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Natural rubber and silicone rubber-based biomaterials
Natural rubber and silicone rubber-based biomaterials
4
Abitha Vayyaprontavida Kaliyathan⁎, Anitha Mathew†, Ajay Vasudeo Rane‡, Krishnan Kanny‡, Sabu Thomas⁎ ⁎ Mahatma Gandhi University, Kottayam, India, †Vimala College (Autonomous), Thrissur, India, ‡Durban University of Technology, Durban, South Africa
Abstract Biomaterials are materials which are used to replace a part or a function of the body in safe, reliable, economical and physiologically acceptable manner. Polymers are used as biomaterial for a long time due to its light weight and biocompatibility. Natural and synthetic rubber are mainly used because of their inertness and bicompatible nature. Silicone rubber are widely used and natural rubber as of yet found limited applications. Through this chapter the relevant use of both the rubbers are described applications are discussed and possible future developments are considered. Keywords: Biomaterials, Biological material, Silicone rubber, Natural rubber, Biocompatible.
4.1 Introduction Biomaterials is more than 50 years old, it is a material which were used by our ancestors to treat themselves in therapeutically or diagnostically. The scientific definition of a biomaterial is “A substance which is tailored and engineered to interact with biological system in a therapeutic or diagnostic way” (see Fig. 4.1). The field of biomaterials science and engineering is growing at a fast rate, considering the scientific work and development of materials carried out. It is cited that biomaterials differ from biological material as the latter is fabricated via biological systems (see Fig. 4.2). Biomaterial is application specific, and hence utmost care should be taken while considering biomaterial as biocompatible; for example, bone is a biological material produced by the biological method. As mentioned earlier, biomaterial is “application specific,” that is, a biomaterial that is biocompatible or suitable for one application may not be biocompatible in another. Biomaterials can be derived either from nature or synthesized in the laboratory using a variety of chemical approaches utilizing various materials as described in Fig. 4.3. We shall consider polymers in this chapter, specifically natural rubber and silicone rubber.
Fundamental Biomaterials: Polymers. https://doi.org/10.1016/B978-0-08-102194-1.00004-9 Copyright © 2018 Elsevier Ltd. All rights reserved.
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Elements of biomaterial science
Medicine
Biology
Chemistry
Tissue engineering
Material sciences
Fig. 4.1 Elements of biomaterials science and engineering.
Biomaterial
Biological material
Fig. 4.2 Biomaterial vs biological material.
Materials
Metallic
Ceramic
Polymeric
Inorganic glasses
Fig. 4.3 Sources of biomaterials.
Biomaterials are used and/or adapted for a medical application, and thus comprise the whole or part of a living structure or biomedical device which performs, augments, or replaces a natural function (see Fig. 4.4). Polymeric materials are used as biomaterials in a wide variety of applications from sutures to drug delivery to implants. The following chart in Fig. 4.5 enlists applications of materials in medicine and dentistry. Now we shall consider in detail natural rubber and silicone rubber as polymeric biomaterials. Prior to that, we will give a summary of natural rubber and silicone rubber. Silicone and natural rubber are two elastomers which differ in their structure and properties. Their frequency of use in medical applications is also different. Silicone rubber has dominated the application of elastomers to medicine, while natural rubber Biomaterials
Autograft
Allograft
Fig. 4.4 Classification of biomaterials.
Xenograft
Transplant
Natural rubber and silicone rubber-based biomaterials 73
Applications of polymeric biomaterials
Cardiovascular
Nonthrombic treatment
Dental implants
Adhesives and sealants
Opthalmologic
Orthopedic
Drug delivery system
Sutures
Burn dressing
Bioelectrodes
Biomedical sensors
Biosensors
Fig. 4.5 Applications of polymeric biomaterials.
has made a relatively minor contribution. Owing to the low- and high-temperature performance, silicones are used in the aerospace industry. Silicones are used as electrical insulation potting compounds and other applications specific to electrical insulation. Their long-term durability has made silicone sealants, adhesives, and waterproof coatings commonplace in the construction industry. Their excellent biocompatibility makes many silicones well suited for use in numerous personal care, pharmaceutical, and medical device applications.
4.2 Natural rubber as biomaterial Natural rubber (latex and solution casted) is used as a biomaterial owing to its chemical, physical, biological, and mechanical properties, imparted after a specified compounding and optimum vulcanization process (see Fig. 4.7 for applications). It is a macromolecule of isoprene (C5H8); as a monomer unit, with likely cis-configuration with one double bond in each repeating unit, however, due to the presence of a double bond in its structure, natural rubber is sensitive to heat and oxidation (see Fig. 4.6 for structure). The blood compatibility of natural rubber is very low as compared to silicone and polyurethanes, but suitable compounding, that is, grafting of natural rubber to improve blood compatibility, has been an area of research for a long time. However, the known disadvantage of natural rubber is allergy in human body due to the protein latex component. Considering the disadvantage for natural rubber as a biomaterial, natural rubber has more number of reasons to be used as a biomaterial, which are given in Fig. 4.8. The mentioned reasons promote tissue replacement and tissue regeneration. Natural rubber formulations have been used to control mosquito larvae. Natural rubber formulation with organotin toxicants are used in prevention of marine fouling [1]. Dick et al., in their study, fabricated hydroxyapatite-filled natural rubber composites toward bone application [2]. Silva et al. fabricated bioglass-filled natural rubber composites and characterized them for mechanical and thermal properties, indicating their applications in biomedical applications. [3] Borges et al. prepared calcium
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CH2
CH2
n
C=C CH3
H
Fig. 4.6 Structure of natural rubber.
Applications - natural rubber (biomaterial)
Membranes
Diaphragms
Blood pressure cuff coils
Seals
Covers
Tracheal tubes
Medical gloves
Condoms
Balloons
Pacifiers
Baby bottle nipples
Medical and dental equipment
Fig. 4.7 Applications of natural rubber as a biomaterial in medical applications [1].
Natural rubber as biomaterial
Stimulates angiogenesis
Cellular adhesion
Extra cellular matrix
Natural rubber latex in wound healing
Vascular permeability
Angiogenesis
Fig. 4.8 Reasons—why natural rubber is used as a biomaterial and in wound healing [1].
Natural rubber and silicone rubber-based biomaterials 75
carbonate-filled natural rubber composites. [4] Nashar et al. added magnetic fillers: nanoiron and nickel particles in natural rubber and proposed biomedical application for fabricated composites. [5] Thanida et al. prepared antibacterial natural rubber latex formulation for gloves filled with N,N,N-trimethyl chitosan stabilized poly(methyl methacrylate) latex particles [6]. Nickel zinc ferrite-filled thermoplastic natural rubber composites fabricated by Moayad et al. were proposed to be used in biomedical applications [7]. Natural rubber latex was also used as an occlusive membrane for guided bone regeneration [8]. Silva et al. fabricated membranes based on natural rubber latex compounded with propolis for biomedical application [9]. Trovatti et al. fabricated cellulose—sponge natural rubber composites as porous composites for biomedical applications [10]. Anyarat et al. fabricated sericin-binded-deprotenized natural rubber film containing chitin whiskers as an elasto-gel dressing [11].
4.3 Silicone rubber as biomaterial Silicone rubbers have been produced commercially for about 35 years. The term silicone was coined by Prof. Kipping who carried out the pioneer work on organosilicon compounds. The silicones are made up of repeating polymer chains which consist of backbones of silicone to oxygen bonds (see Fig. 4.9) [12]. In addition to the oxygen backbones, silicones have also bonded to organic groups, especially methyl groups. This structure has similarity to ketones and due to this Kipping named it “silicones.” Later, based on its use in different areas, new nomenclature was developed. The basic repeating unit is siloxane and the most common silicone is polydimethylsiloxane (PDMS) [13].
4.4 Preparation of silicone rubber Silicones are manufactured by hydrolysis of the appropriate dichlorosilane (R2SiCl2), the silanol product undergoing a condensation reaction in dilute solution to form the cyclic tetramer.
R
Si
R Siloxane
CH3
O
Si
n
CH3
O
n
Polydimethylsiloxane
Fig. 4.9 Structure of silicone and polydimethylsiloxane preparation of silicone rubber.
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( CH3 )2 SiCl2 + 2H 2 O ® ( CH3 )2 Si ( OH )2 + 2HCl ( CH3 )2 Si ( OH )2 ® ( ( CH3 )2 Si O )n After treatment with a strong acid or base, the condensation polymerization is allowed to continue until the required molecular weight is obtained. The first type of siloxane available was dimethyl siloxanes (MQ), followed shortly by methyl phenyl siloxane (PMQ).The phenyl groups give an elastomer of lower stiffening temperature and improved resistance to radiation. The incorporation of a proportion of fluorine or cyano containing groups in place of methyl confers excellent resistance to oils, fuels, and solvents. This type of silicone is known as FVMQ [14].
4.5 Physicochemical properties of silicone rubber Silicones exhibit the unusual combination of an inorganic chain similar to silicates and often exhibit high surface energy. The SiO bonds are quite polar and without protection would lead to strong intermolecular interactions. The methyl groups which are weakly interacting with each other shield the main chain. Polysiloxane is very flexible due to large bond angles and bond lengths. Polysiloxanes tend to be inert due to the strength of the silicon-oxygen bond [15]. Silicone rubbers offer good resistance to extreme temperatures; the working temperature of silicone is normally from −100 to 300°C. Silicone rubber is a material of choice in Industry when retention of initial shape and mechanical strength are desired under heavy thermal stress or subzero temperatures. Organic rubber has a carbon to carbon backbone which can leave it susceptible to ozone, UV, heat, and other aging factors that silicone rubbers can withstand well. This makes silicone rubber one of the elastomers chosen in many extreme environments [16].
4.6 Properties of silicone rubber as biomaterial Many other groups, for example, phenyl vinyl and trifluoropropyl, can be substituted for the methyl groups along the chain. The simultaneous presence of organic groups attached to an inorganic backbone gives silicone a combination of unique properties, which makes them possible for use as fluids, emulsions, compounds, resins, and elastomers in numerous applications and diverse fields. The inorganic backbone present in silicone rubber is the fundamental factor which makes silicone biocompatible. Such an inorganic structure cannot be metabolized by living organic systems and contributes to the inertness of silicone rubber by minimizing the likelihood of chemical reactions between body fluids and a silicone rubber implant [17]. The unique properties of silicone rubber make their use in medical implants and biocompatible materials. Sterilization of biomaterials is facilitated by an excellent heat stability which allows autoclaving without property deterioration. Shelf life and oxidative stability are promoted by a resistance to degradation by oxygen, ozone, or UV light. The solvent
Natural rubber and silicone rubber-based biomaterials 77
Biomaterial properties of silicone Heat stability (sterilization)
Hydrophobicity
Oxidative stability
Hydrophobicity
Physiological inertness
Transparent
Highly flexible
Solvent resistance
Fig. 4.10 Properties of silicone rubber which help as a biomaterial.
resistance of silicone rubber is good and intermittent contact with organic solvents has little influence on the physical properties of polymers [18]. The use of silicone rubber tubing for the passage of biological fluids is enhanced by the release properties of the polymer surface. Silicone rubber is chemically inert so it does not corrode with other materials. It is used thus for fixing rollers printing rollers and sheets of photocopiers and for lost wax casting. Living tissues are less affected by silicone rubber as compared to other organic polymers [19]. Silicone rubber is physiologically inert and is thus used for baby bottle nipples and stoppers in medical applications. In addition, it is pleasant to the touch with a high-grade feel, making it ideal for leisure items such as swimming caps and goggles. The inertness enables stable mechanical properties and long-term use of PDMS in biological environments without degradation of the polymer. Moreover, medical grade silicone is reported to be nonimmunogenic and nontoxic. The properties of silicone which help it to act as a biomaterial are shown in Fig. 4.10 [20].
4.7 Cross-linking or curing of silicone elastomer In the uncured state, silicone rubber is a highly adhesive gel or liquid. In order to convert it into solid, it must be cured, vulcanized, or catalyzed. This is normally carried out in a two-stage process at the point of manufacture into the desired shape, and then in a prolonged postcure process. It can also be injection molded. A majority of silicone rubbers are cured by any one of the following methods.
4.8 Peroxide cure system [21] Peroxide curing is widely used for curing silicone rubber. The curing process leaves behind by-products which can be an issue in food contact and medical applications. However, these products are usually treated in a postcure oven which greatly reduces the peroxide breakdown product content. The following reaction (see Fig. 4.11) mechanism has been proposed for the cross-linking or curing reaction from organic peroxide [15].
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Si
+ CH3
Si
CH
Si
CH2
CH2
CH2
Si
Fig. 4.11 Peroxide cure system of silicone rubber.
4.9 Condensation cross-linking system Condensation curing systems can be one-part or two-part systems. In the one-part or RTV (room-temperature vulcanizing) system, a cross-linker exposed to ambient humidity (i.e., water) experiences a hydrolysis step and is left with a hydroxyl or silanol group. The silanol condenses further with another hydrolyzable group on the polymer or cross-linker and continues until the system is fully cured. Such a system will cure on its own at room temperature and (unlike the platinum-based addition cure system) is not easily inhibited by contact with other chemicals, though the process may be affected by contact with some plastics or metals and may not take place at all if placed in contact with already-cured silicone compounds (see Fig.4.12). These products are ready to apply and require no mixing. Cross-linking starts when the product is squeezed from the cartridge or tube and comes into contact with moisture [22].
4.10 Addition cross-linking system This cross-linking system is also known as the platinum-based cross-linking system. Two different chemical groups react in the presence of platinum. In this reaction (see Fig.4.13), an ethyl group [C(H)2–C(H)2] is formed and there are no by-products. In addition cure, cross-linking is achieved by reacting vinyl end-blocked polymers with SiH groups. The addition occurs mainly on the terminal carbon and is catalyzed by Pt or Rh complexes, preferably as organometallic compounds, to enhance their compatibility. There are no by-products with this reaction. The Pt in the complex is easily bonded to electron donating substances such as amine or organosulfur compounds to form stable complexes with these poisons rendering the catalyst inactive and inhibiting the cure. In biomedical applications, both room temperature vulcanization silicone rubber and liquid silicone rubber are employed. The conditions that must be met are: (i) after
Si
OH + OH
Si
Metal salt
Si
O
Si + H2O
Fig.4.12 Condensation cure system of silicone rubber.
Si
H + CH3
CH
Si
H+ Pt
Fig. 4.13 Addition cross-linking of silicone rubber.
Si
CH2
CH2
Si
Natural rubber and silicone rubber-based biomaterials 79
the vulcanization reaction, there can be no presence of by-products because, after a certain time, they could migrate and come into contact with body fluids causing infections or encapsulation. To address this, the addition-type silicone rubbers are the best option due to their lack of by-products after the reaction. (ii) The components of the silicone rubber must not include any carcinogenic, thrombogenic, or toxic, allergic, or inflammatory materials. The RTV silicone rubbers used are two-part materials based on PDMS vulcanized with platinum, organoplatinum, low molecular tetra (alkyloxysilane), stannous octoate, or through irradiation curing where the scission of CH and CSi bonds generates the cross-linking. For liquid silicone rubbers, two-part LSRs are also used with peroxides, metal salt, condensation, and vinyl addition as curing systems [22].
4.11 Biomedical applications of silicone rubber The advantages of using silicone rubber in biomedical applications are it is easy to process and its stability in contact with tissues in living organisms. Silicone rubbers’ inherent hydrophobicity (material which repels water), however, has caused some problems in some devices over a long period of time (until now) [23]. The Health Industry Manufacturers Association has classified medical devices into four categories as shown in Table 4.1. Silicone Rubber is used in all four categories, with more prevalence in I and II [24]. For many years, silicone rubber has been used in clinical implants because of its inherent bio-inert nature. The most high-profile application is the mammary prosthesis. Silicones which are generally used in the medical field can be grouped into three categories: nonimplantable, short-term implantable, and long-term implantable. Materials approved as Classes V and VI can be considered medical grade. Most medical grade Table 4.1
Different type of medical devices
Type
Environment
Duration
Application
1
Internal devices
Less than 30 days
Intravenous catheters Drainage tubes Hip implants Pacemakers Artificial heart valves Devices that contact the mucous membranes such as urinary catheters and intravaginal devices Hypodermic syringes Transfusion assemblies Dialysis components Dressing trays Packaging materials
More than 30 days
2
External devices
3
Indirect devices
4
Nonpatient contact devices
More than 30 days
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Table 4.2
Application of silicone rubber as implants
Treatment
Application
Plastic and reconstructive surgery Ophthalmology
Reconstruction of nose, chin, ear, breast Correction of detached retina Prosthetic eye Reconstruction of arms, elbows, thumbs, tendons, etc. Maxillofacial applications Penile prosthesis Ball in ball and cage heart valve Coatings on pacemakers and lead wire. Construction on artificial hearts and heart assisted devices
Orthopedic surgery
Cardiovascular surgery
silicones are at least Class VI certified. Silicone suppliers and some silicone prototyping companies provide guidelines for material use. Table 4.2 illustrates the various implant applications of silicone rubber [25]. Some of the medical applications of silicone rubbers are given below in detail: ●
●
●
Extracorporeal equipment: Silicones have good hemocompatibility and gas permeability properties due to which they are is used in many extracorporeal equipments. They are used in dialysis, blood oxygenators, and heart bypass machines. Owing to the blood compatibility of silicone rubber, it is used for heart bypass applications. Hemocompatibilty testing has suggested that platinum-cured silicone tubing may be superior to PVC in several aspects [26]. Catheters, shunts, and drains: The silicone elastomers are also found to have widespread application in catheters, shunts, and drains which are manufactured by silicon extrusion. Some of the devices are silicon coated to provide less host reaction. Several urology catheters are made of latex and their interior and exterior are coated with silicones. Drains are mainly used for bladder drainage after gynecological surgery that complicated or prevented normal urethral urination [27]. Implants: Among synthetic polymers, silicones are the most widely used materials for long-term implantation, although medical grade silicon is an aggressive environment for almost all types of foreign materials which are in contact with body fluids and tissues. Medical grade silicone elastomer comes close to fulfilling the requirements of implants [28].
Silicone elastomers have been used in almost all surgical specialties including neurosurgery, Ophthalmology, plastic surgery, orthopedic surgery, and others. The hydrocephalus shunt, which is used to drain cerebrospinal fluid from the peritoneal cavity, is the oldest and most widely used silicone implant. Ear armatures are used to rebuild ears missing at birth or due to accidents. Chin and nose implants are used to build out receding chins or saddlenoses [29]. The silastic mammary prosthesis has been widely used for augmenting the breast. It is composed of a bag of silastic silicone rubber filled with very soft silicone gel. The prosthesis is lighter than water, weighing very slightly more than the same amount of breast tissue. These devices are not used after radical surgery for breast cancer
Natural rubber and silicone rubber-based biomaterials 81
because, in most instances, so much tissue is removed that there is usually insufficient skin under which to place the prosthesis [30,31]. Medical grade silicones are also used for finger joint prosthesis mainly for the purpose of repairing the painfully deformed hands of arthritis victims. The affected knuckle joint is excised and the finger is straightened. The ends of silicone rubber prostheses are placed into the bones of the fingers and the hand, with the central part of the device in the position of the removed joint [32]. Silicone rubber rods are implanted in the hand for the development of new tunnels through which the tendons can glide in heavily scarred areas. After the new sheaths are formed, the silicone rubber rods are replaced by the patienťs own tendon. In ophthalmology, repair of detached retinas is done by means of a small silicone rubber belt placed tightly around the eye, forcing the detachment back into its proper position. Many thousands of persons have regained sight by this procedure and are living with these bands embedded in the outer tissue layers of their eyes [33]. Silicone rubber-coated Dacron cloth has been used to replace the tough fibrous covering over the brain in those cases where there has been massive loss as a result of auto accidents and explosions. A silicone rubber skull plate molded from silastic has been used to replace the skull in cases of massive skull losses, particularly of war casualties and accident victims. A silicone rubber jaw made of hard medical grade silicone rubber has been investigated by the army as a temporary replacement for missing portions of jaws [34]. Silicone elastomers find application in many devices implanted in the thoracic cavity. A key example is the cardiac pacemaker, where silicone is used to encapsulate and insulate. Two interesting examples involving the stomach are the popular gastric band implant (Lap-Band) for weight loss, and the Angelchik antireflux device for management of gastroesophageal reflux or hiatal hernia, which have not been resolved by more conservative treatments [35].
4.12 Current status of silicone rubber in medical applications Silicone elastomers are used in voice prostheses placed in the throat between the trachea and esophagus after laryngectomy. This is a particularly challenging location for any elastomeric material, as yeast and bacterial biofilm colonization often develop with long-term use. Fujiyama et al. studied on a new technique the DLC coating on silicone-based tubular medical devices. Results have indicated compatible cell morphology of filopodial shape and well expansion on the DLC-coated surface as opposed to the rounding and partial detachment on the bared silicone surface [36]. Ahmedi Mehdi and coworkers studied on the bioactive peptide grafted silicon for wound dressing applications. They have done a simple method of bringing bioactivity in inert silicone rubber with peptides [37]. Jiang et al. worked on the silicone rubber for human tissue replacement of prostate brachytherapy. Biomaterials mimicked with PVA and silicone rubber can be a
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s uitable substitute for prostate tissue and other organs in the pelvic structure for prostate brachytherapy simulation [38]. Silicone catheters are coated by sophrolipids to prevent formation of biofilms. These were invented by Ribeiro et al. These compounds present a novel source of antibiofilm agents for technological development, passing through strategies of permanent functionalization of surfaces [39]. In addition, the incorporation of siloxane into soft contact lens material resulted in the development of the silicone hydrogel contact lens. This innovative lens material greatly increases the amount of oxygen that reaches the cornea, allowing the lenses to be worn for as long as 1 month of continuous wear. The use of these lenses has resulted in fewer complications and much improvement in patient symptoms of dryness and discomfort compared with the previous soft lenses [40]. Silicone elastomers are also used for drug delivery applications. Woolfson and coworkers have incorporated the antibacterial drug metronidazole into the self- lubricating silicone elastomer in order to produce novel biomaterial. The results highlight the potential for developing lubricious silicone medical devices with enhanced drug-release characteristics [41]. Silicone elastomers with different surface roughness were prepared by Rochev et al. With breast implants, for example, the fibrous capsule that forms at the silicone interface can undergo contracture, which can lead to the need for revision surgery. The relationship between surface topography and wound healing—which could impact on the degree of contracture—has not been examined in detail. To address this, they prepared silicone elastomer samples with rms surface roughness varying from 88 to 650 nm and examined the growth of 3 T3 fibroblasts on these surfaces [42]. Normal silicone-based blood vessels will clot the blood in these tubes. Plasma treated silicones can be used as blood vessels as they will improve the anticoagulation of blood fluids. These are studied by Williams et al. [43].
4.13 Future prospects Scientists and researchers the world over are in search of medical devices and implantable materials which can be used for a longer time and which have biocompatibility with the body parts. Hence, research and development in silicone and natural rubber compounding and processing can be future materials in biomedical applications because of their inherent biocompatibility and biodurability. These elastomers can be modified with or cross-linked with other bioactive chemicals in order to improve their stability, inertness, and chemical nature. Modification can be done by irradiation, chemical treatments, or physical adhesion. These modified elastomers can be materials for future application.
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[25] L.C. Hartman, R.W. Bessette, R.E. Baier, A.E. Meyer, J. Wirth, Silicone rubber temporomandibular joint (TMJ) meniscal replacements: Postimplant histopathologic and material evaluation, J. Biomed. Mater. Res. 22 (6) (1988) 475–484. [26] M.F. Harmand, F. Briquet, In vitro comparative evaluation under static conditions of the Hemocompatibility of four types of tubing for cardiopulmonary bypass, Biomaterials 20 (17) (1999) 1561. [27] K.A. Baeham, Suprapubic bladder drainage in Gynaecological surgery, ANZ J. Surg. 43 (1) (1973) 32–36. [28] R.I. Leininger, V. Mirkovitch, A. Peters, W.A. Hawks, Change in properties of plastics during implantation, Trans. Am. Soc. Artif. Intern. Organs 10 (1964) 320–322. [29] K.W. Delank, K. Scheuermann, Praktische aspekte der prothetischen stimmrehabilitation nach laryngektomie, Laryngorhinootologie 87 (3) (2008) 160–166. [30] S.M. Edworthy, L. Martin, S.G. Barr, D.C. Birdsell, R.F. Brant, A clinical study of the relationship between silicone breast implants and connective tissue disease, J. Rheumatol. 25 (2) (1998) 254. [31] S.E. Gabriel, W.M. O’Fallon, L.T. Kurland, C.M. Beard, J.E. Woods, Risk of connectivetissue diseases and other disorders after breast implantation, New Engl. J. Med. 330 (24) (1994) 1697. [32] J.W. Swanson, J.E. LeBeau, The effect of implantation on the physical properties of silicone rubber, J. Biomed. Mater. Res. 8 (1974) 357. [33] S.D. Lee, G.H. Hsiue, C.Y. Kao, P.C.T. Chang, Artificial cornea: surface modification of silicone rubber membrane by graft polymerization of pHEMA via glow discharge, Biomaterials 17 (6) (1996) 587–595. [34] F. Mahyudin, L. Widhiyanto, H. Hermawan, Biomaterials in orthopaedics, Adv. Struct. Mater. 58 (2016) 161–181. [35] A.G. Timoney, J.M. Kelly, M.R. Welfare, The angelchik antirefl Ux device: a 5-year experience, Ann. R. Coll. Surg. Engl. 72 (1990) 185–187. [36] M. Timan Idriss Gasab, M. Uchiyama, T. Nakatani, A. Valanezhad, I. Watanabe, H. Fujiyama, Advanced DLC coating technique on silicone-based tubular medical devices, Surf. Coat. Technol. 307 (2016) 1084–1087. [37] C. Pinese, S. Jebors, P.E. Stoebner, V. Humblot, P. Verdié, L. Causse, X. Garric, H. Taillades, J. Martinez, A. Mehdi, G. Subra, Bioactive peptides grafted silicone dressings: a simple and specific method, Mater. Today Chem. 4 (2017) 73–83. [38] P. Li, S. Jiang, Y. Yu, J. Yang, Z. Yang, Biomaterial characteristics and application of silicone rubber and PVA hydrogels mimicked in organ groups for prostate brachytherapy, J. Mech. Behav. Biomed. Mater. 49 (2015) 220–234. [39] C. Pontes, M. Alves, C. Santos, M.H. Ribeiro, L. Gonçalves, A.F. Bettencourt, I.A.C. Ribeiro, Can Sophorolipids prevent biofilm formation on silicone catheter tubes? Int. J. Pharm. 513 (1–2) (2016) 697–708. [40] S.M. Dillehay, Does the level of available oxygen impact comfort in contact lens wear? a review of the literature, Eye Contact Lens 33 (3) (2007) 148–155. [41] R.K. Malcolm, S.D. McCullagh, A.D. Woolfson, S.P. Gorman, D.S. Jones, J. Cuddy, Controlled release of a model antibacterial drug from a novel self-lubricating silicone biomaterial, J. Control. Release 97 (2) (2004) 313–320. [42] B.R. Prasad, M.A. Brook, T. Smith, S. Zhao, Y. Chen, H. Sheardown, R. D’souza, Y. Rochev, Controlling cellular activity by manipulating silicone surface roughness, Colloids Surf. B Biointerfaces 78 (2) (2010) 237–242. [43] R.L. Williams, D.J. Wilson, N.P. Rhodes, Stability of plasma-treated silicone rubber and its influence on the interfacial aspects of blood compatibility, Biomaterials 25 (19) (2004) 4659–4673.
4
Abitha Vayyaprontavida Kaliyathan⁎, Anitha Mathew†, Ajay Vasudeo Rane‡, Krishnan Kanny‡, Sabu Thomas⁎ ⁎ Mahatma Gandhi University, Kottayam, India, †Vimala College (Autonomous), Thrissur, India, ‡Durban University of Technology, Durban, South Africa
Abstract Biomaterials are materials which are used to replace a part or a function of the body in safe, reliable, economical and physiologically acceptable manner. Polymers are used as biomaterial for a long time due to its light weight and biocompatibility. Natural and synthetic rubber are mainly used because of their inertness and bicompatible nature. Silicone rubber are widely used and natural rubber as of yet found limited applications. Through this chapter the relevant use of both the rubbers are described applications are discussed and possible future developments are considered. Keywords: Biomaterials, Biological material, Silicone rubber, Natural rubber, Biocompatible.
4.1 Introduction Biomaterials is more than 50 years old, it is a material which were used by our ancestors to treat themselves in therapeutically or diagnostically. The scientific definition of a biomaterial is “A substance which is tailored and engineered to interact with biological system in a therapeutic or diagnostic way” (see Fig. 4.1). The field of biomaterials science and engineering is growing at a fast rate, considering the scientific work and development of materials carried out. It is cited that biomaterials differ from biological material as the latter is fabricated via biological systems (see Fig. 4.2). Biomaterial is application specific, and hence utmost care should be taken while considering biomaterial as biocompatible; for example, bone is a biological material produced by the biological method. As mentioned earlier, biomaterial is “application specific,” that is, a biomaterial that is biocompatible or suitable for one application may not be biocompatible in another. Biomaterials can be derived either from nature or synthesized in the laboratory using a variety of chemical approaches utilizing various materials as described in Fig. 4.3. We shall consider polymers in this chapter, specifically natural rubber and silicone rubber.
Fundamental Biomaterials: Polymers. https://doi.org/10.1016/B978-0-08-102194-1.00004-9 Copyright © 2018 Elsevier Ltd. All rights reserved.
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Elements of biomaterial science
Medicine
Biology
Chemistry
Tissue engineering
Material sciences
Fig. 4.1 Elements of biomaterials science and engineering.
Biomaterial
Biological material
Fig. 4.2 Biomaterial vs biological material.
Materials
Metallic
Ceramic
Polymeric
Inorganic glasses
Fig. 4.3 Sources of biomaterials.
Biomaterials are used and/or adapted for a medical application, and thus comprise the whole or part of a living structure or biomedical device which performs, augments, or replaces a natural function (see Fig. 4.4). Polymeric materials are used as biomaterials in a wide variety of applications from sutures to drug delivery to implants. The following chart in Fig. 4.5 enlists applications of materials in medicine and dentistry. Now we shall consider in detail natural rubber and silicone rubber as polymeric biomaterials. Prior to that, we will give a summary of natural rubber and silicone rubber. Silicone and natural rubber are two elastomers which differ in their structure and properties. Their frequency of use in medical applications is also different. Silicone rubber has dominated the application of elastomers to medicine, while natural rubber Biomaterials
Autograft
Allograft
Fig. 4.4 Classification of biomaterials.
Xenograft
Transplant
Natural rubber and silicone rubber-based biomaterials 73
Applications of polymeric biomaterials
Cardiovascular
Nonthrombic treatment
Dental implants
Adhesives and sealants
Opthalmologic
Orthopedic
Drug delivery system
Sutures
Burn dressing
Bioelectrodes
Biomedical sensors
Biosensors
Fig. 4.5 Applications of polymeric biomaterials.
has made a relatively minor contribution. Owing to the low- and high-temperature performance, silicones are used in the aerospace industry. Silicones are used as electrical insulation potting compounds and other applications specific to electrical insulation. Their long-term durability has made silicone sealants, adhesives, and waterproof coatings commonplace in the construction industry. Their excellent biocompatibility makes many silicones well suited for use in numerous personal care, pharmaceutical, and medical device applications.
4.2 Natural rubber as biomaterial Natural rubber (latex and solution casted) is used as a biomaterial owing to its chemical, physical, biological, and mechanical properties, imparted after a specified compounding and optimum vulcanization process (see Fig. 4.7 for applications). It is a macromolecule of isoprene (C5H8); as a monomer unit, with likely cis-configuration with one double bond in each repeating unit, however, due to the presence of a double bond in its structure, natural rubber is sensitive to heat and oxidation (see Fig. 4.6 for structure). The blood compatibility of natural rubber is very low as compared to silicone and polyurethanes, but suitable compounding, that is, grafting of natural rubber to improve blood compatibility, has been an area of research for a long time. However, the known disadvantage of natural rubber is allergy in human body due to the protein latex component. Considering the disadvantage for natural rubber as a biomaterial, natural rubber has more number of reasons to be used as a biomaterial, which are given in Fig. 4.8. The mentioned reasons promote tissue replacement and tissue regeneration. Natural rubber formulations have been used to control mosquito larvae. Natural rubber formulation with organotin toxicants are used in prevention of marine fouling [1]. Dick et al., in their study, fabricated hydroxyapatite-filled natural rubber composites toward bone application [2]. Silva et al. fabricated bioglass-filled natural rubber composites and characterized them for mechanical and thermal properties, indicating their applications in biomedical applications. [3] Borges et al. prepared calcium
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CH2
CH2
n
C=C CH3
H
Fig. 4.6 Structure of natural rubber.
Applications - natural rubber (biomaterial)
Membranes
Diaphragms
Blood pressure cuff coils
Seals
Covers
Tracheal tubes
Medical gloves
Condoms
Balloons
Pacifiers
Baby bottle nipples
Medical and dental equipment
Fig. 4.7 Applications of natural rubber as a biomaterial in medical applications [1].
Natural rubber as biomaterial
Stimulates angiogenesis
Cellular adhesion
Extra cellular matrix
Natural rubber latex in wound healing
Vascular permeability
Angiogenesis
Fig. 4.8 Reasons—why natural rubber is used as a biomaterial and in wound healing [1].
Natural rubber and silicone rubber-based biomaterials 75
carbonate-filled natural rubber composites. [4] Nashar et al. added magnetic fillers: nanoiron and nickel particles in natural rubber and proposed biomedical application for fabricated composites. [5] Thanida et al. prepared antibacterial natural rubber latex formulation for gloves filled with N,N,N-trimethyl chitosan stabilized poly(methyl methacrylate) latex particles [6]. Nickel zinc ferrite-filled thermoplastic natural rubber composites fabricated by Moayad et al. were proposed to be used in biomedical applications [7]. Natural rubber latex was also used as an occlusive membrane for guided bone regeneration [8]. Silva et al. fabricated membranes based on natural rubber latex compounded with propolis for biomedical application [9]. Trovatti et al. fabricated cellulose—sponge natural rubber composites as porous composites for biomedical applications [10]. Anyarat et al. fabricated sericin-binded-deprotenized natural rubber film containing chitin whiskers as an elasto-gel dressing [11].
4.3 Silicone rubber as biomaterial Silicone rubbers have been produced commercially for about 35 years. The term silicone was coined by Prof. Kipping who carried out the pioneer work on organosilicon compounds. The silicones are made up of repeating polymer chains which consist of backbones of silicone to oxygen bonds (see Fig. 4.9) [12]. In addition to the oxygen backbones, silicones have also bonded to organic groups, especially methyl groups. This structure has similarity to ketones and due to this Kipping named it “silicones.” Later, based on its use in different areas, new nomenclature was developed. The basic repeating unit is siloxane and the most common silicone is polydimethylsiloxane (PDMS) [13].
4.4 Preparation of silicone rubber Silicones are manufactured by hydrolysis of the appropriate dichlorosilane (R2SiCl2), the silanol product undergoing a condensation reaction in dilute solution to form the cyclic tetramer.
R
Si
R Siloxane
CH3
O
Si
n
CH3
O
n
Polydimethylsiloxane
Fig. 4.9 Structure of silicone and polydimethylsiloxane preparation of silicone rubber.
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( CH3 )2 SiCl2 + 2H 2 O ® ( CH3 )2 Si ( OH )2 + 2HCl ( CH3 )2 Si ( OH )2 ® ( ( CH3 )2 Si O )n After treatment with a strong acid or base, the condensation polymerization is allowed to continue until the required molecular weight is obtained. The first type of siloxane available was dimethyl siloxanes (MQ), followed shortly by methyl phenyl siloxane (PMQ).The phenyl groups give an elastomer of lower stiffening temperature and improved resistance to radiation. The incorporation of a proportion of fluorine or cyano containing groups in place of methyl confers excellent resistance to oils, fuels, and solvents. This type of silicone is known as FVMQ [14].
4.5 Physicochemical properties of silicone rubber Silicones exhibit the unusual combination of an inorganic chain similar to silicates and often exhibit high surface energy. The SiO bonds are quite polar and without protection would lead to strong intermolecular interactions. The methyl groups which are weakly interacting with each other shield the main chain. Polysiloxane is very flexible due to large bond angles and bond lengths. Polysiloxanes tend to be inert due to the strength of the silicon-oxygen bond [15]. Silicone rubbers offer good resistance to extreme temperatures; the working temperature of silicone is normally from −100 to 300°C. Silicone rubber is a material of choice in Industry when retention of initial shape and mechanical strength are desired under heavy thermal stress or subzero temperatures. Organic rubber has a carbon to carbon backbone which can leave it susceptible to ozone, UV, heat, and other aging factors that silicone rubbers can withstand well. This makes silicone rubber one of the elastomers chosen in many extreme environments [16].
4.6 Properties of silicone rubber as biomaterial Many other groups, for example, phenyl vinyl and trifluoropropyl, can be substituted for the methyl groups along the chain. The simultaneous presence of organic groups attached to an inorganic backbone gives silicone a combination of unique properties, which makes them possible for use as fluids, emulsions, compounds, resins, and elastomers in numerous applications and diverse fields. The inorganic backbone present in silicone rubber is the fundamental factor which makes silicone biocompatible. Such an inorganic structure cannot be metabolized by living organic systems and contributes to the inertness of silicone rubber by minimizing the likelihood of chemical reactions between body fluids and a silicone rubber implant [17]. The unique properties of silicone rubber make their use in medical implants and biocompatible materials. Sterilization of biomaterials is facilitated by an excellent heat stability which allows autoclaving without property deterioration. Shelf life and oxidative stability are promoted by a resistance to degradation by oxygen, ozone, or UV light. The solvent
Natural rubber and silicone rubber-based biomaterials 77
Biomaterial properties of silicone Heat stability (sterilization)
Hydrophobicity
Oxidative stability
Hydrophobicity
Physiological inertness
Transparent
Highly flexible
Solvent resistance
Fig. 4.10 Properties of silicone rubber which help as a biomaterial.
resistance of silicone rubber is good and intermittent contact with organic solvents has little influence on the physical properties of polymers [18]. The use of silicone rubber tubing for the passage of biological fluids is enhanced by the release properties of the polymer surface. Silicone rubber is chemically inert so it does not corrode with other materials. It is used thus for fixing rollers printing rollers and sheets of photocopiers and for lost wax casting. Living tissues are less affected by silicone rubber as compared to other organic polymers [19]. Silicone rubber is physiologically inert and is thus used for baby bottle nipples and stoppers in medical applications. In addition, it is pleasant to the touch with a high-grade feel, making it ideal for leisure items such as swimming caps and goggles. The inertness enables stable mechanical properties and long-term use of PDMS in biological environments without degradation of the polymer. Moreover, medical grade silicone is reported to be nonimmunogenic and nontoxic. The properties of silicone which help it to act as a biomaterial are shown in Fig. 4.10 [20].
4.7 Cross-linking or curing of silicone elastomer In the uncured state, silicone rubber is a highly adhesive gel or liquid. In order to convert it into solid, it must be cured, vulcanized, or catalyzed. This is normally carried out in a two-stage process at the point of manufacture into the desired shape, and then in a prolonged postcure process. It can also be injection molded. A majority of silicone rubbers are cured by any one of the following methods.
4.8 Peroxide cure system [21] Peroxide curing is widely used for curing silicone rubber. The curing process leaves behind by-products which can be an issue in food contact and medical applications. However, these products are usually treated in a postcure oven which greatly reduces the peroxide breakdown product content. The following reaction (see Fig. 4.11) mechanism has been proposed for the cross-linking or curing reaction from organic peroxide [15].
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Si
+ CH3
Si
CH
Si
CH2
CH2
CH2
Si
Fig. 4.11 Peroxide cure system of silicone rubber.
4.9 Condensation cross-linking system Condensation curing systems can be one-part or two-part systems. In the one-part or RTV (room-temperature vulcanizing) system, a cross-linker exposed to ambient humidity (i.e., water) experiences a hydrolysis step and is left with a hydroxyl or silanol group. The silanol condenses further with another hydrolyzable group on the polymer or cross-linker and continues until the system is fully cured. Such a system will cure on its own at room temperature and (unlike the platinum-based addition cure system) is not easily inhibited by contact with other chemicals, though the process may be affected by contact with some plastics or metals and may not take place at all if placed in contact with already-cured silicone compounds (see Fig.4.12). These products are ready to apply and require no mixing. Cross-linking starts when the product is squeezed from the cartridge or tube and comes into contact with moisture [22].
4.10 Addition cross-linking system This cross-linking system is also known as the platinum-based cross-linking system. Two different chemical groups react in the presence of platinum. In this reaction (see Fig.4.13), an ethyl group [C(H)2–C(H)2] is formed and there are no by-products. In addition cure, cross-linking is achieved by reacting vinyl end-blocked polymers with SiH groups. The addition occurs mainly on the terminal carbon and is catalyzed by Pt or Rh complexes, preferably as organometallic compounds, to enhance their compatibility. There are no by-products with this reaction. The Pt in the complex is easily bonded to electron donating substances such as amine or organosulfur compounds to form stable complexes with these poisons rendering the catalyst inactive and inhibiting the cure. In biomedical applications, both room temperature vulcanization silicone rubber and liquid silicone rubber are employed. The conditions that must be met are: (i) after
Si
OH + OH
Si
Metal salt
Si
O
Si + H2O
Fig.4.12 Condensation cure system of silicone rubber.
Si
H + CH3
CH
Si
H+ Pt
Fig. 4.13 Addition cross-linking of silicone rubber.
Si
CH2
CH2
Si
Natural rubber and silicone rubber-based biomaterials 79
the vulcanization reaction, there can be no presence of by-products because, after a certain time, they could migrate and come into contact with body fluids causing infections or encapsulation. To address this, the addition-type silicone rubbers are the best option due to their lack of by-products after the reaction. (ii) The components of the silicone rubber must not include any carcinogenic, thrombogenic, or toxic, allergic, or inflammatory materials. The RTV silicone rubbers used are two-part materials based on PDMS vulcanized with platinum, organoplatinum, low molecular tetra (alkyloxysilane), stannous octoate, or through irradiation curing where the scission of CH and CSi bonds generates the cross-linking. For liquid silicone rubbers, two-part LSRs are also used with peroxides, metal salt, condensation, and vinyl addition as curing systems [22].
4.11 Biomedical applications of silicone rubber The advantages of using silicone rubber in biomedical applications are it is easy to process and its stability in contact with tissues in living organisms. Silicone rubbers’ inherent hydrophobicity (material which repels water), however, has caused some problems in some devices over a long period of time (until now) [23]. The Health Industry Manufacturers Association has classified medical devices into four categories as shown in Table 4.1. Silicone Rubber is used in all four categories, with more prevalence in I and II [24]. For many years, silicone rubber has been used in clinical implants because of its inherent bio-inert nature. The most high-profile application is the mammary prosthesis. Silicones which are generally used in the medical field can be grouped into three categories: nonimplantable, short-term implantable, and long-term implantable. Materials approved as Classes V and VI can be considered medical grade. Most medical grade Table 4.1
Different type of medical devices
Type
Environment
Duration
Application
1
Internal devices
Less than 30 days
Intravenous catheters Drainage tubes Hip implants Pacemakers Artificial heart valves Devices that contact the mucous membranes such as urinary catheters and intravaginal devices Hypodermic syringes Transfusion assemblies Dialysis components Dressing trays Packaging materials
More than 30 days
2
External devices
3
Indirect devices
4
Nonpatient contact devices
More than 30 days
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Table 4.2
Application of silicone rubber as implants
Treatment
Application
Plastic and reconstructive surgery Ophthalmology
Reconstruction of nose, chin, ear, breast Correction of detached retina Prosthetic eye Reconstruction of arms, elbows, thumbs, tendons, etc. Maxillofacial applications Penile prosthesis Ball in ball and cage heart valve Coatings on pacemakers and lead wire. Construction on artificial hearts and heart assisted devices
Orthopedic surgery
Cardiovascular surgery
silicones are at least Class VI certified. Silicone suppliers and some silicone prototyping companies provide guidelines for material use. Table 4.2 illustrates the various implant applications of silicone rubber [25]. Some of the medical applications of silicone rubbers are given below in detail: ●
●
●
Extracorporeal equipment: Silicones have good hemocompatibility and gas permeability properties due to which they are is used in many extracorporeal equipments. They are used in dialysis, blood oxygenators, and heart bypass machines. Owing to the blood compatibility of silicone rubber, it is used for heart bypass applications. Hemocompatibilty testing has suggested that platinum-cured silicone tubing may be superior to PVC in several aspects [26]. Catheters, shunts, and drains: The silicone elastomers are also found to have widespread application in catheters, shunts, and drains which are manufactured by silicon extrusion. Some of the devices are silicon coated to provide less host reaction. Several urology catheters are made of latex and their interior and exterior are coated with silicones. Drains are mainly used for bladder drainage after gynecological surgery that complicated or prevented normal urethral urination [27]. Implants: Among synthetic polymers, silicones are the most widely used materials for long-term implantation, although medical grade silicon is an aggressive environment for almost all types of foreign materials which are in contact with body fluids and tissues. Medical grade silicone elastomer comes close to fulfilling the requirements of implants [28].
Silicone elastomers have been used in almost all surgical specialties including neurosurgery, Ophthalmology, plastic surgery, orthopedic surgery, and others. The hydrocephalus shunt, which is used to drain cerebrospinal fluid from the peritoneal cavity, is the oldest and most widely used silicone implant. Ear armatures are used to rebuild ears missing at birth or due to accidents. Chin and nose implants are used to build out receding chins or saddlenoses [29]. The silastic mammary prosthesis has been widely used for augmenting the breast. It is composed of a bag of silastic silicone rubber filled with very soft silicone gel. The prosthesis is lighter than water, weighing very slightly more than the same amount of breast tissue. These devices are not used after radical surgery for breast cancer
Natural rubber and silicone rubber-based biomaterials 81
because, in most instances, so much tissue is removed that there is usually insufficient skin under which to place the prosthesis [30,31]. Medical grade silicones are also used for finger joint prosthesis mainly for the purpose of repairing the painfully deformed hands of arthritis victims. The affected knuckle joint is excised and the finger is straightened. The ends of silicone rubber prostheses are placed into the bones of the fingers and the hand, with the central part of the device in the position of the removed joint [32]. Silicone rubber rods are implanted in the hand for the development of new tunnels through which the tendons can glide in heavily scarred areas. After the new sheaths are formed, the silicone rubber rods are replaced by the patienťs own tendon. In ophthalmology, repair of detached retinas is done by means of a small silicone rubber belt placed tightly around the eye, forcing the detachment back into its proper position. Many thousands of persons have regained sight by this procedure and are living with these bands embedded in the outer tissue layers of their eyes [33]. Silicone rubber-coated Dacron cloth has been used to replace the tough fibrous covering over the brain in those cases where there has been massive loss as a result of auto accidents and explosions. A silicone rubber skull plate molded from silastic has been used to replace the skull in cases of massive skull losses, particularly of war casualties and accident victims. A silicone rubber jaw made of hard medical grade silicone rubber has been investigated by the army as a temporary replacement for missing portions of jaws [34]. Silicone elastomers find application in many devices implanted in the thoracic cavity. A key example is the cardiac pacemaker, where silicone is used to encapsulate and insulate. Two interesting examples involving the stomach are the popular gastric band implant (Lap-Band) for weight loss, and the Angelchik antireflux device for management of gastroesophageal reflux or hiatal hernia, which have not been resolved by more conservative treatments [35].
4.12 Current status of silicone rubber in medical applications Silicone elastomers are used in voice prostheses placed in the throat between the trachea and esophagus after laryngectomy. This is a particularly challenging location for any elastomeric material, as yeast and bacterial biofilm colonization often develop with long-term use. Fujiyama et al. studied on a new technique the DLC coating on silicone-based tubular medical devices. Results have indicated compatible cell morphology of filopodial shape and well expansion on the DLC-coated surface as opposed to the rounding and partial detachment on the bared silicone surface [36]. Ahmedi Mehdi and coworkers studied on the bioactive peptide grafted silicon for wound dressing applications. They have done a simple method of bringing bioactivity in inert silicone rubber with peptides [37]. Jiang et al. worked on the silicone rubber for human tissue replacement of prostate brachytherapy. Biomaterials mimicked with PVA and silicone rubber can be a
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s uitable substitute for prostate tissue and other organs in the pelvic structure for prostate brachytherapy simulation [38]. Silicone catheters are coated by sophrolipids to prevent formation of biofilms. These were invented by Ribeiro et al. These compounds present a novel source of antibiofilm agents for technological development, passing through strategies of permanent functionalization of surfaces [39]. In addition, the incorporation of siloxane into soft contact lens material resulted in the development of the silicone hydrogel contact lens. This innovative lens material greatly increases the amount of oxygen that reaches the cornea, allowing the lenses to be worn for as long as 1 month of continuous wear. The use of these lenses has resulted in fewer complications and much improvement in patient symptoms of dryness and discomfort compared with the previous soft lenses [40]. Silicone elastomers are also used for drug delivery applications. Woolfson and coworkers have incorporated the antibacterial drug metronidazole into the self- lubricating silicone elastomer in order to produce novel biomaterial. The results highlight the potential for developing lubricious silicone medical devices with enhanced drug-release characteristics [41]. Silicone elastomers with different surface roughness were prepared by Rochev et al. With breast implants, for example, the fibrous capsule that forms at the silicone interface can undergo contracture, which can lead to the need for revision surgery. The relationship between surface topography and wound healing—which could impact on the degree of contracture—has not been examined in detail. To address this, they prepared silicone elastomer samples with rms surface roughness varying from 88 to 650 nm and examined the growth of 3 T3 fibroblasts on these surfaces [42]. Normal silicone-based blood vessels will clot the blood in these tubes. Plasma treated silicones can be used as blood vessels as they will improve the anticoagulation of blood fluids. These are studied by Williams et al. [43].
4.13 Future prospects Scientists and researchers the world over are in search of medical devices and implantable materials which can be used for a longer time and which have biocompatibility with the body parts. Hence, research and development in silicone and natural rubber compounding and processing can be future materials in biomedical applications because of their inherent biocompatibility and biodurability. These elastomers can be modified with or cross-linked with other bioactive chemicals in order to improve their stability, inertness, and chemical nature. Modification can be done by irradiation, chemical treatments, or physical adhesion. These modified elastomers can be materials for future application.
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