Metallic orthopedic implants have been widely used to repair skeletal defects and poorly functioning joints for many years. Among them, titanium (Ti) and its alloys can be described as the most frequently used orthopedic metals, due to their unique properties, such as a good mechanical match with hard tissues, resistance to corrosion in body fluids, and being lightweight. However, Ti and its alloys fail to show bioactivity which is a very important issue for the integration of implants with bone tissue. Therefore, hydroxyapatite [HA, Ca₁₀(PO₄)₆(OH)₂], which is the main constituent of the inorganic part of natural bone, has been traditionally used as a coating to achieve the promoted bioactivity on the metallic implant surfaces. There are various techniques for coating HA on metallic implants such as plasma spraying, electrodeposition, pulsed-laser deposition, sputtering, sol-gel, and biomimetics. Simulated body fluid (SBF) used in biomimetic calcium phosphate (CaP) coatings basically mimics the inorganic composition, pH, and temperature of normal human blood plasma. Normally, a Ti alloy implant can be biomimetically coated in 14-28 days depending on the desired coating thickness if SBF solution is replenished every 2 days. Therefore, more concentrated formulations of SBF such as 1.5x SBF, 5x SBF, and 10x SBF were suggested for faster deposition rates with a drawback of decreased solution stability. To deposit CaPs on Ti alloy substrates, there are many different formulations of SBF with varying ionic compositions of certain ions, such as chloride (Cl^-), bicarbonate (HCO₃ ^-), and sulfate (SO₄ ^2-), and with different buffers such as tri(hydroxymethyl)aminomethane (TRIS) and Hank's balanced salt solution (HEPES). In recent studies, it was shown that it is also possible to coat CaPs doped with specific ions or loaded with antibacterial agents and bone stimulating factors via biomimetic routes.

The failure incidents of orthopedic implants originate from many reasons, for example, the wear corrosion, fibroblast encapsulation, allergic reaction to metal materials, and infection. To minimize these failures, surface modifications of biomaterials have been widely used. Among those, electroplating is one of the methods that are the most convenient, cheap, and environmental friendly. Currently, the electroplating method is used to coat several types of nanomaterials, such as hydroxyapatite (HA), gold, carbon nanotubes, and graphene oxide, on orthopedic implants. This method shows a high capability to replace patient bone fractures with new bone for long-term use. This chapter reviews the current solutions and examples of practical ideas in the area of surface coating using electrodeposition for improving bone implants.

The emergence of carbon-based nanomaterials has changed many aspects of industry and academia, often in revolutionary ways. Carbon-based nanomaterials have found an increasingly wide utilization in numerous and diverse fields since the 1990s such as physics, electronics, optics, mechanics, biology and medicine. The carbon-based nanomaterials are of great promise for biomedical applications due to their unique characteristics. For example, carbon-based nanomaterials are the same scale as some biological components, such as collagen, allowing them to be used to form biomimetic structures. The ultrahigh mechanical strength and conductivity are also attractive in some biomedical applications. In this chapter, the use of carbon-based nanomaterials in the biomedical field is covered from fabrication and design methods to applications and toxicity analysis. First, the common existing forms of carbon on the nanoscale will be summarized, and the unique properties and fabrication methods of different carbon-based nanomaterials will be introduced. Second, how to modify or design carbon-based nanomaterials when one intends to use these materials for biomedical applications will be investigated, as well as common design and modification methods. Third, some potential applications of carbonbased nanomaterials and the performance of these materials in those applications will be shown, in addition to their toxicity concerns. Lastly, a summary and outlook of the carbon-based nanobiomaterials will be given based on the data presented in the chapter.

There are a large number of people suffering from organ or tissue loss due to injury, infection, or disease. Currently, major approaches to solve this problem are surgical reconstruction, transplantation, or the use of prosthesis. Although these therapies have saved and improved countless lives, they remain imperfect solutions due to the occurrence of infection, chronic irritation, donor shortages, tissue rejection, and longer term complications such as the development of malignant tumors. Tissue engineering, the development of cell seeded three-dimensional (3D) biomaterials for introduction to the defect area, is a potential solution for the problems mentioned above. Mesenchymal stem cells (MSCs) such as bone marrow MSCs (BMMSCs) and adipose derived stem cells are widely being used for clinical applications in regenerative medicine. Stem cells from umbilical cord, synovium, and dental tissues have also been started to be used for the same purposes. The use of stem cells for promoting the biologic potential of scaffolds in tissue engineering, especially bone and cartilage tissue regeneration, has gained interest within last 10 years. Stem cell delivery has a potential as an effective treatment alternative for cartilage and bone defects with an impaired healing.

Tissue engineering (TE) has made stark advancements through a greater understanding of the effects of various biomaterials on cell behavior and mediated tissue formation. Human tissue can be readily classified as a nanocomposite owing to the presence of nanoscale organic and/or inorganic constituents found within the extracellular matrix. Research has begun and continues to leverage this understanding in an effort to fabricate more biomimetic nanobiomaterials, which share similar composition and morphology to native tissue components. In addition, novel three-dimension (3D) scaffold manufacturing techniques are being developed to extend the use of these novel materials toward the development of clinically relevant scaffolds exhibiting not only similar composition, but spatial distribution of tissue-specific extracellular components. Interfacial and complex tissue regeneration applications including those related to osteochondral (bone-cartilage interface) regeneration stand to benefit greatly from these advancements. Through the course of this chapter we will explore the most recent developments in nanobiomaterials for osteochondral tissue as well as introduce and discuss 3D bioprinting platforms and techniques for the fabrication of biomimetic scaffolds.

The extracellular matrix (ECM) consists of a complex three-dimensional (3D) fibrous network with a wide variety of fibers and pores, which presents complex biochemical and physical signals. Synthetic biomaterials can be produced from a wide range of materials to form a nanofibrous network similar to collagen in the ECM. Self-assembly is a powerful technique to design and synthesize dynamic complex structures at the nanoscale with atomic control due to noncovalent interactions between the molecules. Self-assembled peptide nanostructures consisting of chemical and physical properties related to the ECM can be used for regenerative medicine and drug delivery applications. Therefore, the self-assembled peptide nanostructure hydrogels have capacity to form a bioactive environment such as biocompatibility, biodegradability, and low toxicity for biomedical applications. The focus of this chapter is on the self-assembled peptide hydrogel synthesis and their applications for tissue engineering and regenerative medicine.

Medical device related infections account for almost 64% of all hospital acquired infections. Even with sterile conditions and handling, infection occurs when the bacteria encounters the patients' protein, and usually leads to biofilm formation. The major infection players are Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa. Some of the bacteria had become resistant to certain widely used antibiotics, but there is also a danger of them becoming multidrug resistant organisms, especially S. aureus. One way of combating these infections is using nanoparticles (NPs) in medical devices. Currently, NPs exhibit promising applications in medical devices to inhibit or prevent these bacterial infections. Some of the NPs are silver bromide (AgBr), metal oxides that include titanium dioxide (TiO₂), zinc oxide (ZnO), Magnetite (Fe₃O₄), and more recently magnesium oxide (MgO). All of these NPs have shown antimicrobial properties against gram-positive and gram-negative bacteria, while TiO₂ and ZnO also exhibit antifungal properties. Even though some NPs (i.e. TiO₂ and ZnO) have toxicity mechanisms against mammalian cells in vitro, they are still promising to be used as coating materials or as components in composites for medical devices to fight infections. This chapter will discuss the properties, characterization, and applications of these NPs for biomedical applications.

Multidrug-resistant (MDR) bacterial infections of deep wounds are hard to be treated. Physical antimicrobial agents can be used to remove bacteria from superficial wounds, but are less effective in removing bacteria deeply buried underneath the dermis. This chapter describes a nanoparticle enhanced X-ray radiation technique that can be used to kill MDR bacteria. Taking Pseudomonas aeruginosa as an example, polyclonal antibody modified bismuth nanoparticles are introduced into bacterial culture to specifically target P. aeruginosa. After washing off uncombined bismuth nanoparticles, the bacteria are irradiated with X-rays, using a setup that mimics a deeply buried wound in humans. Results show that up to 90% of P. aeruginosa are killed in the presence of 200 mg/mL bismuth nanoparticles, whereas only 6% are killed in the absence of bismuth nanoparticles when exposed to 40 kV X-rays for 10 min. The 200 mg/mL bismuth nanoparticles can enhance localized X-ray dose by 35 times higher than the control with no nanoparticles. In addition, no significant harmful effects on human cell lines have been observed with 200 mg/mL bismuth nanoparticles and 10 min of 40 kV X-ray irradiation exposure.

Biomedical device-associated infection is still one of the most serious complications in implant surgeries due to the existence of immune depression in the peri-implant area. Despite considerable research and development efforts, the problem of infections related to biomedical devices and implants persists. Many approaches, which understand the pathogenesis of implant-associated infections, have been applied to prevent infections. Among these approaches, conventional treatment and new nano-based approaches are the skeleton of this chapter. Specifically, current strategies such as systemic and local antibiotic treatment, nonfouling surfaces, utilization of antimicrobial agents and antimicrobial peptides (AMPs), and metal (silver) and metal oxide (zinc oxide) nanoparticles have been explained with advantages and disadvantages for treating infection.

The use of nanomaterials in materials science and engineering has provided the modern world an enhanced inventory of products due to the nanomaterials' unique physicochemical properties. The similar size scale between nanomaterials and biological molecules has opened up many application areas in life sciences such as drug delivery, gene therapy, and tissue engineering. Moreover, the surface and mechanical properties of these novel materials have allowed enhanced biocompatibility and strength. Therefore, they have been extensively investigated for their applications in implants and tissue engineering. The most widely used nanomaterials in these fields are titanium, silver and polymeric nanoparticles, and carbon nanotubes (CNTs). Although these nanomaterials are widely used in the mentioned areas, there is no consensus about their toxicity yet. Therefore, their toxicity should be carefully considered before using these nanomaterials. This chapter aims to summarize the toxicity of nanomaterials used in tissue engineering and implant technology.

This chapter discusses nanomaterial's safety in consumer products from a regulatory perspective. The challenges of risk assessment will be illustrated from four basic aspects, including hazard identification, hazard characterization, exposure assessment, and risk characterization. The technical difficulties in performing a comprehensive physical and chemical characterization of nanomaterials in complex product matrices will be presented. The issues in the toxicity test system, particularly in the assessment of long-term toxic effect and the limitations of the applied methodology in exposure assessment will be investigated. This chapter will also give an overview of the regulatory status in the United States, Europe, and China, and the current approaches that each government agency has adopted in identifying and evaluating the risk associated with the use of nanomaterials.

In order for synthetic materials to be utilized as biomedical implants, their short- or intermediate-term biocompatibility must be validated. However, most biomaterials are not aptly assessed for their ability to successfully interface with the human milieu long-term. To be optimally effective, a biomaterial's state of biocompatibility and tissue integration should increase with time. Yet, the standard for selection of suitable materials today remains primarily bioinertness. In this regard, ceramics are popular because of their perceived stability within the human body. However, complete bioinertness for any material is virtually impossible; and acknowledging this fact is an important first step in the development of better biomedical devices. In this chapter, advanced spectroscopic techniques were employed to delve deep into the performance of several advanced bioceramics used in prosthetic joint implants. In contrast to the conventional notion that these materials are completely bioinert, it was found that surface chemical and structural changes readily occur upon contact with biological fluids. Furthermore, it was discovered that their “non-bioinertness”can be either beneficial or detrimental with respect to long-term reliability. In particular, the peculiar properties of silicon nitride, a non-oxide ceramic, make it a unique candidate for artificial joints and other biomedical devices. In contrast to oxide ceramics, the surface chemistry and mechanical behavior of silicon nitride appear to ideally lead to improved long-term performance.