible orthodontic treatment option [8]. A series of removable polyurethane aligners were introduced as an esthetic alternative to fixed labial appliances. Scanned images are converted to physical models by using different stereolithography (STL) techniques to fabricate a series of aligners that sequentially reposition the teeth. Each aligner is programmed to move a tooth or a small group of teeth 0.25–0.33 mm every 14 days [9, 10]. Align Technology provides orthodontists with ClinCheck (Align Technology Inc., Santa Clara, Calif) models, which reflect the treatment outcomes. The aligners incrementally shift the teeth into place based on the outcome the orthodontist expects to achieve [11].
The primary focus of the clear aligner system was initially to solve cases of low and moderate crowding and to close small spaces [1]. However, it has continually evolved through the development of new aligner materials, attachments on teeth, as well as new auxiliaries, such as “Precision Cuts” and “Power Ridges” to address a wider range of malocclusions and to enable additional treatment biomechanics [2, 5, 12].
Despite the available body of literature pertaining to aligner technology, only a few investigations have focused on the efficacy of clear aligner therapy in controlling orthodontic tooth movement. Furthermore, the stability after treatment has not been thoroughly investigated.
The purpose of this chapter was to update the knowledge of the available evidence about effectiveness and stability of clear aligners and to answer the following clinical research question: “Are clear aligners effective in controlling the orthodontic movement in non-growing subjects and what about stability of this treatment modality?”
A systematic search in the medical literature produced between January 2015 and January 2021 was performed to identify all peer-reviewed articles potentially relevant to the review’s question.
The following databases have been used: CENTRAL, MEDLINE, MEDLINE in Process, Embase and Cochrane Library databases.
The search strategy comprised use of the following terms: (invisalign OR clear aligners OR aligners OR transparent aligners) AND (effectiveness OR efficacy) AND (dental changes OR treatment outcome) AND (stability).
Additionally, a manual search was conducted in orthodontic journals of interest, such as The Angle Orthodontist, the American Journal of Orthodontics and the European Journal of Orthodontics. Title and abstract screening was performed to select articles for full text retrieval.
The following inclusion and exclusion criteria were used:
Study design: meta-analysis, systematic reviews, randomized and non-randomized clinical trials, prospective and retrospective studies were included.
Participants: non growing patients.
Intervention: articles that studied dental movement of cases treated with clear aligners.
Results: the efficacy of clear aligners in performing dental movements and the stability of treatment, superimposing virtual models or radiographs.
We excluded for our study articles older than 6 years, samples with growing patients, articles written in a language other than English, in-vitro studies, author opinions, letters to the editor, isolated cases, series of cases, surgical cases, or reports of patients with syndromes.
The grading system described by the Swedish Council on Technology Assessment in Health Care (SBU) [13] was used to assess the methodological quality and the level of evidence of the articles (Tables 1 and 2).
Grade A—high value of evidence |
All criteria should be met: |
Randomized clinical study or a prospective study with a well-defined control group |
Defined diagnosis and endpoints |
Diagnostic reliability tests and reproducibility tests described |
Blinded outcome assessment |
Grade B—moderate value of evidence |
All criteria should be met: |
Cohort study or retrospective case series with defined control or reference group |
Defined diagnosis and endpoints |
Diagnostic reliability tests and reproducibility tests described |
Grade C—low value of evidence |
One or more of the conditions below: |
Large attrition |
Unclear diagnosis and endpoints |
Poorly defined patient material |
Swedish Council on Technology Assessment in Health Care (SBU) criteria for grading assessed studies.
Level | Evidence | Definition |
---|---|---|
1 | Strong | At least two studies assessed with level “A” |
2 | Moderate | One study with level “A” and at least two studies with level “B” |
3 | Limited | At least two studies with level “B” |
4 | Inconclusive | Fewer than two studies with level “B” |
Definitions of evidence level.
The selection of articles included in this review is shown in the PRISMA flow chart (Figure 1). Study selection procedure was comprised of title-reading, abstract-reading, and full-text-reading stages. After exclusion of not eligible studies, the full report of publications considered eligible for inclusion by the authors was assessed. Eleven studies were included in the qualitative synthesis.
Flow chart according to the PRISMA statement.
Of the eleven included articles, there were five retrospective studies [6, 14, 15, 16, 17], two prospective studies [7, 11], two randomized controlled trials (RCT) [18, 19], two systematic reviews [2, 20] and one meta-analysis [20]. Most of the included studies evaluated mild to moderate malocclusions except for one [17] that involved first premolar extraction cases. The majority of studies used the Invisalign® system except two studies that used Nuvola® system [15] and F22 aligners [14].
Data collected from each of the included articles are described in Tables 3 and 4. Nine of the covered studies assessed predictability of tooth movements comparing post-treatment patient models to the predicted digital planned tooth movement models [2, 6, 7, 11, 14, 15, 16, 17, 18]. Two studies assessed the stability of the clear aligner therapy [19, 20].
Study | Study design | Participants | Intervention | Results |
---|---|---|---|---|
Buschang et al. 2015 [11] | Prospective clinical trial | 27pts |
|
|
Lombardo et al. 2017 [14] | Retrospective case series | 16 pts. F22 aligners |
|
|
Tepedino et al. 2018 [15] | Retrospective case series | 39 pts. First phase of treatment made of 12 aligners by Nuvola® aligner system |
|
|
Charalampakis et al. 2018 [16] | Retrospective case series | 20 pts. Class I patients treated with Invisalign and needed refinement |
|
|
Lopez et al. 2019 [2] | Systematic review | 20 studies |
|
|
Dai et al. 2019 [17] | Retrospective case series | 30 pts. First premolar extraction treatment with Invisalign |
|
|
Zhou et al. 2020 [7] | Prospective clinical trial | 20 pts. arch expansion with Invisalign aligners |
|
|
Al-Nadawi et al. 2020 [18] | Randomized clinical trial | 80 pts. three aligner wear protocols: 7 day, 10 day, and 14 day. |
|
|
Riede et al. 2021 [6] | Retrospective case series | 30 pts. Aligner treatment (Invisalign®) with the current material (SmartTrack®) |
|
|
Design, participants, type of intervention, and results of studies included in the qualitative analysis.
pts, patients; OGS, Objective Grading System; IPR, interproximal reduction; CBCT, Cone beam computed tomography.
Study | Study design | Participants | Intervention | Results |
---|---|---|---|---|
Zheng et al. 2017 [20] | Systematic review and meta-analysis |
| Scientific evidence |
|
Graf et al. 2021 [19] | Double-center trial | 33pts |
|
|
Studies assessing treatment stability of clear aligners.
pts, patients.
According to the SBU tool (Tables 1 and 2), among the selected studies, the methodological quality was low for four studies [6, 11, 16, 17], moderate for four others [7, 14, 15, 19] and high for one study [18] (Table 5). Thus, conclusions with a moderate level of evidence could be drawn from the review process.
Study (first author, year) | Evidence level |
---|---|
Buschang, 2015 [11] | C |
Lombardo, 2017 [14] | B |
Tepedino, 2018 [15] | B |
Charalampakis, 2018 [16] | C |
Dai, 2019 [17] | C |
Zhou, 2020 [7] | B |
Al-Nadawi, 2020 [18] | A |
Riede, 2021 [6] | C |
Graf, 2021 [19] | B |
Evidence grade according to Swedish Council on Technology Assessment in Health Care.
In this review, we aimed to provide data on the effectiveness and stability of treatment with clear aligners. The level of evidence was moderate as we identified one study with level «A» and four studies with level «B».
The effectiveness of clear aligners was judged by the predictability of tooth movement which varies with the type of tooth and the type of movement. Lopez et al. [2] found that the expression of the programmed movement was not fully accomplished with Invisalign®.
Concerning
Many studies showed that intrusion was the most unpredictable movement especially for the maxillary central and lateral incisors [16, 21]. Invisalign has a bite-block effect, because 2 aligners of 0.38-mm width are interposed between posterior teeth throughout treatment. Unexpected intrusion of the molars would cause the incisors to appear extruded on the posttreatment models after superimposition [16]. In fact, according to Grunheid et al. [22], mandibular incisors tend to be positioned more occlusally than predicted. The bite-block effect may make open bites easier to treat with Invisalign [16].
Concerning
Molar distalization was recorded as the highest accuracy with no need for attachments. Simon et al. [25] also reported a high accuracy (88%) of the bodily movement of upper molars when a distalization movement of at least 1.5 mm was prescribed.
Several studies agreed that derotation of rounded teeth especially canines was difficult to achieve with aligners [16, 22, 26]. An amount of rotation greater than 15° has been identified as a risk factor for decreased accuracy for rotational prediction [25]. Interproximal contacts of rotated canines might also be considered a significant predictor for the diminished efficacy of tooth movement, especially in the absence of interproximal reduction of the enamel (IPR) [26]. The direction of derotation has been also documented to influence the accuracy of the maxillary canine, with distal movement demonstrating less accuracy than mesial [21]. This is possibly due to the actual contact area between canine and premolar and the potential challenges of providing enamel reduction in this area.
It has been recommended to plan overcorrections, especially if rotations exceed 15°, to use attachments, and to reduce staging to less than 1.5° per aligner [8, 16, 25]. However, although various types or shapes of attachment grips or practices of interproximal enamel reduction have been reported as potential prognostic factors for better efficacy of rotational tooth movement, this does not necessarily translate into an identified substantial effect in practice [26].
Concerning
According to Lopez and al. [2], Invisalign® was also able to alter intercanine, interpremolar, and intermolar width in the presence of crowding. Kravitz et al. [23] recommended to treat cases with severe lower crowding mostly by interproximal reduction (IPR) instead of dentoalveolar expansion. This recommendation comes from the finding that retraction is more accurate than dentoalveolar expansion of the lower anterior teeth. The expansion of the mandibular intercanine width also poses the greatest risk of relapse following treatment [29].
Concerning the effectiveness of the occlusal contacts with clear aligners, the study by Izhar et al. [10] found that the software models do not accurately reflect the patient’s final occlusion immediately at the end of active treatment. Kassas et al. [30] also stated that clear aligners were not sufficient for providing ideal occlusal contacts. The deterioration in occlusal contacts was caused by the thickness of aligners, which interferes with the settling of the occlusal plane.
As far as the malocclusion type is concerned, the study by Graf et al. [19] showed that Invisalign® treatments are able to significantly reduce malocclusions in adult patients. The study found that all types of sagittal malocclusion (class I, class II, and class III) were ‘greatly improved’ with a rate of 77.44%. Graf and al. [19] also concluded that conventional attachments and the combination with optimized attachments equally led to treatment effectiveness regarding the total PAR score reduction with equally achieved effectiveness in mild, moderate, and rather severe cases. However, for Class II malocclusion, Patterson et al. [31] reported that there was no significant Class II correction or overjet reduction with elastics for an average of 7-month duration in the adult population. Additional refinements may be necessary to address problems created during treatment mainly posterior open bite.
One study of our review by Dai et al. [17] assessed the effectiveness of Invisalign in first premolar extraction treatment. According to this study, first molar anchorage control and central incisor retraction were not fully achieved as predicted. Only medium anchorage control was achieved as the first molars actually moved mesially. The G6-optimized attachment showed similar control in first molar angulation and mesiodistal translation as did 3- and 5-mm horizontal rectangular attachments. On the other hand, setting a distal tipping of 6.6 mm on the first molars might help clinically maintain the tooth angulation, leading to bodily tooth movement. According to the same study [17], the incisors inclined lingually under the retraction force. Accordingly, the use of power ridges or attachments as well as overcorrection by setting greater buccal crown inclination during the virtual setup should be considered to achieve optimal incisor torque control.
Current evidence does not support the clinical use of aligners as a treatment modality that is equally effective to the gold standard of braces [32]. However, clear aligners have advantage in segmented movement of teeth and shortened treatment duration, but are not as effective as braces in producing adequate occlusal contacts, controlling teeth torque, and retention [5, 33].
Many variables influence the accuracy of dental movements, but very few studies have analyzed these parameters in treatments with clear aligners. According to Tepedino et al. [15], several factors determine successful tooth movement such as the attachment’s shape and position, the aligner’s material and thickness, the amount of activation present in each aligner, and the techniques used for the production of the aligners. Treatment outcomes depend also on the patient’s characteristics, bone density and morphology, crown and root morphology of the teeth, as well as on factors related to the clinician. Orthodontists have to incorporate their expert knowledge in determining proper sequencing of tooth movements, tooth attachment design and placement, and prescribing overcorrection when needed for difficult tooth movements to increase efficiency and achieve better treatment outcomes [22, 34]. Patient compliance is also mandatory to achieve good results by wearing the aligners 22 hours a day or more [28].
One study from this review with a high level of evidence [18] evaluated the impact of wear protocol on the accuracy of clear aligners. It has concluded that fourteen-day changes were statistically significantly more accurate in some posterior movements mainly maxillary intrusion, distal-crown tip and buccal-crown torque, and in mandibular intrusion and extrusion.
As in all types of orthodontic treatment, stability is one of the most important issues to discuss regarding clear aligners. According to the systematic review by Zheng et al. [20], only one study compared the post-retention dental changes between patients treated with Invisalign and those treated with conventional fixed appliances. They found that the change in the total alignment score in the Invisalign group was significantly larger than that for the Braces group. There were significantly larger changes in maxillary anterior alignment in the Invisalign group than in the conventional bracket group. Tamer et al. [5] also reported that maxillary anterior leveling relapsed in the Invisalign group. On average, the posttreatment models lost twice as many points for alignment than the respective ClinCheck models. In other words, a full finishing phase of treatment may be needed to achieve the results indicated in the ClinCheck model [11].
The type and degree of tooth movement, the duration of active treatment and the retention protocol are among major influencing factors of posttreatment stability and relapse. The study by Graf et al. [19] is the first one to assess the stability of clear aligners outcome throughout a retention period of 10 months. The retention protocol involved a mandibular multistrand fixed retainer (0.0155 inch; stainless steel, 24 K gold plated) bonded on each lingual surface from canine to canine and a removable modified Hawley retainer for the upper arch (with mandatory Adams clasps on first molars). The study showed that the treatment outcome can be stable throughout this retention protocol. It has also concluded that treating patients with respect to their physiological boundaries and maintaining their original arch form would be key to treatment stability. Overexpansion of the dental arch, especially in the lower arch and in adult patients, is a potential risk for stable results.
There is current evidence with a moderate level of certainty regarding the effectiveness of clear aligner therapy for certain tooth movements. Clear aligners can safely straighten dental arches in terms of leveling and derotating the teeth, except for canines and premolars. The crown tipping can be easily performed. However, important limitations include arch expansion through bodily tooth movements, extraction space closure, corrections of occlusal contacts, and larger antero-posterior and vertical discrepancies. The use of additional attachments might be more effective for various types of movement, such as bodily expansion of the maxillary posterior teeth, canine and premolar rotational movements, incisors torque control and extrusion of maxillary incisors. Overcorrections might also improve the effectiveness of orthodontic movement. However, overcorrections are not as simple for all movements and need to be made on a case-by-case basis depending on the goal of treatment.
Studies on effectiveness of clear aligners had methodological heterogeneity as they assessed predictability of different types of tooth movements for different teeth by using different materials like Invisalign, F22 aligner and Nuvola system. Retention and stability studies regarding aligners also remain limited in the literature. Therefore, further well-designed and reported researches are required on this subject.
Special thanks to the department of Orthodontics of the Faculty of the dentistry of the University Hassan II of Casablanca. We would also like to acknowledge the support of Professor Farid Bourzgui for the realization of this work and for sharing and discussing the initial idea of the project.
The authors declare no conflict of interest.
IntechOpen aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. We uphold a flexible Copyright Policy, guaranteeing that there is no transfer of copyright to the publisher and Authors retain exclusive copyright to their Work.
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\\n\\nWaiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
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\\n\\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
\\n\\nGoverning law: This Publication Agreement and any dispute or claim, including non-contractual disputes or claims arising out of, or in connection with it, or its subject matter or formation, shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of, or in connection with, this Publication Agreement, including any non-contractual disputes or claims.
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\n\nCORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\nSubject to the following Article, the Author grants to IntechOpen, during the full term of copyright, and any extensions or renewals of that term, the following:
\n\nThe foregoing licenses shall survive the expiry or termination of this Publication Agreement for any reason.
\n\nThe Author, on his or her own behalf and on behalf of any of the Co-Authors, reserves the following rights in the Work but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Work as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Author, and any Co-Author, confirms that they are, and will remain, a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Work and all versions of it created during IntechOpen's editing process, including all published versions, is retained by the Author and any Co-Authors.
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\n\nAll rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the specific approval of the Author or Co-Authors.
\n\nThe Author, on his/her own behalf and on behalf of the Co-Authors, will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Work as a consequence of IntechOpen's changes to the Work arising from the translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits as determined by IntechOpen.
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\n\nSeverance: If any provision, or part-provision, of this Publication Agreement is, or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted. Any modification to, or deletion of, a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\nNo partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Author or any Co-Author, nor authorize any party to make or enter into any commitments for, or on behalf of, any other party.
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\n\nPolicy last updated: 2018-09-11
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Besides UV radiation exposure, extrinsic factors including tobacco smoking, exposure to environmental pollutants, infrared radiation, and heat contribute to premature skin aging. Like UV radiation, these factors cause ROS formation and increase expression of MMPs, thus accelerating skin aging by inducing extracellular matrix (ECM) degradation. Accumulated collagen fibrils inhibit the new collagen synthesis and account for the further degradation of the ECM through this positive feedback loop. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a scientist and Principal Investigator at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering the lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"1",type:"subseries",title:"Oral Health",keywords:"Oral Health, Dental Care, Diagnosis, Diagnostic Imaging, Early Diagnosis, Oral Cancer, Conservative Treatment, Epidemiology, Comprehensive Dental Care, Complementary Therapies, Holistic Health",scope:"\r\n\tThis topic aims to provide a comprehensive overview of the latest trends in Oral Health based on recent scientific evidence. Subjects will include an overview of oral diseases and infections, systemic diseases affecting the oral cavity, prevention, diagnosis, treatment, epidemiology, as well as current clinical recommendations for the management of oral, dental, and periodontal diseases.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/1.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11397,editor:{id:"173955",title:"Prof.",name:"Sandra",middleName:null,surname:"Marinho",slug:"sandra-marinho",fullName:"Sandra Marinho",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGYMQA4/Profile_Picture_2022-06-01T13:22:41.png",biography:"Dr. Sandra A. Marinho is an Associate Professor and Brazilian researcher at the State University of Paraíba (Universidade Estadual da Paraíba- UEPB), Campus VIII, located in Araruna, state of Paraíba since 2011. She holds a degree in Dentistry from the Federal University of Alfenas (UNIFAL), while her specialization and professional improvement in Stomatology took place at Hospital Heliopolis (São Paulo, SP). Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). 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