In this chapter the major alternative non-pharmacological, non-synthetic replacement methods to treat disease and injury are introduced. These are various methods of regenerative medicine, which incorporate cell therapies, gene therapies and tissue engineering. The first two of these are mentioned briefly since they involve biomaterials only minimally. Tissue engineering concerns the regeneration of tissues or organs through the stimulation of cells so that they recapitulate the power that they have during tissue development, but which they substantially lose once tissues become mature. This recapitulation may be achieved by either molecular and mechanical signaling, or usually by both. The conventional tissue engineering paradigm involves harvesting cells and stimulating them ex vivo, and implanting the resulting construct into the patient at the appropriate time. Other techniques attempt to use the environment of the patient’s own body as the location for regeneration. We discuss here the types of materials that are used in the so-called scaffolds and matrices that form the template of the regenerated tissue and the interactions between these materials and the target cells. Tissue engineering processes have not yet become used in routine clinical practice and cannot at this stage be defined and classified as clearly as with implantable medical devices, but we do discuss their scientific and clinical status in a wide variety of situations.

Introduction to regenerative medicine

There are two stark conclusions that arise from the discussion of implantable medical devices given in the last chapter. First, although they can give very good performance, they will always be limited to situations involving mechanical or physical functions and will not, by themselves, be able to deal with conditions that require biological solutions. Secondly, even in those situations where the performance is good, it will always be less than 100% effective because so many variables impose themselves on the process, especially in the context of biocompatibility and the influence of clinical skills and patient compliance. Outcomes are variable and often unpredictable.

In this chapter you will be introduced to the principles of the structure and characteristics of materials in general, and the specific features of the main classes of practical materials. These are metals and alloys, the different forms of polymer-based materials, ceramics and glasses, composite materials and natural materials. This is followed by discussions on how these structures give rise to the specific properties of these material classes, with an emphasis on the mechanical and physical properties and the chemical stability of materials in various environments, especially the physiological environment. Attention is given to many different specialized materials that are now used in health care, including nanocomposites, quantum dots, polymeric micelles, dendrimers, hydrogels and biopolymers. The objective is to allow you to understand why these different materials have their own properties and how biomaterials can be designed to meet the very critical performance specifications required in medical technology.

Introduction

It is important to start reading this chapter with no preconceived ideas of what a material should look like or how it should perform. In order to understand and appreciate the high-performance, esoteric materials that are used in advanced engineering applications of the twenty-first century, including medical engineering, it does not help to have fixed in our minds the idea that a material has to look and behave as if it were a macroscopic, solid object that is made by some conventional manufacturing process and which we can hold in our hand and examine visually. Most of today’s sophisticated materials do not behave in a similar manner to the more traditional steel, plastic, textile, glass, concrete or wooden structures that have been the mainstay of materials engineering for many decades. We should not be constrained by concepts of state (materials do not have to be solid), of size (they may be macroscopic, microscopic or of nanoscale dimensions), of activity (they do not have to be inert but may be intentionally active, or even living) or of permanence (they may be intentionally biodegradable). They do not have to be manufactured by conventional means but may be formed in situ by self-assembly. In other words, a collection of intensively active, macromolecular self-assembled nanoparticles is just as much a material as the piece of forged titanium that constitutes the bulk of a total hip replacement prosthesis.

Biomaterials are crucial components of many health care products. They are in the news daily as we hear of new devices that allow deaf people to hear, and of techniques to return patients to a near normal life after a heart attack. Headlines tell us of titanium dental implants, ceramic artificial hips, carbon heart valves, collagen cosmetic injections and clear plastic lenses in the eye. Science magazines talk of new drug–biomaterial combinations that are radically altering cancer chemotherapy and immunotherapy and of nanoscale contrast agents that give far more power to MRI and CT imaging systems for better and earlier disease diagnosis. Biomaterials save lives and improve the quality of life for millions of people.

The science that underpins these advances is, not surprisingly, called biomaterials science. It has grown and developed from tentative beginnings half a century ago into a major academic and clinical discipline today. This science is both multidisciplinary and interdisciplinary since it brings together many classical disciplines of science, engineering and medicine, but also adds new knowledge that fits within the gaps between the classical subjects.

This chapter provides a new way of classifying biomaterials and gives extensive information about the wide range of biomaterials that are either in current clinical use or showing considerable potential for clinical applications in the near future. There are six primary classes of biomaterials – metallic, polymeric and ceramics systems, carbons, composites and engineered tissues. In each of these classes you will see how real biomaterials are based on the principles of materials science, biology and biocompatibility given in the early chapters but also how they are adapted and modified to suit the specific requirements of the various clinical disciplines and medical technologies.

In this chapter, we bring together the details of all currently used biomaterials and those that appear to have considerable potential for the future. This is an extensive although not exhaustive list of the properties and the applications for each material and gives a generic classification of biomaterials, with an indication of their advantages and disadvantages.

This chapter will introduce the concepts underlying the use of biomaterials to deliver various types of active molecules to the body for therapeutic or preventive purposes. This starts with the premise that many traditional pharmaceutical agents have been demonstrated to be effective in certain situations but their efficacy, specificity and safety is often compromised by poor bioavailability and high systemic toxicity when delivered through the conventional oral or intravenous routes. The chapter therefore concentrates on the technologies that can be used to produce more precise, controlled and targeted delivery of these active molecules. It covers drugs, genes, vaccines and other active molecules and deals with mechanical, physical, chemical and other techniques to produce the delivery mechanism. Many of these processes are based on the details of nanobiotechnology.

Introduction to active molecule delivery

Pharmaceutical agents, or drugs, are chemical substances that are applied to the body where they are metabolized and have, or are expected to have, a beneficial effect in treating, mitigating or preventing disease or discomfort, facilitating repair of injury or otherwise beneficially altering human physiological performance. Drugs have been the mainstay of many branches of medicine for centuries and have a powerful impact on both health status and health economics around the world.

In this chapter we introduce some of the latest applications of biomaterials in medical technology. Previous chapters have concentrated on therapeutic processes, either by pharmaceutical components, regenerative medicine processes or implantable devices. All clinically successful therapeutic measures require good diagnosis of the patient’s condition. Although the doctor’s intrinsic clinical skills are extremely important, the need for very accurate, instrument-assisted, diagnosis, with good spatio-temporal resolution, is becoming increasingly significant. This is because early and precise diagnosis is essential if the doctors are able to use the most effective treatments for cancer, degenerative disease and other critical issues. Medical technologies have always played some role in diagnosis, but have rarely, until recently, involved the use of biomaterials. Most techniques are concerned with the application of some physical energy to the affected tissues and organs, using X-rays and other ionizing radiations, ultrasound and light, for example, and detecting the responses of the tissues to that energy. Conventional methods often provide relatively poor contrast between different types of tissues (and any lesions they contain), usually with restricted spatial resolution. They usually produce anatomic rather than functional information. The essential rationale for the use of biomaterials in these imaging systems is to enhance the contrast that can be seen, especially by accentuating differences between the response of different types of tissues and between different disease states. Most of these biomaterials are used in nanoparticulate form. Their applicability is controlled by their differential responses to the applied energy and by their handling within the tissues of the body.

Anatomical and functional imaging

The majority of this book so far has been concerned with the therapeutic methods that may be used to treat diseases and conditions of the human body, where those methods significantly rely on the use of biomaterials. Before any therapy can be considered, it is necessary for the clinicians involved to be aware, as accurately as possible, of the nature of the disease or condition that is affecting the patient in question. For very many years, this process of identifying what is wrong, known as diagnosis, was informed by the skilled observations of the clinicians and the measurement of some relevant physiological parameters such as temperature, heart rate and blood pressure.

In this chapter we shall address many of the practices and procedural issues that affect and control the production, supply and clinical use of biomaterials and products that are based on these materials. These are not trivial matters. They should be considered as essentials, rather than as afterthoughts or “nice-to-haves.” The reason why these issues are addressed towards the end of this book and not at the beginning is a reflection of the need for the reader to first understand the essential scientific, clinical and technological basis before coming to grips with the infrastructure issues, rather than any suggestion of lesser importance. This chapter covers the regulation of biomaterials-based health care products, the pre-clinical testing and clinical evaluation of materials and products, and the ethical, legal and economic matters that have a major influence over this industry.

Introduction

Although it could be argued that, globally, the biomaterials and medical technology industries are quite heterogeneous and fragmented, there are several facets of the industry that are highly structured. These deserve discussion in a textbook on the essentials of biomaterials science. The fundamental reason for this is that biomaterials can do harm as well as good and it is essential that they are used as safely and effectively as possible. This will not happen if each application of a medical device that incorporates biomaterials is developed in isolation, in ignorance of the relevant history of that type of device and without regard to the broader issues of patient (and doctor) safety and the ethical and legal aspects of clinical applications. That there are standards and codes of practice in industrial sectors where safety is a primary concern, such as in aerospace and nuclear industries, is no surprise. The sheer volume of medical devices used on a global scale, and the potential number of individuals that they can affect, for good or bad, suggests that there should be extensive control over these products as well.