Typical Absorption of CocoPLs and CocoPEs functional groups.
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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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He received from the Montpellier University his Ph.D. in 1986. He was a post-doctoral laureate fellow (1987-8) on molecular biology at CNRS. From this date, he has been heading/coordinating several dozens of projects on viral pathogenesis (eg: HIV, Dengue, Hantavirus, Ebola, SARS-CoV-2) funded by international agencies, including the European Commission (2006 -2022). He created biotech companies (ApoH-Technologies) and platforms BSL2/3. He is a member of different evaluation panels (NIH, European Council, Frontiers in Immunology, etc). 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\r\n\tPlant invasion and global climate change are major global change components. The prediction of successful invasive plant species, interactions between plant invasion and other global change factors, as well as evaluation of invasive plant impact on the introduced environments, such as soil nutrient cycling and greenhouse gas emissions, are not well understood. This book aims to gather research in plant invasion studies associated with topics on prediction of successful invasive plants, interactions between plant invasion and other global change factors, and evaluation of invasive plant impacts, providing a thorough understanding of advances in plant invasion ecology on the background of global change. A better understanding of these questions will be helpful for future management of invasive plants, especially during global change mitigation processes, which are crucial for the sustainable development of human society and the maintenance of an environment-friendly world.
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From 2021-2013, he visited the Department of Ecology and Evolutionary Biology, Rice University, USA. He is currently working as a professor at the College of Forestry, Jiangxi Agricultural University, China, supervising graduate students. Dr. Zhang studies global change biology, forest ecology, plant invasion, and soil carbon and nitrogen cycling. He has published more than 50 papers related to global change ecology or forest ecology, and authored or co-authored several books on forest ecology or soil ecology in the recent years. 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Although there were no procedures available to address unwanted excess truncal fat and loose skin, artists in the above cited figures portrayed the ideal male contour and the unattractive body contour in a young child. The child demonstrates early obesity with neck, truncal, and extremity lipodystrophy. Unaesthetic fat deposits or loose skin, especially the ones without response to diet or physical exercise, are a major concern to patients. Witness the frequency of body contouring procedures throughout the world where liposuction is the most common esthetic surgical procedure. There are, however, differences in the distribution of the body fat between male and female patients. Men have less body fat around the waist, especially in the abdominal area; women generally have a higher percentage of body fat than men, especially around their thighs and buttocks, which is called gynoid fat. In overweight women, normally, the deposition is mainly found below the waist.
\nSymbols of beauty from the Persian Culture.
Symbols of beauty from the Persian Culture.
Symbols of beauty from the Persian Culture.
Symbols of beauty from the Renaissance.
Symbols of beauty from the Renaissance.
The earliest procedures that addressed excess skin and subcutaneous fat in the abdominal area were performed for functional indications, not for esthetic improvements. Certainly, removing skin and fat (dermo-lipectomy) had the secondary benefit of having the patient look better. In 1880, in France, Demars and Marx reported a large resection of skin and fat from the abdominal wall. In 1899, Dr. Kelly (a Johns Hopkins Gynecologist) performed a panniculectomy with an elliptical transversal incision around the umbilicus [1]. In 1901, Peters described a similar surgery extracting 7450 g from a patient, including the umbilicus, without the undermining [2]. Gaudet and Morestin extracted fat and skin with correction of an umbilical hernia while preserving the umbilicus. Eventually, Babcock in 1916 described dermo-lipectomies using a vertical incision [3].
\nThorek performed the first umbilicus-preserving abdominoplasty in 1924 [4]. This was the first abdominal contouring procedure with esthetic benefits. Passot’s contribution was to use undermining as a modification of Kelly’s technique [5]. Vernon in the 1950s developed a novel concept by combining extensive undermining with the umbilical transposition and relocation, which is a procedure still in use today. Callia described aponeurotic suturing as an important component of his procedure in 1967, which involved an infra-inguinal incision. Pitanguy in the same year published a series of 300 abdominal lipectomies with an infra-inguinal incision [6]. Previously, the published literature consisted mostly of case reports of a few patients. In the 1970s, Regnault modified the Pitanguy’s incision into the “W” incision [7]. In 1973, Grazer championed the “bikini line” incision used frequently today [8]. Grazer and Goldwyn in 1977 observed that abdominoplasty decreased anterior projection of the abdomen but did little to change waist diameter This led to Psillakis’ assertion in 1978 that muscular aponeurotic suturing was an underutilized tool to decrease waistline dimensions [9]. Somalo and Gonzalez-Ulloa extended the transverse abdominal incision circumferentially and introduced the belt lipectomy [10]. This concept would provide the background for many subsequent more aggressive procedures.
\nDescribing the evolution of body contouring procedures would be entirely inadequate without presenting the chronologic events in the development of closed liposuction techniques. For certain, the most significant advancement in body contouring WITH OR WITHOUT concomitant excision of skIn and subcutaneous fat was the development of closed liposuction.
\nRemoving excess fat from localized body sites is not a new idea [11]. In 1921, in France, Charles Dujarrier tried to remove subcutaneous fat using a uterine curette on a dancer’s calves and knees [12]. Unfortunately, he damaged the femoral artery, and the patient has lost her leg. One of the original and creative initiatives came from Schrudde in 1964, when he extracted fat from lower areas of the limb, through a visibly small incision, utilizing a curette. The unfortunate results from this surgical initiative were unpleasant hematomas and seromas [13]. Pitanguy, on the other hand, was in favor of a removal of both fat and skin in a block, in order to remove excess thigh adiposities in one act [14]. Of course, this was an excisional procedure, not closed liposuction. Significant visible incisions made this method quite unpopular and made closed, non-excisional, procedures preferred, but, at that time, not discovered. The field of modern liposuction began with the technique and new instruments developed by Arpad and Fischer [15, 16]. During their work in Rome, Italy, they managed to develop a blunt hollow cannula, with additional function of suction. Some of the previous cannula designs contained a cutting blade also. They made their results public in 1976 [17] Fischer also started the crisscross tunnel formation method, from several incision sites. The new instruments brought very promising results avoiding the above complications.
\nKesselring and Meyer [18] published their surgery results of sharp curettage aided by a suction device in 1978, but their method did not receive a wide acceptance. Fournier, in Paris, showed an early interest in the Fischer’s liposculpture technique [19]. He was an initial enthusiast of the “dry technique” in which no fluids were infiltrated into the patient prior to liposuction. Fournier would become a world leader in liposuction and fat transplantation, eventually insisting on the benefits of tumescent anesthesia and making a great contribution in opening new horizons and ideas to surgeons from different parts of the world. Illouz, a French gynecologist, was quite attracted by the Fishers’ work. His preferred method was the”wet technique”, which consisted of a solution of hypotonic saline together with hyaluronidase inserted into the adipose tissue before the aspiration. Lllouz thought that the solution itself was a “dissecting hydrotomy” which would catalyze the removal of fat and thus reduce trauma, as there was smaller amount of bleeding. Lllouz received worldwide publicity and promoted this method. The first US surgeon to visit France to learn the new area of liposuction was Lawrence Field in 1977, a Californian dermatologic surgeon. Other surgeons from the States, coming to conferences and educating themselves about new methods in the literature, also showed an interest in the area. One of them was Norman Martin, an otolaryngologist. He visited Illouz in 1980 and quickly started with liposuction surgeries in Los Angeles in 1981 [20, 21]. It was 1982 when a group of physicians from various specialty disciplines received lectures from Illouz and Fournier. At the annual meeting of the American Society of Plastic Surgeons (known at that time as The American Society of Plastic and Reconstructive Surgeons) in 1982, Dr. Illouz, for the first time in front of an audience of Board Certified Plastic Surgeons presented his technique of closed liposuction utilizing hollow cannulas of 1 cm in diameter connected to a suction pump with one atmosphere of negative pressure to extract fat that was pretreated with his wetting solution. The photographs (presented in carousel slide format) showed pre and pos-op photos of women who underwent liposuction of their “saddle bags” with only one cm. scars. This was remarkable in light of the existing treatment option which required large incisions (as published by Pitanguy) for the performance of dermo-lipectomies of this area. After this meeting, a task group formed by the American Society of Plastic and Reconstructive Surgeons visited Europe to learn and form opinions about this new procedure. Several pioneers in the closed technique of liposuction visited Dr. Fred Grazer after the national presentation in 1982 and I had the privilege of attending this small group course. Dr. Frank Ashley, former Chairman of the Division of Plastic Surgery at the University of California attended as well to learn this revolutionary technique. Dr. Grazer named this new procedure Suction Assisted Lipectomy. Important pioneers in the closed liposuction technique had developed cannulas which were quite aggressive when compared to the 5 mm and smaller cannulas in widespread use today. Schrudde, Kesselring, and Ilouz left their cannulas in Dr. Grazer’s office and they are of historical importance as one studies the refinement in the performance of liposuction (Figures 6–9). Julius Newman, otolaryngologist and cosmetic surgeon, together with his associate Richard Dolsky, who was a plastic surgeon, together taught the first American course on liposuction, held in Philadelphia in 1982. The five live surgery workshops were held in Hollywood, California, in June 1983, under the authority of the American Society of Cosmetic Surgeons and the American Society of Liposuction Surgery. There were altogether 10 dermatologists in attendance. The American Society of Plastic Surgeons and The American Society for Esthetic Plastic Surgery subsequently developed teaching courses and symposia to teach closed liposuction to fully trained, Board Eligible and Board Certified Plastic Surgeons. Subsequently, the core curriculum in accredited Plastic Surgery Resident Training Programs included didactic and hands-on training in liposuction. The development of the Tumescent (from Latin meaning swollen or being swollen) Technique for performing Liposuction, described in publications by Dr. Jeffrey Klein [22, 23, 24, 25, 26], a Dermatologist, had an enormous impact in the safe and more easily performed liposuction procedure. The formula currently includes Lidocaine 2%, Sodium Bicarbonate, and Epinephrine (1–1,000,000), added to 1 liter of Sodium Chloride (if Ringers Lactate is substituted for Normal Saline, sodium bicarbonate is not added to the solution). The tumescent technique was modified such that only a 1:1 or 1.5:1 ratio of tumescent fluid to expected aspiration volume is injected rather than a 2 or 3:1 ratio which was the initial ratio in the Klein tumescent solution. The introduction of the tumescent liposuction technique allowed for the office- based removal of fatty deposits under no sedation, minimal Class 1 sedation, intravenous sedation, or general anesthesia. (Safe guidelines and other safety considerations are described below).
\nExamples of first generation suction cannulas.
Examples of first generation suction cannulas.
Examples of first generation suction cannulas.
Examples of first generation suction cannulas.
As the number of cases increased dramatically over the years, important additions to the options in body contouring occurred. Lockwood’s observance and, perhaps the discovery, of the SFS (superficial fascial system) [27, 28, 29] resulted in his landmark publications wherein he utilized this fascial system for important support of elevated soft tissue flaps including abdominal and lower extremity flaps that were elevated and repositioned to correct soft tissue ptosis. Liposuction was a component of his body contouring procedures. Certainly, liposuction allowed remodeling of the abdomen and lower extremities combined with, based upon the clinical anatomical findings, surgical excision of excess skin and subcutaneous tissues. Prior to Lockwood’s description of the SFS, lower extremity medial thigh lifts were accompanied by migrating, unattractive scars. He also utilized the SFS in his High Lateral Tension Abdominoplasty to obtain improved contours and favorable scars as a trade-off for important excision of redundant soft tissues.
\nPrior to liposuction, upper extremity unwanted fatty deposits with or without accompanying excess skin required large excisions of skin and subcutaneous tissue with resultant unfavorable scars. Liposuction has allowed fatty deposits to be removed through small access incisions and the incisions needed for skin and subcutaneous tissue removal have decreased in length.
\nCombined with available energy-based devices, soft tissue retraction can be an important component to body contouring of the head and neck, extremities and anterior and posterior trunk.
\nFat grafting, although introduced by Gustav Neuber (1850–1932) late in the 19th century [30], was authenticated and refined with the landmark work of Sydney Coleman [31]. He introduced structural fat grafting which required small amounts (macrografts) of fat carefully placed in parallel tunnels, separated by adjacent blood vessels which nourish the grafted fat. Without a doubt, his contribution brought fat grafting to the armamentarium of cosmetic physicians and surgeons with a method that proved that grafted fat, when obtained, processed, and carefully injected in tiny amounts (0.1 cc or less) survived. He also showed how the stem cell component of fat grafts rejuvenate the skin, improve dermatologic skin conditions, with improved texture, etc. Fat grafting has evolved to include soft tissue augmentation of the face and breast, revision of breast reconstruction, treatment of post-augmentation mammoplasty contour deformities (including capsular contracture), contour deformities from prior liposuction and/or skin and subcutaneous fat excisions, and treatment of depressed scars. It is included in High Definition Liposuction further defining the underlying abdominal wall musculature. Fat grafting has evolved to the production of smaller particles including nanofat introduced by Tonnard [32].
\nRecently, cosmetic surgeons have injected Tranexemic Acid (TXA) and have observed an impressive decrease in blood loss. It has been used intravenously and topically as well, but the addition of tranexemic acid to the liposuction infusion has seen its’ application in closed liposuction. TXA is safe and its’ application has been studied in other cosmetic procedures with a notable decrease in blood loss [33].
\nWhen one looks at the statistics regarding obesity and morbid obesity with 40% of Americans considered obese and 18% considered severely obese as of 2019 with severe obesity defined as a BMI greater than 35 (Research performed at the Harvard T.H. Chan School of Public Health) it is clear as to why liposuction which is consistently listed in position 1 or 2 of the 5 most frequently performed cosmetic surgical procedures in the U.S. and dermolipectomies (270,670 liposuction and 140,381 abdominoplasties performed by Board Certified Plastic Surgeons) are so popular, increasing in numbers yearly (American Society of Plastic Surgeons Annual Statistics, 2019). Moreover, bariatric procedures to treat morbid obesity have evolved in tandem with body contouring procedures to address excess skin throughout the body after significant weight loss.
\nIn summary, Liposuction has evolved from the removal of fatty deposits in the neck, upper and lower extremities, and anterior and posterior trunk to artistic remodeling of the shape of the face, neck, extremities, and trunk, performed alone or in combined treatment with various energy based devices.
\nSafety in liposuction combines proper education, patient selection, and proper application of science while achieving the goal of esthetics. Providing safe surgery in a hospital or accredited surgery center (or Ambulatory Surgery Center (ASC) has become increasingly a topic of discussion as the roles of fat grafting (breast surgery, Brazilian Butt Lift, facial surgery, etc.) have increased. Office based procedures can be done safely and should still follow proper guidelines. As noted above, the role of wetting solutions allowed safe and reproducible results over the past several decades.
\nThere are various oversight organizations and governmental regulations that have been well established. These are designed to help ensure patient safety. As this is not a comprehensive review of each organization, some general parameters are presented below. For those that will be using freestanding ASCs through Medicare and or Medicaid, rules include An ASC must be certified and approved to enter into a written agreement with CMS, The regulatory definition of an ASC does not allow the ASC and another entity, such as an adjacent physician’s office, to mix functions and operations in a common space during concurrent or overlapping hours of operations., and ASCs are not permitted to share space, even when temporally separated, with a hospital or Critical Access Hospital outpatient surgery department, or with a Medicare-participating Independent Diagnostic Testing Facility (IDTF), as noted on CMS.gov. (REF- CMS.gov). ASCs must comply with a multitude of state as well as federal regulations and statutes. This includes proper licensing, Health Insurance Portability and Accountability Act (HIPAA) and more (REF ASCassociation.org). Furthermore, the ASC is also responsible to ensure that the providers comply with all the standards that govern ensuring professional training, equipment, medications, physical layout of the facility and operational safety. Outpatient surgery is suited best for healthy people undergoing minor or intermediate procedures (plastic surgery, ob-gyn, limited urologic, ophthalmologic, or ear, nose and throat procedures and procedures involving the extremities). However, health care reform and the Affordable Care Act of 2010 have expanded the types and complexity of surgical procedures, with much of the growth driven by advancements in anesthesia and technology. (REF AAAASF.org).
\nWetting solutions were covered earlier in this chapter. The surgeon should become familiar with the various solutions. Furthermore, the amount of blood loss with the different must be accounted for by the surgeon to maintain safety. (ADD TABLE FOR APPROXIMATE BLOOD LOSS?) That percentage of blood loss can range from 1% with solutions such as tumescent and superwet to nearly 40% in the infranatant with the dry technique. (REF?) Preoperatively the patient should be healthy and optimized and laboratory studies should be checked to help guide proper patient selection. These solutions can also vary in terms of lidocaine load to the patient. The surgeon should be familiar with the correct calculations to not over-deliver lidocaine to the patient as well as understanding that absorption can be variable between patients. As lidocaine absorption from the subcutaneous fat, the plasma lidocaine levels may not peak until 10–12 hours after delivery. Furthermore, chronic disease, stress, tobacco use, hormones, and more will influence the protein binding and when the peak will effect the patient. Care must be taken and individualized for each patient.
\nVolume extraction concerns have evolved to help protect patients, but discussions continue how to apply and ensure proper application. In general, the most commonly accepted guideline is based on “Large volume lipoplasty” as greater than 5000 cm3 of supranatant fat during a single surgery. Volumes greater than this can be done, and patient safety parameters should be utilized and regulations followed. These large volume liposuction procedures can be completed in a hospital setting or often mandate overnight monitoring. Patient age, general health and even the percentage of body surface are examples of considerations. While we have discussed lidocaine issues previously, general fluid shifts should be considered for patient safety as well. High quality teamwork and communication with all team members are critical. Volume overload, shock, pulmonary edema, hypovolemia, myocardial infarction are all risk factors, as is fat embolism. Proper teamwork, communication, monitoring, etc., are so important to add to proper patient selection.
\nCannula selection is another component of patient safety, from tissue injury to contour irregularities. Proper cannula selection is a combination of education, experience, esthetic goals and more. While there is a role for some of the cannulae that can cut (release of fibrous bands) or “post-tunneling” (such as basket cannulae), the accepted safe cannula systems are generally blunt tipped. These most commonly range from 2 to 5 mm, but larger are available for harvesting and smaller are often used for fat grafting. Furthermore, the number of holes, location and patterns of the holes will all play a role in both efficiency of fat extraction and patient safety. While the cannulas play a role in patient safety, so do the aspiration devices and assistance devices (syringes, pumps, oscillating tips, energy based, etc.) must be considered for patient safety. Proper education on the devices, mechanisms of action, technique, etc. must be employed to avoid complications such as thermal injury, contour irregularities, incorrect cannula positioning and more.
\nBeyond the previously mentioned complications of liposuction, the surgeon must also be concerned about several other issues and these include Fat Embolism Syndrome, bleeding, and Deep Vein Thrombosis among others. Bleeding and clotting issue concerns should be addressed pre-, intra-, and postoperatively. A complete history should discuss any family history of blood clots, early myocardial infarction, multiple miscarriages, bleeding history, previous deep vein thrombosis, etc. Several measures can be done on the day of surgery such as proper patient and operating room temperature, placement and application of sequential compression devices before induction and not being removed until after the patient is fully awake (home compression therapies are also available), and even consideration for pre and post operative anti-thrombotic (chemoprophylaxis) medications. Early ambulation has been a largely accepted proper therapy to help minimize deep venous thrombosis and pulmonary embolism risk. Fat Embolism Syndrome (FES) is less understood, but classically demonstrates respiratory distress, petechial rash along with cerebral dysfunction. Other concerns include tachycardia, fever, hypocalcemia and even thrombocytopenia. FES is the syndrome that is a secondary consequence of Fat Embolism. Proper diagnosis is critical for the patient long term outcome and the surgeon should be familiar with the diagnosis and willing/able to work with other team members to get early and proper treatment for the patient.
\nProper patient selection, maximizing pre-, intra- and post operative management is the responsibility of the surgeon. The surgeon should coordinate the team and maintain maximum communication so that all team members can maximize their experience and opportunities to protect the patient.
\nAs suction lipectomy became universally accepted as a stand-alone procedure, it was quickly added to other body contouring procedures. Frequently, liposuction is performed along with reduction mammoplasty, abdominoplasty, high-definition liposuction, brachioplasty, thigh lifts, lower body lifts, gynecomastia, breast reconstruction, etc. Although liposuction can be safely added to other body contouring procedures, it has been shown to increase morbidity and mortality when combined with a full abdominoplasty especially worrisome in patients with a high BMI and/or a high Caprini score [34].
\nThe early methods of performing closed liposuction included hand held aspiration (Toomey syringe liposuction) connected to a cannula, or connecting the suction cannula to a suction pump with one atmosphere of negative pressure, but still requiring manual movement of the cannula to break up and remove the fat. One of the most important advances in facilitating the removal of fat in a closed system was the introduction of Power-assisted Liposuction. Several devices were manufactured and quickly adopted to facilitate the removal of fat with less effort.
\nFollowing the introduction of Power-assisted Liposuction, the development of Ultrasonic Energy based emulsification of the fat followed by suction lipectomy was introduced by Michele Zocchi, M.D. [35]. There was an evolution in the machinery required to perform the emulsification procedure, but the surviving technology was manufactured under the name of Vaser, engineered by Sound Surgical Technologies. This method of dissolving fat and causing energy to be delivered to the dermis has found its’ most important application in “High Definition Liposuction”, importantly advanced and refined by Alfredo Hoyos [36]. Other indications for ultrasonic emulsification of fat include the closed treatment of gynecomastia.
\nThe technique of applying freezing temperature to dissolve the fat through apoptosis (CoolSculpt) has received important acceptance in the Cosmetic Surgery community, has enormous social media presence, but complications are common with neo-fat formation and “shark-bite” contour complications being reported.
\nLaser based energy has also been developed (Smart Lipo) where a small diameter probe is inserted into the fatty deposit and energy is applied to dissolve the fat. This requires a two step procedure, is quite tedious due to the small size of the fiber, with the risk of skin burns.
\nRadiofrequency based energy has emerged as the most commonly energy based method of emulsifying fat and stimulating fibrous septae contraction as well as dermal tightening. Impressive pre and post-op measurements of circumference are seen when this energy based system is used alone or in combination with suction assisted liposuction. Real time monitoring of internal and external body temperatures ensure safe application of the energy (InMode,Ltd., Yokneam, Israel).
\nPlasma based energy systems are available (Renuvion J-Plasma) which dissolve the fat, but lack sophisticated temperature monitoring.
\nHigh intensity focused ultrasound devices are available, but has enjoyed limited market penetrance due to the minimal improvement shown when compared to other energy sources.
\nIn summary, physical image has always been important. The history of body contouring began with procedures that were performed for functional benefits and evolved to cosmetic improvement in multiple areas of the body. The introduction of liposuction provided an incredible option in body contouring and became the number 1 or number 2 most performed cosmetic surgical procedure. Often combined with open surgical techniques, liposuction frequently allowed procedures to be performed with smaller incisions and was advanced to allow important sculpting of the face, neck, extremities, and trunk. Fat grafting provided improved volume and contour to soft tissues. The introduction of energy based devices allowed for the tightening of fascial networks and dermal remodeling often performed along with liposuction.
\nPhospholipids are major constituent of cellular membrane hence they have excellent biocompability. They are amphiphilic molecules which usually built by glycerol backbone with two different polarity groups attached to it. On the one hand is the hydrophilic group renowned as the head group which then becomes the basis of species classification of phospholipids, such as phosphatidylcholine (PC), phosphatidyletanolamine (PE), and phosphatidylserine (PS). On the other hand is the hydrophobic fatty acyl chains distinguished as the tails. The variation of the length and the saturation, the bonding position of fatty acyl chains to glycerol backbone as well as the head group type become a crucial part of their application, for instance in drug delivery systems.
The development of phospholipids based drug delivery systems have been proven prominent by the emergence of many phospholipid-related drug formulation. Among of them are doxorubicin in stealth liposomes for cancer treatment, which has been on the market since 1995 [1, 2]; Verteporfin in cationic liposomes for molecular degeneration [3] and vincristine in conventional liposome for Non-Hodgkin lymphoma [2]. They have been used in clinic, and achieve good results. Many more phospholipids based liposomal preparation have been developed to find better therapeutic results [4, 5, 6]. Furthermore various sources, synthetic and natural, have been explored [2, 7].
The isolation of phospholipids from natural sources cost lower than synthesizing them hence the preference is the isolation of natural phospholipids. For natural origin, the more pure they are, the greater the value is [8]. Phospholipids from natural origin can be refined into diverse levels, comprising food and pharmaceutical grade [2, 9]. In term of natural phospholipids, different source enhance the species variety of phospholipids [7]. Egg yolk and soybean phospholipids mainly consist of phosphatidylcholine species but they have differences in the tail portions which influence their physical, chemical properties and their applications. Other natural phospholipids that currently are being explored extensively are sunflower [10, 11, 12], candlenut [13], jack bean [14], sesame [13, 15, 16, 17] and coconut [13, 15, 16, 18, 19, 20, 21, 22].
Coconut is one of the native plantations in tropical countries and produces mainly copra and coconut oil. Exploration of coconut by-products such as coconut phospholipids needs to be done to increase the added value of these coconut plantations. Previous studies have found that dried coconut contain phospholipids from cephaline species with their fatty acyl chains are dodecanoic and octanoic acyl chains [15]. Purification with eluent chloroform: methanol (9:1) follows by identification using thin layer chromatography (TLC) also detects the presence of phosphatidylcholine (PC), phosphatidyletanolamine (PE), and phosphatidylserine (PS) species in coconut phospholipids (CocoPLs) [20, 21].
In the matter of its application, coconut liposomes (CocoPLs liposomes) have been used in the encapsulation of hydrophilic agent namely carboxyfluoresence and vitamin C and resulted in that CocoPLs liposomes has high efficiency of encapsulation [16, 19, 22]. The addition of cholesterol improves the encapsulation efficiency and low storage temperature reduces CocoPLs liposomes leakage. The results advocated the CocoPLs potency as drug delivery material. Moreover since we have established that CocoPLs consist of many phospholipid species therefore it would be valuable to study the component of the species and their capability as drug delivery system. In this study we explore the isolation and purification of coconut phospholipid species specifically coconut phosphatidylethanolamine (CocoPEs) and utilization of their liposomes (CocoPEs liposomes) for vitamin C encapsulation with various cholesterol concentrations. To our knowledge this is the first study of such.
Materials used in this study were ripe coconut meat purchased from local market, TLC silica gel 60 F254 plate, silica gel powder 60 G for thin layer chromatography, various solvents and regents for analytical grade.
Isolation technique was carried out based on the previous method used [20, 21]. Briefly coconut meat powder was macerated in a chloroform: methanol (2:1, v/v) mixture. The filtrate obtained was washed using 0.9% NaCl. The lipid was evaporated until thick coconut lipid extract were obtained. The extract was then subjected to solvent partition using n-hexane and ethanol 87%. The lower phase was evaporated to yield brownish yellow extract of CocoPLs.
About 5 g of CocoPLs was mixed with 5 g of silica gel in a small amount of chloroform: methanol (9:1, v/v) solution to form a silica slurry. The slurry was then stirred until the mixture was dried and formed fine powder of CocoPLs-SG.
A total of 80 mg of silica gel was poured into a chromatography column and compressed by vacuum. The column was rinsed using chloroform:methanol (9:1, v/v) eluent and vacuumed until all the eluent was eluted. The CocoPLs-SG powder was poured onto the column. Then the column was subjected to compression. Elution was performed using 10 ml of chloroform:methanol (9:1, v/v) solution. Fraction eluted from the column was collected into clean vials. The fraction was analyzed using TLC plate. The spot on the TLC plate was identified with 10% H2SO4 and ninhydrin. Elution was repeated every 10 ml of the eluent until the TLC plate did not show any spot when subjected to identification. The CocoPLs fractions contained ethanolamine species were gathered into an evaporating flask and evaporated at 40°C to obtain dark brownish gel of CocoPEs.
Both CocoPLs and CocoPEs obtained were characterized using FT-IR (Prestige 21 Shimadzu), GC-MS (Shimadzu QP2010S), and LCMSMS (Waters Xevo TQD) and DSC (Shimadzu DSC-60A). The FTIR was employed to probe the phospholipids functional groups. The GC-MS was used to determine the phospholipids fatty acyl chains. The LC-MS/MS was for identifying the chemical component of CocoPEs and the DSC analysis was carried out to explore the CocoPEs phase behavior.
In this research, vitamin C (VC) was used as a model for hydrophilic drug to be encapsulated in coconut liposome [13, 16, 17, 22]. Stock solution of 500 ppm CocoPEs with cholesterol concentration (0%, 10%, 20%, 30%, 40% w/w) were made. A total of 2 mL of each stock solution was diluted with chloroform to 10 mL and poured into a test tube. The liquid solution was evaporated using N2 gas flow to form a thin layer. After that hydration process was carried out. Around 10 mL of phosphate buffer solution was added to the thin film. The mixture was subjected to freeze-thawing process until the thin film was dispersed completely. The dispersions contained empty coconut liposome and was used as control. Other set of dispersions were prepared by adding 8 ppm (
where
A brownish yellow gel of CocoPLs was obtained from dried coconut meat (
CocoPLs.
In the separation process using vacuum column chromatography, CocoPLs was eluted continuously using chloroform:methanol (9:1, v/v). Each fraction of 10 mL eluent was collected and subjected to identification. As much as 520 fractions were obtained to elute CocoPEs from the CocoPLs samples completely. Identification by TLC using 10% H2SO4 and ninhydrin spotting agent [23] resulted in that CocoPEs were present in the 105th to the 520th fraction.
The fraction contained CocoPEs were then combined and evaporated to remove the eluent that resulted in dark brown CocoPEs gel (
CocoPEs.
The functional groups identification of CocoPLs and CocoPEs was conducted by FTIR spectra analysis. The FTIR spectra of both CocoPLs and CocoPEs were displayed on Figure 3. To analyze further the spectra were scrutinized using a deconvolution program [21, 24], at wavenumbers 3500–2800 cm−1 and 1800–700 cm−1 as presented in Figure 4.
CocoPLs and CocoPEs absorption spectra.
Deconvolution results: (a) CocoPLs at wavenumbers 1800–700 cm−1; (b) CocoPLs at wavenumbers 3500–2800 cm−1; (c) CocoPEs at wavenumbers 1800–700 cm−1; (d) CocoPEs at wavenumbers 3500–2800 cm−1.
The absorption data obtained from both FTIR spectra and deconvolution analysis were compared (see Table 1) to the specific infrared absorption area for phospholipids proposed by Stuart [25] and Hudiyanti et al. [20, 21]. The presence of a typical spectrum of phospholipids was clearly revealed. Significant differences between CocoPLs and CocoPEs spectra was disclosed by the typical absorption of choline and ethanolamine groups on both spectra of CocoPLs and CocoPEs. The choline group absorptions; (CH3)3N+ asymmetric bending and (CH3)3N+ asymmetry stretching; were not present on the CocoPEs spectra. The typical absorption that indicate the presence of ethanolamine species by N-H vibration absorptions was displayed on CocoPLs and CocoPEs spectra. This evident indicated that CocoPLs contained choline and ethanolamine species while CocoPEs did not contain choline species. From The FTIR spectra point of view this data disclosed that the CocoPEs separation from CocoPLs was successful.
No. | Absorption type | References [15, 20, 21, 25] (cm−1) | CocoPLs (cm−1) | CocoPEs (cm−1) | CocoPLs Deconvolution (cm−1) | CocoPEs Deconvolution (cm−1) |
---|---|---|---|---|---|---|
1. | ||||||
2. | =C-H stretching | 3010 | — | — | 3001 | 3002 |
3. | CH3 asymmetric stretching | 2956 | — | — | 2958 | 2956 |
4. | CH2 asymmetric stretching | 2920 | 2924 | 2924 | 2923 | 2919 |
5. | CH3 symmetric stretching | 2870 | — | — | 2885 | 2890 |
6. | CH2 symmetric stretching | 2850 | 2854 | 2854 | 2850 | 2848 |
7. | C=O stretching, sn-1 chain trans-conformation | 1730 | 1735 | 1735 | 1738 | 1739 |
8. | ||||||
9. | CH2 scissoring | 1473, 1472, 1468, 1463 | — | — | — | — |
10. | CH3 asymmetric bending | 1460 | 1458 | 1458 | 1461 | 1464 |
11. | (CH3)3N+ symmetric bending | 1405 | — | — | — | — |
12. | CH3 symmetric bending | 1378 | 1373 | 1373 | 1376 | 1378 |
13. | CH3 rocking ribbon progression | 1400–1200 | — | — | 1333 | 1266 |
14. | PO2−asymmetric stretching | 1228 | 1226 | 1242 | 1225 | 1222 |
15. | CO-O-C asymmetric stretching | 1170 | 1165 | — | 1150 | 1165 |
16. | PO2− symmetric stretching | 1085 | — | 1080 | 1106 | 1107 |
17. | CO-O-C symmetric stretching | 1070 | 1072 | — | 1071 | 1070 |
18. | C-O-P stretching | 1047 | — | — | 1020 | 1003 |
19. | ||||||
20. | P-O asymmetric stretching | 820 | 817 | — | 813 | 819 |
21. | CH2 rocking | 730, 720, 718 | 717 | 725 | 714 | 713 |
Typical Absorption of CocoPLs and CocoPEs functional groups.
Bold entries represented the typical absorption of choline and ethanolamine groups on both spectra of CocoPLs and CocoPEs.
The fatty acyl chains content of CocoPLs and CocoPEs was analyzed by GC-MS. The CocoPLs chromatogram was presented on Figure 5. A total of nine peaks was recognized. Seven peaks were with abundance above 1%. The chromatogram suggested that there were at least 9 types of fatty acyl chains present on the CocoPLs. The MS reading revealed the identity of these fatty acyl chains. Three fatty acyl chains worth mentioning with the abundance more than 10%, i.e., lauric acid, palmitic acid and oleic acid which were indicated by peak number 3 (abundance of 11.31%); peak number 5 (15.26%); and peak number 7 (55.18%). The result was in agreement with previous research [15, 20, 21]. The seven fatty acyl chains recognized in CocoPLs was displayed on Table 2.
CocoPLs chromatogram.
Peak number | tR (min) | Fatty acyl chains | Area (%) |
---|---|---|---|
3. | 29.164 | Lauric acid, C12:0 (dodecanoic acid) | 11.31 |
4. | 34.037 | Myristic acid, C14:0 (tetradecanoic acid) | 5.71 |
5. | 38.497 | Palmitic acid, C16:0 (hexadecanoic acid) | 15.26 |
6. | 41.872 | Linoleic acid, C18:2 (9(Z),12(Z)-octadecadienoic acid) | 6.00 |
7. | 42.117 | Oleic acid, C18:1 (9(Z)-octadecenoic acid) | 55.18 |
8. | 42.482 | Stearic acid, C18:0 (octadecanoic acid) | 3.97 |
9. | 52.794 | Lignoceric acid, C24:0 (tetracosanoic acid) | 1.49 |
The fatty acyl chains of CocoPLs.
The chromatogram of CocoPEs was disclosed on Figure 6. The resulting chromatogram exposed the presence of five peaks with abundance above 1% which suggested the presence of five types of fatty acyl chains in the CocoPEs. Three of them had great abundance i.e. capric, linoleic and oleic acids as indicated by peak number 2, 3 and 4 and with abundance of 17.09%, 43.17% and 31.88% respectively. The MS reading of fatty acyl chains content in the CocoPEs was tabulated on Table 3.
CocoPEs chromatogram.
Peak number | tR (min) | Fatty acyl chains | Area (%) |
---|---|---|---|
2. | 38.566 | Capric acid, C10:0 (decanoic acid) | 17.09 |
3. | 42.041 | Linoleic acid, C18:2 (9(Z),12(Z)-octadecadienoic acid) | 43.17 |
4. | 42.198 | Oleic acid, C18:1 (9(Z)-octadecenoic acid) | 31.88 |
5. | 42.555 | Stearic acid, C18: 0 (octadecanoic acid) | 5.93 |
8. | 46.186 | Arachidic acid, C20:0 (eicosanoic acid) | 1.04 |
The Fatty acyl chains of CocoPEs.
Tables 2 and 3 revealed differences to some extent in fatty acyl chains composition between CocoPLs and CocoPEs. CocoPLs had more variation in fatty acyl chains type compared to CocoPEs. This fact plausible considering that CocoPEs was obtained from the separation of CocoPLs. The separation was mainly based on the common head group namely ethanolamine that reflected on the polarity of the separated CocoPEs molecules hence the choice of the separation eluent. More over fatty acyl chains profile were closely related to the position of phospholipid species in the bio-membrane bilayer [26, 27, 28]. Phosphatidylethanolamine (PE) species generally would be positioned in the inner leaflet of bilayer due to their molecular geometry, i.e. cylinder [2]. The PE species molecular shape was supported by more abundance composition of unsaturated fatty acyl chains in the CocoPEs extract, Table 3.
Based on the fatty acyl chains of the CocoPEs we conducted parent ion screening using LCMSMS. The CocoPEs parent ion spectrogram was presented on Figure 7. The spectrogram gave us a representation of the molecular species composing CocoPEs extract. At least 11 molecular species of CocoPEs were found. The CocoPEs molecular species was tabulated on Table 4. The molecular species was predicted based on the head group and combination of two fatty acyl chains for the nonpolar part of CocoPEs species. These similar species would govern the CocoPEs phase behavior and other properties as well.
CocoPEs spectrogram.
No. | m/z (M-H) | Molecular weight | CocoPEs molecular species | |
---|---|---|---|---|
Head group | Fatty acyl chains | |||
1. | 554 | 555 | Ethanolamine | Capric acid Capric acid |
2. | 662 | 663 | Ethanolamine | Capric acid Linoleic acid |
3. | 664 | 665 | Ethanolamine | Capric acid Oleic acid |
4. | 666 | 667 | Ethanolamine | Capric acid Stearic acid |
5. | 694 | 695 | Ethanolamine | Capric acid Arachidic acid |
6. | 770 | 771 | Ethanolamine | Linoleic acid Linoleic acid |
7. | 774 | 775 | Ethanolamine | Oleic acid Oleic acid |
8. | 776 | 777 | Ethanolamine | Oleic acid Stearic acid |
9. | 802 | 803 | Ethanolamine | Linoleic acid Arachidic acid |
10. | 806 | 807 | Ethanolamine | Stearic acid Arachidic acid |
11. | 834 | 835 | Ethanolamine | Arachidic acid Arachidic acid |
CocoPEs molecular species prediction.
Every phospholipid species has unique phase behavior that related to their molecular structure and phase behavior. The phase behavior of CocoPLs and CocoPEs were investigated by thermal analysis using DSC. The thermogram for CocoPLs, Figure 8, exhibited a small peak at 28.85°C and larger peak at 83.95°C. These peaks indicated that CocoPLs underwent phase changes as temperature changes. A pre-transition process from planar-shaped gel (Lb′) to the rippling phase (Pb′) was at a temperature of 28.85°C (Tp), then proceed with the main transition from gel (Lb′) to the liquid crystal phase (La) at a temperature of 83.95°C (Tm) [29, 30, 31]. Tp and Tm were the pre-transition and melting temperature correspondingly.
Thermal analysis of CocoPLs.
Different phase behavior of CocoPEs was exhibited in Figure 9. The thermogram for CocoPEs was more complex than CocoPLs indicated that CocoPEs had more complex phase transition than CocoPLs. CocoPEs displayed pre-transition process from planar-shaped gel (Lb′) to a rippling phase (Pb′) at a temperature of 25.29°C (Tp), followed by a major transition from gel (Lb′) to liquid crystal phase (La) at a temperature of 32.62°C (Tm), and then a transition from the liquid crystal phase (La) to hexagonal phase (H) at a temperature of 65.53°C (Th) [32]. The hexagonal phase formation was consistent to cylindrical molecular shape attributed to CocoPEs. The CocoPEs gradual change of phase was estimated because of the similar molecular species composing CocoPEs.
Thermal analysis of CocoPEs.
The phase behavior of CocoPEs dan CocoPLs above indicated that they were both had complex self-assembly structures which would be beneficial for future applications [2].
Phospholipids has long been known as drug delivery substance due to their liposome forming ability. Liposome was a spherical aggregation structure with bilayer phospholipid as its shell surrounding aqueous core. This unique structure was especially a perfect vehicle for delivering hydrophilic and hydrophobic drugs with storage and controlled release purposes. In this paper as a preliminary study for further application of coconut phospholipid as drug delivery material we used vitamin C as a hydrophilic drug model to be encapsulated in coconut liposomes. Vitamin C was a hydrophilic drug and would be encapsulated inside the aqueous core of liposome. The study lead to that encapsulation efficiency of vitamin C in CocoPEs were higher than CocoPLs i.e. 94.44% and 92.40% respectively, Figure 10.
Encapsulation efficiency of CocoPLs and CocoPEs liposomes with cholesterol composition variation.
In relation to their application as drug delivery, liposomes were usually made from phospholipid and a small amount of cholesterol. Cholesterol was added to the liposome membrane to control liposome rigidity and penetrability [33]. Therefore to explore the effect of cholesterol on the encapsulation efficiency of coconut liposomes we also prepared coconut liposomes with several different concentration of cholesterol namely 10%, 20%, 30% and 40%. The encapsulation efficiency of the liposomes were presented on Figure 10. The results suggested that addition of cholesterol up to 40% in the liposome’s membrane reduced the encapsulation efficiency of CocoPEs and CocoPLs liposomes. Furthermore CocoPEs liposomes demonstrated slighter reduction than CocoPLs liposomes. The encapsulation efficiency of CocoPEs diminished gradually as the cholesterol concentration increased while for CocoPLs liposomes the decline was arbitrary. Addition up to 30% of cholesterol only reduced the CocoPEs encapsulation efficiency to around 80% while CocoPLs was as low as 52%. Cholesterol effect on the encapsulation efficiency of CocoPEs liposomes more consistent than CocoPLs. We suspected it was due to the molecular composition of the phospholipid in the membrane. The molecular composition was represented by the composition of functional group and fatty acyl chains in the CocoPEs and CocoPLs, Tables 1–3. In the liposome membrane cholesterol interacted with CocoPEs and CocoPLs through their functional groups and fatty acyl chains. Cholesterol with small hydrophilic head group i.e., –OH and big and rigid hydrophobic steroid ring would interact better with small head group phospholipid species like CocoPEs than CocoPLs which had big spherical choline group and possibly other head groups as well. The composition of fatty acyl with double bonds also suspected would give more room for cholesterol hydrophobic moiety. The fatty acyl chains would assume “kink” structure at the double bond position [34, 35] and allocate more space hence more comfortable for cholesterol to integrate. With smaller number of fatty acyl chains type and higher concentration of double bond made cholesterol effect became more systematic in the CocoPEs liposome membrane. The data gave an insight about the application of CocoPEs as encapsulation material. CocoPEs was a good candidate for encapsulation hydrophilic material.
A total of (
DH and KA would like to express their gratitude of financial support by DIPA Selain APBN FSM UNDIP Riset Madya, 2018.
The authors declare that there is no conflict of interests regarding the publication of this chapter.
Ove Odredbe i uvjeti ističu pravila i regulacije u svezi korištenja IntechOpenove stranice www.intechopen.com i svih poddomena u vlasništvu IntechOpena, tvrtke sa sjedištem u 5 Princes Gate Court, London, SW7 2QJ, Ujedinjeno Kraljevstvo.
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\\n\\nSljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
\\n\\nKlijent, stranka, vi, vaš odnosi se na vas, osobu koja pristupa ovoj stranici i prihvaća IntechOpenove Odredbe i uvjete;
\\n\\nKompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
\\n\\nStranke, strane odnosi se na klijenta i na nas, ili samo na klijenta ili nas.
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\\n\\nOsim ako nije suprotno navedeno, IntechOpen i/ili svi davatelji licence vlasnici su intelektualnog vlasništva nad svim materijalima na www.intechopen.com. Sva prava intelektualnog vlasništva su pridržana. Stranice sa www.intechopen.com možete gledati, preuzimati, dijeliti, dijeliti poveznice i printati za osobnu uporabu, a temeljem pravila sadržanih u ovim Odredbama i uvjetima.
\\n\\nMi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\\n\\nIntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\\n\\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
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\\n\\nBez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\\n\\nIntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
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\n\nSljedeća terminologija odnosi se na Odredbe i uvjete, te na sve naše ugovore:
\n\nKlijent, stranka, vi, vaš odnosi se na vas, osobu koja pristupa ovoj stranici i prihvaća IntechOpenove Odredbe i uvjete;
\n\nKompanija, tvrtka, mi, naše odnosi se na tvrtku IntechOpen;
\n\nStranke, strane odnosi se na klijenta i na nas, ili samo na klijenta ili nas.
\n\nSve odredbe koje se odnose na ponudu, prihvat ili razmatranje plaćanja, a za koja mi pružamo asistenciju klijentu, bilo na ugovoreni ili fiksni način, a s ciljem da se ostvare potrebe i želje klijenta u svezi s našim uslugama, su podložne zakonskim odredbama Ujedinjenog Kraljevstva.
\n\nOsim ako nije suprotno navedeno, IntechOpen i/ili svi davatelji licence vlasnici su intelektualnog vlasništva nad svim materijalima na www.intechopen.com. Sva prava intelektualnog vlasništva su pridržana. Stranice sa www.intechopen.com možete gledati, preuzimati, dijeliti, dijeliti poveznice i printati za osobnu uporabu, a temeljem pravila sadržanih u ovim Odredbama i uvjetima.
\n\nMi koristimo kolačiće. Korištenjem IntechOpenove stranice slažete se s korištenjem kolačića u skladu s IntechOpenovom Politikom privatnosti. Većina modernih, interaktivnih stranica koristi kolačiće kako bi omogućila ponovno pronalaženje korisničkih detalja kod svakog posjeta. Na našoj stranici kolačići se uglavnom koriste kako bi omogućili funkcionalnost i olakšali posjetiteljima korištenje stranice.
\n\nIntechOpen ili njegovi suradnici niti u jednom slučaju neće biti odgovorni za štete (štete uključuju gubitak podataka ili profita, druge poslovne prekide, te sve ostale štete) koje nastanu zbog korištenja materijala na IntechOpenovoj stranici ili nemogućnosti da se iste koriste, čak i ako je IntechOpen ili njegov predstavnik o takvoj šteti obaviješten pismenim ili usmenim putem. Neke jurisdikcije ne dozvoljavaju ograničenja garancija ili ograničenja obveza za posljedične ili slučajne štete pa se u tom slučaju ova ograničenja možda ne odnose na vas.
\n\nMaterijali koji se pojavljuju na IntechOpenovoj stranici mogu sadržavati manje greške, tipfelere ili fotografske greške. IntechOpen može napraviti promjene na bilo kojem materijalu koji se nalazi na stranici u bilo koje vrijeme.
\n\nIntechOpen nije formalno povezan niti s jednom vanjskom stranicom čije poveznice vode na www.intechopen.com, osim ako to nije izravno navedeno. Iz tog razloga IntechOpen nije odgovoran za sadržaj koji se pojavljuje na takvim stranicama. Poveznica na IntechOpenovu stranicu ne implicira povezanost sa IntechOpenom. Korištenje takvih poveznica isključiva je odgovornost korisnika.
\n\nZadržavamo pravo vlasništva nad cjelokupnom stranicom www.intechopen.com i nad svim materijalom na toj stranici. Koristeći se našim uslugama, slažete se da maknete sve poveznice na našu stranicu odmah nakon što to od vas zatražimo. Također, zadržavamo pravo da ove Odredbe i uvjete, i politiku o poveznicama izmjenimo u bilo koje vrijeme. Koristeći se poveznicama na naše stranice slažete se s ovim Odredbama i uvjetima.
\n\nAko smatrate da je bilo koja poveznica na našoj stranici sumnjiva iz bilo kojeg razloga, molimo vas da nas kontaktirate. U tom slučaju razmotrit ćemo micanje poveznice s naše stranice, iako nismo obvezni to napraviti.
\n\nBez prethodne privole i izričite pisane dozvole, ne možete stvarati okvire oko naših stranica ili koristiti druge tehnike koje na bilo koji način mogu promijeniti prezentaciju ili izgled naše stranice.
\n\nIntechOpen može ove Odredbe izmijeniti u bilo koje vrijeme i bez prethodne obavijesti. Koristeći ovu stranicu vi se slažete s trenutnim Odredbama i uvjetima koje su na snazi.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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