**1. Introduction**

Obesity is becoming increasingly common, with at least 400 million obese adults worldwide and the World Health Organization (WHO) projecting that this statistic will reach 700 million in another five years [1]. The body, which is altered by excessive weight, has its biological process modified. This results in several diseases. Different diseases such as heart disease and strokes, high blood pressure, type 2 diabetes, cancer, asthma, sleep apnea, osteoarthritis are all related to obesity [2].

According to a recent survey by the Brazilian Society of Endocrinology and Metabolism (SBEM) obesity in Brazil has increased, on average, 240% over the past 20 years. Today, methods of treatment for obesity are: a) diets; b) non-pharmacological treatments; c) pharmacological treatments; d) surgeries. All the aforementioned methods have the same principle –an energy deficit is necessary to cause weight loss.

Among the techniques available for treating obesity, surgical techniques are more efficient. It is known that surgical methods offer effective results, maintaining 50% weight loss for 10 years. Two types of surgical treatments are practiced: a reduction of the stomach volume to diminish food ingestion and the use of a stomach-intestine bypass to produce practically no absorption of nutrients [3].

In type 2 diabetes mellitus (T2DM), treatment with pharmacologic therapies in order to control blood sugar only slows progression of the disease. Bariatric surgery has been implicated in the complete resolution of type 2 diabetes mellitus in several clinical studies [4].

Multidisciplinary studies for treating obesity and type 2 diabetes mellitus have been developed. Doctors and Engineers are working together to deal with the problem and find

solutions. This is being carried out especially with biomaterials and in biomedical engineering where new devices are being developed.

Prosthesis for Flow Control in the Esophagus as a New Technique for the Treatment of Obesity 171

for treating ischemic leg ulcers. Here, the goal is for the biomembrane to act as an inducing agent for healing tissues [9]. In [10], this membrane was employed in recurrent umbilical

In orthopaedic research aimed at more effective bone regeneration, latex was efficient in repairing tibial fractures in a rabbit, demonstrating great potential for this kind of application. In skull fractures in rats, the results were similar and the researchers believe that new investigations indicate its use in osteoporosis, odontology and facial bone reconstruction [11]. In [12], they developed a new microperforated vascular prosthesis model, made of tissue covered with a compound derived from rubber tree natural latex (*Heveabrasiliensis*) and used an expanded a polytetrafluoroethylene prosthesis as control in the contralateral pelvic limb in the same animal. The study was done applying two prostheses in 15 dogs. The microperforated latex and fabric graft showed satisfactory structural qualities (adaptability, elasticity, impermeability and possibility of suture) as a vascular substitute. It stimulated endothelial growth, beyond contact regions with the artery in anastomoses and was bicompatible with the dog's arterial system, showing adequate tissue integration. In [13], they evaluated using a natural latex mould in the postoperative surgical preparation of the neovagina with the objective of inducing healing and to keep the cavity functional in nine patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. The results confirmed the properties of tissue replacement and regeneration of natural latex derived from *Hevea brasiliensis* and acceleration of the healing process with no rejection. In [14], they developed a topical latex membrane for controlled drug release. In other medical areas, latex has been studied and successfully utilized in the healing process of ulcers, and in burned areas on the body's surface and in conjunctiva reconstruction [8]. Due to these promising results, using latex was the basis for making the new device

A study was conducted concerning esophageal diseases in order to propose a device and its placement technique. It was found that patients with obstructive diseases of the esophagus (caustic stenosis, chagasic megaesophagus and esophageal cancer) have high weight loss as a result of reducing the flow of food,which can be seen in [15,16,17,18]. Because these esophageal diseases cause a reduction of the esophageal lumen or obstruct the emptying of the organ, they lead to the patient losing weight. In this context, the CFE® module was developed for helping in the treatment of obesity and it also can be used for diabetes treatment due to the significant weight loss achieved with its use. This chapter describes the engineering and design used in the development of the device and the tests already carried on it aiming at its efficacy and security evaluation in order to offer to the global community

Whereas a decrease in food consumption may be secondary to esophageal obstruction and considering that there is the possibility for inserting devices that may alter its diameter (which takes place in the treatment of bleeding due to esophageal varices), it was plausible

hernias and its effectiveness was established in twelve dairy cows.

proposed here for treating and controlling diabetes and obesity.

a new option for obesity and diabetes treatments.

**2. Materials and methods** 

GI Dynamics® is developing a novel endoscopic treatment for obesity and T2DM. The EndoBarrier™ gastrointestinal liner is a removable implant that resides in the proximal intestine [3]. Toga, from Satiety, Inc., still in its trial stages, inserts flexible stapling devices through the mouth and into the stomach, and then uses suction to gather stomach tissue and staple it together, creating a small stomach pouch near the esophageal junction and thereby increasing satiety [1]. Furthermore, the methods used neuroregulation activation and gastric implants for activation of the vagus nerve as a way to control hunger [1,4].Thus, it is worth noting that there are difficulties in proposing an efficient obesity treatment. In other words, the control and cure of the multiple causes of obesity associated with eating habits is a difficult problem.

In this study, we designed an esophageal flow control module (CFE) made from a biosynthetic material based on natural latex (extracted from the rubber tree *Hevea brasiliens*). The intended purpose of the CFE is to help to control the speed and the volume of food ingested, and, as a result, to help in treatments to reduce weight.

The CFE proposed is classified as a restrictive surgical procedure. It is inserted into the esophagus (3 cm after the passage of the upper sphincter) and filled with gas. Experimental animal research has shown satisfactory results. The device has the mechanical characteristics necessary for use inside the esophagus. Furthermore, the animals did not have problems with gastric and behavioral changes, nutrition, blood disorders or irritation because of the CFE. Therefore, this unprecedented technique, which can solve the obesity problem, allows a decreased food intake by decreasing the flow through the esophagus.

Therefore, even though the device needs to be tested on humans, the efficiency of this procedure has been ratified, especially given the success of the evaluation in dogs. Weight loss was confirmed (and validated) between two groups of animals tested. One group had the module and the other did not (however both maintained the same dietary and environmental routine). A biomaterial, latex, is used in its development, given its prominence (in Brazil). There are non-gummy, rubber, hydrocarbon particles in the composition of natural latex. The particles are suspended in an aqueous solution phase in which there is on average 36% hydrocarbons, 1,4% proteins, 1,6% carbohydrates, 1% neutral lipids, 0,6% glycolipids plus phospholipids, 0,5% inorganic components, 58,5% water and 0,4% of other substances. For this reason, *Hevea brasiliensis* latex is a complex cytoplasmic system in which the rubber particles and the nonrubbery particles (also called non-gummy) are dispersed in an aqueous cytosolic phase. It is a national low-cost product, which is also easy to handle. Latex, plus other substances, was initially used as a material that induces healing in damaged esophageal walls. Results showed that a natural latex biomembrane with polylysine has biochemical characteristics that make it capable of interfering in the process of tissue repair thus promoting the rapid and regular formation of new tissue. It is also easy to handle, dispensing with complex techniques for manufacturing and use [5, 6, 7]. Based on these data, other studies utilizing latex have been done, such as using latex for myringoplasty in humans [8] and applying latex biomembranes for treating ischemic leg ulcers. Here, the goal is for the biomembrane to act as an inducing agent for healing tissues [9]. In [10], this membrane was employed in recurrent umbilical hernias and its effectiveness was established in twelve dairy cows.

In orthopaedic research aimed at more effective bone regeneration, latex was efficient in repairing tibial fractures in a rabbit, demonstrating great potential for this kind of application. In skull fractures in rats, the results were similar and the researchers believe that new investigations indicate its use in osteoporosis, odontology and facial bone reconstruction [11]. In [12], they developed a new microperforated vascular prosthesis model, made of tissue covered with a compound derived from rubber tree natural latex (*Heveabrasiliensis*) and used an expanded a polytetrafluoroethylene prosthesis as control in the contralateral pelvic limb in the same animal. The study was done applying two prostheses in 15 dogs. The microperforated latex and fabric graft showed satisfactory structural qualities (adaptability, elasticity, impermeability and possibility of suture) as a vascular substitute. It stimulated endothelial growth, beyond contact regions with the artery in anastomoses and was bicompatible with the dog's arterial system, showing adequate tissue integration. In [13], they evaluated using a natural latex mould in the postoperative surgical preparation of the neovagina with the objective of inducing healing and to keep the cavity functional in nine patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. The results confirmed the properties of tissue replacement and regeneration of natural latex derived from *Hevea brasiliensis* and acceleration of the healing process with no rejection. In [14], they developed a topical latex membrane for controlled drug release. In other medical areas, latex has been studied and successfully utilized in the healing process of ulcers, and in burned areas on the body's surface and in conjunctiva reconstruction [8]. Due to these promising results, using latex was the basis for making the new device proposed here for treating and controlling diabetes and obesity.

A study was conducted concerning esophageal diseases in order to propose a device and its placement technique. It was found that patients with obstructive diseases of the esophagus (caustic stenosis, chagasic megaesophagus and esophageal cancer) have high weight loss as a result of reducing the flow of food,which can be seen in [15,16,17,18]. Because these esophageal diseases cause a reduction of the esophageal lumen or obstruct the emptying of the organ, they lead to the patient losing weight. In this context, the CFE® module was developed for helping in the treatment of obesity and it also can be used for diabetes treatment due to the significant weight loss achieved with its use. This chapter describes the engineering and design used in the development of the device and the tests already carried on it aiming at its efficacy and security evaluation in order to offer to the global community a new option for obesity and diabetes treatments.

#### **2. Materials and methods**

170 Practical Applications in Biomedical Engineering

difficult problem.

engineering where new devices are being developed.

ingested, and, as a result, to help in treatments to reduce weight.

a decreased food intake by decreasing the flow through the esophagus.

solutions. This is being carried out especially with biomaterials and in biomedical

GI Dynamics® is developing a novel endoscopic treatment for obesity and T2DM. The EndoBarrier™ gastrointestinal liner is a removable implant that resides in the proximal intestine [3]. Toga, from Satiety, Inc., still in its trial stages, inserts flexible stapling devices through the mouth and into the stomach, and then uses suction to gather stomach tissue and staple it together, creating a small stomach pouch near the esophageal junction and thereby increasing satiety [1]. Furthermore, the methods used neuroregulation activation and gastric implants for activation of the vagus nerve as a way to control hunger [1,4].Thus, it is worth noting that there are difficulties in proposing an efficient obesity treatment. In other words, the control and cure of the multiple causes of obesity associated with eating habits is a

In this study, we designed an esophageal flow control module (CFE) made from a biosynthetic material based on natural latex (extracted from the rubber tree *Hevea brasiliens*). The intended purpose of the CFE is to help to control the speed and the volume of food

The CFE proposed is classified as a restrictive surgical procedure. It is inserted into the esophagus (3 cm after the passage of the upper sphincter) and filled with gas. Experimental animal research has shown satisfactory results. The device has the mechanical characteristics necessary for use inside the esophagus. Furthermore, the animals did not have problems with gastric and behavioral changes, nutrition, blood disorders or irritation because of the CFE. Therefore, this unprecedented technique, which can solve the obesity problem, allows

Therefore, even though the device needs to be tested on humans, the efficiency of this procedure has been ratified, especially given the success of the evaluation in dogs. Weight loss was confirmed (and validated) between two groups of animals tested. One group had the module and the other did not (however both maintained the same dietary and environmental routine). A biomaterial, latex, is used in its development, given its prominence (in Brazil). There are non-gummy, rubber, hydrocarbon particles in the composition of natural latex. The particles are suspended in an aqueous solution phase in which there is on average 36% hydrocarbons, 1,4% proteins, 1,6% carbohydrates, 1% neutral lipids, 0,6% glycolipids plus phospholipids, 0,5% inorganic components, 58,5% water and 0,4% of other substances. For this reason, *Hevea brasiliensis* latex is a complex cytoplasmic system in which the rubber particles and the nonrubbery particles (also called non-gummy) are dispersed in an aqueous cytosolic phase. It is a national low-cost product, which is also easy to handle. Latex, plus other substances, was initially used as a material that induces healing in damaged esophageal walls. Results showed that a natural latex biomembrane with polylysine has biochemical characteristics that make it capable of interfering in the process of tissue repair thus promoting the rapid and regular formation of new tissue. It is also easy to handle, dispensing with complex techniques for manufacturing and use [5, 6, 7]. Based on these data, other studies utilizing latex have been done, such as using latex for myringoplasty in humans [8] and applying latex biomembranes

Whereas a decrease in food consumption may be secondary to esophageal obstruction and considering that there is the possibility for inserting devices that may alter its diameter (which takes place in the treatment of bleeding due to esophageal varices), it was plausible

to suppose that developing the CFE® module may lead to reducing food intake.The objective is to evaluate the possibility of CFE® insertion into the esophagus which causes, during its use, resistance to the passage of food bolus. This makes food ingestion slower due to a reduction in the lumen of the esophagus, resulting in the need for prolonged chewing.

Prosthesis for Flow Control in the Esophagus as a New Technique for the Treatment of Obesity 173

With the objective of estimating the minimal time to carry out an intervention, in the event that it descends to the stomach and in order that it not cause intestinal obstruction, an experiment was conducted in the Laboratory of Engineering and Innovation – LEI at the Gama Campus of the University of Brasília. This experiment compared the volume of BIB (400 ml to 700 ml) and (CFE 146 ml) with the goal of comparing its volumes and its emptying capacity in the case it is punctured. The calculation employed for obtaining the CFE volume used a technique based on solids of revolution and the time was obtained from simple arithmetic means. There were four CFE modules used as samples and these were immersed into an environment similar to the stomach. The method utilized was to inflate the CFEs with the same pressure to be applied in humans (60 mmHg – minimum), withdrawal of the scalp1 number 27, immersion of the CFE in the environment with the hole made in the sample by the scalp on the upper part of the module thereby forcing partial emptying, since if it were not punctured, it would not empty as in the test done in [7].

The choice for using a dog – as an animal for testing and for weight loss and/or as a validator of the CFE module – was made in light of findings raised with medical veterinarians. It was verified that the animal would be an excellent subject for analysis in this study keeping in mind the anatomical-physiological similarity between human and canine esophagi. Allied with this, above all, factors that denote affability with such animals and also, the facility of controlling their eating routine, as well as the food ingestion speed of the animal, associated with little chewing and the absence of psychological pressure (as opposed to what a human develops when the goal is losing weight). To conduct the experimental procedure, eight adult dogs, of no specific breed, males and females, with body weights varying between 9.2 and 17.8 kg were selected. Before the experiment, the animals were kept at the Veterinarian Hospital kennel at the Federal University of Goiás to be submitted to quarantine procedures that include: vaccination (Duramune Max, single dosage), application of ecto and endoparasiticides (administered through 100 mg of mebendazole, twice a day for three days), in addition to laboratory exams like blood count, urinalysis, hormonal and blood biochemical evaluations. Furthermore, improvements in the nutritional conditions of the animals was sought, through the implementation of a daily diet of dry dog food, supplemented with semi-moist dog food rich in nutrients (Dudog®). The animals were vaccinated against rabies and DHLPPC (distemper, hepatitis and adenovirus, leptospirosis, parainfluenza, parvovirus, and coronavirus) and dewormed with a broad spectrum dewormer. Ectoparasites were eliminated with a two-dose application of pour-on parasiticide. Blood was taken from all the animals and when hemoparasitoses was present, doxycycline was applied for 21 days, and diminazene in

1 The scalps peripheral intravenous comprise: siliconized needle stainless steel bezel with thin walls and biangular and three faceted; wings malleable and flexible, adjustable anatomically as handling (known as "butterfly"); transparent

**2.4.** *In-vitro* **study** 

**2.5. Preparation for clinical trial** 

two applications with an interval of 15 days.

vinyl tube.

#### **2.1. Latex preparation**

The latex used here had already been through the centrifuging process, with sulfur and resin suspensions, having the objective of providing elasticity and the necessary strength for the final compound. From this preparation process, the latex is configured as a compound which upon contact with the skin, vulcanizes, making it adhesive. To be removed, however, just pure water is used. On glass surfaces, its removal is facilitated due to the low friction that glass provides.

When handling the latex, glass rods were used for mixing, as well as a glass container for storage, plastic wrap to protect it from contact with the air and cotton flannel for cleaning. An important point for any application that uses raw latex is the uniformity of its properties, since this is an essential characteristic. To obtain this characteristic, the latex source should be the same, i.e. the latex should come from trees of the same clone.
