Biomaterials for Musculoskeletal Regeneration

In this chapter, the importance of implantable biomaterials in bone tissue engineering is introduced. A logical discussion on the use of different primary classes of materials (metals, ceramics, and polymers) as implants follows thereafter. Apart from the use in orthopaedic applications, the use of Ti-alloys in craniofacial, dental and cardiovascular applications has also been highlighted. The idea of developing synthetic composites with the motivation of achieving a better combination of properties than monolithic material is discussed towards the end of this chapter. Several examples of the commercially available biomedical devices are also illustrated to enthuse the readers to realise the scope of translating labscale research on biomaterials development to commercial scale fabrication of implants for musculoskeletal applications.

In this chapter, a number of important terms as well as concepts are defined for the readers to follow subsequent chapters. These terms/concepts are mostly related to cell biology (proteins, eukaryotic /prokaryotic cells, stem cells, cell fate processes, etc.), the biomaterial science (biocompatibility, host response, tissue engineering, etc.), bone tissue engineering (osteoinduction, osteoconduction, osseointegration, implant, scaffold), and antimicrobial properties (bacteriostatic, bactericidal, etc.). The structure if this chapter may appear as a glossary of terms, but it is not. The content of this chapter is primarily meant for non-biologist readers to capture the essence of various terms or concepts beyond formal definitions, so that they do not need to absorb the extensive details of the biological sciences. Some of the fundamental concepts and properties at the interface of Materials Science and Biological Science are also briefly described in this chapter.

The central theme of this book is to discuss the development of synthetic materials in the context of bone tissue engineering applications. From this perspective, the present chapter discusses the hierarchical structural characteristics and functional properties of natural bone. In particular, the complex biological structure of collagen and the crystal structure of hydroxyapatite are discussed with reference to their size and morphology. This chapter also provides a brief overview of the origin of the inherent electrical properties of natural bone with reference to piezoelectricity, pyroelectricity and ferroelectricity behaviour. While reviewing the mechanical properties of natural bone, emphasis has been placed on establishing the microstructure-property correlation. Bone mineralisation dependent fracture resistance properties are also briefly discussed. In order to develop new dental restorative materials, it is imperative to evaluate and understand the structure-property relationships of human teeth. To this end, this chapter closes with a discussion on the microstructure property correlation of natural teeth. In particular, three major structural parts of the human tooth i.e. enamel, dentin and the dentin-enamel junction (DEJ) have been characterized in terms of microstructure, phase analysis and compositional gradient.

The fabrication of implantable biomaterials is an important step and a researcher should have an overall idea of the various important processing approaches used for different classes of materials (metals, ceramics and polymers). In view of the fact that the manufacturing of metallic implants is well established, this chapter starts with a brief discussion of the processing aspects of metallic biomaterials. With reference to the discussion in a preceding chapter, ceramic biomaterials are being widely researched for bone tissue engineering applications due to their outstanding properties like hardness, compression strength and high corrosion resistant properties in body fluid. Additionally, polymers are also being used for soft tissue-engineering applications. It is important to highlight that the properties of ceramics and polymeric biomaterials are sensitive to the processing parameters. From this perspective, the fundamental aspects of the processing of ceramics and polymers are covered in the present chapter. In particular, the mechanisms of the consolidation of powder compacts i.e. the sintering process are discussed with reference to the major variables influencing the neck growth rate. An attempt has been made to illustrate how various parameters can be optimized to achieve densification without grain growth. Some advanced sintering techniques, e.g. spark plasma sintering are also briefly discussed. Concerning polymer processing, the consolidation of polymeric materials via compression molding and injection molding is described. Additionally, other manufacturing methods like extrusion are also mentioned.

In the last two decades, additive manufacturing (AM) has made significant progress towards the fabrication of biomaterials and tissue-engineering constructs. One direction of research is focused on the development of mechanically stable implants with patient-specific sizes/shapes and another direction has been to fabricate tissue-engineered scaffolds with designed porous architecture to facilitate vascularization. Among AM techniques, three dimensional powder printing (3DPP) is suitable for the fabrication of bone related prosthetic devices, while three dimensional plotting (3DPL) is based on the extrusion of biopolymers to create artificial tissues. The central theme of this chapter is to discuss the critical roles played by the binder and powder properties together with the interplay among processing parameters in the context of the physics of binder-material interaction for the fabrication of implants with predefined architecture and structural complexity. Summarising, this chapter encompasses the process and the underlying governing parameters of low temperature additive manufacturing methods.

The reliability of implantable biomaterials in load bearing orthopedic and dental applications significantly depends on their mechanical properties, which should closely match with the neighboring bones. The development of new biomaterials for such applications therefore necessitates attaining application-specific properties requirements as well as an understanding as how to tailor mechanical properties. To this end, one also has to understand the key factors that determine the mechanical properties of materials. Since metallic implants are characterized by a good combination of mechanical strength and toughness, we will here discuss more on ceramics and polymeric biomaterials. It is, however, worthwhile to point out that large elastic modulus of steel or Ti-alloy, as compared to natural bones, cause aseptic loosening, which is widely considered while developing new metallic implants. Since a large number of chapters in this book discuss the development of bioceramic or bioglass implants, the focus in this chapter is the mechanical properties of ceramics. Due to the increase in the applications of polymeric biomaterials, the viscoelastic properties of polymers are also discussed towards the end of this chapter.

In load bearing articulating joints, friction and wear play an important role in determining the durability and long-term performance of implantable biomaterials. In view of this importance, this chapter introduces the theoretical perspective of friction at tribological interfaces experiencing sliding motion. After describing the laws of friction and defining wear, this chapter also discusses some major wear mechanisms of major relevance to biomedical applications, including abrasion, adhesion, fatigue and fretting wear. In particular, many articulating load bearing joints involve fretting wear over small relative displacement amplitudes and therefore, more emphasis is given to the discussion on fretting wear. While a major part of this chapter focuses on the physics of material removal mechanisms at tribocontacts, an effort has also been made to discuss the quantified correlation of material removal with material parameters (hardness, toughness, elastic modulus) as well as operating parameters (load, sliding velocity etc.).

In view of the complex and dynamically changing physiological conditions inside the body of a human patient, the corrosion and degradation of implantable biomaterials is to be critically assessed. In this backdrop, this chapter introduces the fundamental theory of corrosion of metallic implants. Apart from discussing briefly the thermodynamic aspects and kinetic measurement of corrosion induced degradation, some of the basic mechanisms of material removal of some of the potential metallic implants are described. This is followed by an introduction to the basic concepts of the degradation mechanisms of the biodegradable polymers. The degradation mechanisms and kinetics of degradation are also discussed.

As discussed in the introductory chapter of this book, significant research on orthopedic implants focuses on the development of a new generation of biomaterials as hard tissue replacement. In the context of their applications in different anatomical locations, a newly developed biomaterial has to undergo a series of biocompatibility tests to assess any toxic/harmful effect to the host tissues. The biocompatibility testing on synthetic biomaterials includes some or most of the following assessments: cytotoxicity, sensitization, irritation, intracutaneous reactivity, systemic toxicity, subacute and chronic toxicity, genotoxicity, haemocompatibility, carcinogenicity, reproductive or developmental toxicity, biodegradation and mechanical testing. In this chapter, an overview of cytotoxicity and genotoxicity assays is provided together with relevant details related to pre-clinical studies using experimental animals. Prior to pre-clinical testing, relevant biochemical screening assays are to be performed at the cellular and molecular level. A study of the chronic effects, in terms of local and systemic toxicity, becomes the major criterion in the toxicity evaluation of implantable bioceramics. From this broad perspective, this chapter summarizes some of the currently used techniques and knowledge in assessing the cytotoxicity and genotoxicity of implantable biomaterials. To this end, this chapter also discusses some of the case studies related to the cytotoxicity of some bioceramic materials. It also addresses the need to conduct a broad biocompatibility evaluation before claiming the clinical efficacy of any new orthopedic biomaterial. While discussing the in vivo biocompatibility aspect, significant emphasis has been provided to discuss the rationale of specific animal model as well as bone defect models. Also, the ethical issues related to pre-clinical and clinical trials are emphasized.

In this chapter, the fundamental aspects of design and property requirements of 3D scaffolds for hard tissue engineering are discussed. While discussing the low temperature additive manufacturing (3D printing and 3D plotting) of biomedically relevant scaffolds, the critical role played by the process parameters or material compositions towards mechanical and biocompatibility properties (in vivo and in vitro) are demonstrated. Overall, this chapter highlights the need to adopt intelligent structural approaches and targeted application-specific biocompatibility characterization, while fabricating mechanically stable and biologically functionalized 3D tissue equivalents.

Lab research involving new implantable biomaterials often ends up in research publications. Such publications regularly report the fabrication of test samples with regular geometric shapes together with material property measurements and biocompatibility assessments. In spite of continued research on new biomedical materials spanning the last few decades, efforts to develop patient-specific prototypes of such biomaterial devices are rather scarce. This is due to the lack of a translational research initiative across the biomedical scientific community. Also limited is our knowledge of a range of testing of biomedical devices and their components in a closely-simulated physiological environment. In this context, this chapter first discusses the biomechanical aspects of various human anatomical joints of relevance to orthopaedic surgery. In particular, the clinical terms related to joint movement and gait cycle have been introduced. This is followed by a brief description of standard biomechanical testing methodologies of orthopaedic devices, with some emphasis on hip joint simulator experiments. It is envisaged that this chapter will provide a platform for researchers to realise the extensive efforts that one needs to make while developing biomedical device prototypes.

One of the emerging concepts in the field of biomedical engineering is the ‘Bedside-Bench-Bedside’ concept. The development of any new biomaterials/tissue engineered product/translational approach should be driven by the patient’s need. The specific need to treat a specific disease should trigger the cascade of research activities at the labscale (‘bench’ work), which should involve material fabrication followed by in vitro and in vivo biological property assessment of a select group of implants. The final stage of taking the scientific research related to device/implant development to a patient’s bedside requires clinical trials, regulatory approval and product commercialization. In the above backdrop, this chapter summarises the author’s perspective on some of the issues relevant to the ‘Bedside-Bench-Bedside’ concept together with the smart and innovative design concepts of bone tissue engineering.