Gelatin and collagen uses in biomedical applications.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"2257",leadTitle:null,fullTitle:"Quantum Dots - A Variety of New Applications",title:"Quantum Dots",subtitle:"A Variety of New Applications",reviewType:"peer-reviewed",abstract:"The book “Quantum dots: A variety of a new applications” provides some collections of practical applications of quantum dots. This book is divided into four sections. In section 1 a review of the thermo-optical characterization of CdSe/ZnS core-shell nanocrystal solutions was performed. The Thermal Lens (TL) technique was used, and the thermal self-phase Modulation (TSPM) technique was adopted as the simplest alternative method. Section 2 includes five chapters where novel optical and lasing application are discussed. In section 3 four examples of quantum dot system for different applications in electronics are given. 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\r\n\toxygen-free atmosphere. Biochar has been used for many years as a soil amendment and in general soil applications. Nonetheless, biochar is far more than a mere soil amendment. In this review, we report all the applications of biochar including environmental remediation, energy storage, composites, and catalyst production. In this book, we intend to collect contributions from worldwide experts in the field of biochar production and utilization providing a general overview of the recent uses of biochar in material science, thus presenting this cheap and waste-derived material as a high value-added carbonaceous source. Furthermore, we are aiming to give readers a handy and effective tool to easily understand how this field is interesting and diverse. It is a goal that this book could be easily used by any reader with a strong scientific background ranging from scientific company advisors to academic members. Nonetheless, students enrolled in scientific undergraduate and graduate programs could be consulted to this text for any further and deeper investigation. In the end, we intend to propose a very high scientific content book that could represent the reference text for any consideration and future study about biochar for the next years.
Electrospinning technique is used for the production of fibers at nanometer scale, which has been used previously for the production of cutaneous dressings and a great variety of scaffolds with biomedical interest. It consists of the injection of a polymer solution properly homogenized in a polar solvent, in order to obtain a conductive material; by applying a current of the order of kilovolts (kV), it allows the solution to form a Taylor cone, which permits the formation of fibers. Another widely used technique is the electrospray that starts from the same principle of electrospinning but through a solution that allows the formation of suspended nanoparticles in the solvent, so that they are deposited on the collector (Figure 1) [1].
\nElectrospinning/electrospray scheme with polymer solutions.
Generally, the polymers used in electrospinning for biomedical applications are biodegradable and biocompatible; thus, they can be in contact with physiological medium without generating undesired reactions. Among them is GEL, which is a natural polymer obtained from collagen (COL) which is a protein obtained from the connective tissue of animals when boiled in water, GEL is a very useful polymer in electrospinning because of its ability to produce fibers of nanometric scale independently of the changes in the temperature and humidity of the environment, for this reason it was used as a base for the formation of bioactive electrospun [2].
\nElectrospinning has recently been extensively studied; it is a well-known technique for the manufacture of nanoscale fibers because of its various advantages such as high surface-volume ratio, adjustable porosity, and ease of surface functionalization. The resulting fibers are extremely useful for applications in the fields of tissue engineering, drug delivery, and wound dressing. In addition to the morphological, physical, and chemical properties, electrospun scaffolds are often evaluated through various cell studies. Researchers have adopted approaches such as surface modification and drug loading to improve scaffold ownership and function [3].
\nThe electrospinning technique has been used as an efficient and accessible method for the manufacture of nanofibers with a wide variety of applications in the fields of pharmaceutics and medicine. Among the most outstanding applications, we can see wound dressings, drug delivery systems, or tissue engineering scaffolds [4]. Animal polysaccharides such as chitosan, hyaluronic acid, heparin, and collagen have been studied with this technique; these compounds are natural biopolymers with numerous advantages for biomedical applications such as biocompatibility, biodegradability, nonantigenicity, and nontoxicity [5].
\nGEL nanofibers have been prepared using an electrospinning process in previous studies. To improve water-resistant capacity and thermomechanical performance for potential biomedical applications, GEL nanofibers were cross-linked with glutaraldehyde-saturated steam at room temperature. Exposure of this nanofibrous material to the glutaraldehyde vapor was performed for 3 days to provide sufficient cross-linking to preserve the fibrous morphology assayed by immersion at 37°C warm water. On the other hand, cross-linking also led to improved thermostability and substantial improvement in mechanical properties. The denaturation temperature corresponding to the transition from the helix to the coiled structure of the air-dried samples increased by about 11°C and the tensile strength and modulus were nearly 10 times greater than those of the electrospun GEL fibers. In addition, cytotoxicity was evaluated based on a cell proliferation study by culturing human dermal fibroblasts on the fibrous scaffolds of cross-linked GEL for 1, 3, 5, and 7 days. It was found that cell growth occurred and increased almost linearly over the course of the entire cell culture period. Initial inhibition of cell growth on the cross-linked fibrous substrate of GEL suggested some cytotoxic effect of residual glutaraldehyde on cells [6].
\nThe GEL was successfully electrospun using a solvent based on ethyl acetate, acetic acid, and water. Since natural polymers including GEL have limited solubility in water, toxic or highly acidic solvents are usually used to dissolve them for electrospinning. Instead of using such solvents, ethyl acetate was used with acetic acid in water; the beneficial effect of its use was investigated in terms of the spinning capacity of the nanofiber and the acidity of the solvent. It was found that the substitution of acetic acid with ethyl acetate improved the spinning capacity of the nanofiber by reducing the surface tension of the solution, as well as increasing the pH of the solvent significantly. The optimum composition of the co-solvent was found to correspond to a ratio of ethyl acetate to acetic acid in a ratio of 2:3. Under this solvent condition, the GEL could be dissolved at concentrations up to 11% by weight and successfully electrospun to produce nanofibers of various diameters (47–145 nm on average) depending on the GEL concentration. The water-based co-solvent method proposed herein may be useful for generating other natural nanofibrous polymers, as well as being applicable in delivery systems for bioactive molecules within the nanofiber matrices [7].
\nIn another study, electrospinning was performed in aqueous GEL solution, increasing the spinning temperature. To improve stability and mechanical properties in the wet state, the GEL nanofibrous membrane is chemically reticulated by 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride and N-hydroxyl succinimide. The crosslinker concentration was optimized by measuring the degree of swelling and weight loss. The nanofibrous structure of the membrane was maintained after lyophilization, although the fibers were crimped and conglutinated. The tensile test revealed that the hydrated membrane becomes flexible and provides predetermined mechanical properties [8].
\nIt can be said that electrospinning has been one of the simplest, most versatile, and promising processes for producing continuous nanofibers. In the case of GEL, this polymer has been widely used in food for the purpose of thickening and stabilization. At nanometer scale, electrospun nickel/GEL nanofibers can be used in food for the same purpose in smaller quantities that give more results that are efficient. A study investigated the influence of the parameters that affected during electrospinning on the properties of the electrospun GEL. GEL concentrations of 7 and 20% (w/v) were electrospun under 28 or 35 kV applied voltage. The feed rate was 1 or 0.1 ml/h. Before electrospinning, the electrical conductivity, surface tension, and rheological properties of the feed solutions were determined. Morphological analysis showed that only the 20% GEL solution produced nanofibers. The electrical conductivity, surface tension, consistency index, and flowability of the 20% GEL solution were 4.77 mS/cm, 34.91 mN/m, 1.37 Pa, and 0.93 sn, respectively. The range of diameters of nanofibers increased with the applied voltage. The zeta potential and diffusion coefficients of dispersions containing the GEL and the electrospun GEL were determined. Both values were higher for dispersions containing electrospun GEL than for dispersions with GEL at the same concentration. The zeta potential and diffusion coefficient values of dispersion coefficients containing electrospun GEL decreased as the voltage applied during the electrospinning increased. The applied low voltage resulted in higher values of the diffusion coefficient and zeta potentials for dispersions containing electrospun GEL nanofibers, which may indicate that these nanofibers can be used for the stabilization of food emulsions, as compared to the smooth nanofiber morphology without pearl formation obtained at the highest stress [9].
\nOn the other hand, electrospinning is a very useful technique for producing polymeric nanofibers by the application of electrostatic forces. It has been reported that the modeling and optimization of the GEL/chitosan electrospinning process have been achieved, where the interaction effects of the GEL/chitosan blend ratio (50/50, 60/40, and 70/30) were investigated, the applied voltage (20, 25, and 30 kV), and the feed rate (0.2, 0.4, and 0.6 ml /h) on the optical fiber diameter and the standard deviation of the fiber diameter by scanning electron microscopy. To manufacture the GEL/chitosan nanofibers mixture, trifluoroacetic acid/dichloromethane was selected as the solvent system. The model obtained for the hinge diameter has a quadratic relation with the applied voltage and the feed rate. The interaction between the applied voltage and the flow rate was found to be significant, but the interactions of the mixing ratio and the flow and the mixing ratio and the applied voltage were insignificant. Scanning electron micrographs of human dermal fibroblast cells in the structure of gel/chitosan nanofibers show coupling and proliferation on the surface of fabricated scaffolds. These microfibers have great potential to be used as scaffolding for the engineering of cutaneous tissues [10].
\nIn another study, poly (lactic-co-glycolic acid) (PLGA) and PLGA/GEL nanofibrous sheet materials embedded with mesoporous silica nanoparticles were fabricated using an electrospinning method. The mean diameters of the nanofibers were 641 ± 24 nm for pure PLGA scaffolds versus 418 ± 85 and 267 ± 58 nm for PLGA scaffolds/silica nanoparticles at 10% w/w PLGA/GEL silica nanoparticles to 10% w/w, respectively. The results of the contact angle measurement (102°± 6.7 for the pure PLGA scaffold versus 81 ± 6.8 and 18 ± 8.7 for PLGA/silica nanoparticles and the PLGA/GEL scaffolds/silica nanoparticles revealed improved hydrophobicity of scaffolds by the incorporation of GEL and silica nanoparticles. In addition, the incorporation of scaffolds with silica nanoparticles resulted in better tensile mechanical properties. The culture of PC12 cells in the scaffolds showed the introduction of silica nanoparticles into the matrices. The DAPI staining results indicated that cell proliferations in the PLGA/silica and PLGA/GEL/silica nanoparticle matrices were surprising (almost 2.5%), and the proliferation of PLGA and PLGA/GEL leads to improved cell attachment and proliferation (three times, respectively) higher than in pure aligned PLGA scaffolds. These results suggest superior properties of mesoporous silica nanoparticles incorporated into electrospun PLGA/GEL scaffolds for stem cell culture and tissue engineering applications [11].
\nOn the other hand, we studied the mass production of GEL nanofibers by spiral electrospinning and investigated the performance of different cross-linking methods such as glutaraldehyde vapor and liquid phase cross-linking. Compared with conventional single-needle electrospinning, spiral electrospinning nanofibers were finer, where an increase of more than 1000 times over the productivity of traditionally obtained nanofibers was obtained. Mechanical tests showed that the tensile strength of nanofiber membranes increased from 1.33 to 2.60 MPa after cross-linking of glutaraldehyde vapor and from 1.33 to 5.08 MPa after liquid phase cross-linking. In addition, the SEM and FTIR analysis indicated that the membrane of nanofibers obtained by liquid phase cross-linking presented better properties, resulting in an ideal material for wound dressing applications [12].
\nA study where GEL scaffolds were prepared by electrospinning using aqueous acetic acid and thermally cross-linked with glucose showed the effect of the amount of glucose used as the cross-linking agent on the mechanical properties of the GEL fibers, and it was found that cross-linking with glucose increases the elastic modulus of GEL fibers from 0.3 GPa to 0% glucose content at 1.1 GPa with 15% glucose. This makes fibrous GEL scaffolds cross-linked by glucose, a promising material for biomedical applications [13].
\nIn another study, GEL nanofibers were prepared from ternary mixtures of GEL/acetic acid/water with the aim of studying the feasibility of making GEL nanofiber membranes at room temperature using an alternative benign solvent by significantly reducing the concentration of acetic acid. The results showed that GEL nanofibers can be optimally electrospun with a low concentration of acetic acid (25%, v/v) combined with GEL concentrations above 300 mg/ml. GEL mats made from low acetic acid solutions had some advantages such as maintaining the decomposition temperature of the pure GEL (230°C) and the reduction of the acid content in the electrospun mats, which allowed a cellular viability of more than 90% [14].
\nThe manufacture of fibroin nanofibers/silica GEL loaded with ceftazidime without the loss of structure and bioactivity of the drug was demonstrated using the electrospinning method. The results show that the average diameter of the drug-loaded nanofibers at the optimum ratio of polymer to drug [10, 1] was 276.55 ± 35.8 nm, while increasing the feed ratio to 1:1 increased the mean diameter at 825.02 ± 70.3 nm. In FTIR analysis of drug loaded on the nanofibers revealed that the drug ceftazidime was successfully encapsulated in the nanofibers while the feasibility study approved the cytocompatibility of the system. The drug was released from the nanofibers for 6 h, and the formation of the zone of inhibition in the diffusion test demonstrated the antibacterial effect of the drug-loaded nanofibers. Together, the fibroin/GEL/ceftazidime nanofibrous system can enhance drug effectiveness particularly in the prevention of postsurgical adhesions and wound dressing infections [15].
\nSince GEL undergoes a gelation process, Furuike et al., used a new dry spinning process for GEL. In this case, the nonwoven GEL fabrics were electrospun by applying dry spinning principles. The diameter of the fibers, the viscosity, and flow rate of the solution depended directly on the GEL concentration. Spunted nonwoven fabrics with a concentration of 25% (w/w) GEL exhibited a nanoscale diameter. In order to improve the properties of the nonwoven fabrics, they were cross-linked with glutaraldehyde vapor after spinning by the addition of N-acetyl-d-glucosamine to the GEL solution before spinning followed by heating of these fibers. Nonwoven fabrics cross-linked by glutaraldehyde vapor exhibited improved mechanical properties compared to those without cross-linking or cross-linking of N-acetyl-d-glucosamine. Swelling and water absorption did not produce morphological changes in glutaraldehyde cross-linked fibers. The thermogravimetric analysis (TGA) thermogram did not confirm any phase change in the composite structure. In addition, in vitro cytocompatibility studies using human mesenchymal stem cells showed the compatible nature of the developed nonwoven fibers, where they demonstrated that these nonwoven fibers could be useful in medical care [16].
\nDelivery of hydrophobic drug into the hydrophilic polymer matrix as a carrier is usually a challenge. Therefore, in one study, the synthesis of GEL nanofibers by electrospinning was presented, which were evaluated as a potential carrier for the oral system of hydrophobic drugs, piperine. GEL nanofibers were cross-linked by exposing to saturated glutaraldehyde vapor, to improve their water-resistive properties. An exposure of only 6 min was not only adequate to control early degradation with intact fiber morphology, but also significantly marginalized any adverse effects associated with the use of glutaraldehyde. The results illustrated good compatibility of the hydrophobic drug in GEL nanofibers with promising patterns of controlled drug release by varying the cross-linking time and the pH of the release medium [17].
\nCollagen (COL) is the most widely distributed class of proteins in the human body. The use of COL-based biomaterials in the field of tissue engineering applications has been growing strongly during the last decades. It is for this reason that multiple cross-linking methods have been investigated and different combinations with other biopolymers have been explored to improve tissue function. The COL has a great advantage, as it is biodegradable, biocompatible, readily available, and highly versatile. However, since COL is a protein, it remains difficult to sterilize without alterations in its structure [18].
\nWe have investigated the possibility of preparing COL-inspired nanofibers by electrospinning aqueous suspension of telopeptide-free COL molecules avoiding organic solvents and blends with synthetic and natural polymers. The results underscored the need for a basic atmosphere between the needle and the ground collector in order to increase the pH of the environment during auto-assembly of COL molecules along the electrostatic force lines in order to prepare a biomimetic component of reinforcement of new biomaterials for medical and surgical use [19].
\nIt has been reported that he designed a durable sandwich wrap preparation system with high liquid absorption, biocompatible, and with antibacterial properties. For this purpose, various weight ratios of the COL solution to chitosan were used to immobilize on the polypropylene nonwoven fabric, which was pre-grafted with acrylic acid or N-isopropyl acrylamide to construct a durable wound sandwich liner membrane with high water absorption, easy removal, and antibacterial activity in an animal skin model. The results indicated that tissue immobilized with N-isopropyl acrylamide and COL/chitosan/PP/N-isopropyl acrylamide-COL/chitosan) showed a better healing effect than COL/chitosan immobilized polypropylene tissue. The poly (propylene)/N-isopropyl acrylamide/COL/chitosan-treated wound showed an excellent remodeling effect on histological examination with respect to the construction of the vein, epidermis, and dermis at 21 days post-cutaneous lesion. The water absorption values and water diffusion coefficient for polypropylene/N-isopropyl acrylamide/COL/chitosan were higher than those of polypropylene /acrylic acid/COL/chitosan under a weight-volume ratio of COL/chitosan. Both polypropylene/N-isopropyl acrylamide/COL/chitosan and poly (propylene)/acrylic acid/COL/chitosan showed antibacterial activity [20].
\nElectrospinning is a process that is used to create nanofibers, which have the potential to be used in many medical and industrial applications. The molecular structure of the raw material is an important factor in determining the structure and quality of the electro-chip fibers. COL has been extracted from a cold-water hoki species (
Nerve tissue engineering is one of the most promising methods in nerve tissue regeneration. The development of combined scaffolds of COL and glycosaminoglycans can potentially be used in many soft tissue-engineering applications. In a study by Timnak
On the other hand, COL and hyaluronic acid are the main components of the extracellular matrix naturally and have been successfully used in the electrospinning. In this case, a solution of COL/hyaluronic acid polymer was electrospun creating a scaffold for patients with osteoporosis who have reduced bone strength. The membranes were cross-linked to render them insoluble and conjugated to gold nanoparticles to promote biocompatibility. Their results showed that COL/hyaluronic acid scaffolds were insoluble in aqueous solutions and promoted cell fixation that could be used as a tissue engineering framework to promote cell growth [23].
\nZulkifli
The development of biomaterials with the capacity to induce the healing of cutaneous wounds is a great challenge in biomedicine. In one study, COL sponges were developed from tilapia skin and electro-nylon nanofibers for wound dressing. It was found that nanofibers could significantly promote the proliferation of human keratinocytes and stimulate epidermal differentiation through the expression of regulated genes involved, filaggrin and type I transglutaminase in human keratinocytes. In addition, COL nanofibers could also facilitate the regeneration of rat skin, in one study, electrolyzed nanofibers of COL were prepared from biomimetic tilapia skin and were shown to have a good bioactivity and could accelerate the healing of wounds from rat quickly and efficiently. These biological effects can be attributed to the structure of the biomimetic extracellular matrix and to the multiple amino acids of the COL nanofibers. Therefore, tilapia COL nanofibers could be used as a new wound dressing, effectively avoiding the risk of transmitting diseases in future clinical application [25].
\nAnother study using the double-extrusion electrospinning technique prepared with multilayer 3D scaffolds stacking poly-lactic-co-glycolic acid (PLGA) microfiber membranes alternately to micro- /nano-mixed fibrous membranes of PLGA and COL. The density of the COL fibers in multilayered scaffolds obtained was able to control the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. Demonstrating that the homogeneous dispersion of glutamic acid-modified hydroxyapatite nanoparticles (nHA-GA) in the COL solution improved the osteogenic properties of the multilayer scaffolds fabricated. In addition, it found that PLGA-COL-HA micro-nano fibrous scaffolds were highly bioactive compared to pristine microfibrous PLGA and PLGA and COL micro/nano-mixed fibrous platforms [26].
\nThe development of biomimetic scaffolds represents a promising direction in the engineering of bone tissue. This was demonstrated by Ma
The hybrid constructs from marine organism material for porous scaffolds of COL, such as fibrillated jellyfish and alginate hydrogel, mimic the two major components of cartilage, thus being a promising approach as a model for the chondrogenic differentiation of mesenchymal stem cells human beings. This is why Pustlauk
Angarano
Tylingo
In Table 1, other studies with the electrospinning technique are summarized.
\nPolymers | \nApplication | \nCharacteristics | \nReferences | \n
---|---|---|---|
GEL (type B porcine) | \nFood industry | \nSoft nanofibers without pearl formation | \n[9] | \n
GEL (type B porcine) | \nTissue engineering Cell regeneration in fibroblasts (BJ-5ta) and human embryonic kidney cells (HEK 293 T) | \nNanofibers with up to 90% cell proliferation | \n[14] | \n
GEL (type A porcine) | \nTissue engineering Cell regeneration in fibroblasts (3 T3) | \nNanofibers cross-linked in glutaraldehyde. | \n[5] | \n
GEL (25.43 kDa) | \nRegeneration of Periodontal Tissues. | \nReticulated membrane, hydrated and flexible. | \n[8] | \n
GEL (bovine Type B) | \nDelivery system for bioactive molecules in nanofiber matrices | \nNanofibers between 47 and 147 nm. | \n[7] | \n
GEL | \nScaffolds for cell regeneration in human gingival keratinocytes and human gingival fibroblasts. | \nWater-resistant glyoxal cross-linked nanofibers. | \n[29] | \n
GEL/fibroin | \nTissue engineering Cell regeneration in human fibroblasts | \nNanofibers loaded with ceftazidime as an antimicrobial agent. | \n[15] | \n
COL (type I)/poly (lactic-co-glycolic acid)/hydroxyapatite | \nTissue engineering Osteogenic differentiation of MC3T3-E1 cells | \nMicro/nano-bioactive scaffolds | \n[26] | \n
COL/hyaluronic acid | \nTissue Engineering Regeneration of bone tissues in murine fibroblasts (L - 929) | \nFibers insoluble in aqueous solutions that promote cell binding. | \n[23] | \n
COL Free telopeptide type I (equine tendon) | \nBiomedical and Surgical | \nSimple molecular set of nanometric size | \n[19] | \n
Gelatin and collagen uses in biomedical applications.
The authors thank for financial support to “Consejo Nacional de Ciencia y Tecnología (CONACYT)” for its grant known as “Fondo de Cooperación Internacional en Ciencia y Tecnología del Conacyt (FONCICYT)” in its grant named as “Convocatoria Conjunta de Movilidad 2015 CONACYT-DST México-India” with CONACYT project number 266380 and SICASPI-UABC number 351/375/E.
\nThe method of operation for the vast majority of esthetic energy-based devices (EBD’s) is through the generation of heat causing physiologic modifications to the human tissue. RF energy is a method to deliver heat into the human body at a level and distribution required for the specific application. For sub-necrotic thermal applications, this heat can be a relatively low temperature for fibroblast stimulation and metabolism acceleration (hands free RF devices). Alternatively, the heat can be more aggressive, ablative coagulative and necrotic in nature (RF assisted lipolysis or Fractional micro-needling technology). It may occur that during the same treatment, RF energy effects will be both non-ablative on the skin and ablative-coagulative sub-dermally.
\nIn most instances with RF, microwave and light-based technologies, heat is the result of a common pathway for the desired thermal effects. This understanding has given rise to an entire generic category of esthetic and medical EBD’s
Selective thermal targeting of tissue by focusing energy at the desired spot internally or externally. Energy can be delivered to the selected volume in a minimally invasive manner by focusing energy to penetrate the tissue under the skin surface. An example of a minimally invasive treatment is electro-surgical devices which deliver thermal energy into the body via a tiny cannula or needle. Alternatively, electrocautery devices focus the energy on the tissue surface, ablating the tissue in proximity of the tip of the instrument to dissect the a soft tissue.
Non-selective bulk heating, used mostly for sub-necrotic heating to stimulate natural processes in the body leading to increased production of collagen, elastin and ground substances. The result may include tissue tightening, circumferential reduction and wrinkle reduction.
RF energy is an important part of the armamentarium for treatment options comprising tissue cutting and coagulation, minimally invasive selective tissue targeting and bulk heating. RF current is the accepted type of energy used in four out of five surgeries conducted in the world and most industry leaders in the aesthetic field employ RF energy in at least one of their applications.
\nElectromagnetic (EM) energy travels in waves and spans a very broad wavelength spectrum from DC voltage, to very short wavelengths in gamma radiation (Figure 1).
\nElectromagnetic Spectrum.
RF energy is small part of electromagnetic spectrum having frequencies in the range of Kilohertz to Gigahertz. The shorter wavelength and the higher frequency, the more energetic are quanta of EM radiation and the more destructive it can be for the tissue. RF energy, Microwaves, Infrared and Visible Light has relatively low frequencies and represent non-ionizing radiation which is not able to modify the DNA (genes) inside the cells. High frequency radiation as UV, X-ray and Gamma are ionizing radiation which in natural conditions is generated by plasma or by radiative isotopes.
\nA very small part of RF spectrum range is used in EBD, and its properties will be the primary focus of the current chapter.
\nRF energy has been used in medicine for over 100 years. Nikola Tesla, (1856–1943), Croatia-born electrical and mechanical engineer, is reputed as being the father of alternating high frequency current. But it was Dr. William Bovie (yes, of the “Bovie cautery fame”) that developed the first electrosurgical device during the period of 1914–1927 at Harvard University [1]. The first reported use of an electrosurgical generator in an operating room occurred on October 1st, 1926 in a surgery performed by Dr. Harvey Williams Cushing [2, 3]. Since Dr. Bovie introduced RF energy and the electrocautery, RF had been used for ablation [4] and coagulation [5] in surgery and medicine. Over the past 20 years, RF energy has evolved and come to dominate esthetic medicine (for good reasons, as will be explained in this chapter). RF was first being used in non-ablative form for skin collagen remodeling and other esthetic applications (Figure 2) [9, 10].
\nThe early pioneers of RF energy in medicine, [
The specificity of RF energy in medicine is that it acts as an electrical current flowing through the tissue but differently than radiation. RF energy is associated with electro-surgical devices and can be defined as high frequency alternating electrical current heating soft tissue without significant electrical nerve stimulation. It is critical to minimize nerve impact to avoid electric shock which may cause muscle spasm and cardiac arrest.
\nIt is important to remember that tissue has ion conductivity with the most prominent varieties being Na+, K+, and Cl– (sodium, potassium, and chlorine ions respectively). Nerves are affected as a result of ion penetration through the membrane of neuron. Under normal conditions the nerve is surrounded by electrically neutral liquid where ions with positive and negative charge compensate each other and bound by Coulomb force preventing free diffusion of the electrical charge. As an electrical field is applied the ion starts to move and the nerve stimulating effect depends on ion displacement (D) in alternating electrical field that can be presented as following:
\nwhere \n
It is obvious the displacement of the ions is higher when electrical field is stronger and it is applied for longer time (Figure 3).
\nIone displacement for a) low amplitude and high frequency of electric field; b) low amplitude and low frequency; c) high amplitude and low frequency.
In general, polarity of RF voltage is changed so fast that ions vibrate in the same place without significant movement. However, users of RF may occasionally observe small muscle tweaking when high RF parameters are used. Therefore, RF energy used in electrosurgery is limited by lowest frequency of 100 kHz, while the recently developed esthetic devices operate at frequencies above 300 kHz.
\nThe typical range of RF is 100 kHz to 5 MHz according to the FDA guidance [11]. This is intended to exclude other frequencies that may technically fall within the RF portion of the electromagnetic spectrum, but operate in a fundamentally different manner. However, there are few products with higher RF frequency of up to 40 MHz. If RF is higher than 5 MHz there is significant radiative component with reduced capability to predict the distribution in the patient’s body and can even potentially affect the treatment attendant.
\nThe ions oscillating in RF field interact with the surrounding tissue, losing its kinetic energy and generating the heat. The heat generated by electrical current in conductive media is described by Joule’s law:
\nThe heat generated in each point of tissue is proportional to tissue conductivity (\n
The Ohm’s low in vector form allows to calculate the density of RF current (
While continuity equation allows to analyze RF current distribution in the tissue
\nThe Eq. 4 states that electrical current coming into any volume of tissue is equal to the current going out of the same volume (Figure 4).
\nSchematic illustration of continuity law.
The other conclusion from the charge continuity equation is that all RF current emanating from one electrode into the tissue flows to the other electrode. The current density on the electrode surface depends on the size of the electrode.
\nPenetration depth of RF energy depends on the electrode geometry and divergence of the RF current inside the tissue. We will determine RF penetration depth as the depth where RF energy is decreased by exponential factor (
RF current distribution for typical geometries of electrodes.
The first case in Figure 5 illustrates small electrode distant from the return electrode. The RF current density and consequently electric field in vicinity of the electrode diverges spherically and current density drops as square of distance from electrodes. Taking into the account that heat is proportional to square of electric field. Therefore, heat created by RF energy can be represented as following:
\nWhere
\nFigure 5b shows two long electrodes having cylindrical surface contacting the tissue. The distance between the electrodes is larger than an electrode size. In this case the heat distribution near the electrode can be calculated using the following equation:
\nThe heating drops by exponential factor at the distance of
The case shown in Figure 5c represents two parallel electrodes having size comparable with the distance between them. Analysis of heat distribution required computer simulation but RF penetration depth can be estimated as half distance between the electrodes [10].
\nThe thermal measurements conducted for the three cases described above are shown in Figure 6.
\nThermal measurements of tissue temperature generated by RF current for typical geometries of electrodes.
Thermal experiments were conducted using porcine tissue and a RF generator with the frequency of 1 MHz and 50 W power. The thermal camera FLIR A320 was used for thermography of tissue during RF application.
\nHeat conductivity, real geometry of electrodes and non-uniformity of tissue effect the thermal imaging but measurements correlate well with theoretical consideration.
\nThe electrical properties of tissue play important role in understanding of RF-tissue interaction.
\nTissue conductivity is a strong function of tissue type. The fundamental article of Gabriel et al. [12] summarized data on electrical conductivity for different types of tissue. Figure 7 shows tissue conductivity of fat and skin in broad range of frequencies.
\nElectrical conductivity of skin and fat as a function of frequency of electrical current.
In the RF range, the tissue conductivity is a weak function of frequency. The tissue has resistive and capacitive properties. The capacitance of tissue in RF diapason is determined by recharging of cell membrane.
\nThe properties of different types of tissue are presented in Table 1.
\nTissue | \nConductivity, S m−1\n | \n
---|---|
Blood | \n0.7 | \n
Skin | \n0.25 | \n
Fat | \n0.03 | \n
Bone | \n0.02 | \n
Tissue conductivity at 1 MHz [12].
Our measurements in-vivo for tumesced adipose tissue show that fat’s conductivity is very similar to the one of skin and is in the range of 1 to 2 S m−1.
\nConductivity of tissue is a function of temperature and is changed in the range of sub-necrotic heating by 2%/oC [13]. Our measurements of tissue conductivity between two electrodes in-vivo showed smaller change for the temperature close to the normal body temperature and larger change when tissue temperature deviated more (Figure 8). The tissue was pre-heated to 43 °C during 15 min and then tissue impedance was measured for short RF pulses during two hours as skin cooled down.
\nImpedance of tissue measured between two electrodes applied to the skin surface.
As tissue is heated to higher temperatures resulting in tissue coagulation and dehydration, the tissue impedance is increased dramatically [10]. Schematic change of tissue impedance as function of temperature is shown in Figure 9.
\nSchematic impedance behavior as function of temperature.
As mentioned above regarding conductivity, heating of tissue reduces its impedance with a rate of about 2% per degree Centigrade [13]. This change is related to reduction of tissue viscosity which is reduced with temperature increase. Coagulation of the tissue causes a chemical change in tissue structure, subsequently changing the trend of impedance behavior. When heating up to 100 °C, the evaporation of liquids dehydrates the tissue, dramatically increasing tissue impedance. Additional heating of the tissue leads to its carbonization. Dependence of tissue conductivity on temperature is utilized by ELOS (Electro optical synergy) technology where tissue is preheated using optical energy creating a preferable path for RF current [14, 15]. This can provide treatment advantages for some applications.
\nThe RF energy can be delivered in continuous wave (CW) mode, burst mode and pulsed mode (Figure 10).
\nTypical RF waveforms.
For gradual treatment of large areas, the CW mode is most useful, allowing for the slow increase in temperature in large tissue volume. It is used for treatment of cellulite, subcutaneous fat and skin tightening. CW mode typically delivered in device intended for moving over the treatment area.
\nThe burst mode delivers RF energy with repetitive pulses of RF energy. It is used in applications where peak power is important while average power should be limited. Such an example would be blood coagulation. Also, it is used in hands free devices where energy is added by small portions maintaining the required temperature.
\nPulsed mode is optimal when small tissue volume should be affected without heat spreading to the surrounding tissue. Pulsed mode is used in micro-needling devices.
\nIn order to create tissue ablation, very high energy density is required. In electro-surgical cutting instruments, a very small electrode, or needle type electrode is used to concentrate electrical current to very small area, which increases the energy density to ablative levels. Coagulation instruments, which create energy and thermal profiles coagulating the cells and shrinking the collagen, usually have larger surface area electrodes than ablative devices. Typically, the surface area of such electrodes is a few square millimeters to generate heat in larger volume but at a lower level to create coagulation rather then ablation. Sub-necrotic heating is usually used for treatments related to stimulation of natural processes in the tissue, such as collagen remodeling, revascularization, speeding fat metabolism. In this case the spot size is about 1 square centimeter or larger. Schematical illustration of spot size effect is shown in Figure 11.
\nThe effect of electrode size, or spot size on the energy and power density.
Generally, the smaller the electrode, the higher the energy density and the effect tends to be ablative (e.g., cutting cautery tips), whereas larger sized electrodes, have a gentler tissue effect, either coagulation (hemostasis) or sub-necrotic tissue heating [16].
\nRF current always flows between two electrodes having opposite polarity. The FDA definition of monopolar devices relates to the size and position of electrodes in respect to patient during the treatment. According to FDA guidance [11], monopolar is an electrosurgical technique in which the current flows from a single active electrode at the surgical site, through the patient, to a relatively distant return electrode.
\nThe most common feature of a mono-polar device is a single electrode applied in the treatment area while the return electrode has a much larger contact surface and is placed outside of the treatment zone, usually in the form of a grounding pad. In this electrode geometry, the high RF current density is created near the active electrode and RF current diverges toward the large return electrode. The heat zone for this geometry can be estimated using analytic spherical model for continuity equation stating that electrical current flows continuously from one electrode to another.
\nTaking into account Ohm’s law in differential form (Eq. 3) and the definition of an electric field, Eq. 5 can be rewritten as:
\nWhere
Where
For the instance when the return electrode is much larger than the active electrode, the equation can be simplified as:
\nCorrespondently, heat power according to Joule’s law can be estimated as:
\nThis simple equation leads to a few interesting conclusions:
\nHeat generated by RF current near the active electrode does not depend on position of the return electrode when return electrode is much larger in size than the active electrode and located at a distance which is much larger than the active electrode size.
\nHeating decreases dramatically as distance increases from the active electrode. As was shown before, RF energy penetration depth is about one third of electrode radius (Figures 5 and 6). However, heating temperature on the electrode surface may reach hundreds of degrees centigrade and coagulation effect may be extended much larger than RF penetration depth. The other factor enlarging thermal zone is heat conductivity spreading heat around.
\nRF current behavior in the body for monopolar systems is visualized schematically in Figure 12.
\nSchematic RF current distribution between electrodes for monopolar system.
RF current is concentrated on the active RF electrode and rapidly diverges toward the return electrode.
\nMonopolar devices are most commonly used for tissue cutting. Schematically, the RF current flow through the patient for monopolar devices is shown in Figure 13.
\nElectrical current flowing through the patient and monopolar electrosurgical device.
The RF current is always flowing through a closed loop via the human body. As we showed above, the current density out of the vicinity of the return electrode is negligible. However, a malfunction where some low frequency current escapes out of a monopolar configuration holds high risk because the entire body is exposed to the electrical energy. Most commercially available devices have isolated output to avoid any unexpected RF current path to the surrounding metal equipment.
\nTreatment effects with monopolar devices depend on RF power and size of electrode. The classic use of monopolar technique is tissue cutting and ablation while occasionally it is used for soft tissue coagulation or sub-necrotic heating [9, 17, 18, 19].
\nThe main features of monopolar devices are:
Predictability of thermal effect near the active electrode
Ability to concentrate energy on a very small area
High non-uniformity of heat distribution which is strong at the surface of the active electrode and is reduced dramatically at a distance exceeding the size of electrode, thereby limiting penetration depth
According to FDA [11], bipolar is an electrosurgical device in which the current flows between two active electrodes placed in close proximity. In bipolar devices both electrodes create a similar thermal effect and are applied to the tissue treatment area (Figure 14). Bipolar devices create larger thermal zones and this circuit is used in electro-coagulators. The advantage of bipolar systems is the localization of all RF energy in the treatment zone (Figure 14).
\nElectrical current flowing through the patient and bipolar electrosurgical device.
Bipolar devices concentrate all RF energy between electrodes in the treatment area. This geometry is more suitable than a monopolar system to create uniform heating in larger volume of tissue. In order to understand heat distribution between electrodes the following three rules should be taken into the account:
Heating is always higher near the electrode’s surface and reduces with a distance because of current divergence. Divergence of RF current between electrodes reduces current density and correspondently generated heat.
For any geometry, RF current density is higher along the line of shortest distance between the electrodes and reduced with distance from the electrodes.
RF current is concentrated on part of the electrode having high curvature creating the hot spots.
A schematic distribution of electrical currents in uniform media in bipolar device is shown in Figure 15.
\nElectrical current distribution for bipolar system.
In bipolar devices, both electrodes create an equal thermal effect near each of the electrodes and the divergence of RF current is not as strong because of the small distance between the electrodes. For bipolar systems shown in Figure 15, most of the heat is concentrated between the electrodes.
\nPenetration depth of RF for bipolar devices is a function of electrode size and the distance between them. By increasing the distance between the electrodes, the electrical current can go deeper, but divergence is also increased. In case the distance between the electrodes is much larger than the electrode size, the heating profile will be similar to two monopolar electrodes. Schematically, bipolar current distribution and measured thermal effect are presented in Figures 5b and 6b, respectively.
\nThe most uniform distribution of RF current is obtained in planar geometry when tissue is placed between two large parallel electrodes. This can be realized when negative pressure forces the tissue to fill the cavity between the parallel electrodes. Measured RF energy distribution for the cavity filled with the tissue is shown in Figure 16.
\nThermal image of heat distribution created in the skin folded between two parallel electrodes.
High frequency current is able to penetrate through the dielectric material which behaves as capacitor. This effect is used to isolate metal electrode from patient. This method is called capacitive coupling. There are a number of devices in the medical esthetic market that use this technology for RF delivery [18, 19].
\nThe capacitance of planar dielectric layer is described by the following equation:
\nWhere \n
Impedance of the dielectric layer depends on frequency of current (f)
\nFor example, polyimide layer with area of 4cm2 and thickness of 100micron has capacitance of about 106 pF and impedance of this layer is 1.5 kOhm at 1 MHz and 375 Ohm at 4 MHz.
\nFor cylindrical geometry capacitance is represented by the following equation
\nWhere
The leakage of RF current through the dielectric coating should be taken into the account at design of electro-surgical instruments.
\nThe temperature dissipation is characterized by thermal relaxation time (TRT) of the targeted area. For localized treatment, in order to avoid significant heat transfer, the pulse duration should be less than the TRT.
\nThe TRT is a function of tissue thermal properties, heated volume shape and size. Soft tissue has thermal properties close to the water.
\nFor the planar object the TRT can be estimated as [20].
\nWhere
For a cylindrical object, such as a blood vessel or hair, a similar equation can be used with different geometrical factors.
\nwhere
Thermal relaxation time should be taken in to the account when thermal effect should be localized. It is critical in fractional RF technologies when thermal coagulation should by limited by small zones around the needle electrodes.
\nThe thermal effect of RF on tissue is not different from laser or any other heating method. Multiple studies [21, 22] discuss the temperature effect on tissue. Since treatment effect is not only a function of temperature, but also of the period of time (when this temperature is applied), it is known that in the millisecond range the coagulation temperature is 70-90 °C, while if temperature is applied for a few seconds, the temperature of 45 °C causes irreversible damage. Hyperthermia studied intensively for treatment of cancer confirms strong dependance of tissue vitality on time that temperature is maintained [23]. RF induced hyperthermia was measured for adipocytes in a clinical study [24]. The fat cell viability was 89% after RF heating for 1 min at 45 °C while after heating during 3 min the vitality dropped down to 40% (Table 2).
\nTemperature | \nTissue effect | \n
---|---|
37-44 °C | \nAcceleration of metabolism and other natural processes. | \n
45–50 °C | \nConformational changes, hyperthermia (cell death) | \n
50–80 °C | \nCoagulation of soft tissue | \n
50–80 °C | \nCollagen contraction | \n
90–100 °C | \nFormation of extracellular vacuoles, evaporation of liquids | \n
>100 °C | \nThermal ablation, carbonization | \n
Tissue thermal effect.
There is extensive data on the correlation between tissue temperature, pulse duration and treatment effect. Moritz and Henriques demonstrated that the skin thermal damage threshold is a function of temperature and time [25]. Later it was demonstrated that skin damage function can be described by Arrhenius equation where pre-exponential factor is a linear function of pulse duration [22].
\nPulse duration is one of the most critical parameters when utilizing RF energy in order to achieve a clinical response. It affects treatment results because timing influences the thermo-chemical process in tissue. The other effect of pulse duration is energy dissipation away from the treatment zone due to heat conductivity from the exposed area to the surrounding tissue.
\nIn other words, the degree of damage is a linear function of pulse duration and an exponential factor of tissue temperature. This means that tissue temperature is more influential on the degree of damage than the pulse duration.
\nIt is well known that sustained hyperthermia at 42 °C for tens of minutes causes death of most sensitive cells such as in the brain [26]. In laser medicine the pulse duration in the millisecond range causes tissue to burn at a temperature above 60-70 °C.
\nDehydration and carbonization of the ablated treated tissue may cause the accumulation of a non-conductive tissue layer on the electrode surface. This tissue is sometimes called eschar and if it accumulates on the surface of the treatment electrode, it may affect significantly the energy delivery to the electrode and hence the treatment zone or even damage the hand piece. Carbonization or Eschar reduces or totally blocks the working area of electrodes and affects treatment efficiency, reducing the electrical current flow to the tissue (Figure 17).
\nCutting Bovie electrocautery, with an eschar built upon the fine needle tip.
Usually, the surgeon must clean an electro-surgical instrument periodically during the treatment to remove any eschar from the treatment electrode. Alternatively, companies, like InMode created a technological solution avoiding this problem. In InMode devices, impedance monitoring measures the increase resistance to flow (increased impendence) caused by eschar on one of the electrodes and cuts off the RF energy and flow of RF current briefly, minimizing the risk of the eschar built up at all.
\nThe most important tissue modification induced by RF heating is a contraction of collagenous tissue. This effect is known for decades and is used intensively in orthopedy [27, 28] and ophthalmology [29].
\nSkin contraction was a primary focus for the first RF devices in esthetic medicine [9, 15, 17, 19]. Only in the last decade there is the understanding that the skin appearance is more affected by collagen in the reticular dermis and fibro septal network (FSN) binding skin with superficial fascia and muscles. A study published in 2011 [30] showed that skin has very dense collagenous tissue and shrinkage of collagen fibers is limited, while connective tissue in the subdermal space may contract above 30% during a few seconds of heating. The threshold temperature for collagen contraction was measured in the range of 60-70 °C.
\nIn the experiments in our facility, the contraction of FSN was quantified on ex-vivo post abdominoplasty human tissue. The area was marked proximal to the RFAL cannula tip and monitored during RF energy application. The resulting measurements are presented in Figure 18.
\nSubcutaneous fat before and after application of RF energy.
One can see that thermal exposure of subcutaneous tissue with RF energy during three seconds resulted in area contraction by 42%.
\nRFAL technology was developed by InMode Ltd. to improve treatment results during liposuction procedure. The thermal contraction of collagen in dermis and subdermal FSN allows treatment of patients with saggy skin and patients for whom previously excessive skin was a main concern [31].
\nThe uniqueness of RFAL technology is that it does not fall under any standard device definitions. It combines features of monopolar and bipolar technologies, minimally-invasive and non-invasive technologies, creating very specific energy profile treating simultaneously subcutaneous fat, connective tissue forming FSN and dermis. Each of these tissue components requires different thermal exposure. Adipose tissue should be destroyed, FSN should be remodeled without denaturation of collagen while skin should be exposed to sub-necrotic heat to modify it without superficial burn [31, 32, 33].
\nThe RFAL device geometry is shown in Figure 19. The RF current flows back and forth from the internal electrode (cannula tip), where the thermal effect is coagulative, to a larger, external electrode. The external electrode moves along the skin surface, in tandem with the internal electrode and creates a gentle, non-ablative bulk heating effect on the dermis. Ratio between size of internal and external electrode is selected to limit skin heating at sub-necrotic heating while temperature in the fat should reach 50-70 °C.
\nSchematic depiction of RFAL treatment geometry.
Moving the hand piece back and forth through the intended treatment area, uniform coagulation of adipose and vascular tissue is achieved. While the external electrode is always moved over the skin surface, the internal electrode should pass through the deep, intermediate and/or superficial fat layers to treat the adipose tissue up to the depth of 5 cm. The Lipo-coagulation, results in liquefaction of the adipose tissue, hemostasis and stimulated contraction of adjacent vertical, oblique and horizontal fibers of the FSN, that connects the overlying soft tissue to the underlying muscle.
\n\nFigure 20 shows thermal profile created by RFAL cannula inside porcine tissue.
\nThermal profile in the tissue created by RFAL device.
The temperature around the internal electrode is 70 °C. The volume exposed to high temperature around the cannula. The tissue between internal and external electrode is exposed to directional RF flowing between the electrodes.
\nComputer simulation shows similar thermal profile (Figure 21) to the measured thermography.
\nComputer simulation of temperature field created by RFAL device.
One of the advantages of RF energy is that it is can be delivered into the body though the very tiny sub-millimeter cannula. That allows to minimize incision and mechanical trauma at treatment of such delicate zones as face and neck [33]. Large size cannula results in higher non-uniformity and especially for subcutaneous fat.
\nAnother RF based technology enhancing liposuction results is micro needling RF. The fractional coagulation of subcutaneous tissue helps tight the skin and reduce skin sagginess after liposuction [34].
\nFractional skin treatment was introduced in esthetic medicine about two decades ago and has become one of the most popular modalities for the improvement of skin quality. This procedure is based on the coagulation of multiple small spots with a size of 100 microns to 0.5 millimeter. This allows the procedure to be very tolerable and with relatively short down-time. Focused laser beams or needle sized RF electrodes are used for ablation of micro-spots resulting in high efficiency and consistency of the treatment, with low risk of side effects and fast skin healing.
\nIn contrast to lasers where the thermal effect is limited by the ablation crater, the RF energy flows through the whole dermis, adding volumetric heating to fractional treatment. This volumetric bulk heating adds a skin tightening effect to the more superficial improvement generated by tissue ablation.
\nRF fractional technologies are differentiated by needle length and size. The flat electrodes provide a more superficial effect improving texture and fine lines [34, 35] while longer needles penetrate deeper, providing deeper dermis remodeling and causing substantial skin tightening [36].
\nThe needles can penetrate to the different depths allowing epidermal ablation and deep subdermal treatment. Recently the FDA cleared Morpheus8 device of InMode Ltd. for treatment up to depth of 7 mm.
\n\nFigure 22 shows Morpheus8 tip schematically with needles extended to the subdermal fat.
\nSchematic illustration of Morpheus8 tip with needles penetrating into the sub-dermal space.
Needles coated with polymer and releasing RF energy only at the needle end provide better protection of epidermis and provide lower down time.
\nA microscope image of a coated needle is shown in Figure 23. The gold plated needle has diameter of 0.3 mm and coated with polymer of 20 microns thickness.
\nCoated needle.
There are several different configurations of RF electrodes for micro-needling devices. The most common configuration is by applying RF energy between adjacent rows of needle electrodes. This method creates a coagulation zone in vicinity of the needle end.
\nThe alternative technology is used in the InMode Morpheus8 device where RF energy is applied between the needle and an external electrode applied to the skin surface. Each needle has a strong thermal effect near the needle end and gradient of bulk heating toward the external electrode, similar to RFAL technology. Each needle generates small bulk heating but superposition of the heat from multiple needles results in essential thermal effect. Morpheus8 device automatically treats tissue in multiple layers delivering RF energy sequentially during needle retraction. This burst mode creates three-dimensional matrix of coagulation zones and strong bulk heating. Schematically the burst mode treatment is shown in Figure 24.
\nSchematic illustration of burst mode treatment using Morpheus8 device.
Micro needling technology was developed for treatment of facial wrinkles but further development of the technology has extended its use to treat the body as well.
\nThe micro needling technology supplements both regular liposuction and energy-based minimally invasive technologies and addresses the first few millimeters of body coagulating adipose tissue and tightening FSN.
\nOne of the risks of any thermal treatment (laser, ultrasound, plasma or RF) is the possibility of a thermal skin injury. Thermal treatment in subcutaneous or subdermal layers may create full thickness skin burn. Therefore, monitoring of delivered energy, predictability of energy distribution and accurate measurement of tissue parameters during the treatment has crucial importance for the energy-based devices.
\nNon uniform treatment or over-heating the treatment area may result in the risk of unwanted thermal damage to the skin during the treatment. To avoid or minimize this risk of a skin burn, real time thermal measurements are necessary. There are two basic methods of skin temperature measurements:
Infrared (IR) thermometers measuring IR radiation of heated object.
Contact measurements using a thermocouple, thermistor or thermo-transistors.
Advantages of IR thermometers is the speed of measurements and that they do not need to be built into the device thus are independent of the treatment. The obvious weakness of this method is collecting IR radiation from relatively large area which depends on distance from the measured area. You are also relying on a third party that is not linked in time of space to the thermal treatment being performed. Most importantly, you are not measuring the internal thermal profile.
\nA typical IR thermometer measures area which depends on distance between skin and thermometer and it varies from 1cm2 to a few square inches at large distance from the patient. It allows you to monitor average skin temperature in treatment area but does not protect from appearance of small hot spots that lead to the full thickness skin burns.
\nThe thermistors or thermocouples are extremely miniature and can be embedded into the electro-surgical instrument. Limitation of such contact measurements is response time which depends on heat transfer from the tissue to the sensor. However, special design allows to reduce response time to sub-second range.
\nIdeally, the user should know the temperature inside the body where energy is utilized for the fat coagulation and FSN tightening, and temperature on the skin surface above the treatment zone to ensure skin safety.
\nIn addition, during the procedure sophisticated mechanisms monitor the tissue temperature together with its dynamic characteristics as the speed of temperature rise, allowing precautional measures before the critical temperature is reached.
\nTemperature monitoring for EBD is important not only for safety but also for treatment efficacy. Collagen contraction occurs in relatively narrow range of temperatures from 50 °C to 80 °C and overheating may result in denaturation of collagenous tissue and uncontrolled scar formation.
\nRFAL technology has maximum thermal safety measurements including:
Skin temperature monitoring;
Fat temperature monitoring;
Temperature surge protection catching fast temperature changes.
Most types of energy cannot be monitored directly but rather electrical supply to the energy source is monitored. RF energy has unique properties resulting from continuity Eq. (4) allowing to measure RF voltage and RF current flowing through the tissue and get in real time all information about energy deposition in the tissue. Measurement of electrical RF parameters is not difficult engineering project and it can be performed every micro-second that allows to control the RF energy delivery even for very short pulses.
\nMeasurements of RF current (
and Joule’s law
\nThe RF energy can be calculated as integral of RF power measurement over the time:
\nRFAL and Morpheus8 technologies of InMode Ltd. utilize all these measurements to control the treatment safety and efficacy.
\nMeasurements of tissue impedance should be considered separately because of importance of this parameter for different aspects of treatment. The most obvious use of the impedance measurements is indication of contact between electrodes and treated tissue. Contact measurements are important to avoid poor coupling of the RF device with patient and avoid arcing. Contact monitoring has become a common feature for most RF-based devices.
\nReferring to Figure 9 one can see that coagulation, dehydration of tissue and eschar formation result in impedance increase. Monitoring of tissue impedance can be used to limit heating process and avoid undesired treatment effect.
\nAnother use of impedance monitoring is to control the lower limit, which may indicate that the distance is too small between electrodes. In RFAL technology it is used to reduce the risk of the cannula coming too close to the skin surface.
\nAll above mentioned measurements of RF parameters worth nothing if its not used for enhanced treatment safety helping physician to optimize the procedure.
\nThe BodyTite device from InMode Ltd. uses RFAL technology, combines the maximal number of safety features, and should be used as the gold standard for safety features for RF devices.
\nPerforming liposuction, the physician should be concentrated on safe manipulation with the minimally invasive accessory. Safety features related to the thermal component of the treatment should be implemented in automatic or in a very intuitive way not disturbing physician attention.
\nThe skin impedance for each patient is different and may vary for the different treatment zones, amount of tumescent applied or treatment depth. RF energy is adjusted by the device automatically to provide the required optimal energy to the patient.
\nTissue impedance is monitored constantly by the BodyTite and the device automatically cuts RF energy if some of the limits are exceeded.
\nThe user may set desired temperature cut-off limits for skin and internal electrode. The device applies full power when the temperature is significantly below the threshold and starts to reduce power automatically as treatment approaches the required target temperature. This scheme allows to avoid thermal overshooting and maintains desired heat profile. RF energy delivery is accompanied by an audible signal which speeds up as the cut-off temperature is approached, similar to modern car approaching wall while parking. RF power is switched on and off automatically to maintain the desired temperature as the user scans the treatment area with the cannula.
\nIf the cannula accidentally comes too close to the dermis, the tissue volume between the electrodes is reduced and the applied RF power heats the tissue extremely fast. To address this issue, a temperature surge protection is implemented in BodyTite device. When the temperature sensor measures a temperature increase as too fast, the device automatically shuts RF energy and produces an audible sound to attract the physician’s attention.
\nRF based medical devices are a common tool for plastic surgeons, used during most surgical procedures. RFAL and RF fractional technologies have become important modalities for about 20% of plastic surgeons, for enhancing liposuction results or by its own for patients for whom reduction of adipose compound is not a main esthetic goal. Over the last 100 years extensive knowledge has been acquired about RF technology and RF-tissue interaction. The information in this chapter can help a potential buyer of new equipment make a rational choice, based on goals of treatment and physics of the RF device in question. Even more importantly, expanding the physician’s understanding of his or her devices already in use can maximize treatment outcomes and minimize unwanted side effects and complications.
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Ciurean, Dagmar Schröter and Thomas Glade",authors:[{id:"163703",title:"Prof.",name:"Thomas",middleName:null,surname:"Glade",slug:"thomas-glade",fullName:"Thomas Glade"},{id:"164141",title:"Ph.D. Student",name:"Roxana",middleName:"Liliana",surname:"Ciurean",slug:"roxana-ciurean",fullName:"Roxana Ciurean"},{id:"164142",title:"Dr.",name:"Dagmar",middleName:null,surname:"Schroeter",slug:"dagmar-schroeter",fullName:"Dagmar Schroeter"}]},{id:"58010",doi:"10.5772/intechopen.72304",title:"Fourth Industrial Revolution: Current Practices, Challenges, and Opportunities",slug:"fourth-industrial-revolution-current-practices-challenges-and-opportunities",totalDownloads:6315,totalCrossrefCites:41,totalDimensionsCites:67,abstract:"The globalization and the competitiveness are forcing companies to rethink and to innovate their production processes following the so-called Industry 4.0 paradigm. It represents the integration of tools already used in the past (big data, cloud, robot, 3D printing, simulation, etc.) that are now connected into a global network by transmitting digital data. The implementation of this new paradigm represents a huge change for companies, which are faced with big investments. In order to benefit from the opportunities offered by the smart revolution, companies must have the prerequisites needed to withstand changes generated by “smart” system. In addition, new workers who face the world of work 4.0 must have new skills in automation, digitization, and information technology, without forgetting soft skills. This chapter aims to present the main good practices, challenges, and opportunities related to Industry 4.0 paradigm.",book:{id:"6291",slug:"digital-transformation-in-smart-manufacturing",title:"Digital Transformation in Smart Manufacturing",fullTitle:"Digital Transformation in Smart Manufacturing"},signatures:"Antonella Petrillo, Fabio De Felice, Raffaele Cioffi and Federico\nZomparelli",authors:[{id:"161682",title:"Prof.",name:"Fabio",middleName:null,surname:"De Felice",slug:"fabio-de-felice",fullName:"Fabio De Felice"},{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"},{id:"205141",title:"Dr.",name:"Federico",middleName:null,surname:"Zomparelli",slug:"federico-zomparelli",fullName:"Federico Zomparelli"},{id:"208748",title:"Dr.",name:"Raffaele",middleName:null,surname:"Cioffi",slug:"raffaele-cioffi",fullName:"Raffaele Cioffi"}]},{id:"40977",doi:"10.5772/53885",title:"The Emergence of Scientific Reasoning",slug:"the-emergence-of-scientific-reasoning",totalDownloads:4501,totalCrossrefCites:7,totalDimensionsCites:56,abstract:null,book:{id:"654",slug:"current-topics-in-children-s-learning-and-cognition",title:"Current Topics in Children's Learning and Cognition",fullTitle:"Current Topics in Children's Learning and Cognition"},signatures:"Bradley J. 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Therefore, this chapter deals with the philosophical systems and paradigms of scientific research, the epistemology, evaluating understanding and application of various theories and practices used in the scientific research. The key components of the scientific research paradigm are highlighted. Theories on the basis of which this research was focused on identification of the level of development of the management culture in order to implement corporate social responsibility are identified, and the stages of its implementation are described.",book:{id:"5791",slug:"management-culture-and-corporate-social-responsibility",title:"Management Culture and Corporate Social Responsibility",fullTitle:"Management Culture and Corporate Social Responsibility"},signatures:"Pranas Žukauskas, Jolita Vveinhardt and Regina Andriukaitienė",authors:[{id:"179629",title:"Prof.",name:"Jolita",middleName:null,surname:"Vveinhardt",slug:"jolita-vveinhardt",fullName:"Jolita Vveinhardt"}]},{id:"74550",title:"School Conflicts: Causes and Management Strategies in Classroom Relationships",slug:"school-conflicts-causes-and-management-strategies-in-classroom-relationships",totalDownloads:2098,totalCrossrefCites:1,totalDimensionsCites:10,abstract:"Conflicts cannot cease to exist, as they are intrinsic to human beings, forming an integral part of their moral and emotional growth. Likewise, they exist in all schools. The school is inserted in a space where the conflict manifests itself daily and assumes relevance, being the result of the multiple interpersonal relationships that occur in the school context. Thus, conflict is part of school life, which implies that teachers must have the skills to manage conflict constructively. Recognizing the diversity of school conflicts, this chapter aimed to present its causes, highlighting the main ones in the classroom, in the teacher-student relationship. It is important to conflict face and resolve it with skills to manage it properly and constructively, establishing cooperative relationships, and producing integrative solutions. Harmony and appreciation should coexist in a classroom environment and conflict should not interfere, negatively, in the teaching and learning process. This bibliography review underscore the need for during the teachers’ initial training the conflict management skills development.",book:{id:"7827",slug:null,title:"Interpersonal Relationships",fullTitle:"Interpersonal Relationships"},signatures:"Sabina Valente, Abílio Afonso Lourenço and Zsolt Németh",authors:null},{id:"58969",title:"Corruption, Causes and Consequences",slug:"corruption-causes-and-consequences",totalDownloads:27405,totalCrossrefCites:11,totalDimensionsCites:13,abstract:"Corruption is a constant in the society and occurs in all civilizations; however, it has only been in the past 20 years that this phenomenon has begun being seriously explored. It has many different shapes as well as many various effects, both on the economy and the society at large. Among the most common causes of corruption are the political and economic environment, professional ethics and morality and, of course, habits, customs, tradition and demography. Its effects on the economy (and also on the wider society) are well researched, yet still not completely. Corruption thus inhibits economic growth and affects business operations, employment and investments. It also reduces tax revenue and the effectiveness of various financial assistance programs. The wider society is influenced by a high degree of corruption in terms of lowering of trust in the law and the rule of law, education and consequently the quality of life (access to infrastructure, health care). There also does not exist an unambiguous answer as to how to deal with corruption. Something that works in one country or in one region will not necessarily be successful in another. This chapter tries to answer at least a few questions about corruption and the causes for it, its consequences and how to deal with it successfully.",book:{id:"6487",slug:"trade-and-global-market",title:"Trade and Global Market",fullTitle:"Trade and Global Market"},signatures:"Štefan Šumah",authors:[{id:"228073",title:"Mr.",name:"Stefan",middleName:null,surname:"Sumah",slug:"stefan-sumah",fullName:"Stefan Sumah"}]},{id:"55499",title:"Human Resources Management in Nonprofit Organizations: A Case Study of Istanbul Foundation for Culture and Arts",slug:"human-resources-management-in-nonprofit-organizations-a-case-study-of-istanbul-foundation-for-cultur",totalDownloads:2198,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The aim of this study is to investigate the efficiency and importance of human resources management in nonprofit organizations. The understanding was included to the literature as personnel management at the beginning of the twentieth century and it turned into an approach as human resources management in the 1980s. It could be observed that many organizations, which deem the human as the most critical stakeholder, adopt a traditional way of personnel management in operating human resources. The employees play a key role in the success of an organization. For this reason, subjects such as recruitment, training, development, career management, performance appraisal, occupational health, and safety are the fundamental functions of human resources management. The study examines to what extent these roles are evaluated through a case study. The subject matter of the study is the most powerful culture and art foundation in Turkey. Compared to many other nonprofit organizations, the foundation actively performs a variety of services within a year worldwide. The fact that the total number of employees might rise up to 800, including the field personnel, indicates the need of a good functioning human resources management. The human resources practices of the foundation are examined and evaluated within that scope.",book:{id:"5826",slug:"issues-of-human-resource-management",title:"Issues of Human Resource Management",fullTitle:"Issues of Human Resource Management"},signatures:"Beste Gökçe Parsehyan",authors:[{id:"189113",title:"Dr.",name:"Beste",middleName:null,surname:"Gokce Parsehyan",slug:"beste-gokce-parsehyan",fullName:"Beste Gokce Parsehyan"}]},{id:"59152",title:"Marketing Strategies for the Social Good",slug:"marketing-strategies-for-the-social-good",totalDownloads:1534,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Social network sites (SNS) have proven to be a good environment to promote and sell goods and services, but marketing is more than creating commercial strategies. Social marketing strategies can also be used to promote behavioral change and help individuals transform their lives, achieve well-being, and adopt prosocial behaviors. In this chapter, we seek to analyze with a netnographic study, how SNS are being employed by nonprofits and nongovernment organizations (NGOs) to enable citizens and consumers to participate in different programs and activities that promote social transformation and well-being. A particular interest is to identify how organizations are using behavioral economic tactics to nudge individuals and motivate them to engage in prosocial actions. By providing an understanding on how SNS can provide an adequate environment for the design of social marketing strategies, we believe our work has practical implications both for academicians and marketers who want to contribute in the transformation of consumer behavior and the achievement of well-being and social change.",book:{id:"6583",slug:"marketing",title:"Marketing",fullTitle:"Marketing"},signatures:"Alicia De La Pena",authors:[{id:"196878",title:"Dr.",name:"Alicia",middleName:null,surname:"De La Pena",slug:"alicia-de-la-pena",fullName:"Alicia De La Pena"}]}],onlineFirstChaptersFilter:{topicId:"4",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81882",title:"The Importance of Supporting Creativity Development as the Main Skill of the Twenty-First Century",slug:"the-importance-of-supporting-creativity-development-as-the-main-skill-of-the-twenty-first-century",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.104919",abstract:"This chapter calls into question the ways of creativity development as the main skill of the twenty-first century. Attention is paid to the analysis of key notions and concepts of creativity. This chapter discusses how to enhance creative thinking skills during training in higher institutions. The study presents the results gained from the literature overview. The examples of assignments aimed at creative thinking skills development during training are given. The paper investigates approaches to the construction of tasks to develop creative thinking and criteria for creativity assessment. An analysis has allowed highlighting the positive experience of different experts researched creativity, which can be implemented in future training in Ukrainian higher educational institutions. The findings of this study support the idea that heuristic tasks, creative projects, mind maps, and case study are significant assignments in the enhancement of creativity development that can be supported in the educational process and everyday life.",book:{id:"11303",title:"Creativity",coverURL:"https://cdn.intechopen.com/books/images_new/11303.jpg"},signatures:"Iryna Simkova, Kateryna Tuliakova, Oksana Serheieva and Oksana Pastushenko"},{id:"81735",title:"Research Status in Computational Thinking in STEM Education",slug:"research-status-in-computational-thinking-in-stem-education",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.104472",abstract:"Computational thinking (CT) is an approach to problem-solving that has its roots in computer science. However, its inherent value in the science, technology, engineering, and mathematics (STEM) disciplines cannot be over-emphasized, considering that we are in the fourth industrial revolution. The chapter draws attention to its close affinity to problem-solving and programming, and the impact of computational thinking on the labour market, and in turn the digital economy is highlighted. A global overview of recent research findings and initiatives to implement CT education in school curricula are discussed. Because of the importance of STEM education, and the inherent value of CT, it is necessary to explore the status and inclinations of CT in STEM disciplines. Hence, a snapshot of research over the last two years was used in a systematic review to determine the trends and challenges for integrating CT in the curriculum of STEM related fields. Using the ERIC database of journals, and specific criteria for selection of publications, 31 articles were examined in this study. Overall, it was found several tools and instructional strategies are used to develop CT, but more needs to be done to increase teachers’ knowledge and enactment for CT in the STEM fields.",book:{id:"11279",title:"Advances in Research in STEM Education",coverURL:"https://cdn.intechopen.com/books/images_new/11279.jpg"},signatures:"Irene Govender"},{id:"81642",title:"Sustainability of Soil Chemical Properties and Nutrient Relationships in Dairy and Beef Cattle in Antioquia, Colombia",slug:"sustainability-of-soil-chemical-properties-and-nutrient-relationships-in-dairy-and-beef-cattle-in-an",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.104647",abstract:"This chapter has been written with the purpose of increasing knowledge regarding the characteristics of soils dedicated to dairy and beef cattle farming in Antioquia, Colombia. Statistical analysis included several generalised additive models, with additive, smoothing, and tensor effects, such as geographic position and chemical parameters. Findings showed most farms belonged to small producers, 86.5% of cattle farms being family owned. Rotational grazing is the predominant system in 93% of farms; 58% of dairy farms and 94% of beef cattle farms do not fertilise their pastures. Results show high variability of soil chemical parameters. There are high levels of iron and low levels of sodium. Macronutrients, such as phosphorus and potassium show high levels in some dairy subregions and medium to low levels in others. Calcium (Ca) and magnesium levels are low for all subregions, excluding “Urabá” and “Occidente.” Most subregions have organic matter (OM) levels below 13%. The distribution of some chemical parameters is related to geographical location, such as pH and Ca, which change according to latitude and longitude. Different correlations were found amongst OM, total nitrogen, Ca, and exchangeable aluminium. Due to the high variability of soil fertility parameters, management programmes should be implemented for each distinctive production system.",book:{id:"11253",title:"Sustainable Rural Development",coverURL:"https://cdn.intechopen.com/books/images_new/11253.jpg"},signatures:"Marisol Medina-Sierra, Mario Cerón-Muñoz and Luis Galeano-Vasco"},{id:"81831",title:"Deep Network Model and Regression Analysis using OLS Method for Predicting Lung Vital Capacity",slug:"deep-network-model-and-regression-analysis-using-ols-method-for-predicting-lung-vital-capacity",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.104737",abstract:"With the advancement of technology, many new devices and methods with machine learning and artificial intelligence (ML-AI) have been developed and these methods have begun to play an important role in human life. ML-AI technology is now widely used in many applications such as security, military, communications, bioengineering, medical treatment, food industry, and robotics. In this chapter, deep learning methods and medical usage techniques that have become popular in recent years will be discussed. Experimental and simulation results and a comprehensive example of the biomedical use of the deep network model will be presented. In addition, the regression analysis using the ordinary least squares (OLS) method for estimating lung vital capacity (VC) will be discussed. The simulation results showed that the VC parameter was predicted with higher than 90% accuracy using the proposed deep network model with real data.",book:{id:"11604",title:"Decision Science - Recent Advances and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11604.jpg"},signatures:"Harun Sümbül"},{id:"81829",title:"Down to Earth?: A Crisis of the Environmental Crisis",slug:"down-to-earth-a-crisis-of-the-environmental-crisis",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.104595",abstract:"Are we down to earth in our connection to earth? If we are environmentalists concerned with “environmental crisis,” then does our guiding notion of “environment” (and the by necessity implied notion of a center—most often with a human there) get closely enough to the earth? Departing from either localism or cosmopolitanism in thinking earth, globe, and the environment, this chapter aims at a theoretical critique of the very notion of “environment” as the guiding notion of what the expression “environmental crisis” spells. Perhaps, “environmental crisis” is less a description of “our” situation, and more an indication of a problem formulated not strongly enough? The notion of “environment” and “environmental crisis” predetermines the currently regnant approaches to global warming, air and soil pollution, nature preservation, and reducing the human impact on the environment. At the same time, the notion of “environment” steers its adherents toward the modern natural science as both (1) the ultimate contributor to the environmental crisis due to technology and (2) the ultimate instrument to save us from the apocalyptic swirl, in which technology drives humanity. Linking environmental crisis to science, which is only an instrument of both its creation and management, forecloses a more fundamental human dimension of that crisis. This essay asks to attend to one element of that more fundamental dimension.",book:{id:"11429",title:"Sustainability, Ecology, and Religions of the World",coverURL:"https://cdn.intechopen.com/books/images_new/11429.jpg"},signatures:"Sergey Dolgopolski"},{id:"81771",title:"Psychotherapy in Nature: Exploring an Alternative Psychotherapeutic Framework to Address the Limitations of Working in Traditional Settings in Order to Move with the Times",slug:"psychotherapy-in-nature-exploring-an-alternative-psychotherapeutic-framework-to-address-the-limitati",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.104627",abstract:"This paper introduces nature therapy and single session therapy as alternative psychotherapeutic frameworks in addition to more traditional ways of working, offering a modern perspective on evolving societal and individual needs. In particular, the concern for human coping mechanisms and survival in today’s fast paced environment dictates a growing need to address conflicts of inner and outer lived experiences, dissociation, and trauma, where traditional settings are failing or inadequate. Ethical considerations and applications for working outside in nature are discussed, as well as limitations for traditional settings. This paper can be used as an introductory guide for practitioners seeking to work therapeutically in nature.",book:{id:"11305",title:"Counseling and Therapy - Recent Developments in Theories and Concepts",coverURL:"https://cdn.intechopen.com/books/images_new/11305.jpg"},signatures:"Philippa Williams"}],onlineFirstChaptersTotal:314},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems.
\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.