Chapter 1
Nanobiomaterials: State of the Art

Jing Wang1, Huihua Li2, Lingling Tian3 and Seeram Ramakrishna3,4

1Donghua University, College of Chemistry and Chemical Engineering and Biotechnology, 2999 North Renmin Road, Shanghai, 201620, China

2Jinan University, College of Science and Engineering, Department of Material Science and Engineering, Biomaterial Research Laboratory, 601 Huangpu Road, Guangzhou, 510632, China

3National University of Singapore, Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, 2 Engineering Drive 3, Singapore, 117576, Singapore

4Jinan University, Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), 601 Huangpu Road, Guangzhou, 510632, China

1.1 Introduction

Nanoscience and nanotechnology, an interdisciplinary research activity that deals with sub-nanometer to several hundred nanometer materials, has been developing explosively worldwide in the past decade. Biomaterial is the material used for diagnosis or treatment of disease, evaluation, repair, or replacement of any tissue, organ, or function of the body [1]. Nanobiomaterial - the combination of nanotechnology and biomaterials - has provided great opportunities to improve the preclusion, diagnosis, and treatment of various diseases. Nanobiomaterial, traditionally defined as a special category of biomaterials with constituent or surface sizes not more than 100 nm [2], is a new class of extraordinary materials with unique structures and properties such as mechanical, optical, and electrical compared to bulk traditional materials with microscopic or macroscopic structures. It has been broadly applied in a wide range of biological and biomedical applications such as tissue engineering, drug delivery, imaging and biosensor, and so on. These nanobiomaterials include nanoparticles, nanotubes, nanofibers, and so on.

Although nanobiomaterials have been applied to many aspects of biomedical fields, the accurate interface interaction between cells/tissues and materials is not completely clear. The safety and toxicity of nanobiomaterials have caused extensive concern at both occupational and research levels. Biocompatibility is an essential issue that requires evaluation for a nanobiomaterial under consideration for clinical application. Currently, researches on nanobiomaterials have entered a more comprehensive and systematic stage. The researchers are seeking further understanding of the mechanism behind the biological response to biomaterials and better design of such materials.

The absolute efficiency of nanobiomaterials on the human body has not been confirmed completely and the full benefit of nanobiomaterials cannot be evaluated precisely at this stage. Therefore, it is meaningful to review the current state of the art regarding the application of nanobiomaterials. This chapter provides a discussion on prospective applications of nanobiomaterials in different biomedical fields covering tissue engineering, drug delivery, imaging, and so on. In addition, an overview of the unique properties of nanoscale materials, the assessment of biocompatibility and toxicity, and the future development is also presented.

1.1.1 Properties of Nanobiomaterials

Nanomaterials refer to those materials with constituent components or surface sizes within 1-100 nm in at least one dimension [3], and the definition has been extended to several hundred nanometers today. Nanomaterials possess numerous novel and significantly changed properties, such as mechanical, electrical, magnetic, optical, and others [4], compared to those traditional materials in the micron or larger scales. Firstly, nanomaterials have much larger specific surface area than their conventional forms, which is beneficial to greater biochemical reaction. Secondly, the mechanical properties such as yield strength and ductility are enhanced because of the many mechanisms hinging on their chemistry such as grain boundary sliding and short-range diffusion healing. Thirdly, the nanostructure can lead to novel optical, electrical, and magnetic properties for materials due to the quantum effects playing a prior role in determining the properties and characteristics in nanoscale. In addition, the homogeneousness and purity in ingredient and structure are improved due to reaction or mixture at the molecular and atomic levels. These novel and unique properties enable nanomaterials to be suitable candidates for applications in electronics, medicine, and other fields. Specifically, nanobiomaterials possess some important properties provided by nanoscale structures. First, the chemical properties and structure are similar to the native tissues with nanometer hierarchical components. For example, the collagen fibers and nanosized hydroxyapatite (HA) can mimic the components of bone tissue. Second, researchers can easily identify, handle, and mediate biocomponents because of the comparable size of nanoscale materials to biomolecules and bio-microstructures. At last, it is possible to modify the surface properties of nanostructured materials through advanced techniques [5].

1.1.2 Interaction between Nanobiomaterials and Biological System

The nanometer-scaled functional elements in the biological system determine that the interaction between nanobiomaterials and the biological system is at the molecular level [6], and the understanding of the interactions between them is of great importance. For example, embryonic and adult stem cell behavior can be controlled by modifying the material surface with intrinsic signals (e.g., growth factors and signaling molecules) if the interaction between a particular nanobiomaterial and stem cells could be understood [5, 7]. Up to now, details of the reaction at the interface between nanobiomaterials and biological systems (e.g., cells, blood, and tissues) have not been completely understood. Given the current knowledge, the interaction between cells and biomaterials surface at the cellular and molecular level can be described as the interaction between the binding sites on the surface of the cell membrane and nanobiomaterials. In the physical environment, the interaction between cells and biomaterials is actually the molecular recognition between the receptors on the cell membrane and the ligand on the biomaterials surface, followed by a series of biological specific and nonspecific interactions. The previous researches showed that a sequence of events occur at the interface between biomaterials and cells [8, 9]. Firstly, the proteins in blood and tissue fluids are adsorbed onto the nanomaterial surface and protein desorption also usually occurs in the meantime. Then the tissue cells and/or immunocytes come close to the biomaterials. Next, the matrix proteins released from the biomaterial and specific proteins are adsorbed selectively. Eventually, the cells adhere to the surface of biomaterials and commencement of subsequent cell functions (the proliferation, migration, differentiation, and phagocytosis) occurs. These are a series of host responses toward the nanobiomaterials. Correspondingly, there is also a sequence of material responses to the host such as material decomposition that exists at the interface between cells and nanobiomaterials [9]. These events truly reflect the cytocompatibility and inflammatory/immune host responses that eventually determine the efficiency and safety of nanobiomaterials, which are vital for the successful design and application of nanobiomaterials. Thus, the deep understanding of the interaction between nanobiomaterial surface and cells is the key to clinical application of nanobiomaterials.

The response between cells/tissues and biomaterials can be altered or controlled by the surface properties of materials [3, 10, 11], such as topography, surface chemistry, charge, and energetics, which are closely related to cell or tissue responses [3, 10-16], due to the fact that cells/tissues can recognize the surface properties and synthesis nature of nanobiomaterials both in vitro and in vivo. Surface modification of biomaterials can make specific recognition sites for cellular and molecular responses, which has been widely applied in modulating cell and tissue responses by nanobiomaterials both in vitro and in vivo.

1.1.3 Biocompatibility and Toxicity of Nanobiomaterials

Nanobiomaterials have been applied to tissue engineering applications, and the researches demonstrated that nanobiomaterials can enter the body through different ways [17]. There is a well-developed system called the immune system in the human body which can protect it from invading organisms such as bacteria, viruses, and other parasites. The nanomaterial implanted into the body may be identified as foreign matter and consumed by immune cells. The pathway and route of biomaterial-like particles into the human body rest with the size, even at the nano-level. The agglomeration of nanobiomaterials is one of the vital factors that can affect their toxicity [18]. A research showed that the aggregation of nanoparticles can be problematic and even cancer may be induced because of the shape of nanomaterials [19]. The biocompatibility and toxicity of nanostructured biomaterials are important issues that require investigation for clinical development. For example, the nanoparticles used to deliver drugs to targeted cells can normally traverse the cell membranes and be uptaken by the cells. Moreover, many implants undergo biodegradation in vivo. The effect of degradation on the cells and tissues in the physiological environment should be investigated [20]. The toxicity of nanobiomaterials is...