Characteristics of polymeric materials used in medicine

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Characteristics of polymeric materials used in medicine

14

Ernesto David Davidson Hernandez1 and Jacobo Rafael Reyes-Romero2 1

Tecnicatura Superior Universitaria en Palenteologia, Universidad del Chubut, Rawson, Repu´blica Argentina 2Escuela Ba´sica, Facultad de Ingenierı´a, Universidad Central de Venezuela, Caracas, Venezuela

14.1 INTRODUCTION Biomaterials are substances or a combination of substances of natural or synthetic origin, designed to act interracially with biological systems in order to replace any tissue, organ, or function of the human body. Another way of defining a biomaterial is as a material of nonbiological origin that is used in the manufacture of devices that interact with biological systems and that are applied in different areas of medicine. The science of biomaterials is made up of fundamental pillars concerning branches of science, engineering, and medicine. More specifically, this consists mainly of biology, materials science, tissue engineering, and biomedicine. Fig. 14.1 presents a scheme of organizations of each of these disciplines. Biomaterials must possess certain characteristics in order to be used in the medical field. The porosity of these is important, since pore size and microstructure influence axonal growth, motility, morphology, and cell adhesion (Mata et al., 2009), as well as the space between the pores as it is involved in cell adhesion and the rate at which the cells propagate (Mitragotri and Lahann, 2009). Also is important to consider the degradation mechanism of polymers because a biomaterial has to replace the natural components of living tissue. This property influences cell migration, proliferation, differentiation, and even cellular morphology (Carvalho et al., 2013). In addition, the elasticity of a biomaterial should be appropriate according to the tissue in question, since the biomaterial should not to deform easily or lose its structure, which also involves in the organization of cells (Mitragotri and Lahann, 2009). Biocompatibility is a fundamental aspect because each organism reacts differently to an implant. This means that the response of the immune system to a

Materials for Biomedical Engineering: Thermoset and Thermoplastic Polymers. DOI: https://doi.org/10.1016/B978-0-12-816874-5.00014-1 © 2019 Elsevier Inc. All rights reserved.

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FIGURE 14.1 Main axes that make up the science of biomaterials.

foreign body or antigen changes from one organism to another. When a biomaterial is referred to as being biocompatible it is thought that the biomaterial does not cause adverse effects within an organism. This means, that it is an inert, nontoxic material and that it is accepted by the organism (Wang, 2013). Finally, the compartmentalization of some biomaterials is frequently used for the release of molecules in the tissue where they are implanted; generally used for the release of drugs or growth factors that aid in tissue recovery (Wang, 2013; Palakurthi et al., 2013). Historically, applications of biomaterials in the medical field date back to 1860 with the introduction of aseptic techniques, and some unique biomaterials used include steels and alloys, extending their applications from bone repairs to drug delivery systems (Collet Gonzalez, 2004). At first, the search for biomaterials was carried out in a purely empirical way. This then changed profoundly to the point that the science and engineering of biomaterials can now be defined as interdisciplinary activities (Abraham et al., 1998). In other words, the development of biomaterials requires specialists in the different branches of medicine, engineering, and pure sciences. This interdisciplinary challenge allows advances in biomedical sciences and tissue engineering, considering the use of a simple biomaterial, drug use, living cells, and hybrid biomaterials (consisting of drugs and living cells). Another important group of biomaterials is the so-called intelligent biomaterials, which respond to signals from the biological environment. All of them make up a series of devices for mass and daily use in hospitals, clinics, and other healthcare centers. The most commonly used are syringes, bandages,

14.1 Introduction

catheters, serum and blood bags, waste containers, as well as sophisticated pieces that are applied to promote tissue regeneration or organ replacement (Abraham et al., 1998). One of the first polymers used as a biomaterial was polymethyl methacrylate (PMMA) during World War II for the purpose of repairing the human cornea (Hernandez Martı´n, 2012). Dr. Sir Harold Ridley invented the first intraocular lens manufactured in acrylic, and performed the first implants in patients with cataracts (Duffo, 2011). Occasionally, due to a malfunction of the eye lens (cataracts), it is necessary to surgically remove and surgically implant an intraocular lens to correct vision. Well, PMMA is also used to make such an intraocular lens (Hernandez Martı´n, 2012). The use as an artificial cornea or keratoprosthesis of this biomaterial, commercially known as “Plexiglas,” was first discovered during World War II. Later, polyethylene was used as an alternative to metal catheters in the 1950s and 1960s, and then in the 1960s acrylic was used as bone cement in hip and knee replacements. From then on the use of polymers has seen tremendous growth in the field of biomedicine. For example, PMMA is mainly used as bone cement in hip and knee replacements, and UHMWPE of medical grade is the main component that forms the articulating surfaces of hip and knee joints (Ramakrishna et al., 2001). In addition, the medical grade UHMWPE is also used in the spine as a convex plate interchangeable in the type of cervical prosthesis prodisc C and as a bearing that fixes chromocobalt in the prosthesis of pourus coated motion (PCM) (Van Dijk et al., 2003; Phillips and Garfin, 2005). The most important properties of polymers that are used as biomaterials are: low density, high molecular weight and biocompatibility, nontoxicity, easy sterilization, excellent mechanical properties that support the application until the tissue is scarred, absorptivity, and slow degradation. These are suitable for use as: prostheses, joints, implants, equipment and surgical instruments, and in elements such as bone cements, membranes, and components of artificial organs in order to replace others materials. The use of natural substances is of great importance to protect the biomaterials used within living tissue from oxidation, specifically for medical grade UHMWPE used in orthopedics. The antioxidant mechanism is based on the annihilation of free radicals that circulate in the body, mainly radical peroxides. Investigations reported by many authors show the effectiveness of polyphenols from vitamin E and vitamin C in synthetic polymers, such as medical grade UHMWPE, to prevent oxidation cascades, such as occurs in humans (Oral et al., 2006; Davidson et al., 2010, 2011). Polyolefins, mainly medical grade UHMWPE, are the most important polymers used in orthopedics. Its main applications are: sliding surfaces for artificial joints. Polyethylene (PE) can undergo oxidation, especially gamma sterilization, which increases hydrophilicity, recrystallization, and makes the polymer more brittle (Maitz, 2015).

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Since 1962, medical grade UHMWPE has been a component of prostheses and implants of the hip and knee. The most important characteristics or properties of this material are: low density, high molecular weight (in the range of 2 6 million g mol21), nontoxicity, natural chemical composition, simple structure, low water absorption, excellent chemical and physics properties, and high resistance to ionizing radiation. It increases mainly in an inert atmosphere, which is an important property of polyethylene. Because of these and other properties, this polymer has been used on both an industrial and medical level. For example, in the space industry it is used as aerospace costume design due to the fact it has carbon and hydrogen in its structure (Stephens et al., 2005). Currently many researchers are trying to modify the structure and properties of medical grade UHMWPE in vitro in order to use this material in minimizing the intolerance of living tissue. Many studies report excellent results in UHMWPE samples as bearing artificial joints and joint prostheses components (Maitz, 2015; McKeen and Lawrence, 2014). However, the average lifetime of prostheses is near to 15 years. In other words, UHMWPE is susceptible to wear, exhibiting an aseptic loosening of the prosthesis or implant, which it is the main cause of failure in UHMWPE components used in orthopedics. Due to this situation many researchers have been attempting improve the properties of this material. Investigations have been reported that the combinated use of ionizing radiation, in both inert and air atmosphere, thermal treatments and use of natural substances result successful, mainly with the use of ionizing radiation in inert atmosphere (Davidson et al., 2010, 2011; Kim et al., 2006; Oral et al., 2006). On the contrary, is a well-known the fact that the radiation in air atmosphere results in oxiadtion and degradation processes. In addition, studies by Davidson et al. (2011) on UHMWPE medical grade samples irradiated in air and stored in simulated body fluid (SBF) showed a predominance of degradation processes. The radiation in atmosphere air lead to the oxidation process and subsequent chain breaking mechanism of UHMWPE samples due to peroxide radicals (ROO ) being formed and transformed into carbonyl groups. On the other hand, in an inert atmosphere a predominance of crosslinking mechanisms is observed, thus, forming long chains leading to a high molecular weight. Other studies have been reported that the combinated effects of ionizing radiation in inert atmosphere, thermal treatments of annealing and remelting andh vitamin E as transport media as storage substance improve the crosslinking and decreasing the chain break mechanism. The results showed an increase in crosslinking formation and an improvement in chemical and physical properties (Davidson et al., 2011; Oral et al., 2006; Kim et al., 2006). The thermal treatments as annealing and remelt led to a decrease the residual stress during the processing of UHMWPE, in order to avoid structural failure. The use of natural substances, such as vitamin E, vitamin C, aloe vera, etc., as a means of transport and storage reduces the oxidation processes after of irradiation. The mechanism is based on a neutralization reaction between the phenol and peroxide radicals (ROO∙) yielding hydroperoxide and phenyl radical, which are

14.2 Applications of Biomaterials

FIGURE 14.2 Mechanism of reaction for peroxide and fenoxi radical.

more stable and keep for a long time in polymers, thus, retarding the oxidation cascades (Oral et al., 2006). This mechanism is described in Fig. 14.2. The importance of crosslinking is that it optimizes the properties of UHMWPE. In other words, modifying the crystal structure of the polymer may improve its properties in vitro. The changes observed could be beneficial to reduce the problem of the wear of joints, bearings, and others components of prostheses and implants once placed in living tissue. In this chapter, the types of biopolymers, mainly medical grade UHMWPE, characteristics, applications, behavior in vitro, and behavior in living tissue are described. In addition, is analyzed the behavior of biopolymers and bioplastics and its relation with nanomatarials. Moreover, the mechanisms of failure in orthopedic prostheses inside living tissue are discussed. Finally, a forward projection in the use of these materials is given.

14.2 APPLICATIONS OF BIOMATERIALS Most synthetic polymers that have been used as biopolymers are thermoplastic. Thermosetting polymers are also used but to a lesser extent. It refers to materials that are used to produced syringes, serum or blood bags, hoses or flexibles tubes, adhesives, clips, elastic bands, sutures, bandages, functional imaging (positron emission tomography), etc. The materials used are of synthetic origin and are nonbiodegradable, such as polyethylene, mainly UHMWPE and HDPE, polypropylene, polyvinylchloride, polymethyl methacrylate, polycarbonate, polystyrene, nylon, etc. (Gonza´lez, 2004). For example, nylon and polypropylene are used as suture materials and PVC is used in tubes and bags for storing blood and pharmaceuticals, as well as in antibacterial membranes (Science in School, Polymer in Medicine, 2011). Moreover, thin films and coatings of PVC are use as storage bags and packaging surgical blood and others solutions; parts esophageal segment

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arteries, biodegradable sutures, implants joints parts fingers acetabular hip and knee, among others (Science in School, Polymer in Medicine, 2011). Polyethylene terephthalate (PET) is used for large diameter vascular grafts. Polymethyl methacrylate (PMMA) is used as a cement material for the femoral fixation of intraocular lens and for hip prosthesis. Polytetrafluorethylene (PTFE) is used in membranes for vascular periodontal ligament prosthesis as grafts. Various hydrogels are beginning to be used in applications such as: contact lens due to low protein adsorption and ease lubricity. Polyurethanes are an example of materials with excellent resistance to fatigue; and they are, therefore, used in artificial hearts (Blanco Rebeca Infante et al., 2015). PET is used in functional imaging (positron emission tomography) (Go´nzalez et al., 2002). Coating polymers (silicones, hydrogels, and fluorocarbons) are used for many cardiovascular applications. Bioreadsorbable materials are interesting because they are eliminated without further surgery. Generally, they are materials that degrade without being toxic to the body and are then eliminated. The most polymer materials commonly used, like bioreadsorbible biopolymers and hidroxy acids, are degraded to half of their mass in a few months (Blanco). Polyvinyl alcohol (PVA) is used in drug delivery systems; while polyacrylamide is used in medical diagnoses. Poly(lactic acid) (PLA) has become an indispensable material in the medical industry, where it has been used for 25 years due to its biodegradable and bioabsorbable properties (which means that it can be assimilated by the biological system). Its features and absorbability make PLA an ideal implant material for bone or tissue, orthopedic surgery, ophthalmology, orthodontics, controlled cancer drugs release, and for sutures (eye surgery, breast surgery, and abdomen) (Guerra et al., 2016). In addition, poly-L-lactic acid is a suitable biodegradable polymer for use as an implant material, mainly in screws for bone fractures, since it promotes bone regeneration, as confirmed by tests on rabbits and gross and histologic analyses of specimens studied. Its mechanical properties can be improved with the use of alcohols as coinitiators or by copolymerization with e-caprolactone (Zhang et al., 2013). Poly(glycolic acid) or polyglycolide (PGA: poly(hydroxyacetic)) is important both industrially and in the field of medical biodegradable linear polyesters. This area is focused on wound closure, such as surgical suture material, as well as bone fixation devices, such as rods, plates, or screws, and likewise on implants to replace bone fragments and on drug delivery systems. Natural biopolymers or macromolecules are extremely important substances for use in biomedical systems as they are commonly synthesized by living organisms. They are also important for use in new medical disciplines, such as tissue engineering, as biopolymers also include synthetic materials with the particularity of being biocompatible with living organisms (usually with human beings). The main families of natural biopolymers, are proteins (fibroins, globulins, amino acids), polysaccharides (cellulose, alginates, etc.), and nucleic acids (DNA, RNA, etc.); although others more unique, such as polyterpenes, among

14.2 Applications of Biomaterials

which natural rubber is included, as well as polyphenols (such as lignin) or some polyesters, such as polyhydroxyalkanoates produced by certain bacteria, due to it forming most of the Earth’s biomass. The polyhydroxyalkanoates is a polysaccharide. This biopolymers can be use in the diet of humans as dietary fiber, this works when is mixed with feces and this result give us digestion, defecation and prevents bad gases (Institute of medicines, 2005). Chitosan is a natural polysaccharide that is biodegradable, biocompatible, nontoxic, and has low immunogenicity so it is of great interest in the medical field for use as a biopolymer material. This substance is extracted from the shells of shrimps and prawns (Lo´pez Rubio, 2015). It is the second most abundant biopolymer available after of cellulose. In addition, for more the 20 years many researchers have published work on chitosan as a potential drug delivery system (Bernkop-Schnu¨rch and Sarah Du¨nnhaup, 2012). The chitosan in contrast with others polysaccharides having a monograph in a pharmacopeia, chitosan has a cationic character because of its a primary amino groups. These primary amino groups are responsible for properties such as controlled drug release, mucoadhesion, in situ gelation, transfection, permeation enhancement, and efflux pump inhibitory properties (Bernkop-Schnu¨rch and Sarah Du¨nnhaup, 2012). DNA is a polymer composed of monomers called nucleotides, which are transcribed in the cell in the form of a small chain of ribonucleic acid: messenger RNA. A study on women with advanced triple negative breast cancer found that those who received a poly (ADP-ribose) polymerase (PARP) inhibitor called iniparib along with chemotherapy had a longer survival rate than those who only received chemotherapy. Other small and preliminary studies showed some positive results using another PARP inhibitor, olaparib, in combination with chemotherapy in cases of triple negative breast cancer. The results were presented at the 2010 annual meeting of the European Society for Medical Oncology (ESMO) (Breasttcancer.org, 2010). Agarose is a thermoreversible natural biomaterial that is obtained from red algae (Jain and Bellamkonda, 2007). The term “thermoreversible” refers to a substance that can be converted from gel phase at room temperature to liquid phase at an elevated temperature above ambient temperature and which can be reconverted to gel phase when cooled to room temperature. The grievance has the same of a disaccharide composed of 3,6-anhydro-α-L-galactose and β-D-galactose (Wong et al., 2004). Another interesting and important group that is widely used both industrially and in medicine is referred to as “bioplastic.” These plastics are derived from plants, such as from soybean oil and corn or potato starch products, unlike conventional plastics which are derived from oil. Its origins go back to 1926, when scientists from the Pasteur Institute in Paris were able to produce polyester from the bacterium, Bacillus megaterium. The main characteristic of bioplastics that make them attractive for use is that they are based on natural resources and not on petroleum as in the case of synthetic polymers. This is of great interest because it reduces the energy consumption involved in their production and it eliminates the emission of gases that

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cause the greenhouse effect. In addition, producing plastics from biomass implies independence from petroleum. Major bioplastics are described here: Starch-based bioplastics are important not only because starch is the least expensive biopolymer, but because it can be processed by different methods used for synthetic polymers, like film extrusion and injection molding (Jogdand, 2014). Soybean have been revived, recalling Ford’s early efforts. In research laboratories it has been shown that soy protein, with and without cellulose extenders, can be processed with modern extrusion and injection molding methods (Jogdand, 2014). Many water soluble biopolymers, such as starch, gelatin, soy protein, and casein, form flexible films when properly plasticized. Although such films are regarded mainly as food coatings, it is recognized that they have the potential to be used as nonsupported stand-alone sheeting for food packaging and other purposes (Lo´pez Rubio, 2015). Starch is found in corn (maize), potatoes, wheat, tapioca (cassava), and some other plants. The annual world production of starch is well over 70 billion pounds, with much of it being used for nonfood purposes, like making paper, cardboard, textile sizing, and adhesives (Jogdand, 2014). Casein, commercially produced mainly from cow’s skimmed milk, is used in adhesives, binders, protective coatings, and other products. Soy protein and zein (from corn) are abundant plant proteins. They are used for making adhesives and coatings for paper and cardboard. Cellulose is the most abundant renewable material on Earth and is widely used in various industries, such as the paper and textile industries. Cellulose is formed by the union of glucose molecules by β-1,4 glycosidic bonds. In addition, it has a linear structure in which multiple hydrogen bonds are established between the OH group of the glucose chains, which play an important role in determining the strength and rigidity of the cellulose structural support (Bastioli, 2001). Cellulose represents 40% of the organic matter on the planet. Overall, bioplastics obtained from cellulose, either pure or in mixtures, are used in toys, sports equipment, medical applications, interior decoration, automobiles, and construction (Pacheco et al., 2014; Mutlu Hatice and Meier Michael, 2010). More than 150 different types of PHA have been studied, the analysis have been shown, the most representative being polyhydroxybutyrate (PHB), which accumulates in bacteria such as Alcanigenes eutrophus and Azotobacter vinelandii (Lakshman and Shamala, 2003). These polymers are used for the manufacture of cosmetic container products, in feminine hygiene products, utensils, packaging products, and bags (Valero et al., 2013). Collagen is the most abundant protein found in mammals. Gelatin is denatured collagen, and is used in sausage casings, capsules for drugs and vitamin preparations, and other miscellaneous industrial applications, including photography (Jogdand, 2014). Polyesters are now produced from natural resources, like starch and sugars, through large-scale fermentation processes and used to manufacture waterresistant bottles, eating utensils, and other products (Jogdand, 2014).

14.3 UHMWPE Behavior Under the Action of External Factors

Triglycerides have become the basis for a new family of sturdy composites. With glass fiber reinforcement they can be made into long-lasting, durable materials with applications in the production of agricultural equipment, the automotive industry, construction, and other areas. Fibers other than glass can also be used in this process, like fibers from jute, hemp, flax, wood, and even straw or hay. If straw could replace wood in composites that are currently used in the construction industry, it would provide a new use for an abundant, rapidly renewable, agricultural commodity and at the same time conserve less rapidly renewable wood fiber. Polyamide 11 is a polymer that although it comes from natural resources, is not biodegradable as are biopolyesters, such as bio-PET or bio-PE. Polyamide 11 or nylon 11 comes from the degradation of castor oil. Its properties include water resistance and high temperatures, which is reason it is used in electrical cables and in the automotive industry (Pacheco et al., 2014). Polyphenols are used as antioxidants to prevent premature aging of the body. The advantage of these biopolymers is that they are present in many foods and natural substances that are regularly used. It is present in substances such as vitamin E and aloe vera, and in beverages such as coffee, tea, beer, as well as in foods such as chocolate, nuts, olive oil, red wine, legumes, grains, etc. Biopolyethylene represent a type of renewable polyethylene obtained from the polymerization of bioethanol, possessing a similar structure to polyethylene, it is a nonbiodegradable compound, but to have the same characteristics as that obtained from oil becomes multipurpose material.

14.3 UHMWPE BEHAVIOR UNDER THE ACTION OF EXTERNAL FACTORS UHMWPE has previously been described here as a material that possesses excellent chemical and physical properties. In addition, it presents ideal characteristics as a biomaterial, and for this reason has been an important material used in orthopedics since 1962. Many hip and knee prosthesis components, such as joints, bearing, femoral heads, and friction pairs are made of medical grade UHMWPE. Fig. 14.3 shows a prototype of a hip prosthesis made with this material (Davidson, 2012). Presently in hip prostheses, UHMWPE is used instead of hydroxyapatite in order to form friction pairs with titanium and its alloys and/or tantalum. UHMWPE is located in the smooth part corresponding to the UHMWPE is in contact with the femoral head of Titanium in order to reduce the wear prostheses. Titanium is placed directly in contact with the bone of the femur because it is biocompatible and has a Young’s modulus of 110 GPa, while that of bone is between 20 and 30 GPa (Oldini, 2014). This means that the elastic modulus of titanium is five times higher than that of bone. In other words, this difference creates a high metal stiffness in the osseous fabric and so here, titanium, its alloys, and alloys of

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FIGURE 14.3 Hip prostheses prototype top view. Doctoral Thesis Davidson Ernesto, 2012.

other steels, generate the phenomenon of “stress shielding” (bone retraction because of lack of bone work). For this reason, other alloys containing aluminum and lighter metals are being investigated and evaluated (Oldini, 2014). In the case of knee prostheses, currently the most common options for knee replacement usually include metal alloys (stainless steel, Co Cr, and TI), UHMWPE, alumina (Al2O3), or Zirconia (ZrO2) (Plaza Torres and Aperador, 2015). However, the use of UHMWPE as a replacement for knee and hip prostheses is increasing rapidly each day, to the point that projections for 2030 are estimated to be 100% for patients over 65 years of age and 26% for patients less than 65 years (Kurtz, 2015). Due to the importance of UHMWPE and its increasing clinical use in orthopedics over more than five decades, many investigations using different systems have been reported. Studies show the use of ionizing radiation, mainly with gamma rays, in both inert and oxidative atmospheres and less frequently with neutrons, electrons, and heavy ions have been considered. Moreover, other works show the use of sterilization methods with peroxide and ethylene oxide, thermal treatments such as annealing and remelting, and the use of natural substances, mainly vitamin E, vitamin C, animal serum, and SBF. The majority of studies have shown encouraging results, mainly those involving ionizing radiation in an inert atmosphere, annealing and refining thermal treatments, and the use of natural substances for storage and transportation. There have also been reports of interesting results with the use of bovine serum, sterilization methods with peroxides and ethylene oxide, and the use of neutron and electron radiation. In an investigation, Davidson (2012) reported that ionizing radiation combined with gamma rays at different integral doses in an inert atmosphere, with storage in vitamin E, and annealing and remelting, showed improvements in the mechanical properties, wear resistance, and coefficient of friction of UHMWPE medical

14.3 UHMWPE Behavior Under the Action of External Factors

grade samples. In Fig. 14.4A and B the results of these analyses are shown. Davidson (2012) concluded that the combined effect of irradiation with gamma rays, storage and transport in vitamin E, and thermal annealing and melting treatments favor the mechanism of crosslinking. In other words, the combination of

FIGURE 14.4 (A) Wear versus integral dose for UHMWPE-Gur-1050 samples. (B) Coefficient of friction versus integral dose for UHMWPE-Gur-1050 samples. Doctoral Thesis Davidson, 2012.

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these external factors allows for the modification of the structure of UHMWPE in order to reduce the mechanisms that lead to the formation of oxidation cascades. This result shows for the first time the effectiveness of aloe vera as a storage substance in medical grade UHMWPE samples. The importance of this finding is that it will allow the use of a natural substance directly extracted from aloe vera. In other words, it is beneficial to reduce operational costs and generate a positive environmental impact, as it avoids the use of synthetic compounds in the design, development, and manufacture of prostheses. Moreover, the most relevant of these results is that it reduces the wear of the material to a large degree; it is of great interest for the design and manufacture of implants, prostheses, friction pairs, and tribological systems using UHMWPE, as wear is the most important factor that reduces the lifespan of prostheses. In other results, Davidson (2012) showed changes in the thermal properties of UHMWPE-Gur-1050 samples irradiated with gamma rays in an inert atmosphere using vitamin E as a storage substance and heat treatment for annealing (See Table 14.1). Davidson explains that the results obtained in the UHMWPE samples analyzed under the established conditions are due to the predominant mechanism of crosslinking. There the alpha tocopherol present in the vitamin E acts as neutralizing substance to the radical peroxides, thereby drastically reducing oxidation cascades. Moreover, the annealing prevents the formation of residual stresses, which favors the improvement of the mechanical properties (Davidson et al., 2011). Additionally, the decrease observed in the melting and crystallization temperatures and the decrease in the degree of crystallinity are caused by crosslinking, which leads to an increase in molecular weight and, therefore, longer and heavier

Table 14.1 Thermal Properties for UHMWPE-GUR-1050 Samples Properties Crystallinity Grade (%) ( 6 1) (kGy) 0 50 100 0 50 100 0 50 100

Control Sample 25 C 45

137

114

UHMWPE GUR 1050 120 C Vitamin E

UHMWPE GUR 1050 130 C Vitamin E

UHMWPE GUR 1050 140 C Vitamin E

UHMWPE GUR 1050 145 C Vitamin E

35 30 32 137 135 133 113 113 113

31 30 30 138 134 132 113 113 113

31 32 28 141 133 132 113 113 113

30 31 30 138 133 133 114 112 113

Source Davidson, E., 2012. Estudio y Análisis de las Propiedades del Polietileno de Ultra Alto Peso Molecular (PEUAPM-GUR-1050) de Grado Médico, para el Desarrollo y Fabricación de Prótesis Acetabulares a Nivel Nacional. Doctoral Thesis Doctoral.

14.3 UHMWPE Behavior Under the Action of External Factors

chains. There the presence of crosslinks and branches and chains of different sizes cause a decrease in thermal properties (Davidson et al., 2011). In addition, these long chains prevent molecular packing by preventing crystallization because they generate a smaller amount of crystals with more imperfections and as a consequence they produce a decreased degree of crystallinity. The application of thermal treatments inhibits the formation of crystals. Crosslinking, on the other hand, prevents the recrystallization of molten UHMWPE (Kim et al., 2006; Davidson et al., 2011). Therefore, the crystallinity in the irradiated samples stored in vitamin E and thermally treated is lower than in the virgin UHMWPE samples. This result agrees with those obtained in the analysis of the degree of crosslinking and that of the mechanical properties. From these results, the combined effects of irradiation with gamma rays, heat treatments of annealing, and storage in vitamin E, allow for the crystalline structure of UHMWPE to be modified, favoring the mechanisms of crosslinking and reducing the mechanisms of oxidation cascades. Likewise, the increase observed in mechanical properties, mainly in the wear resistance, is an important contribution to the development of UHMWPE prostheses and implants used in orthopedics. Other researches have reported successful and interesting results regarding the effects of natural substances, uses of ionizing and nonionizing radiation, and thermal treatments (external factors) on the structure and properties of medical grade UHMWPE. In their investigations they show how the changes in the structure of the materials modify their mechanical and thermal properties. In other words, their results show how the combined effects of these external factors modify the crystal structure of UHMWPE by avoiding oxidation cascades, thus, increasing the formation of crosslinking. Bracco and Oral (2011), studied the effect of vitamin E on medical grade UHMWPE samples for total joint implants The purpose in their review was to summarize preclinical research on the development and testing of vitamin Estabilized UHMWPEs for total joint implants. In their methodology, they conducted searches in PubMed, Scopus, and the Science Citation Index to review the development of vitamin E-stabilized UHMWPEs and their feasibility as clinical implants. They compared the behavior of UHMWPE irradiated and stabilized with vitamin E, irradiated UHMWPE, and UHMWPE fused after irradiation with gamma rays. They observed that UHMWPE samples stabilized with vitamin E, showing oxidation resistance and superior mechanical properties; nevertheless they had values of resistance equivalent to those of wear. They concluded that vitamin E-stabilized UHMWPE offers a joint arthroplasty technology with good mechanical, wear, and oxidation properties (Puertolas et al., 2010). Vitamin E (or a-tocopherol) is an alternative to thermal treatments to achieve the oxidative stability of gamma or electron beam irradiated UHMWPE used in total joint replacements. Their purpose was to study the effects of vitamin E on the molecular dynamics and microstructural properties of UHMWPE samples. They started with the hypothesis that the antioxidant would plasticize the UHMWPE. Vitamin E was incorporated

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into UHMWPE at different concentrations by diffusion and blending, and detected by ultraviolet and infrared spectroscopies at 500 and 4000 ppm respectively. A dynamic mechanical thermal analysis was used to characterize the influence of this antioxidant on the relaxations of the raw material. DSC and TEM served to characterize thermal and microstructure properties respectively. They obtained the results that vitamin E concentrations above 3% (by weight) significantly reduced the degree of crystallinity and increased the melting transition temperature of raw UHMWPE. Additionally, an increase in the concentration of a-tocopherol introduced and/or strengthened the beta relaxation, which was also gradually shifted toward lower temperatures and had rising energies up to 188 kJ mol21. Moreover, the gamma relaxation remained unaltered upon the addition of vitamin E. Finally, they concluded that no plasticizing effects of vitamin E on the molecular dynamics of UHMWPE could be confirmed from mechanical spectroscopy data. However, the relaxation was modified in intensity and location due to the changes in the degree of crystallinity introduced by the incorporation of vitamin E. Rı´os et al. (2013) studied the behavior in microstructure, oxidation behavior, and mechanical properties of UHMWPE-Gur-1050 irradiated with gamma rays and annealed with respect to post annealed material. Changes in the thermal transitions, degree of crystallinity, and thickness of the crystals were analyzed by differential scanning calorimetry (DSC). Additionally, they used transmission electron microscopy to analyze the crystalline morphology. They finally adopted a TGA technique to evaluate the resistance to thermooxidation and the induced changes in crosslinking by the effect of irradiation with gamma rays. The different results obtained show that sequentially crosslinked UHMWPE exhibited improved thermooxidation resistance and thermal stability compared to UHMWPE annealed after irradiation. In addition, the mechanical behavior, including fatigue and fracture toughness, of these materials were generally comparable regardless of the annealing strategy. Therefore, the sequential irradiation and annealing process could provide increased oxidation resistance, but not a significant improvement in mechanical properties compared to that of a single radiation dose and the subsequent annealing procedure. They concluded that the annealing treatments improved the oxidation resistance compared to the results obtained post-irradiation for the UHMWPE-Gur-1050 samples analyzed. Microstructural characterization shows that both the crosslinked and pristine UHMWPE have the same crystal thickness and degree and crystallinity. While the thermogravimetric behavior confirms that the crosslinked UHMWPE has the highest crosslinking density.

14.4 BEHAVIOR OF MEDICAL GRADE UHMWPE IN LIVING TISSUE Medical grade UHMWPE` for use in living tissue is an excellent material due to is bioinert property, high molecular weight (between 2 and 6 million), low weight,

14.4 Behavior of Medical Grade UHMWPE in Living Tissue

easy sterilization, resistance to ionizing radiation, simply structure, mechanical and chemical strength. These properties have led to polyethylene being the material of choice for use in prosthetics and joint replacement. Normally prostheses and replaced components have an average lifespan of 15 20 years in living tissue. However, the medical grade UHMWPE once placed in the living tissue, is present failed for aseptic loosen. This mean that appearance of debris (microparticles due to wear of material by friction with the titanium) lead a failed for asptic loosen in a period from 15 to 20 years. This is caused by two mechanisms: osteolysis and debris. Fig. 14.5 shows both osteolysis and debris mechanisms. Osteolysis or Gorham’s disease is when the bones wear as result of an inflammatory response or a lack of growth of bone cells by obstruction caused by prostheses or implants. On the contrary, detritus involves the formation of microparticles of polyethylene around tissue causing postoperative problems. Both mechanisms cause the loss of longevity of prostheses and components. Osteolysis is a rare disease characterized by bone destruction and resorption. Of unknown pathogenic mechanism, it causes anatomical alterations and leaves variable functional sequelae that depend on the location and intensity of lesions (Ferna´ndez Tejada et al., 2015). The types of osteolysis are idiopathic and secondary. Idiophaticy osteolysis is due to by reasorption of bone. The forms of idiopathic osteolysis are very rare diseases, characterized by destruction and bone resorption. The bones, apparently normal at the beginning, undergo progressive

FIGURE 14.5 Wear mechanism for UHMWPE-Gur-1050 samples: (A and B) osteolysis; (C and D) debris.

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destruction until they disappear partially or in their entirety. The secondary osteolysis is due to a variety of diseases in the bone tissue. It is a heterogeneous group of diseases that can affect very different bones of the organism. The final result, depending on the location and intensity of the affected bones, shows a wide range of variability, from patients with intense damage to others with few functional repercussions (Ferna´ndez Tejada et al., 2015). The mechanism of osteolysis has a negative impact on prostheses and implants. The appearance of this mechanism as well as debris leads directly to the failure of prosthesis as it is the cause of aseptic loosening, which reduces the useful lifespan of the prosthesis. According to Gallo et al. (2013), the process of aseptic loosening is initially governed by factors such as implant/limb alignment, device fixation quality, and muscle coordination/strength. Later large numbers of wear particles detached from total knee arthroplasties (TKAs) and trigger and perpetuate particle disease, as highlighted by the progressive growth of inflammatory/granulomatous tissue around the joint cavity (Gallo et al., 2013). Aseptic loosening secondary to periprosthetic osteolysis is the leading cause of revision procedures, especially in patients with a hip or knee total joint replacement (TJR), in the long-term. In the context of joint replacements, osteolysis refers to bone destruction as seen on conventional radiographs and corresponds to bone defects seen during revision surgery (Nich et al., 2014). In a large series of total hip arthoplasties (THAs), Lu¨bbeke et al. (2011) reported femoral osteolysis in up to 24% of cases in the decade following the procedure, with more active patients at increased risk of developing osteolytic lesions. In other investigations of TKA, osteolysis has been found in 5% 20% of cases at follow-up times ranging from less than 5 15 years (Fehring et al., 2004). As a result, up to 15% of patients are likely to be revised for aseptic loosening in the decade following a total joint arthroplasty (TJA). Although arthroplasty may be successful because of the availability of biocompatible materials. However, its half-life is diminished by inadequate fixation, mechanical loss over time, or biological loss due to osteolysis, the latter being produced as a tissue response to the wear particles of the implanted material located in the bone prosthesis interface (Astillero, 2012). In another study by Schwarz (2016), aseptic loosening in TJRs were observed due to periprosthetic osteolysis. Investigations over the past two decades have elucidated a central mechanism for osteolysis, in which wear debris generated from implants stimulate inflammatory cells, thus, promoting osteoclastogenesis and bone resorption (Schwarz, 2016). Total hip arthroplasty relieves chronic pain and improves movement in millions of patients in the advanced stages of osteoarthritis or arthritis. There arthroplasty is successful because of the availability of biocompatible materials (Solis Astillero, 2012). At present, the prescription of antiinflammatory and bone-resorbing suppressing agents is reported to inhibit osteolysis caused by bone cement. Among the former are cyclooxygenase 2 (cox-2) inhibitors, which plays an important role in wear debris-induced osteolysis. Studies conducted by Zhang et al. (2001) show the effectiveness of the drug as applied in mice.

14.5 UHMWPE Versus Other Biomaterials

Other researchers have reported that bisphosphonates, a class of molecules which inhibit bone resorption, showed an inhibitory effect on osteolysis-induced particles in vitro and in animal models (Trevisan et al., 2013). The debris mechanism is due to the fact of wear in implants, prostheses, joint, or bearing of medical grade UHMWPE uses in ortophaedia. The friction between the metal and the polyethylene causes wear and generates the formation of microparticles. Debris wear is a serious clinical problem because it generates aseptic loosening of prostheses and implants and activates the osteolysis mechanism. UHMWPE debris particles produced in hip implant wear simulation tests are classified as round debris, flake-like debris, and stick debris, which are closely related to the primary mechanisms of abrasive wear, adhesive wear, and fatigue wear (Wang, 2013). Many investigations have reported on the behavior of UHMWPE in living tissue (Kurtz, 2015). Macdonald et al. (2013) studied the damage mechanisms and oxidative stability of remelted UHMWPE. Remelted, highly crosslinked polyethylene (HXLPE) has been introduced into total knee replacements (TKR) since 2001 to reduce wear and particle-induced lysis. They observed that remelted HXLPE inserts had lower oxidation indices compared to conventional inserts. They were able to detect slight regional differences within the HXLPE cohort, specifically at the bearing surface. In conclusion, remelted HXLPE was effective at reducing oxidation in comparison to gamma inert sterilized controls. Moreover, long-term HXLPE retrievals are necessary to ascertain the long term in vivo stability of these materials in TKRs.

14.5 UHMWPE VERSUS OTHER BIOMATERIALS Medical grade UHMWPE has qualities that have led it to be selected as the material of choice for use in orthopedics in relation to other biomaterials, such as: ceramics, mainly hydroxyapatite and oxidized zirconium oxide, metals such as cobalt, chrome, titanium, and even polymers. Many investigations have been performed by several authors. Studies show the high effectiveness of both conventional and highly crosslinked UHMWPE in orthopedic components, such as bearings, joints, and implants. First-generation HXLPE tibial inserts became commercially available for TKA in 2001 (Kurtz, 2009). Since polyethylene wear is a major cause of osteolysis and related complications, it was assumed that HXLPE inserts would reduce wear, as has been observed in THA patients. The success of highly crosslinked HXLPE inserts in THA surgery was shown relatively soon after its introduction onto the market in the late 1990s. Several clinical studies of THA inserts showed the benefit of this HXLPE, namely the reduced incidence of osteolysis and reduced wear compared to conventional polyethylene (CPE). Studies performed by Berry et al. (2014) show that wear and corrosion are the most important and major causes of failure in joint arthroplasty. From the point

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of view of its current clinical importance, they mention the main four categories of wear and tribocorrosion: wear of polyethylene, wear of ceramic ceramic (CoC) bearings, wear of metal-to-metal (MoM) bearings, and tapered tribocorrosion. Problems with knee wear have become less prominent as they have many problems with hip PE bearings that result from the success of crosslinked UHMWPE. However, MoM and conical tribocorrosion joints have been associated with soft tissue inflammatory responses and, as a result, have become prominent clinical concerns. An investigation by Inacio et al. (2013) compared the short-term revision risk in alternative surface bearing knees (oxidized zirconium (OZ) femoral implants and HXLPE inserts) with that of traditional bearings (cobalt chromium (CoCr) on CPE). They analyzed 62,177 primary TKA cases registered in a total joint replacement registry from April, 2001 to December, 2010. The final steps for the analysis were all-cause revisions, septic revisions, or aseptic revisions. Bearing surfaces were categorized as OZ-CPE, CoCr-HXLPE, or CoCr-CPE. HXLPE inserts were stratified according to brand name. The results showed that in all review processes, both aseptic and nonaseptic, the risk of early revision does not show statistically significant damage. Another relevant outcome is that no specific brand of HXLPE insert was associated with a higher risk of all-cause, aseptic, or septic revision compared to CoCr-CPE. They concluded that their study did not show any evidence of damaging effects from the use of alternative bearings for TKA on short-term outcomes. Longer-term followups will be required to determine whether the potential benefits of wear reduction justify continued use of these bearings (Inacio et al., 2013).

14.6 BACKGROUND ON BIOPOLYMERS IN LIVING TISSUE The use of biopolymers is growing more and more, and its characteristics, such as biocompatibility, biodegradability, and easy organic absorption, have allowed it to grow as a substitute for other materials in the biomedical area and in the food industry. The main biopolymers used are starch, polylactic acid, chitosan, poly (glycolic acid), and polycaprolactone. Its main applications are in the area of tissue engineering, drug release, and packaging. Due to the increasing demand in the application of these biomaterials, many research projects have been developed. The use of biopolymers in the specific field of tissue engineering requires properties such as biodegradability, biocompatibility, bioadhesivity, hemocompatibility, nontoxicity, and stretchability (compatibility with the mechanical properties of the tissue where it is to be implanted). Biopolymers derived from polysaccharides and proteins possess these characteristics, but have poor mechanical properties (Zhang et al., 2013). They are nontoxic, have the ability to interact with living cells, and have low costs (Cascone et al., 2001).

14.7 Present and Future of Biopolymers, Bioplastics

Some of the most commonly used are collagen, chitin/chitosan, alginate, keratin, fibrin, hyaluronic acid, albumin, starch, cellulose, and pectin (Mano et al., 2007; Sionkowska, 2011; Zeeshan et al., 2015).

14.7 PRESENT AND FUTURE OF BIOPOLYMERS, BIOPLASTICS, AND NANOBIOMATERIALS The use of polymers throughout history has been linked with the knowledge about its structure and even synthesis. However, it is a well-known fact that synthetic polymers from the petrochemical industry represent a problem from an environmental point of view because of their long periods of degradation that exceed 100 years. Polymers that are biodegradable or made from renewable resources also represent an alternative possibility. These are newer and less well-known materials that promise a greater sustainability of plastics in the future. Currently, typical polymers, such as starch, cellulose, wool (which are biopolymers), have long been used by society. Paradoxically, the first polymer of industrial use that created a high social impact was a biopolymer called rubber. This is obtained from the bleeding of the bark of trees, from which a very viscous white substance called latex is extracted, with which a variety of plastic products can be made. After this event, in 1839 a scientist named Charles Goodyear modified the structure of rubber by applying a process known as vulcanization, with which it was possible to obtain a highly resistant elastomeric type structure. Another fact of great interest was the modification of cellulose, forming synthetic fibers called rayon. These developments paved the way for the production of polymers from biopolymers, as with what happened with vulcanized rubber and cellulose. Currently, the applications of biopolymers are steadily growing mainly in the medical, food, and tissue engineering sectors; as surgical equipment and instruments, implants inside the body, edible containers, pharmaceuticals, creams for external use, etc. As previous topics developed in the chapter maintained; biopolymers are of great interest for their wide variety of applications, ranging from drugs to cardiovascular implants, including orthopedics, ophthalmology, spine, ear, skin substitutes, biodegradable polymers, etc. The main examples of these applications are bioplastics, drugs, medicines (drugs, smart sensors, and nanomaterials), edible packaging, and tissue engineering. As explained in previous sections, bioplastics are natural polymers based on cellulose, soy, starch, molasses, vegetable oil, and natural rubber, and have the advantage of being biodegradable. Bioplastics can also be defined as a form of plastic derived from renewable biomass sources, such as vegetable oil, corn starch, pea starch, or microbiota, rather than plastic from fossil fuels, which are derived from petroleum.

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At present, polymers derived from natural resources are divided into three large groups depending on their origin: (1) Polymers from biomass (polysaccharides and proteins), such as starch, cellulose, casein, and gluten. (2) Polymers from chemical synthesis using natural monomers, such as biopolyester and PLA (Pacheco et al., 2014). (3) Polymers obtained from microorganisms, such as PHA and PHB. These bioplastics contribute to sustainable development because of their origin (renewable resources), but they are still not up to standard plastic, due to the limited and high production cost of bioplastics compared to plastic produced from petroleum (Bolufer, 2009). Other interesting and important biomaterials to be applied in the medical area are nanobiomaterials, since they have demonstrable properties, such as biocompatibility, hardness, elasticity, mechanical strength, biodegradability, and stability within living tissue. These properties have been a determinant for the growth in the use of nanomaterials in different areas, such as food, pharmaceutical, electronic, industrial, and biomedical industries. Nanobiomaterials, together with bioplastics and other biopolymers, have now become materials of great demand for their range of applications and because they are environmentally sustainable. In addition, biomaterials have been used for the treatment of diseases, such as spinal cord lesions. Moreover, nanocompounds, mainly nanopolymers, are being used for the treatment of rheumatoid arthritis; as biosensors for the control of biomolecules, such as glucose; or in biological synthesis nanoparticles, such as quantum dots. This represents a potential future alternative to the use of organometallic and aqueous synthesis (Zhang et al., 2013; Cai et al., 2007; Cai and Hong, 2012). However, the high prices of some bioplastics and the lack of knowledge regarding technology, as recent as that of nanomaterials, do not provide a sufficiently clear picture for its future use. Due to the importance of nanomaterials, many studies involving these novel compounds have been carried out, such as nanorafeno, nanochitosan, polylactic acid, nanoparticles, etc. Graphene is a newly discovered nanomaterial composed only of carbon atoms, forming an overlapping structure with sp2 type hybridization, arranged in a Bravais crystal network in hexagonal form, and forming a structure similar to that of honeycomb. The main properties of graphene are: high thermal conductivity (5000 m21 k21), electric conductivity, high elasticity, hardness, high surface area (2360 m2 g21), light weight, transparency, easy synthesis, high mechanical strength (200-times higher than that of steel), and highly porous structure. These characteristics, unlike other biomaterials, allow it to be used as an extracellular matrix in the regeneration of tissues and variants, including graphene oxide (Veliz, 2016a,b; Felli et al., 2015). This structure is advantageous since it is physiologically stable, compatible, and capable of transporting drugs and biomolecules; in turn permitting it to have great application in the biomedical area (Veliz, 2016a,b; Shen et al., 2012). In addition, graphene is used as a

14.7 Present and Future of Biopolymers, Bioplastics

reinforcement for other biomaterials because it provides a heterogeneous structure with mechanical, chemical, and electrical properties that it did not previously possess. For example, the mechanical strength and elasticity of PVA and PMMA was increased by reinforcement with graphene oxide (Zhang et al., 2011; Ramanathan et al., 2008). The most important applications of graphene include its use in biosensors of biomolecules, in photothermal and gene therapy, in the study of bioimagenes, in tissue engineering, and as drug release systems (Astillero, 2012). In addition to its use in biomedicine, graphene has been explored for use in other areas, such as electronics where graphene transistors are used; it has also been used in engines to improve efficiency as well as in renewable energy (Gamero Este´vez, 2010). Due to the findings of a study on nanomaterials, the diversity of uses and accelerated growth that nanocomposites have every day in key areas of biomedicine, such as tissue engineering, biochemistry, genetics, biomedical engineering, among others, mean that the applications of these materials increase daily. Investigations carried out by Felli et al. (2015) give a review of the different types of graphene used in tissue engineering, and in this review they intend to give a sample of the family of graphene as well as to give an idea of the progress made to date in this field of research. They analyzed the production methods of graphene; conventional and green, and found that their excellent physical and chemical properties as well as their biocompatibility with living tissue are of interest to be used with a high probability of success in engineering. However, research into the toxicity of the graphene family of nanoparticles is still in its blooming stages and it is difficult to conclude the potential health risks associated with their use and whether they should be modified chemically; in some cases, to reduce their toxic risk (Syama and Mohanan, 2016). Similarly, the biodegradation process is not entirely clear and much remains to be studied. However, the enzymatic degradation of different types of graphene oxide dispersions with the human enzyme, myeloperoxidase, has already been demonstrated, which makes this material very promising for applications in tissue engineering (Kurapati et al., 2015). Other encouraging materials for tissue engineering are biomaterials of marine origin, such as alginate and chitosan (Ratner et al., 2013). The mechanical properties necessary to produce scaffolds with great porosity could be improved on by the addition of graphene and its derivatives. Sodium alginate can be considered as a biodegradable biomaterial that has been used in various fields, such as controlled drug release, tissue engineering, and biological studies. Guedes et al. (2015) in their book in the chapter on polyethylene blends, composites, and nanocomposites, investigated the behavior of UHMWPE as a joint in total arthroplasty as well as THK. The analysis did so by studying the behavior in the presence of antioxidants, such as vitamin E and vitamin C, under the action of gamma rays. Subsequently they did a review and discussion on biocompatibility, manufacturing processes, tribological behavior, aging by

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oxidation, and the observed changes in mechanical properties. Finally, they analyze the viscoelastic behavior of UHMWPE and its implications on the long-term survival of TJA. The first conclusion from the results was to highlight the impressive rise that medical grade UHMWPE has had in the past five decades. Another relevant aspect is the complexity of UHMWPE, which complicates the lifetime analysis and mechanical behavior prediction of UHMWPE as a load bearing component in TJA and TKA. Additionally, they infer that wear is dependent on many events occurring simultaneously and sequentially. This means that the amorphous and crystalline UHMWPE structure constantly undergoes interactions, which cause changes both in the mechanical properties and in the contact area of the amorphous crystalline phase; but they affirm that the interaction process is not completely understood. In addition, they emphasize that the oxidation processes that occur are due to the oxygen being fed by the fluids surrounding the UHMWPE component, which deteriorate the mechanical properties. Finally, they conclude that the viscoelastic properties of UHMWPE increase the creep of the material, a situation that should be corrected in later investigations.

14.8 CONCLUSIONS This chapter describes the characteristics of different biomaterials, mainly biopolymers, both natural and synthetic, as well as bioplastics that are of organic, vegetable, and mixed origin, such as biopolyethylene, and finally, nanomaterials such as graphene and its derivatives. The graphene specifically dates from little time of discovery, presents exceptional qualities to be used in the biomedical area. Its nanomolecule sensing properties, biocompatibility, coupled with its excellent thermal and electrical properties, make it one of the main biomaterials used in tissue engineering. The main biopolymers used are starch, PLA, chitosan, PGA, and polycaprolactone. The most used blends are between polysaccharides and aliphatic or aromatic polyesters. These biopolymers have important properties, such as biocompatibility and biodegradability, but lower mechanical properties and require the forming of “hybrid” biopolymers with synthetic polymers, such as PP or polyurethane, to be effectively applied in tissue engineering. Nanobiopolymers, such as nanoparticles of chitosan and PLA, are also presented as possible drugs in the near future. Studies show the importance of these new technologies at the level of living tissue, as well as their importance at an environmental level, for their easy biodegradability compared to other materials. In addition, reference is made to the future use of these materials. However, here the results obtained can not be considered completely satisfactory at the level of the organism as is the case of nanomaterials due to the presence of a synthetic polymer in the structure of the bioplastic. In other words, although they present an environmental advantage due to their degradation through microorganisms, the presence of synthetic

14.8 Conclusions

polymers in the structure of the mixed bioplastics undermines their sustainability from an economic point of view. Several investigations carried out, mainly on the use of nanocomposites and nanoparticles, have led to the conclusion that more tests, studies, investigations, and analyses are required, since their safety or side effects in drugs or food have not been completely verified. The behavior of medical grade UHMWPE is extensively detailed because of its great importance as a component used in orthopedics, both inside and outside of living tissue. From the different analyses, it can be seen that medical grade UHMWPE varies its behavior according to the type of atmosphere of ionizing irradiation. The results show resistance to oxidation in the absence of oxygen, with the predominance of crosslinking. On the contrary, in air it is observed that oxidation processes predominate as well as the formation of oxidation cascades, and as a consequence of which, the reactions and mechanisms of chain rupture prevail. The successful results observed in the behavior of medical grade UHMWPE, when subjected to combined external factors, mainly ionizing irradiation, annealing and melting heat treatments, and storage in natural substances, such as vitamin E and aloe vera are also mentioned. In this case, it is observed that the properties of the material, mainly its resistance to wear, improve as a result of crosslinking; Davidson (2012) showed an improvement of nearly 20% with the use of vitamin E. In this case, improvements around 17% in the value of this property were observed (see Fig. 14.4A and B). The appreciated behavior result innovative and important in the use of this substances, due to allows reducing operating costs of storage and transport that favor the properties of medical grade UHMWPE in vitro. On the contrary, other investigations with components such as SBF and bovine serum on UHMWPE samples were shown to lead to oxidation cascades. Section 14.4 describes in detail the mechanisms of debris and osteolysis as the main cause of the aseptic failure of orthopedic prostheses in tribological systems involving UHMWPE as an orthopedic component of the prostheses in hip and knee arthroplasty. Finally, different investigations comparing UHMWPE crosslinked with other tribological components used in orthopedics, such as conventional PE with zirconium oxide, and cobalt-chromium with PE, show that tribological systems involving crosslinked UHMWPE (HXLPE) show higher wear resistance than the rest. This means that the presence of HXLPE decreases the harmful mechanisms of osteolysis and debris, but cannot prevent them. These analyses are highly useful since they are fundamental to optimizing the properties of the material. This means that by understanding the in vitro behavior of UHMWPE, it is possible to reduce the wear that represents the leading cause of failure in prostheses and UHMWPE components when used in living tissue, and of decreasing the longevity of prostheses and orthopedic components. This knowledge in turn is of great interest for the design and manufacture of these components; however, tests of the components on living tissue are required.

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Further Reading

Singhal, R., Salim, J., Walker, P., 2005. Idiopathic multicentric osteolysis: a case report and literature review. Acta Orthop. Belg. 71, 328 333. Sionkowska, A., 2011. Current research on the blends of natural and synthetic polymers as new biomaterials: Review. Prog. Polym. Sci. 36 (9), 1254 1276. Stephens, C., Benson, R., Martı´nez-Pardo, M.B., Naaker, E., Walter, J., Stephens, T., 2005. The effect of dose rate on the crystalline lamellar thickness distribution in gammairradiation of UHMWPE. Nucl. Inst. Methods Phys. Res. Sect. B: Beam Interact. Mater. Atoms 236, 540 545. Syama, S., Mohanan, P.V., 2016. Safety and biocompatibility of graphene: a new generation nanomaterial for biomedical application. Int. J. Biol. Macromol. 86, 546 555. Trevisan, C., Nava, V., Mattavelli, M., Garcia Parra, C., 2013. Bisphosphonate treatment for osteolysis in total hip arthroplasty. A report of four cases. Clin. Cases Miner. Bone Metab. 10 (1), 61 64. Valero, M., Ortegon, Y., Uscategui, Y., 2013. Biopolimeros: avances y perspectivas. Dyna 181, 171 180. Van Dijk, M., Smit, T.H., Arnoe, M., et al., 2003. The use of poly-L-lactic acid in lumbar interbody cages: design and biomechanical evaluation in vitro. Eur. Spine 28, 1802 1808. Veliz, O., Miguel, J., 2016a. El grafeno y sus derivados en la ingenierı´a tisular, revista nereis, vol. 8, pp. 71 81. Veliz, O., Miguel, J., 2016b. Biomedical Applications of Graphene, MoleQla. Wang, X., 2013. Overview on biocompatibilities of implantable biomaterials. Rosario Pignatello. Advances in Biomaterials Science and Biomedical Applications. INTECH, pp. 111 155. Wong, J., Leach, J., Brown, X., 2004. Balance of chemistry, topography, and mechanics at the cell-biomaterial interface: issues and challenges for assessing the role of substrate mechanic on cell response. Surf. Sci. 570, 119 133. Zeeshan, S., Najeeb, S., Khurshid, Z., Verma, V., Rashid, H., Glogauer, M., 2015. Biodegradable materials for bone repair and tissue engineering applications. Materials 8 (9), 5744 5794. Zhang, X., Morham, S.G., Langenbach, R., Young, D.A., Xing, L., Boyce, B.F., et al., 2001. Evidence for a direct role of cyclo-oxygenase 2 in implant wear debris-induced osteolysis. J. Bone Miner. Res. 16 (4), 660 670. Zhang, L.Z., Wang, Z., Xu, C., Li, Y., Gao, J., Wang, W., et al., 2011. High strength graphene oxide/polyvinyl alcohol composite hydrogels. J. Mater. Chem. 21, 10399 10406. Zhang, Y., Chan, H.F., Leong, K.W., 2013. Advanced materials and processing for drug delivery: the past and the future. Adv. Drug Deliv. Rev. 65 (1), 104 120.

FURTHER READING Brandi, F., Sommer, F., Goepferich, A., 2007. Rational design of hydrogels for tissue engineering: impact of physical factors on cell behavior. Biomaterials 28, 134 146. Dri Dietary Reference, 2005. Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Institute of medicins.

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Fishman, M., Coffin, D., Onwulata, C., Willett, J., 2006. Two stage extrusion of plasticized pectin/poly(vinyl alcohol) blend. Carbohydr. Polym. 65 (2006), 421 429. Li, M., Mondrinos, M.J., Chen, X., Gandhi, M.R., Ko, F.K., Lelkes, P.I., 2006. Coelectrospun poly(lactide-co-glycolide), gelatin, and elastin blends for tissue engineering scaffolds. J. Biomed. Mater. Res. Part A 79A (4), 963 973. Maitz, M.F, 2015. Applications of synthetic polymers in clinical medicine. Biosurf. Biotribol. 1 (3), 161 176. Mingyong, G., Lu, P., Bednark, B., Lynam, D., Conner, J.M., Sakamoto, J., et al., 2013. Templated agarose scaffolds for the support of motor axon regeneration into sites of complete spinal cord transection. Biomaterials 34, 1529 1536. Parra-Cid, C., Tiscaren˜o Pe´rez, A., Go´mez Garcı´a, R., 2014. Investigacion en discapacidad. 3(1):27. Www.medigraphic.org.mx. Rodrı´guez, S., Joana, L., Alzate, O., Eduardo, C., 2016. Aplicaciones de mezclas de biopolı´meros y polı´meros sinte´ticos. Revisio´n bibliogra´fica 2, 25. Rogers, M.J., Gordon, S., Benford, H.L., Coxon, F.P., Luckman, S.P., Monkkonen, J., 2000. Cellular and molecular mechanisms of action of Bisphosphonates. Cancer 88 (Suppl. 12), 2961 2978. Shi Rong, G., Liu, H.T., Huang, X.L., 2010. Behaviour and wear debris characterization of UHMWPE on alumina ceramic, stainless steel, CoCrMo and Ti6Al4V hip prostheses in a hip joint simulator. J. Biomimet. Biomater. Tissue Eng. 7, 7 25. Solis-Arrieta, L., Leo´n-Herna´ndez, S.R., Villegas-Castrejo´n, H., 2012. Ana´lisis de partı´culas de desgaste en tejido periprote´sico de cadera y rodilla con microscopia electro´nica de barrido. Cir. Cir. 80, 239 246. Vigara Astillero, G., 2012. Grafeno, el material del futuro. posibilidad real o pura fantası´a?, Revista MoleQla, no8. Sevilla: Universidad Pablo de Olavide, Diciembre 51, % pp. 62 65. Yuqi Yang, Y., Asin Abdullah, M., Zhiwen, T., Yuehe, D.D.L., 2013. Graphene based materials for biomedical applications. Mater. Today. 16(10):365 373. Zuluaga, C., Fabio, H., 2013. Alguna aplicaciones del a´cido poli-l-la´ctico: Revista de la Academia Colombiana de ciencias exactas, fı´sicas y naturales, ISSN 0370-3908. 37 (142):125 143. ?

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