Synthesis of Nanomaterials

By Felipe López-Saucedo

Synthesis of Nanomaterials is a beginner’s guide to the synthesis and characterization of biomaterials for medical devices and implants. It presents 8 chapters explaining the use of biomaterials in medicine and pharmacology. The concepts are explained with the guidance of specialists who present the principal techniques and methods to obtain high-performance polymers and composite materials.

Starting with an introduction to the subject, the book explains nanomaterials synthesis and progresses towards engineering applications. The chapters also cover modern biomaterials such as stimuli-responsive biomaterials, hydrogels, and self-healing materials.

One chapter is dedicated to computational and theoretical techniques in biomedicine and a final chapter covering microencapsulation for advanced drug delivery rounds up the contents.

Synthesis of Nanomaterials is a primary reference book for undergraduate and graduate students as well as professors involved in multidisciplinary research and teaching programs.

• Language: English
• Publisher: Bentham Science Publishers
• Release date: May 25, 2023
• ISBN: 9789815136920

Book preview

Biomaterials Applied to Medical Devices and Pharmacy

Tri-Dung Ngo¹, *

¹ Bioindustrials Research and Development, InnoTech Alberta (Formerly Alberta Research Council (1921-2010) and Alberta Innovates Technology Futures (2010-2016)), 250 Karl Clark Road, Edmonton, Alberta, T6N 1E4, Canada

Abstract

Biomaterials have been utilized in healthcare applications a number of times. Nowadays, subsequent evolution and the increase in the life expectancy of world’s population have made biomaterials more attractive and versatile, and have increased their utility. Concerning the manufacturing of medical devices and pharmacy, the development of new biomaterials, new manufacturing methods and techniques has always been the researchers’ focus. Recently, nanotechnology and nanomedicine have attracted a great deal of attention, which would further enhance the use of biomaterials in medical devices and pharmacy. In the development of medical devices and pharmacy, the selection of the proper material to be used is of utmost importance. This chapter aims to provide a review of the most used biomaterials. After an explanation of what biomaterials are and what defines them, a more in-depth approach to the major types of biomaterials is presented, such as metal, polymer, ceramic, and composites; also, the advantages and disadvantages of biomaterials, their main characteristics, and preferred applications in the area of medical devices and pharmacy are discussed.

Keywords: Biodegradable, Biomaterial, Ceramic, Composite, Drug delivery, Material, Medical devices, Medicine, Metal, Nanomedicine, Nanotechnology, Pharmacy, Polymer, Tissue, Treatment.

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* Corresponding author Tri-Dung Ngo: Bioindustrials Research and Development, InnoTech Alberta (Formerly Alberta Research Council (1921-2010) and Alberta Innovates Technology Futures (2010-2016)), 250 Karl Clark Road, Edmonton, Alberta, T6N 1E4, Canada; E-mail: [e-mail]

INTRODUCTION

Biomaterials are often defined as substances that have been engineered to interact with biological systems for medical and pharmaceutical purposes. The materials are utilized in many biomedical and pharmaceutical areas, such as the treatment, augmentation, reparation, or replacement of biological function, and in medical devices and pharmacy. Biomaterials also play an integral role in medicine today, such as restoring function and facilitating healing after an injury or disease.

Biodegradable materials have also revolutionized controlled drug delivery design and biomaterial applications for implants and tissue engineering. Pharmaceutical biomaterial is a connecting branch of pharmacy and biomaterial sciences that commonly deals with the strategies related to manipulating bio-originated or bio-applicable materials in a way that can be advantageous for patients in the treatment, diagnosis, or prevention of diseases [1, 2]. Examples of biomaterials utilized for various drug delivery systems and tissue replacement are shown in Fig. (1).

Fig. (1))

Biomaterials for various drug delivery (white-green circle) and tissue replacement (orange) [2].

The biomaterial science field is about 50 years old. As biomaterials science has matured, it has taken on much more biological content, moving from an approach that emphasizes inertness to one that embraces biological activity. Researchers are also developing smart biomaterials that can respond biologically to environmental conditions by changing their biomechanical or drug-releasing properties.

CLASSIFICATION

Bioactive biomaterials have wide applications as medical devices and in drug delivery systems. Bioactive biomaterials can be natural (bovine bone mineral matrix, hyaluronic acid, collagen, gelatine, fibrin, agarose, alginate, chitosan, silk) or synthetic (ceramics, metals, polymers, hydrogels, and composites). Biomaterials can be derived either from nature or synthesized in the laboratory using a variety of chemical approaches. From the healthcare perspective, biomaterials can be divided into the following categories: (1) synthetic (metals, polymers, ceramics, and composites); (2) naturally derived (animal and plant-derived); (3) semi-synthetic or hybrid materials.

Ceramics: Traditionally, ceramics have seen widescale use as restorative materials in dentistry. These include materials for crowns, cement, and dentures. Ceramics are defined as inorganic, non-metallic materials. The ceramic materials are hard, brittle, have great strength and stiffness, wear and corrosion resistance, and low density. Ceramics work well with compressive forces and are electrical and thermal insulators. They are used in dentistry, orthopaedic, some nondental biomedical applications and as medical sensors. Conversely, ceramics are also at risk of having cracks or other defects, and the use of ceramic biomaterials in other fields of biomedicine has not been as extensive, compared to metals and polymers. The poor fracture toughness of ceramics severely limits their use for load-bearing applications. Some ceramic materials are used for joint replacement and bone repair and augmentation [3-5]. Ceramic biomaterials are important in the biomedical field due to their chemical similarity to the bone, and are ideal for surgical implants due to their thermal and chemical inertness, and they have high strength, wear resistance, and durability. Ceramic biomaterials also stimulate bone growth and have low friction coefficients. They do not create strong biologically relevant interfaces with bones, but they do promote strong adhesions to bones. Ceramics are biocompatible materials, also known as bioceramics. In the 1950s, inert ceramic materials were found and used for structural bone replacement because of their biocompatibility and mechanical properties. In the 1980s, ceramic materials, like glass-ceramic, bioactive glasses, calcium sulphates and phosphates, were used as bone grafts or for the metallic implant’s coatings because of their degradation behaviour [6]. There are different generations of bioceramic materials, and each of them includes some specific type of material as follows: 1) Alumina: aluminium oxide; 2) Zirconia: zirconium dioxide carbons; 3) Calcium phosphates: calcium sulphate, calcium phosphates and sulphates + zinc oxide, iron (III) oxide, calcium carbonate, hydroxyapatite, glasses, glass ceramics, and 4) Bioglass: porous bioactive and biodegradable ceramics, mesoporous materials, and organic-inorganic hybrids.

Metals: Metal materials have intrinsic properties, such as high strength, elasticity, mechanical reliability, good corrosion resistance, wear resistance and fatigue, toughness, and thermal and electrical conductivity. These properties make medical metal devices predominate over other materials. Metallic biomaterials have been used in implants spanning all areas of use in the human body. It is estimated that between 70 and 80% of implants are metallic. Metals are the most widely used for load-bearing implants. These range from simple wires and screws to fracture fixation plates and total joint prostheses (artificial joints) for hips, knees, shoulders, ankles, and so on. In addition to orthopedics, metallic implants are used in maxillofacial surgery, cardiovascular surgery, and as dental materials. Metallic biomaterials will remain central to these applications because of their unique properties compared to those of other classes of materials. Although many metals and alloys are used for medical device applications, the most employed are stainless steels, commercially pure titanium and titanium alloys, and cobalt-base alloys. Metals currently used for implant manufacturing include Co, Cr, Fe, Ni, Ta, Ti, Mo, and W [7].

Polymers: A wide variety of polymers are used in medicine as biomaterials. The polymers can degrade into metabolites of the body or are eliminated from the body. Polymers can be found in three states: amorphous, crystalline, and semi-crystalline [8]. The polymer can be 1) natural polymers, such as fibrin, chitosan, carrageenan, collagen, alginate, or hyaluronate, or 2) synthetic polymers, such as acrylics, polyamides, polyesters, polysiloxanes, and polyurethane. Polymers have low density, hence being lighter, which translates into an enormous advantage for an implant. In addition, complex shapes can be obtained by processing, such as injection moulding. The larger part can be easily produced, which greatly reduces its cost, flexibility and facility in designing material for a specific application [9]. With the increasing use and with the technological advancement in the field of materials, attempts have been made to replace medical devices made of metal by a polymer. Their applications range from facial prostheses to tracheal tubes, from kidney and liver parts to heart components, and from dentures to hip and knee joints.

Composites: A composite material may be defined as the material resulting from the combination of two or more materials in order to obtain a material having properties of both constituents. The purpose of this combination of materials is to improve hardness, mechanical strength, and fatigue. Composites are generally stronger than single materials from which they are made. Composites have permeated our everyday lives, such as products that are used in aerospace, construction, medical applications, sports, medical and pharmacy, and many more [10, 11]. Some of the natural composites are wood, bone, dentin, skin, and cartilage. The most successful composite biomaterials are used in the field of dentistry as restorative materials or dental cement. Although carbon-carbon and carbon-reinforced polymer composites are of great interest for bone repair and joint replacement because of their low elastic modulus levels, these materials have not displayed a combination of mechanical and biological properties appropriate to these applications. Composite materials are, however, used extensively for prosthetic limbs, where their combination of low density/weight and high strength make them ideal materials for such applications. Composite biomaterials have advantages like great biocompatibility, no corrosion as in metals and fracture strength in comparison to ceramic materials [12].

Natural Biomaterials: There are several materials derived from the animal or plant for use as biomaterials. One of the advantages of using natural materials for implants is that they are similar to materials familiar to the body. In this regard, the field of biomimetics (or mimicking nature) is growing. Natural materials do not usually offer the problems of toxicity often faced by synthetic materials. Also, they may carry specific protein binding sites and other biochemical signals that may assist in tissue healing or integration. However, natural materials can be subject to problems of immunogenicity. Another problem faced by these materials, especially natural polymers, is their tendency to denature or decompose at temperatures below their melting points. This severely limits their fabrication into implants of different sizes and shapes.

ADVANTAGES AND DISADVANTAGES OF BIOMATERIALS AND THEIR USES

The biomaterials, such as ceramic, metal, polymer, and composites, have their own advantages and disadvantages. Their advantages and disadvantages also define their application areas in medical devices and pharmacy, as presented in Table 1.

Table 1 Materials, advantages, disadvantages, and applications [13, 14].

There are several uses of ceramic, metal, polymer, and composite biomaterials in medical and pharmacy applications. Some of the applications are shown in Table 2.

Table 2 Commonly used biomaterials for biomedical applications [4, 15-20].

PDMS: polydimethyl siloxane, PE: polyethylene, PET: polyethylene terephthalate, PHEMA: poly(2-hydroxyethyl methacrylate), PMA: polymethacrylate, PS: polysulfone, PTFE: polytetrafluoroethylene, PU: polyurethane, PVC: polyvinyl chloride, CF: carbon fiber, GF: glass fiber, KF: Kevlar fiber.

REQUIREMENTS FOR BIOMATERIALS IN MEDICAL DEVICES AND PHARMACY

The biomaterials come in direct contact with the body tissues and body fluid; therefore, basic features are required for the materials, such as biocompatibility, inertness, safety, stability, cost-effectiveness, and ease of fabrication. The main requirement property for a biomaterial is that it does not trigger an adverse reaction when it is in service, which means biocompatibility is an essential requirement. As some biomaterials are exposed to human tissues and fluids, so predicting the results of possible interactions between host and material is an important and unique consideration in using synthetic materials in medicine. Two particularly important issues in biocompatibility are thrombosis, which involves blood coagulation and the adhesion of blood platelets to biomaterial surfaces, and the fibrous-tissue encapsulation of biomaterials that are implanted in soft tissues. Selection of the right biomaterials for medical devices and pharmacy applications is very important since a poor choice of materials can lead to clinical problems. The design or selection of a biomaterial depends on the relative importance of the various properties that are required for the intended medical application. Besides biocompatibility, good mechanical properties, high corrosion resistance, osseointegration and excellent resistance to wear, ductility and high hardness are also required. Physical properties that are generally considered include hardness, tensile strength, modulus, and elongation; fatigue strength, which is determined by a material’s response to cyclic loads or strains; impact properties; resistance to abrasion and wear; long-term dimensional stability, which is described by a material’s viscoelastic properties; swelling in aqueous media; and permeability to gases, water, and small biomolecules.

Biocompatibility is defined as the ability or capacity of the material to be used in close connection with living tissues without causing adverse effects to them [21, 22]. The human body consists of a significant number of natural elements. The water is about 65 to 75% by weight of the total composition of the human body. Consequently, most of the mass of the human body contains oxygen and carbon. The elements, such as O (65.0%), H (9.5%), C (18.5%), and N (3.3%), are about 96.3 wt%. However, the human body also consists of other elements, such as Ca (1.5%), P (1.0%), K (0.4%), S (0.3%), Na (0.2%), Cl (0.2%), Mg (0.1%), and trace element (<0.01). New biomaterials developed should be based on these elements. The materials would be compatible with the human body [22-25].

BIOMATERIALS’ MANUFACTURING AND MARKET

Research and innovation in developing new biomaterials is an interdisciplinary effort. The activities often involve collaboration among materials scientists, chemical engineering, chemistry, physics, mechanical engineering, biomedical engineers, electrical engineering, biology, biotechnology, medicine, pharmacy, pathologists, mathematics, and computer modelling, and clinicians to find solutions or solve clinical problems. Biomaterial processing is a crucial stage that involves thermal, mechanical, and chemical treatment of the source biomaterials to be developed into a biocompatible and bioactive product for specific clinical applications. Manufacturing and processing are becoming increasingly important for biomaterials, bioinspired materials, and biological materials.

Biomaterial processing techniques can be divided according to the form of the base material used as well as the form and shape of the end products for medical and pharmacy applications. The most common methods for forming ceramics include extrusion, slip casting, pressing, tape casting and injection moulding or hot wax moulding. Casting, cutting, drawing, extrusion, folding, forging, machining, punching, shearing, stamping, and welding are the most used processes for fabricating metal materials. Polymer processing involves forming either thermoset or thermoplastic polymer materials usually by moulding but also by subtractive methods, such as machining. Various moulding methods, such as extrusion, calendaring, coating, compression, blow, rotational, transfer, and injection moulding, are the most used for polymer material fabrication. Thermoforming is another processing technique for polymer materials. Hand lay-up, spray-up, resin transfer moulding, vacuum-assisted resin transfer moulding, resin film infusion, compression moulding, injection moulding, filament winding, centrifugal casting, pultrusion, hybrid injection-moulding/thermoforming, automated fiber placement, and autoclave are the processing methods that have been utilized in composite manufacturing. However, the selection of a processing method will base on the base material, form and shape of the end products and applications. Porous structures can be obtained by using the foaming process or particle leaching technique. Solvent casting and melt spinning are also suitable methods to produce biomedical devices, provided that the residual solvent amount is below the minimum value. Solvent casting, particulate leaching and electrospinning, sintering, plotting and filament winding can be used for biocomposite materials.

Besides the above processing techniques, several other processing methods for biomaterials have also been considered, including additive manufacturing techniques (three-dimensional (3D) printing), advanced manufacturing techniques, such as freeze casting, and advanced materials processing methods based on microwaves and light. These techniques allow for increasing degrees of complexity, which is particularly helpful to mimic structures observed in natural materials. However, since biomaterials and biological materials require the use of material classes and often have additional requirements, such as biocompatibility, significant research is required to implement these new manufacturing techniques.

Electrospinning

The electrospinning process has gained great attention in the last decade for spinning a wide range of polymeric fibers at micro to nanosize. In the electrospinning process, an electrostatic force is used to spin polymer solution or melts to produce fine fibers ranging from nanometer to micrometer [26, 27]. One of the main advantages of the electrospinning technique is its versatility of processing to create fibers with multiple arrangements and morphological structures, and the diameter of these fibers typically ranges between tens of nanometres to a few micrometres. The most basic setup for this technique is shown in Fig. (2) [28-30]. Electrospinning has been applied to many natural and synthetic polymers, including polylactic acid, polyurethanes, silk fibroin, collagen, hyaluronic, polycaprolactone, acid, cellulose, and chitosan collagen for the development of scaffolds for tissue engineering [31].

Fig. (2))

The schematic diagram of setting up of the electrospinning process; horizontal setup (left) and vertical setup (right).

Additive Manufacturing

Recently, the rise in digital fabrication techniques, such as additive manufacturing, has enabled the exploitation of geometrical biomaterials. Additive manufacturing or 3D printing is a material´s processing approach to create parts or prototypes layer-by-layer directly from a computer-aided design. Though not immediate, what is more interesting is the possibility of biomaterials that respond to bioactive stimuli that can be used to activate genes in a preventative treatment to maintain the health of tissues as people age. Biomaterials are used in medical devices, pharmacy, and different parts of the human body, such as artificial valves in the heart, stents in blood vessels, replacement implants in the shoulders, knees, hips, elbows, ears, and orthodontics structures. 3D printing or larger additive manufacturing has got attention in scaffold design and manufacturing for tissue engineering applications. However, there are several challenges for 3D printing, such as vascularization and printing-related problems; further research on the development of bio-inks, integration of different 3D bioprinting technologies, improvement of the mechanical properties of existing biomaterials, and biomaterials’ biocompatibility needs to be improved.

The global biomaterials’ market size was USD 35.5 billion in 2020. The biomaterials’ market is projected to reach USD 47.5 billion by 2025, at a compound annual growth rate of 6.0% during the forecast period. Several factors, such as the increased funds and grants by government bodies worldwide for the development of novel biomaterials, rising demand for medical implants, the rising incidence of cardiovascular diseases, and increasing research on regenerative medicine drive the biomaterials’ market growth. In addition, high growth is expected for plastic surgery and wound healing applications, which will further drive the growth of the biomaterials’ market in the coming years [32]. The global implantable biomaterials’ market is expected to grow from $103.9 billion in 2020 to $114.35 billion in 2021 at a compound annual growth rate of 10.1% [33].

CONCLUSION

Biomaterials can be multidisciplinary in all fields of science. A biomaterial helps to improve the quality of life and longevity of humans. Over the last decades, it has become clear that the demand for biomaterials has increased rapidly due to the aging population that occurs in practically all the countries of the world, with the elderly being at higher risk of hard tissue insufficiency. With the current progress in biomaterials, we expect that future healthcare will be available at an affordable price and with better services. In addition, nanotechnology and nanomedicine have attracted a great deal of attention, which would further enhance the use of biomaterials in medical devices and pharmacy. Biomaterials must meet several criteria, such as excellent biocompatibility, adequate mechanical performance, high corrosion, and wear resistance. Research is being performed to improve the existing methods and for the development of new approaches. Bioengineering is one of the most viable options with the potential to improve the existing healthcare scenario. However, the use of biomaterials must follow the regulation of government organizations, which vary from country to country.

CONSENT FOR PUBLICATION

Not applicable.

CONFLICT OF INTEREST

The author declares no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENT

Declared none.

REFERENCES

Material Synthesis, Structures and Characterization

Luis Alberto Camacho Cruz¹, Marlene Alejandra Velazco Medel¹, Luis Ramón Ortega Valdovinos², Angélica Cruz Gómez¹, Emilio Bucio¹, *

¹ Department of Radiation Chemistry and Radiochemistry, Institute of Nuclear Sciences, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico

² Faculty of Chemistry, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico

Abstract

Polymers have been employed for the development of medical devices and implants as some of them are biocompatible. Synthetic procedures and extraction techniques have allowed the obtention of different polymers, classified in this chapter as synthetic and natural polymers. In the process of synthesis of the polymer, its properties can be modulated to obtain more flexible or thermostable materials, non-toxic or transparent, depending on the desired properties of the final product. A wide range of polymers have been used for the manufacturing