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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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\r\n\tIn general, dehydration is defined as a process of water loss. More specifically, dehydration is a heterogeneous physicochemical process that leads to a decrease in water molecules concentration in some material, and more specifically at the surface of solid material. Dehydration is a reversible, endothermal reaction that happens at the interface of interaction. The most striking property of dehydration is the active involvement of intermediate products in the process of water removal. Dehydration has enormous practical and theoretical significance in various fields, from bio-medical and environmental to materials and physicochemical sciences. Despite that, and the existence of numerous literature data concerning dehydration, which is most frequently described as drying, dehydration is not enough systematically investigated. The critical overview of the available literature data reveals that the main field in up-to-date investigations of dehydration are the following: novel theoretical models of the mechanism of the dehydration process and models developed for describing the kinetics of the dehydration process, non-equilibrium thermodynamics features of the dehydration process, dehydration assisted with different external fields and their effects on the process and kinetics of the dehydration, the effects of the phase-state of adsorbed water on the processes and kinetics of the dehydration, phase, and structural changes in adsorption materials during dehydration and dehydration of specific groups of materials, such as inorganic oxides, crystals- hydrates, zeolites, silicates and clays, polysaccharides, amino acids, peptides, composites, nanocomposites, polymers, hydrogels, aerogels, foods and food products, fruits, vegetables, meats, and biological materials ( tissues, algae, mushrooms, etc.), pharmaceuticals, etc. It is worth mentioning that dehydration of hydrogels, as a specific class of materials, gets more important in the last decade. The proposed book aims to give a comprehensive overview of the up-to-date state-of-the-art in the most relevant topics in dehydration with special emphasis on novel materials and novel methods in mathematical modeling of dehydration’s kinetics, but not limited to them. The author’s contributions in the highlighted potential of novel findings in dehydration processes and their miscellaneous application will be acknowledged.
",isbn:"978-1-83768-141-9",printIsbn:"978-1-83768-140-2",pdfIsbn:"978-1-83768-142-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"91d7853d4e74d161d7a8f5913626cf94",bookSignature:"Ph.D. Jelena Jovanovic",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11563.jpg",keywords:"Mechanism of Dehydration, Phase State, Phase Transformations, Kinetics, Dehydration Isotherms, Enthalpy, Gibb’s Free Energy, Activation Energy, Inorganic Materials, Natural Materials, Composites, Hydrogels",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 24th 2022",dateEndSecondStepPublish:"June 21st 2022",dateEndThirdStepPublish:"August 20th 2022",dateEndFourthStepPublish:"November 8th 2022",dateEndFifthStepPublish:"January 7th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Experienced researcher in smart materials, polymers, hydrogels, synthesis, and kinetics, with a BS and MS, focused in Organic Chemistry and Polymers from the Faculty of Technology and Metallurgy, University of Belgrade and a high h index (27).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"447810",title:"Ph.D.",name:"Jelena",middleName:null,surname:"Jovanovic",slug:"jelena-jovanovic",fullName:"Jelena Jovanovic",profilePictureURL:"https://mts.intechopen.com/storage/users/447810/images/system/447810.jpg",biography:"Dr. J. Jovanovic is a research professor at the Institute of General and Physical Chemistry (IOFH) in Belgrade, R. Serbia, as since 2019 and previously she was employed at the University of Belgrade, Faculty of Physical Chemistry during 2005-2019 The main academic and scientific career of Dr. J. Jovanovic is extensive and covers several areas: advanced and smart materials, polymers, polymer composites, carbon composite materials, hydrogels. Synthesis with special emphasis on non-conventional synthesis, e.g. under microwaves, ultrasonic, or cavitation. Green chemistry synthesis and physicochemical processes. Synthesis of various types of hydrogels both under conventional and unconventional conditions. She works extensively on the investigation of the effects of different fields on the reaction kinetics of chemical and physicochemical processes. Hydrogel swelling properties and kinetics, dehydration kinetics, and drug-delivery kinetics using up-to-date and novel methods are extensively involved. The isothermal and non-isothermal kinetics analyses of various physicochemical processes and chemical reactions (adsorption, polymerization, extraction, dehydration). Dr. J. Jovanovic worked on the development of new physicochemical processes and examination of the phase state of sorbent matter.",institutionString:"University of Belgrade",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Belgrade",institutionURL:null,country:{name:"Serbia"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"8",title:"Chemistry",slug:"chemistry"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"478200",firstName:"Dominik",lastName:"Samardzija",middleName:null,title:"Mr.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"dominik@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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Among them, one of the most challenging issues is to visualize optical-related phenomena such as reflection and refraction. Although ray tracing is the most powerful method, it takes huge amount of time to trace the ray that has emitted from a light source and reaches the eye through each pixel of an image. The method searches the trace by dividing it to two phenomena: reflection and refraction. It generates the image with a recursive process so that the image can be generated with a simple algorithm. However, the image generated on a glass by reflection and refraction is so complicated that we cannot understand which part of the image is generated by reflection and/or refraction.
Then, this chapter describes an analytical method that draws an image generated on a geometrically defined object such as parallel glass, cubed glass, or cylindrical glass by reflection and/or refraction. The method analyzes the trace of the ray in a transparent object and generates a virtual object, which is constructed with vertices translated from original ones by considering reflection and refraction. In addition, the mechanism of total reflection and the attenuation of light power are also investigated. Thereafter, each image with reflection and/or refraction is generated by rendering the virtual object without considering reflection and refraction. Then, the final image is generated by combining every image drawn separately with the virtual objects.
Moreover, two types of applications with the proposed method are presented. One is to generate the image with reflection and refraction on a cubed glass, where there are six facets that have different number of reflection and refraction, and also total reflection happens on some facets depending on the eye position. The other is to represent a refractive image on a cylindrical glass, where four refractions happen when the light passes in the interior of the cylindrical glass.
At last, in order to demonstrate that the images generated with the proposed method are realistic, the simulation images are compared with real photos. One is the image that has reflection and refraction on a cubed glass, and the other is one that has refraction on a cylindrical glass.
In generation of realistic images with computer graphics, Whitted invented ray tracing [1, 2], which is the most simple and powerful method; however, it requires a lot of time to trace the ray for every pixel of the image. Then, Heckbert et al. proposed beam tracing [3] and Amanatides suggested cone tracing [4]. These methods are faster than ray tracing because they trace the ray not for each pixel but for the bundle of it by utilizing spatial coherence. On the other hand, Blinn et al. had invented texture mapping [5] to generate realistic images with a simple and fast method. Then, Pauline et al. used texture mapping to represent waves [6], and Hakura et al. proposed parameterized environment mapping [7], which is an extended method of texture mapping and reproduces local reflection from pre-rendered viewpoints. Texture mapping can create realistic images in real time since some pre-generated texture images are used in the rendering; however, multiple images must be prepared especially when the viewpoint changes. Then, G’enevaux et al. suggested another method to obtain realistic and interactive effect of refraction [8].
On the other hand, Ofek et al. had proposed a method to generate reflective images by using virtual objects that are previously transformed from the original ones [9]. Conversely, Iwasaki et al. used texture mapping to render caustics on water surfaces [10]. Wang et al. also utilized environment mapping and interpolated the map in real time by using depth buffer [11].
Nowadays, graphics processing unit (GPU) is utilized for general purpose calculation that is used to be performed by central processing unit (CPU). Then, Wyman used GPU and performed an interactive image-space approach to represent refractive images on transparent objects [12]. Hu et al. also utilized GPU power and proposed an interactive computing scheme for rendering of reflection, refraction, and caustics [13]. In addition, Oliveira et al. utilized programmable GPU for image-space technique that calculates the intersection between the ray and objects efficiently [14]. Furthermore, Rodgman et al. proposed another rendering method for refraction in volume graphics [15], and Rousiers et al. also proposed another method for representing refraction through a transparent object that has rough surfaces [16]. On the contrary, Chen et al. suggested a depth acquisition method from refractive images, which method can measure the depth from the eye if the cause of refraction is already known [17]. If we use this method, we can estimate the original shape of objects deformed by refraction.
Generating realistic images with reflection and refraction requires huge amount of time so that most of research use texture mapping with the help of GPU power. Although these techniques produce realistic images with reflection and refraction very fast, we do not understand which part of the image is generated by reflection and/or refraction. On the contrary, the virtual object that Ofek et al. [9] proposed has vertices translated from the original ones by considering reflection. Then, if we can understand how the original object is transformed by reflection and refraction, the image can be generated very fast. Therefore, Mukai et al. investigated how the vertices of an object are translated from the original ones by refraction in a cylindrical glass [18] and also represented the complex image on a cubed glass by combining each image that has simple reflection and/or refraction [19]. Therefore, this chapter describes how an object is transformed by reflection and refraction and how the vertices constructing the object are translated from the original positions. First, the analysis of reflection and refraction is described, and a virtual object, which is transformed from the original one by reflection and refraction, is generated. Then, the image with reflection and refraction is generated by combining each image rendered with the virtual object. At last, the proposed method is used for two types of applications: the image with reflection and refraction generated on a cubed glass and the image with refraction generated on a cylindrical glass. In addition, the result shows that the simulation images are the same as the real ones by comparison between the generated images and the real photos.
This section describes how to generate a virtual object, which has vertices translated from original ones by considering reflection. Figure 1 illustrates the reflection on a parallel glass. In the figure,
Virtual vertex due to reflection on a parallel glass.
Figure 2 shows the refraction through a parallel glass, which has the thickness of H. In the figure,
Virtual vertex due to refraction through a parallel glass.
However,
By substituting Eqs. (4) and (5) to Eq. (3), the following equation is obtained:
Finally, by solving Eq. (6) with an iterative method, the incidence angle
The above description is true for the case that the reflective or the refractive plane is parallel to X axis of the coordinate system. However, the rotation of the coordinate system is required for the case that the plane is inclined against X axis. Figure 3 shows the process of the vertex translation with the coordinate system rotation. In Figure 3(a), the plane is inclined against X axis by the angle
Vertex translation with the coordinate system rotation. (a) Rotation (b) Movement and (c) Inverse rotation.
Figure 4 shows the case where both reflection and refraction happen on a parallel glass.
Reflection and refraction on a parallel glass.
We can also obtain the following equation from Eq. (4) by replacing
By substituting Eqs. (5) and (11) for Eq.(10), the following equation is obtained:
From Eq. (8),
The same calculation can be applied to the general phenomenon with
Figure 5 shows the relation between the number of repetitive reflections inside the parallel glass and the thickness of the virtual glass. The original thickness of the glass is D. When there is
Relation between the number of reflection and the thickness of the glass.
When light enters the side plane of the glass, the incident angle changes. If the incident angle on the back plane of the glass is over the critical angle, total reflection happens. That is, there is no refraction and all light energy is reflected on the back plane. Even in this case, we can consider the phenomenon, which has one total reflection on the back plane and two refractions on the both side planes, as another phenomenon that has only two refractions on the side planes and no reflection on the back plane. In addition, we can generate the image by rendering the virtual object that has virtual vertices. Figure 6 illustrates this situation. In the figure, it is supposed that the back plane of the parallel glass is placed on
Total reflection.
Here,
From the figure, the following equations are obtained:
With Eqs. (5), (20), and (21), the following equation is derived:
Then, the incident angle
Figure 7 shows the case that has two total reflections. In this case, we can consider the phenomenon, which has two total reflections on the front and back planes, and two refractions on the both sides, as another phenomenon that has one total reflection on the back plane and two refractions on the both sides by using a virtual vertex
Two total reflections.
Figure 8 shows another case that has three total reflections. Even in this case, we can consider the phenomenon as another one that has no total reflection and two refractions on the both sides by using a virtual vertex
Three total reflections.
The same calculation can be applied to the case that has
Figure 9 shows the case that has multiple reflections and refractions in the parallel glass, where light energy attenuates gradually every time reflection or refraction happens.
Multiple reflections and refractions.
Fresnel equations mention that the reflection rate changes depending on the incident angle; however, the following approximated equation is usually used for the reflection rate calculation in computer graphics field:
where
In the rendering, the reflection and the refraction rates are used as an alpha value for alpha blending, when multiple images are combined together.
Figure 10 shows an image generated on a cubed glass, which image has some reflections and refractions. We can estimate that there is a string of “GRAPHICS” under the cubed glass; however, we do not know how the image is generated and which part has the effect of reflection, refraction, or the combination. We can see that the top plane is divided into four regions and some images are flipped horizontally, vertically, or on both directions. On the other hand, Figure 11 illustrates the ray path in the cubed glass. In Figures 10 and 11, eight points indicated as A to H are the vertices constructing the cubed glass. In Figure 10, four numbers indicated as (1) to (4) show the divided regions on the top plane, and in Figure 11, the same four numbers show four rays that pass the same regions as those in Figure 10. In addition, Figure 11 shows that the numbers outside the parenthesis are near to the eye point, while the numbers inside the parenthesis are far from the eye. Each divided region in Figure 10 has the effect of reflection and/or refraction as the following:
Reflective and refractive image on a cubed glass.
Ray path in a cubed glass. (a) YZ cross section and (b) XY cross section.
Two refractions on the bottom and the top planes.
Two refractions on the bottom and the top planes and one total reflection on the side of ABFE.
Two refractions on the bottom and the top planes and one total reflection on the side of BDHF.
Two refractions on the bottom and the top planes and two reflections on two sides of ABFE and BDHF.
For generation of the image drawn on the top plane of the cubed glass, we need to decide the boundary between regions. In Figure 10, the image is flipped on the boundary line, and the flip is caused by total reflection inside the cubed glass. For example, the region (2) has one total reflection on the side of ABFE in addition to two refractions on the bottom and the top planes. Then, the boundary line on the top plane can be decided by the ray that passes the bottom edge line (EF) of the cubed glass. In addition, the boundary line between the regions (1) and (2) or the regions (3) and (4) is parallel to Z axis, and the boundary line between the regions (1) and (3) or the regions (2) and (4) is parallel to X axis. Therefore, the searching algorithm is as follows for the boundary line that divides the regions (1) and (3) or the regions (2) and (4). Figure 12 shows the process of the algorithm:
Boundary line search algorithm. (a) Process of 1-5 (b) In case of AQ<AE and (c) In case of AQ>AE.
<Boundary line search algorithm>
Set A as A′ and C as C′.
Set the initial point P as the middle point of A′C′.
Calculate the refractive light with the incident and the refractive angles (
Calculate the intersection point of the refractive light and the line of AE, and set the point as Q.
If Q nearly equals to E, the line that passes P and is parallel to X axis is the boundary. Stop here.
If the length of AQ is shorter than that of AE, set the middle point of C′P as the next point of P, and set the original P as A′. Otherwise, set the middle point of A′P as the next point of P and set the original P as C′.
Figure 13 shows the simulation result with the proposed method for the case of Figure 10 and the comparison with the real photo. The top plane is divided into four regions, and the images on some regions are flipped due to total reflection on the side planes.
Simulation result and the real photo for a string of “GRAPHICS.” (a) Simulation result and (b) Real photograph.
Figure 14 shows another simulation result and the real photo for an eraser that has texture on the surfaces. In this case, the front plane is divided into four regions, and some images on the regions are flipped due to total reflection. We can see that the two images are very similar.
Simulation result and the real photo for an eraser with texture. (a) Simulation result and (b) Real photograph.
Figure 15 shows the process to generate Figure 14(a). Figure 15(c) is the image without reflection and refraction because the part is directly seen from the eye position and the ray does not pass the cubed glass. All images except for (c) have two refractions on the back and the front planes. The image (b) has only two refractions on the back and the front planes of the cubed glass. It does not have any total reflection. On the other hand, the image (a) has one total reflection on the side plane so that the string on the eraser is generated by flipping the image (b) horizontally. The image (e) also has only one total reflection on the bottom plane so that the image is generated by flipping the image (b) vertically. In addition, the image (d) has two total reflections on the side and the bottom so that the image is generated by flipping the image (b) horizontally and vertically. The image (f) is the combined image. Then, we can understand which part is generated by reflection and/or refraction by using the proposed method.
Divided images and the combined image generated on one plane. (a) Reflection on side (b) No reflection (c) Image outside the class (d) Total reflections on side and bottom (e) Total reflection on bottom and (d) Combined image.
In Figures 13 and 14, the simulation result has an image only on one plane: top or front. However, the method can be applied to multiple planes. Figure 16 shows the application, where the images are generated on three planes.
Simulation result and the real photo for an image generated on three planes. (a) Simulation result and (b) Real photograph.
In addition, Figure 17 shows the process to generate Figure 16(a). In the figure, all parts have an image seen directly from the eye position, so that it has no reflection and refraction. The image (c) has no total reflection and refraction. It has only the direct reflection of the eraser on the top plane; however, it is difficult to identify it because the image is not so clear, which is the same as that of the real photo (Figure 16(b)). Both (a) and (b) have only two refractions; however, the refractive planes are different. The refractive planes are parallel since there is no total reflection. The one is the plane that has the image, and the other is the plane that is parallel to it. On the other hand, both (e) and (f) have one total reflection on the bottom plane so that the string on the eraser is vertically flipped. The images (d) and (e) are generated by flipping the images (a) and (b) vertically, respectively. Finally, (f) is the combined image. The process of the image generation helps us to understand which part is generated by reflection and/or refraction.
Divided images and the combined image generated on three planes. (a) No reflection on left front (b) No refraction on right front (c) Direct reflection on top (d) Total reflection on left bottom (e) Total reflection on right bottom and (f) Combined image.
This section describes how to generate the image for a cylindrical glass. In the inside of a cylindrical glass, there are four refractions at the most, and the position of a virtual vertex moves dynamically. Figure 18 shows the movement of a virtual vertex by each refraction through a cylindrical glass. In the figure, the thickness of the cylindrical glass is W, and Q is the original vertex. Vertex
Movement of a virtual vertex.
Then, each virtual vertex can be calculated as follows. The virtual Vertex
If the final virtual vertex
Figure 19 shows the simulation image generated with the proposed method and the real photo. The eraser is distorted inside the cylindrical glass due to four refractions. The simulation result is very similar to the real photo, and the image can be generated in real time. That is, the simulation image changes in real time according to the movement of the real eraser.
Simulation result and the real photo for a cylindrical glass. (a) Simulation result and (b) Real photograph.
In this chapter, a new method to generate reflective and refractive images has been proposed. The method generates virtual objects that have virtual vertices translated from the original ones by considering reflection and refraction. By rendering the virtual objects, we can generate the reflective and/or refractive images without considering reflection and refraction. For the parallel glass, the calculation equations for the virtual vertex have been derived. In addition, total reflection and attenuation of light energy have been considered, and the attenuation is used as an alpha value to blend some images in alpha blending. On the other hand, the position of a virtual vertex moves dynamically for a cylindrical glass, and the position can be calculated as the intersection of two lines. Finally, the proposed method has been applied to two types of glass: cubed glass and cylindrical glass. On the both cases, the simulation results have been very similar to the real photos, and the image can be generated in real time.
The proposed method helps us to understand which part of the image is generated by refraction, reflection, or total reflection. In addition, we can understand on which plane the reflection happens or which pair of planes causes the refraction. However, by comparing the simulation results with the real photos, we see that the image quality is different, especially the transparency. Then, in order to improve the image quality, we have to try another technique such as blending the simulation result with environment map.
Gels can be defined as three-dimensional cross-linked polymeric networks which swollen in contact with a liquid. When the polymers forming the gel contain mainly hydrophilic functional groups, the liquid that causes the swelling is water, and the gel is called hydrogel [1]. Biopolymers are often used for the synthesis of hydrogels as the natural composition of the polymer leads to extremely high biocompatibility and potential applications in the biomedical field [2].
Hydrogels can be classified as physical hydrogels when the properties of the gel depend on chain entanglements and other interactions, mainly hydrogen bonds or hydrophobic interactions [3]. In this case, properties are highly dependent on chain molecular weight as well as concentration, as mobility of the chains modifies the structure of the hydrogel and therefore its physical properties. Water temperature, salt content, and pH can also affect the mobility of the chains and interactions and must be controlled [4].
Chemically crosslinked hydrogels present a much more stable structure than physical hydrogels. In chemical hydrogels, the polymeric chains are covalently bonded using one or more crosslinking agents, using a chemical process [5]. In general, crosslinked hydrogels are less biocompatible than physical hydrogels, but this is compensated by other advantages: cross-linked hydrogels are insoluble, more stable, and rheological properties such as elasticity or viscosity, their pore size, and their degradation rate can be more optimized than with physical hydrogels.
Hydrogels can present different physical forms: from macrogels to micro and nanogels, which are particulate systems with similar chemical structure but different macroscopic size; implantable gels, with strong physical properties, or injectable gels, more fluids or composed of nano-microparticles which can pass through a needle; hydrogel coatings, where hydrogel nano or microlayer is immobilized on a surface; thermoresponsive or pH-responsive gels, where a trigger modulates the sol–gel properties, can be easily injected in a liquid form before gelation in physiological conditions [6].
Physical properties of physically and chemically crosslinked hydrogels, are similar to several soft biological tissues, and therefore they can be used as substitutes or supplements when the biological function of these soft tissues is compromised. Such hydrogels have been widely used as medical devices for different applications: in traumatology, as substitute or supplement of synovial fluid in osteoarthritis; in ophthalmology, as a substitute of aqueous humor during in cataract surgery; in esthetics and reconstructive surgery, as dermal fillers for rid correction and lipoatrophy for patients with VIH; in wound healing, as wound dressings to promote regeneration and healing of wounds [7].
The biomedical use of the hydrogels can be expanded by the employ of the hydrogels as a sustained release system. Concerning this the controlled release of pharmaceutical ingredients leads to important advantages as a control of the biodisponibility, dose control, local delivery and less side effects [8]. This chapter aims to cover a general overview concerning the sustained drug release from hydrogels and hydrogel coatings. In that regard,
The release of drugs from hydrogels can be achieved by different mechanisms such as swelling/deswelling, diffusion, and chemical mechanism. As previously mentioned, hydrogels are three-dimensional crosslinked polymeric networks that swelled in the presence of water. The crosslink can be physical (hydrophobic interactions, electrostatic interactions and hydrogen bonding) or chemical (covalent bonding) and is responsible of the network structure of the hydrogel. Such networks display open spaces, the size of which is referred to as the mesh size of the hydrogel [9]. Importantly, the mesh size of the hydrogels is one of the main parameters that affect how drugs diffuse through the hydrogel network, being dependent on polymer and crosslinker concentrations, as well as external stimuli. The gelation of hydrogels by polymerization means leads to network irregularities and polymer polydispersity upon formation, and as a result, the mesh size is usually heterogeneous. A number of approaches exist to determine the mesh size [9].
When the mesh is larger than the drug (rmesh/rdrug > 1), the drug release process is dominated by diffusion. Small drug molecules migrate freely through the network, and diffusion is largely independent of the mesh size. The diffusivity, D, in this situation depends on the radius of the drug molecule (rdrug) and the viscosity of the solution (η) via the Stokes–Einstein equation Eq. (1) [10]:
where R is the gas constant and T is the absolute temperature.
When the mesh size is close to the drug size (rmesh/rdrug ≈ 1), the effect of steric hindrance on drug diffusion becomes relevant. Finally, for an extremely small mesh size and/or very large drug molecules (rmesh/rdrug < 1), strong steric hindrance immobilizes the drugs and it remains physically entrapped inside the network, unless the network degrades or the mesh size expands in response for example, to external stimuli.
Several methods accompanied by mathematical model development have been created in parallel to hydrogel technology, in order to predict drug release from the network. The drug release fitting models (i.e. the zero order equation; the first order equation; the Higuchi’s equation; the Korsmeyer-Peppas’ equation; the Hixon-Crowell’s equation, the Weibull equation, among others) are the most abundant, however, they are not predictive but simple mathematical fitting equations. In the last years, mechanistic and statistical models are growing quite fast. Mechanistic models combining the mass transport with the system mechanics developed with a “fully coupled” approach considers the influence of the mass transport on the mechanics as well as the opposite, which makes this approach the only candidate to produce reliable first-principle models.
Statistical models, are receiving a lot of attention due to the consensus of the regulatory authority and the possibility to predict the hydrogels behavior, in the analyzed design space, regardless the complicate phenomenology, with quick and inexpensive experimental designs [11]. Recently, Wu and Brazel developed a method for the simulation of water uptake profile and drug release from homogeneous hydrogels. This model successfully predicted the initial burst release observed experimentally [12]. Sheth et al. developed a mathematical and computational model using time snapshots of diffusivity and hydrogel geometry data measured experimentally as inputs to predict release profiles of two model proteins of varying molecular weights from degradable hydrogels [13].
Physical hydrogels are those formed by reversible and dynamic crosslinks grounded on noncovalent interactions. In this regard the network of physical hydrogels is reversibly held together by molecular entanglements, resulting from a dynamic competition between pro-assembly forces (for example, hydrophobic interactions, attractive electrostatic forces and hydrogen bonding) and anti-assembly forces (for example, solvation and electrostatic repulsion [3]. These interactions that occur in this type of hydrogels are usually weak. However, they are numerous and contribute to the presence of complex behaviors.
Polyampholytes may also be used to construct physical hydrogels, with randomly dispersed cationic and anionic groups. The randomness leads to a wide distribution of strengths: The strong bonds serve as structural crosslinks, imparting elasticity, whereas the weak bonds reversibly break and re-form, dissipating energy. Consequently, physical hydrogels have reversible liquid to solid transition, also called sol–gel transition, in response to different changes in environmental conditions such as temperature, ionic strength, pH, or others [14]. Since the interactions depend significantly on external stimuli, they allow hydrogels to be highly versatile concerning the environment, unlike covalently bonded materials [15].
Physical hydrogels can be engineered to undergo spontaneous biodegradation under physiological conditions, which constitutes another way of controlling the release of active molecules [16]. Degradation is typically mediated by hydrolysis [17, 18] or enzyme activity [19]. The erosion or loss of polymer mass through degradation, can take place simultaneously in the bulk or on the surface of the hydrogel. For a variety of hydrogels, the bulk and surface erosion can be tuned to obtain desirable release kinetics ranging from weeks to months. Bulk erosion occurs because of the permeability to water or degrading enzymes when the rate of diffusion of these agents is rapid compared to the rate of bond degradation. Surface erosion, in contrast, results when the rate of bond breakage is more rapid than the rate of enzyme or water diffusion from the exterior into the bulk of the gel [13].
Representatives of reversible physical hydrogels are the shear-thinning hydrogels which flow like low-viscosity fluids under shear stress during injection, but quickly recover their initial stiffness after removal of shear stress in the body [3]. Alginate hydrogels are shear-thinning, formed via electrostatic interactions between alginate and multivalent cations (for example, calcium and zinc). They can be readily injected via a needle after gelation in a syringe and have been used to achieve sustained local delivery of bioactive vascular endothelial growth factor (VEGF) in ischemic murine hindlimbs for 15 days [20, 21].
Another example of physical hydrogels forming materials are the self-assembling peptide systems, where amino acid-based chains undergo the sol–gel transition without the need of any chemical crosslinking agent. This property makes them useful materials to safely in situ encapsulate living cells or sensitive drugs, among others. In addition, this peptide-driven self-assembly into physical hydrogels is highly specific, sourced mainly by the biorecognition of peptide segments scattered among the macromolecular chains. They form dynamic well-defined, hierarchically organized 3D structures with reversibility of the assembly and disassembly processes [22]. Another example are elastin-like polypeptides cross-linked via electrostatic interactions between their cationic lysine residues and anionic organophosphorus cross-linkers [23]. Non-covalent interactions between heparin and heparin-binding peptides and proteins can also be used to form hydrogels for growth factor delivery [24, 25].
Peptide self-assembly can also be achieved by taking advantage of interactions between metal cations and amino acid residues of the peptides. This was demonstrated with gelation of a β-sheet-rich fibrillar hydrogel with zinc ions [26].
Additional interesting example of physical hydrogels for drug release applications are pectin-chitosan hydrogels, which showed to be thermo-reversible and capable of prolonging the release of three different model hydrophobic drugs: mesalamin, curcumin and progesterone. In vitro drug-release studies revealed that lower percentage of pectin in the hydrogel led to slower release rates owing to smaller mesh size arising from stronger interactions between the polyelectrolytes. Also, the release was slower when the total polymer concentration was higher. Finally, a slower release in PBS solution compared to HCl solution was attributed to the fact that at pH 7.4, both polymers are charged, with strong electrostatic forces and consequently, smaller mesh size. At the molecular scale, the polymer chains can possess abundant binding sites for the drugs. DSC and FTIR analysis exhibited some interactions between the drugs and both chitosan and pectin that can contribute to the prolonged release of the drugs [27]. Another in situ-gelling hydrogel was formed with a polyelectrolyte complex, which showed a sustained release of insulin and avidin proteins [28].
Crosslinking of biopolymers provide a stable and non-soluble biomaterial which preserves the properties of the original biopolymer and displays a longer durability. Consequently, the half-life time of the hydrogels is increased when performing its biological application [5].
Usually, biopolymer crosslinking can be accomplished in two ways: by direct addition of a cross-linking agent followed by formation of a the three-dimensional (3D) network, or by chemical modification of the biopolymer chains with functional groups suitable for crosslinking with a compatible cross-linker. The first approach takes advance of the functional groups already present in the biopolymer, typically amine (NH2), hydroxyl (-OH), carboxylic acid (-COOH), amide (-CONH-, -CONH2), thiol (-SH) or sulfate (-SO3H) groups [29]. Examples of cross-linkers are dialdehyde derivatives, NH2-PEG-NH2 molecules, COOH-PEG-COOH derivatives, diglycidyl ether compounds, vinyl sulfone groups, etc. These agents cross-link through Michael-type addition, thiol exchange/disulfide cross-linking or Schiff-base processes among others [30]. In some case the addition of coupling agents such as carbodiimides derivatives, N-hydroxysuccinimide (NHS) or N-hydroxybenzo triazole (HOBt), is required for the cross-linking. In the second approach new active functionalities are created in the biopolymer [31, 32] which are appropriate for a broad range of cross-linking processes such as azide–alkyne cycloadditions, Diels–Alder reactions, ultraviolet (UV) photoinitiated crosslinking, (meth)acrylation reactions [5, 32]. Examples of cross-linkers are oxanorbornadiene, cyclooctyne, maleimide, trans-cyclooctene, norbornene, PEG-di(meth)acrylates among others.
The crosslinking of biopolymers produces hydrogels with elastic and deformable structures and great topochemical accessibility which is able to accommodate different kind of active molecules, such as drugs, for sustained release (Figure 1).
Left: Image of a hydrogel based on crosslinked hyaluronic acid. Right: Scanning electron microscopy (SEM) picture of the hydrogel. Figure produced by the authors.
Chitosan (CHI) is a linear polysaccharide formed by arbitrarily allocated β-(1 → 4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit). Chitosan is one of the most versatile biopolymers due to its unique properties: biodegradability, biocompatibility, non-toxicity, antioxidant, anti-inflammatory, antifungal, and antibacterial “contact killing” [33]. Therefore the applicability of this polysaccharide extends to a wide range of various biomedical areas, such as cosmetics, drug delivery, and tissue engineering, among others [34].
In this regard a covalently crosslinked chitosan hydrogel was produced Diels Alder reaction of furan and maleimide functionalized CHI. The resulting biopolymer held the typical pH sensitivity and antibacterial properties of non-functionalized CHI. The drug delivery capabilities of this system were evaluated with model drug antibiotic chloramphenicol (ClPh). Drug release experiment did not show an initial burst, which indicated that the ClPh was successfully encapsulated, whereas it displayed a sustained delivery of the drug with a complete release of the total amount of drug loaded (2.61 ± 0.036 mg ClPh/g hydrogel) after 4 hours [35].
CHI was also crosslinked with genipin (GP) to obtain biocompatible, antibacterial and anti-inflammatory hydrogels with wound healing properties. Sustained release of acetylsalicylic acid (ASA), cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) from the hydrogels displayed a Pharmacologic Half Life t1/2 values of 88 h, 62 h, 135 h, and 240 h for ASA, CFX, TCN and AMX respectively. These antibiotic releases generated antibacterial activity against
Moreover, dialdehyde-β-cyclodextrin (DA-β-CD) crosslinked carboxymethyl chitosan (CMCS) hydrogels were prepared from carboxymethyl chitosan (CMCS) and periodate oxidized β-CD. Phenolphthalein (PhP), a formerly used laxative agent, [16] was selected as a model molecule to investigate the drug loading and sustained release capabilities of such hydrogels. PhP release results show that increasing crosslinking rate between DA-β-CD and CMCS delays the drug liberation process. On the other hand, DA-β-CD/CMCS system displays faster releases, with a 50% release in 2 h and about 90% within 12 h, compared to CMCS crosslinked with glyoxal dialdehyde which only releases 19% of PhP after 24 h [37].
CHI based hydrogels (N-succinyl chitosan-g-Poly(acrylamide-co-acrylic acid) were synthesized by free radical mediated cross-linking of N-succinyl chitosan, acrylamide and acrylic acid [38]. Drug delivery capabilities of the system were tested by encapsulation of theophylline, a phosphodiesterase inhibiting drug used for the treatment of respiratory diseases. The drug release experiments showed a pH dependent behavior. In this regard, at pH 1.2 the theophylline released rate was found to be between 14 and 24% whereas at pH 7.4 the release of the drug reached 67–93%. CHI itself has been used as a cross-linking agent for poly(acrylic acid). The resulting hydrogels display pH sensitive properties that have been exploited to control the release of antibiotic amoxicillin and anti-inflammatory drug meloxicam. Concerning this, the release rates of these molecules rise with increasing pH due to the disruption of hydrogen bonds between the hydrogel components and the drugs. As a result 30%, ∼60% and ∼80% of amoxicillin is released after 800 min at pH 1.2, 6.8 and 7.4, respectively. The corresponding release data for meloxicam are ∼20%, ∼70% and ∼90% at pH 1.2, 6.8 and 7.4, respectively [39].
Hyaluronic acid (HA) is a non-sulfated glycosaminoglycan constituted by repeating disaccharide β-1,4-D-glucuronic acid–β-1,3 N-acetyl-D-glucosamine units that form hydrogels in aqueous solutions. This naturally occurring polysaccharide is found in connective tissues, skin, and synovial joint fluids of the human body. HA displays bio-functionality, biocompatibility, and physicochemical properties, such as viscoelasticity and high-water retention. As a result hyaluronic acid is used for the treatment of dry eye disease, dermatological conditions as well as a as a viscosupplement for the treatment of osteoarthritis [5].
Biocompatible antibacterial hydrogels of HA were synthetized by crosslinking HA solution with divinyl sulfone (DVS) followed by loading with antibiotic molecules. This way cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) loaded hydrogels displayed in vitro antibacterial activity against S. aureus. The antibacterial properties of the hydrogels were synergically enhanced by merging antibiotics with anti-inflammatory agent acetyl salicylic acid (ASA). Consequently it was observed an increase in the log10 reduction value (R) from 3.2, in the absence of ASA, to R 5.55 when TCN or CFX were combined with ASA [40].
Hyaluronic acid was crosslinked with 1,4-butanediol diglycidyl ether (BDDE) and loaded with quetiapine (QTP), an antipsychotic drug, and quercetin (QCT), a hyaluronidase (HAase) inhibitor that decreases the biodegradation of HA. Subcutaneous injection in rats of the system showed that the cHA hydrogel with QCT exhibited a lower maximum QTP concentration (Cmax. 782.6 ± 174.4 ng/mL) and longer half-life (t1/2 23.5 ± 2.7 h) and mean residence time values (MRT 30.9 ± 3.9 h) compared to the hydrogel without QCT (Cmax. 1827.6 ± 481.3 ng/mL, t1/2 13.4 ± 4.9 h, MRT 14.3 ± 4.8 h). These results demonstrated that HAase containing HA hydrogels are suitable systems for sustained drug delivery applications [41].
A thiol functionalized hyaluronic acid HA-SH was used, together with DMSO, for the fabrication of HA-SS-HA hydrogels. This system was loaded with antitumoral drugs such as doxorubicin (DOX), zinc phthalocyanine (ZnPc), and indocyanine green ICG, for implant post peritumoral administration. In vivo experiments validated that drug loaded hydrogel implant possessed satisfactory biocompatibility and succeeded in long term sustained release of drugs. As a result the system to ensured high tumor aggregation efficiency and adequate tumor suppression [42]. Hyaluronic acid (HA) functionalized with thiol and hydrazide moieties has been combined with oxidized sodium alginate (ALG)to produced cross-linked hydrogels (HA/ALG). These materials display tunable physicochemical properties and drug release behavior as a function of the HA/ALG precursor concentration. In this regard for HA2/ALG2 (2% w/v), HA3/ALG3 (3% w/v) and HA4/ALG4 (4% w/v) the yield stress of hydrogels were 1724, 4349 and 5306 Pa, and the degradation percentage were about 64%, 51%, and 42% after 35 days incubation, respectively. Thus, in vitro cumulative release of Bovine serum albumin (BSA) for HA2/ALG2, HA3/ALG3 and HA4/ALG4 were 79%, 72%, and 69% respectively for a 20 day release assay [43].
Near-infrared (NIR) light-triggered and reactive oxygen species (ROS)-degradable hyaluronic acid hydrogels (HPTG) were synthesized through the formation of dynamic covalent acylhydrazone bonds. Such system was loaded with photosensitizer protophorphyrin IX (PpIX) and anticancer drug doxorubicin (DOX), to obtain a with light-tunable on-demand drug release for chemo-photodynamic therapy. In this regard NIR light irradiation generated ROS that induced the required degradation of hydrogel and subsequent on-demand DOX release for cascaded chemotherapy. In vivo imaging-guided antitumor study using 4 T1 tumor- mouse model demonstrated that the treatment of DOX-loaded HPTG with laser irradiation nearly accomplished the suppression of tumor growth without noticeable regrowth [44].
Tyramine functionalized HA solutions were combined silk fibroin (SF) to produce a series of HA/SF hydrogels for application in cartilage tissue engineering an and drug delivery. These hydrogels were loaded with Vanillic acid (VA) or Epimedin C (Epi C), both with anti-catabolic, anti-inflammatory and anabolic effects on human cartilage cells. Hydrogels with HA20/SF80 polymeric ratios displayed the longest and the most sustained release profile with 70.1% release of VA after 60 days of release assay and 54% release of Epi C after 7 days of release. Such behavior makes HA20/SF80 hydrogels a prospective material for the treatment of osteoarthritic joint conditions [45].
Polyethylene glycol (PEG)-HA was modified also with a small biologically active molecule, as dopamine, to fabricate a HD-PEG polymer. This polymer was crosslinked with α -cyclodextrin (α-CD) to afford a polypseudorotaxane supramolecular complex HD-PEG/α-CD. The system was loaded with poly(lactic-co-glycolic acid) (PLGA)/donepezil microspheres (PDM) in order to evaluate the drug delivery capabilities of the system. The released amounts of donepezil, a drug used for the treatment of mental conditions, reaches 39.9% and 56.7%, after 7 and 14 days respectively. These results demonstrate that the HD-PEG/α-CD/PDM system could be used for the subcutaneous injection of long acting donepezil [46]. Similarly, poly(L-lactide-co-glycolide) (PLGA) – dexamethasone (DEX) nanoparticles PLGADEX were combined with crosslinked HA for drug release applications. In this case the chemical crosslinking occurred doubly, by mixing amino-hyaluronic acid and aldehyde-hyaluronic acid in the presence of genipin as a cross-linker agent. Drug delivery experiments showed full DEX release after 2 months for a HPLGADEX hydrogel [47].
Oxidized hyaluronic acid (OHA) was combined with carboxymethyl chitosan (CMC) via Schiff base reaction to fabricate a hydrogel (OHA-CMC) with antibacterial and hemostatic activities. The drug delivery potential of the system was exploited by encapsulating PLGA-PEG nanoparticles of curcumin (CNP) and epidermal growth factor (EGF) that afforded a OHA-CMC/CNP/EGF hydrogel. This system displayed outstanding anti-inflammatory, antioxidant and cell migration-promoting effects
Finally, HA has been used as well as a biopolymer for the fabrication of a 3D printable dual-network hydrogel with drug delivery capabilities. For that acrylamide-modified HA was synthesized and subsequently mixed with folic acid and Fe3+ to form a physical crosslinking network. Afterwards acrylamide residues were polymerized by ultraviolet radiation affording a material suitable for wound dressing with high elasticity and fatigue resistance. The drug delivery properties were investigated using acetylsalicylic acid (ASA) as a drug model and resulted in a pH responsive hydrogels with the sustained release of ASA over 300 hours [49].
Lignin is a sustainable biopolymer derived from lignol precursors that has been historically related to the paper industry. Hydrogels of hardwood lignin (TCA) have been synthesized through crosslinking with poly(ethylene) glycol diglycidyl ether (PEGDGE) and loaded with paracetamol for drug release applications. Here, decreasing amounts of crosslinker diminishes the interaction paracetamol - hydrogel network and, as a result, the release of paracetamol increases. In this regard, hydrogels produced with a lignin:PEGDGE 1:1 ratio displayed up to 30% of paracetamol release after 120 h assay. The release data follow a pseudo-Fickian behavior of diffusion when fitted to the Korsmeyer-Peppas model [50]. Furthermore, lignin polymers have been mixed with cellulose to generate drug delivery systems. Mechanical and sustained release performances of these gels are tailored by varying the ratio of the precursors: cellulose, hardwood lignin (TCA), and epichlorohydrin (ECH) cross-linker. TCA containing hydrogels display the best release rate (>90%) for drug model paracetamol comparing to the pure cellulose hydrogels (~40%) after 7 hours of release experiment. This behavior is attributed to the lower affinity of paracetamol for lignin compared to cellulose [51].
Cellulose itself have been used for the fabrication of hydrogels with drug release properties. In this regard, carboxymethyl cellulose (CMC) functionalized with ꞵ-cyclodextrin and nucleic acids have been crosslinked by using of arylazopyrazoles (AAPs) and loaded with anti-cancer molecule Doxorubicin (DOX). The resulting hydrogel behaves as a functional matrix for the UV light mediated ON/OFF release DOX. Irradiation of the matrix provokes the photoisomerization of the trans-AAP to cis-AAP residues and the generation of the low-stiffness hydrogel that releases DOX. Therefore, the liberation of the DOX could be changed between ON and OFF states by oscillating the photoisomerization of the hydrogel by employing UV/Vis irradiation [52].
Xanthan is a heteropolysaccharide produced by fermentation from the bacteria
Casein is a proline-rich, open-structured protein found in raw milk. It displays high hydrophilicity, good biocompatibility and a lack of toxicity that makes of it a potential candidate for hydrogel development. Casein can be chemically cross-linked with enzymes such as microbial transglutaminase (MTG). This feature was utilized to produced crosslinked casein -γ-polyglutamic acid (PGA) hydrogels in 1/5 and 1/9 ratio. Drug release experiments showed that both composition displayed similar release rate values for aspirin (~ 100% after 10 h), while 1/9 hydrogels possessed a higher release rate for vitamin B12, ~100% after nearly 12 h versus ~20% for 1/5 casein/γ-PGA hydrogels [56].
Historically, the development of medical implants has been a great concern for biomedical community. Besides, their need has risen dramatically due to the increased number of surgical procedures that are predicted to be even higher in 2030 [57]. Thus, improving the performance of implantable biomaterials has become a high-priority trend, which is reflected in the large number of research realized to successfully meet the upward demand [58].
Implantable medical devices (e. g. coronary stents, cardiac pacemakers, prostheses, insulin pumps) are classified in four main groups: ceramics [59], polymers [60], composites [61], and metals [62]. Among them, metallic biomaterials as titanium and its alloys are of outmost interest thanks to their inert chemical and biological behavior
The use of these bioactive coatings entails the development of an improved version of bioactive materials that modulates biological systems response by the establishment of interactions with adjacent tissues and bones [65]. Nevertheless, these coatings require the most suitable physicochemical, mechanical, and biological functionality for a successful implantation and integration so as not to produce any counterproductive disorder in humans [66]. Therefore, it is imperative to develop functional bioactive coatings onto the surface of biomaterials (Figure 2, produced by the authors) that combine biocompatibility [67], antibacterial [68], anti-inflammatory [69], self-healing [70], wound healing [71], bone tissue engineering [72], and osseointegration [73] properties.
Bioactive properties of functional hydrogel coatings for biomaterials successful implantation. Figure produced by the authors.
Such features can be incorporated onto the surface of biomaterials by the use of biopolymer-based coatings, mostly based on hyaluronic acid and chitosan [74]. Moreover, these coatings acquire hydrogel-like three dimensional microstructure after crosslinking for bioactive agents delivery applications (Figure 3, produced by the authors). In such manner, bioactive properties that already possess biomaterials can be upgraded or even provide novel outstanding properties [75]. Specifically, hydrogel coatings take advantage of hydrogels peculiar ability of releasing in a controlled space–time manner to the therapeutic target the entrapped bioactive agents (drugs, proteins, peptides, growth factors, inorganic or polymeric nanoparticles, and nucleic acids) through their polymeric network [76].
Bioactive agents loading and controlled release ability from hydrogel-based coatings. Figure produced by the authors.
Bioactive agents controlled delivery reduces side effects in patients undergoing implant procedures. In addition, highly stable (from hours to months) hydrogel coatings with great loading ability provide a not sudden, uniform, and prolonged release of specific low- to high-doses [77]. This way, therapeutic effect of bioactive substances is extended, and the over-excessed concentration peaks of conventional methods are diminished. These features endow hydrogel coatings with privileged pharmacokinetic profiles, which can be modulated for personalized therapies [78]. Further, hydrogel coatings do not need to modulate specific linkages to release bioactive agents since their release mechanisms are mainly governed by simple diffusion, swelling, and degradation processes [79].
Nowadays, researchers are focusing their attention is the hinder of hydrogel coatings attachment to surfaces, which occurs due to hydrogels excessively huge swelling and macroscale thickness. One promising alternative approach to create highly adhesive hydrogel coatings with strong and resistant hydrogel-surface attachment is the
A) Conventional and B)
The number of works related to the development of novel biopolymer-based hydrogel systems, mainly those synthesized with hyaluronic acid and chitosan, that promote the sustained release of bioactive agents increases year by year. In the current chapter we have summarized the recent accomplishments of biopolymer based physical and chemically crosslinked hydrogels, as well as hydrogel coatings for drug delivery and sustained release applications. The future perspectives in this field involve the development of hydrogel based medicines with specific temporal and spatial controlled release of drugs. Such medicines afford dose control, local delivery and reduced side effects that increase the efficacy and security of the treatment and the adherence of the patient to it. This strategy will lower pharmaceutical costs and improve the quality of life of the patient and the society overall.
Jon Andrade del Olmo thanks Basque Government for “Program of Industrial Doctorates. Bikaintek 2018” (exp number 01-AF-W2-2018-00002).
All the authors are employees of the company i+Med S. Coop.
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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:229,paginationItems:[{id:"318170",title:"Dr.",name:"Aneesa",middleName:null,surname:"Moolla",slug:"aneesa-moolla",fullName:"Aneesa Moolla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/318170/images/system/318170.png",biography:"Dr. Aneesa Moolla has extensive experience in the diverse fields of health care having previously worked in dental private practice, at the Red Cross Flying Doctors association, and in healthcare corporate settings. She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\r\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\r\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Orthodontist, Assoc Prof in the Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. 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She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. 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