Nanomaterials and Their Biomedical Applications

Nanotechnology offers a significant advantage in science, engineering, medicine, medical surgery, foods, packing, clothes, robotics, and computing from the beginning of the twenty-first century. As the potential scientific discovery always contains some good and bad effects on human civilization and the environment, nanotechnology is not an exception. The major drawbacks include economic disruption along with imposing threats to security, privacy, health, and environment. The introduction of the chapter discusses the historical background of nanotechnology. Later it also discusses the advancement of nanotechnology to date with its benefits. Major drawbacks of nanotechnology arise in human health due to the enormous involvement in medicine, food, agriculture, etc. This chapter also deals with environmental nano pollution and its effect on society, highlighting the social-economic disruption due to the rapid use of nanotechnology. Nano pollution affects not only human beings but also other living beings like microorganisms, animals and plants, which are briefly reviewed. This chapter also demonstrates the safety and security of nanotechnological developments, current policy and regulation status, challenges, and future trends. Finally, it is concluded, while nanotechnology offers more efficient power sources, faster and modern computers and technologies, life-saving medical treatments, but due to some negative impacts, it bounds us to think twice before any further advanced technological applications.

Metallic nanoparticles have found various biomedical applications due to their intrinsic physicochemical properties. As the size decreases, the high surface area of particles gives rise to distinctive features, which are entirely different from that of a macro-sized structure. Several methods are involved in synthesizing metallic nanoparticles, and in general, it can be categorized into either bottom-up or top-down approaches. The top-down method consists of cutting down the bulk materials into nano-sized particles through physical, chemical, or mechanical treatments, whereas, in a bottom-up approach, nanoparticles are formed by joining individual atoms or molecules. The top-down approach produces metallic nanoparticles in naked form, which can further agglomerate and hence not suitable for biomedical applications. The bottom-up approach involves solid-state, liquid state, gas phase, biological, microfluidic-technology based, and other methods. Chemical reduction in the bottom-up approach is the most common method of metallic nanoparticle synthesis, which is flexible, simpler, inexpensive, and produces particles in homogenous form. Recently biological method of nanoparticle synthesis has become popular due to its toxic-free nature, inexpensiveness, sustainability, and eco-friendly. In this chapter, we describe the top-down and bottom-up approach and current trends in the synthesis of metallic nanoparticles for biomedical purposes. Further, it explains how the parameters can be tuned to get metallic nanoparticles with the desired shape, size, morphology, composition and crystallinity.

Structure dependent (size and shape) properties are fundamental to nanoscience and technology. Metal oxide nanomaterials (MONMs) are considered suitable for a variety of chemical and biological applications due to their stability. Preparation of oxide NMs does not require energy-intensive methods to protect their surface nature as compared to metallic counterparts. Size and shape are controlled by alternations in the reaction parameters such as temperature, concentration, method of preparation, and utilization of small quantities of surfactant materials. Normal wet chemical approach is extremely cheaper, hydrothermal methods are excellent for preparing uniform shape NMs, and recent atmospheric pressure plasma assisted approaches are powerful for obtaining one-dimensional structures which are usually difficult by following other techniques. The MONMs are considered an excellent system for anti-bacterial and biomedical applications. This chapter deals with definitions of NMs, suggested growth and nucleation theories, different preparation methods for obtaining powder MONMs, characterization techniques, and MONMs usage in different biomedical applications. In addition, mechanism of interaction between NMs and internal structures of micro-organisms and various institutes working on the NMs standardization are discussed.

Medical implants are developed to replace the diseased or fractured hard and soft tissues. Materials scientist and clinicians initially opted for materials which exhibited high strength, non-toxic behaviour and inert as they are not any rejection by the human body. However, with time, the failures of these materials were encountered as their properties were not close to that of human tissues (Sakka and Coulthard in Med Oral Patol Oral Cir Bucal 16:e42–e44, 2011). Developing the right environment for cells to grow with the necessary biomolecules is the major focus and to achieve this scaffolds are being developed with various materials ranging from polymers to ceramics using different processes. Advancements in characterization techniques has thrown more light on the structure of human tissues and bone. Studies have shown that the unique properties of bone were attributed to its micro/nanostructures formed by the nanostructured collagen and apatite crystals (Palmer et al. in Chem Rev 108:4754–4783, 2008; Perez et al. in J Tissue Eng Regen Med 7:353–361, 2013). In order to mimic the bone, materials were modified at micro/nano level both at the bulk and surface level. Studies have also revealed that materials with nanograins have superior osseointegration capability when compared to conventional micron materials (Thakral et al. in J Clin Diagn Res 8:ZE07–ZE10, 2014). Surface characteristics such as surface chemistry, topography, roughness, stiffness and surface charge influenced the biocompatibility [Ferrari et al. in Colloids Interfaces 3:48, 2019). This understanding led to development of several nanomaterials for biomedical applications. In the case of metals, several processing techniques were developed to form nano grained materials, whereas, in polymers, various nanofibers were prepared and tested for their bioactivity. This chapter presents some of the important surface properties and their influence on the biocompatibility and describes the effect of nano versus micron surfaces on the cellular attachment.

Further, nanofibers development on polymers has enhanced the scope for fabricating scaffolds that can potentially mimic the architecture of natural human tissue at the nanometer scale (Vasita and Katti in Int J Nanomedicine 1:15–30, 2006). The biomimicry by nanofibers made from biocompatible polymers has opened novel and innovative therapeutic avenues in the area of tissue regeneration. In recent years, a plethora of bio-nanofibers has been fabricated to imitate the natural extracellular matrix for cartilage tissue engineering. Nanofibers have broadened their horizons in the past five years for potential biomedical applications from triaxial fibers to electrospinning of drug-loaded polymer and ceramic composites (Kiran et al. in Ceram Int 45:18710–18720, 2019). However, the effect of surface topology on stem cells for cartilage regeneration and the biophysics involved in the stress distribution of nanofibers needs to be elucidated. Apart from this, the fine-tuning of metallic implant surfaces for enhanced chondro-integration and antibacterial activity is a need of the hour and clear understanding towards the sensitivity of various surface characteristics is also needed. Various modifications on the surface of metallic implants are done using different chemical and physical modification techniques. The commonly used techniques are anodization, laser texturing, hydrothermal treatments and sand blasting (Vishnu et al. in Nanomedicine Nanotechnology, Biol Med 20, 2019; Manivasagam and Popat in ACS Omega 5:8108–8120, 2020). Studies have shown that these modification have enhanced suitability for the implant material for the chondrocyte conduction by providing the necessary roughness and surface chemistry in the nanoscale level. Hence, in this chapter, a detailed discussion about different synthesis routes associated with nanofibers’ development for cartilage regeneration will be discussed. Along with this, the fabrication and effect of nanosurfaces on metallic implants for enhanced chondrocyte conductivity will also be highlighted.

Nanoceramics are ultrafine particles with particle size less than 100 nm and have greater advantages over macroscale ceramics which are brittle and rigid. They are inorganic, metallic and non-metallic compounds that have high heat resistance. Their small particle size offers them unique properties which have led to their widespread use in various fields. Their improved properties include bioactivity, dielectricity, ferromagnetism, piezoelectricity, magnetoresistance and superconductivity. Hardness and strength of ceramics are greatly improved by reducing their particle size to be in the nanoscale. Nanoceramics can be conveniently prepared by various physical and chemical methods in various sizes and shapes such as nanoparticles, nanorods, nanotubes, nanoribbons, nanosheets and nanofluids which determines their properties. Characterization of nanoceramics can be carried out by surface characterization methods such as X-ray diffraction analysis, Infrared spectroscopy, Scanning electron Microscopy, Transmission Electron Microscopy, Atomic Force Microscopy, etc. Nanoceramic particles can be used for bone repair, drug delivery, energy supply and storage, communication, transportation systems and construction. The current article discusses in detail the nanoceramics, their preparation methods, various characterization techniques, their unique properties and their application in the biomedical field arising due to their excellent properties.

Nanomaterials are the solid colloidal particles in size ranging from 1 to 100 nm. Nanomaterials provide novel physicochemical properties with the increased surface to volume ratio from their bulk particles. Over the last two decades, several nanomaterials have been engineered precisely for their applications in diagnosis, targeted drug delivery, bio-imaging, biosensors, and also in therapeutics. Since the discovery of carbon allotropes, carbon-based nanomaterials have become important in the field of biomedicine due to their unique physio-chemical properties, high mechanical strength, and optical properties. In this chapter, carbon-based nanomaterials such as Nanodiamonds (NDs), Carbon nanotubes (CNTs), Buckminsterfullerene (C₆₀), Carbon quantum dots (CQDs), Carbon nanohorns (CNs) and its biomedical applications are described briefly. These nanoparticles allow the diagnosis and detection at the molecular scale with the addition of fluorescent probes. They provide more specificity and sensitivity in bio-imaging in drug delivery and cancer treatment.

Calcium phosphate (CaP)-based bioceramics are widely used in orthopedics and dentistry for bone regeneration due to their good biocompatibility, osseointegration and osteoconduction. Synthetic hydroxyapatite (HAp) is the most widely used bioceramic coating in biomedical implants as it has a chemical composition similar to that of the bone. The properties of the coating depend on the nature of powders and in turn on the source of the powders. Hydroxyapatite powders can be prepared by a variety of chemical routes like co-precipitation, hydrothermal, sol-gel, solution combustion, etc. Among these methods, the solution combustion method is promising as it is a single step, cost-effective and energy-efficient process and yields high purity ceramic powders compared to conventional multi-step wet chemical processes. This method can also yield powders in nano and micron size range and can be used for the fabrication of coatings using methods like plasma spraying, suspension plasma spraying, electrophoretic deposition, etc. This chapter gives an overview of the solution combustion synthesis of pure and doped hydroxyapatite powders and their characterization. The last section of this chapter discusses the solution combustion synthesis of plasma sprayable hydroxyapatite powder, fabrication of HAp coating and characterization of the developed plasma-sprayed coating.

For decades, man has explored the cures for many diseases and illnesses. Scientists now believe that nanotechnology can perform that miracle. Nanomaterials in medicine are an attempt to limit or reverse pathological processes, and its advantages are due to their specific characteristics, such as the capacity to interact with biological systems with a high degree of specificity. The ultimate goal of nanomedicine is to identify and treat diseases as early as possible at the subcellular level. The application of nanotechnology in medicine ranges from diagnostics to therapeutics. In diagnostic imaging, nanomaterials are used to target a specific type of cancer cell, which would enable radiologists to visualize insignificant features at a better resolution possible. Moreover, nanomaterials are thought to stimulate and interact with target cells and tissues in controlled ways and to induce desired physiological responses with minimal side effects. Nanomedicine researchers developed an assay for early diagnosis of Alzheimer’s disease with better accuracy and sensitivity than conventional methods. This new assay uses gold nanoparticles (NP) and magnetic microparticles (MMP) to bind to the biomarkers of Alzheimer’s disease. Physicians use nanoparticles to target drugs at the source of the infection, thereby increasing the efficiency and minimizing the side effects. Nanoparticles are also used to stimulate the body’s innate repair mechanisms by artificially activating and controlling the adult stem cells. To promote neuronal repair and regeneration, researchers use bio-reactive nanoscaffolding. In this chapter, we will explore how nanomaterials are used in medicine and its prospects.

Hydrogels are three dimensional (3D) cross-linked polymer networks capable of holding a large volume of water. The hydrophilic polymeric system sometimes exists as a colloidal gel inside water, i.e., dispersion medium. Hydrogels aim to mimic the 3D microenvironment of cells with the advantage of surpassing adverse gastrointestinal effects on the drug, therefore increasing patient compliance. This polymer-based hydrogel formulation has tunable properties such as porosity, tensile strength, drug loading capacity, and release kinetics that contribute towards better biocompatible hydrogel design. The monomeric units in hydrogels bind through physical and chemical forces such as hydrophobic interaction, hydrogen bonding, UV crosslinking, and many others. Albeit hydrogel is known for its water holding capacity and high biocompatibility, the cytotoxicity of hydrogel depends on the polymer selection. Deformable and injectable hydrogels that can alter its physical state in room and body temperature are in the research pipeline to avoid surgery for implantation. Further, environmental stimuli-responsive hydrogels like pH, temperature-sensitive hydrogels are evolving as ‘Smart drug delivery’ systems. This distinctive property of tunable hydrogel design and formulation finds its application in sustained and localized drug delivery. This chapter discusses the different classifications of the hydrogel, along with its crosslinking chemistry involved. We also have summarised various forms of hydrogel from lab scale to industrial level. Finally, this chapter also covers the synthesis, functionalization, tailoring mechanism of the hydrogel matrix, followed by in vitro, ex vivo, and in vivo characterization and drug loading/delivery efficiency.

Certain medicines and therapies have emerged for the treatment of different ailments. But in many cases, they have poor solubility, lower bioavailability, inability to cross the blood-brain barrier (BBB), and drug resistance. It becomes essential to establish standard treatment systems for overcoming such challenges. In this connection, the nanomaterial application in medicine and pharmaceuticals has rapidly gained interest with revolutionary prospects. The idea of nano-carriers first observed in a biological system consisting of nanoparticles is committed to locomotory function and protein cargos like importin, exportin. This observation led to the development of biomimetic nanomaterials for drug delivery. The synthesized nanomaterials exhibit useful properties such as large surface area, maximum bioavailability, reduced toxicity, high specificity along with enhanced permeability and retention (EPR) effect. These properties contribute to enhancing the efficacy of drugs having short half-lives, monitoring drugs for sustained release, enhancing the rate of dissolution of drugs, and reducing required dosage volume. Thus, increased therapeutic action and fewer side effects are to improve the quality of human life. Currently, many nano-carriers such as niosomes, dendrimers, fullerene, polymer-based nanoparticles, micelle, liposomes, hydrogels, metallic, mesoporous silica, quantum dots, etc. show potential for better drug delivery systems. These help in carrying entities like drug molecules, DNA/RNA, proteins, viruses, cell receptor sites, lipid bilayers, and variable antibody region for drug delivery in therapeutics. Such nano-therapeutics and diagnostics will unfold the secrets of human longevity and help reduce human illness, including cardiovascular disease, genetic disorder, immunodeficiency, cancer, and even viral infections. This chapter highlights recent advancements and applications of nano-carriers for drug delivery in medicine, especially wound healing therapeutics. It also discusses different approaches to enhance drug cargo capacity, improve cell delivery efficiency, to avoid host immune systems, and to achieve specific cell targeting.

Nanotechnology has spread worldwide because of its wide applications, in particular with its novel and unique properties. Various kinds of nanomaterials have been investigated as their properties are mainly dependent on the size, shape, and composition of the materials, widely applied in the biomedical field. Various biomedical devices like dental implants made of Ti, Mg, Co, etc. surgically placed in the jawbone where the teeth are absent. The hip joint implant is carried out by surgical procedures through a replacement of a prosthetic implant. Cardiovascular implants include pacemakers of artificial heart valves or prosthetic implants, stents implanted inside the body etc. Furthermore, in this chapter, we will discuss more on the general consideration of using nanomaterials in implantable devices, dental implants/prosthodontics, spinal, orthopaedic implants, hip and knee replacements, cardiovascular implants and others—phakic intraocular lens and cosmetic implants.

The field of tissue engineering is rapidly growing nowadays, and the development of the bio-functional scaffolds to mimic the natural environment of the body tissue to replace the damaged or diseased tissues. Use of nanomaterials to develop nanostructured biomaterial scaffolds showing enhanced biological functions than microstructured materials. Nanostructured materials have higher surface area and biomimetic nature, hence allow better cell adhesion than conventional materials, which is needed for materials used for tissue engineering applications. Unlike conventional materials, nanomaterials mimic resembling natural extracellular matrix (ECM) to support better protein adsorption and also stimulate enhanced tissue regeneration. Here, we address different categories of biomaterials used to fabricating nanostructured scaffolds for tissue regeneration applications. The desired properties required for various tissue engineering scaffolds and its methods of fabrication, current development, and future directions of these methodologies are discussed. In addition to that, the special emphasis is given on bone tissue engineering and three dimensional (3D printing) technologies to manufacture tissue engineering scaffolds using various nanomaterials are also discussed in this chapter.

Pre-clinical imaging is a technique that could help in investigating deep inside the rodents to obtain information regarding disease site and drug development process using a non-invasive approach. Diverse FDA approved contrast agents have been implemented since the evolution of these imaging technologies. The current limitations of these contrast agents include faster clearance and photo instability and could be unsuitable for multi-modal and hybrid imaging. These impediments can be overcome with the aid of developing new nanotechnology-based contrast agents. This opens up a new paradigm for researchers to visualize cancer to obtain nanomolecular information. During the past two decades, nano-based contrast agents have revolutionized pre-clinical imaging science, which offers to detect cancers early, rapidly, and effectively. Despite the fact, the concept and technology of imaging are old, the way we look at the disease using nanomaterials in a different perspective. Additionally, the imaging techniques combined with nanotechnology-based contrast agents can be used to investigate the interaction of drugs at a pre-clinical stage and the cellular level. Pre-clinical imaging is performed with two different strategies. The former techniques give anatomical information, which includes computed tomography, magnetic resonance imaging, and ultrasound. While the latter presents molecular information using optical techniques, photon-acoustic imaging, and positron emission tomography. Recent developments in nanotechnology-based contrast agents have opened new avenues to alter and improve the current imaging modalities resulting in hybrid and multi-modal imaging approaches. Here, we intend to provide fundamental knowledge and general considerations of using nanomaterials in pre-clinical imaging modalities. This chapter provides extensive information about the advancements in nanomaterials for pre-clinical imaging applications. In the later part, we discuss the science behind individual nanomaterials with different imaging systems and its improvements in pre-clinical imaging. Also, the advantages and drawbacks associated with nanomaterials are presented. Finally, we discuss the application of different nano-based contrast agents and their application in biomedical imaging.

A solid substance is considered as a nanomaterial if it has at least one face in the dimension range of 1–100 nm. Nanomaterials, because of their small size and exceptionally high surface area, display electromagnetic, optical, and piezoelectric properties, and have enormous applications in various fields such as wastewater treatment, oil, and gas industry, energy storage, bio-imaging, and healthcare diagnostics and treatment. Nanomaterials provide flexibility to the sensing platforms and also even allow mobility between various detection techniques. In the last few decades, many nanomaterials have been developed for various applications, and considerable interest has been gained in the field of medical diagnosis and therapy in recent years. The innovations in nanomaterial preparation and their modifications have led to the development of devices and assays used for biomedical applications, which are faster, less expensive, accurate, and sensitive. Despite having excellent material properties, many nanomaterials are affected by the lack of surface heterogenic reactivity, which is critical for the surface immobilization of essential biomarkers. Thus the nanomaterials need to go through surface modifications to improve the adsorption capacity of biomolecules to the functionalized surface. In this chapter, various surface modifications of nanomaterials, including metallic nanoparticles, carbon nanomaterials, nanoceramics, and self-assembled materials, have been discussed for various applications in general and more attention has been given to biomedical applications in particular.

Laser processing is one of the precise techniques to achieve functional surfaces with micro/nanostructures on metallic materials. The controlled laser-induced structures on metallic implants significantly alter the mechanical properties, chemical stability, and bioactivity. Therefore, the present chapter emphasizes the recent research works on laser processing such as selective laser melting (SLM), laser surface melting (LSM), laser surface patterning of various metallic implant materials. The surface characteristics, and biomedical applications of processed surfaces are summarized. Various textures from micron to the nanometer-scale on permanent and degradable implants produced using high energy pulsed lasers enhanced the biomineralization and cell proliferation behaviors. Furthermore, the laser micro/nanotextured surfaces with different surface roughness and chemical composition improved the antibacterial activity of the implants, and also directed the cell attachment depending on the size/nature of the nanostructures. The femtosecond laser was used to develop the laser-induced periodic surface structure (LIPSS) on titanium alloys. The surface-enhanced Raman scattering (SERS) response of adsorbed biomolecules and fluorescence enhancement on the hierarchical LIPSS surfaces for clinical applications are also discussed.

Nanostructured metallic materials are progressively investigated for numerous biomedical implant applications due to their superior mechanical properties, biocompatibility and, ability to promote cell adhesion and proliferation. Several materials processing routes have been explored to prepare bulk and surface nanostructured metals/alloys. Surface nanostructuring by changing the surface chemistry through deposition or diffusion processes is limited by porosity and contamination besides uncertainty in achieving a good bonding between substrate and coating. The surface nanostructuring process must enable an improvement in the overall properties of materials such as high hardness and strength, higher thermal expansion coefficient, improved tribological properties, and better fatigue properties, etc., to avoid premature failure of implant materials. In this perspective, surface severe plastic deformation (S²PD) processes assume significance as they could impart the desired characteristics to a variety of metals and alloys by grain refinement mechanism, without changing the overall composition and/or phases present in the material. The improvement in properties is fundamentally derived from grain refinement mechanism by the introduction of a large amount of defects/strain. Surface mechanical attrition treatment (SMAT) is an effective way of inducing localized plastic deformation (S²PD method) that results in grain refinement down to nanometer scale without changing the chemical composition of the material. It is a very promising method to produce functionally gradient materials, in which the nanocrystalline surface layer provides suitable surface properties while the coarse-grained matrix provides the ductility. SMAT provides desirable surface topography and increases the average surface roughness. The surface topography of materials determines its hydrophilic or hydrophobic nature. For implants, a hydrophilic surface is considered to be more desirable than a hydrophobic one because of its better interaction with biological fluids, cells, and tissues. In addition, generating the desired surface topography could provide significant enhancement in osteoblast adhesion, proliferation, maturation, and mineralization. SMAT decreases the grain size, induces compressive residual stress, microstrain, defects/dislocations, and phase transformation, all of which enable a significant improvement in hardness, fatigue resistance, and tribological properties of materials. In addition, the extent of grain refinement, extent of deformation, extent of change in surface roughness, phase transformation, residual stress, microstrain, and defect/dislocation density could influence the performance of materials subjected to SMAT. This could ultimately influence the biological performance of the implant materials. The present chapter aims to provide detailed coverage of SMAT of stainless steel, Ti alloys, Ni-Ti alloy, CoCrMo alloy, and how the nanostructured surface enables an improvement in the characteristic properties that are suitable for biomedical applications.

Self-organized vertically aligned nanostructures grown on metallic substrates via anodization have attracted significant scientific attention for a wide range of applications. These nanotubular structures integrate highly controllable geometry at the nanoscale with fascinating biological and mechanical properties. This chapter attempts to cover the key electrochemical factors that control the tube geometry and also demonstrate various surface functionalization approaches for modifying the surface properties of TiO₂ nanotubes to develop new and pioneering functional biomaterials for biomedical applications. Furthermore, the anodization parameters that have led to the formation of nanotubes on various titanium alloys were also discussed.