such as polyethylene (PE); polymethyl methacrylate (PMMA); nylon; silicone (polydimethylsiloxane);
Composites composed of one or more of the abovementioned classes of materials.
Figure 1.3 Schematic of the classes of materials used as biomaterials, along with examples of specific biomaterials in each class.
Metals, ceramics, and polymers are said to make up the primary classes of synthetic biomaterials. Semiconductors are sometimes described as a fourth class of synthetic materials but the few semiconductors that find use as biomaterials typically have structures similar to ceramics. Consequently, in this book, they are included, where appropriate, within the category of ceramics.
Degradable, Nondegradable and Resorbable Biomaterials
Biomaterials can also be classified in terms of their ability to degrade, typically in an aqueous medium such as a phosphate‐buffered saline or the physiological fluid. Degradation refers to the conversion of the material into smaller constituents, such as ions, molecules or fine particles. Degradation of biomaterials in an aqueous environment can occur by chemical attack by water molecules (hydrolysis), enzyme‐mediated hydrolysis, dissolution, oxidative reaction, or some combination of these mechanisms. For example, the synthetic polymer polyglycolic acid has a composition that makes it susceptible to degradation by hydrolysis into smaller molecules composed of glycolic acid.
The term biodegradable is often used in the literature instead of, or interchangeably with, degradable. Sometimes it may be used in a more restrictive sense to describe degradation by enzyme‐mediated reactions in the physiological environment, and so would not include unmediated hydrolysis. Another term is resorbable that, like biodegradable, is often used instead of, or interchangeably with, degradable. This term may be used in a more restrictive sense to emphasize what eventually happens to the biomaterial degradation product composed of ions, molecules, or particles. Commonly, the degradation product (or most of it) is removed from the body via renal clearance, hepatic processing, phagocytosis, or by other processes. Alternatively, the degradation product of some biomaterials can be taken up into the body tissues, and it can then be said to be resorbed back into the body tissues. For example, calcium and phosphate ions produced by the degradation of some calcium phosphate biomaterials can be resorbed into bone as these ions are constituents of bone.
In this book, we will simply use the term degradable regardless of the mechanism of degradation or the fate to the degradation products. The terms biodegradable or resorbable will be used only when necessary to emphasize a distinction from the general term degradable.
Whereas all materials show some degree of degradation, no matter how small, over some appropriate duration, the term nondegradable is often used in a qualitative manner to describe a biomaterial that is normally not susceptible to chemical attack in an aqueous environment. Qualitatively, these nondegradable biomaterials can also be said to be chemically inert, chemically stable, or resistant to degradation. In this sense, then, the synthetic polymer PE can be described as nondegradable or chemically stable, even though it can undergo some degree of degradation by oxidative reactions under certain conditions, such as the presence of highly oxidizing molecules in the aqueous environment (Chapter 15).
The term bioinert has often been used to describe these nondegradable biomaterials. However, it is generally recognized that no biomaterial is totally inert in the biological environment. Although they may not degrade themselves when implanted, all biomaterials elicit a response from ions, molecules, cells, or tissues in the body. Consequently, a biomaterial cannot be said to be truly bioinert.
Bioactivity
An original definition of bioactivity is:
“Bioactivity refers to the ability of a material to elicit a specific reaction at its surface when implanted in the body, leading to the formation of a strong bond at its interface with bone or soft tissue.”
The calcium phosphate ceramic hydroxyapatite and certain compositions of glasses, referred to as bioactive glasses, satisfy this definition (Chapter 7). If the requirement of forming a strong bond with bone and soft tissues is omitted, the definition becomes broader. The term is now used more commonly in this broader sense.
Tissue Engineering and Regenerative Medicine
Since antiquity, the conventional approach to repairing diseased or damaged tissues or organs in the body has been to replace them with transplanted tissues or organs, or with durable synthetic implants composed of metals, ceramics or polymers. While this approach has worked well, it suffers from limitations related to factors such as supply of donor tissue or organs, or the inadequate lifetime of the implanted biomaterial. A radical shift in this conventional approach was proposed approximately three decades ago. Instead of focusing on repairing or replacing tissues and organs with transplanted tissues or organs, or with durable materials, this new approach, referred to as tissue engineering, is based on regenerating functional tissues and organs. A definition of the term is:
“Tissue engineering is an interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function” (Langer and Vacanti 1993).
The tissue engineering approach involves harvesting cells, incorporating them into a suitable biomaterial, and stimulating them ex vivo (outside the body). Then the resulting construct is implanted into the patient at the appropriate time. Alternatively, the cell‐seeded biomaterial can be implanted directly into the body (Chapter 25). More recently, the term regenerative medicine has been used to describe a broader approach to regenerating the patient’s own tissues or organs. Regenerative medicine includes tissue engineering as well as two other approaches based on cell therapy and gene therapy. Biomaterials form an important component of the tissue engineering approach, whereas cell therapy and gene therapy involve biomaterials only minimally.
In Vivo, Ex Vivo, and In Vitro
In vivo refers to procedures performed inside the body whereas ex vivo refers to procedures or manipulations performed outside the body. In vitro refers to studies, such as cell culture, evaluating the degradation rate of a biomaterial, or evaluating the release profile of molecules from a biomaterial, that are performed outside the body, typically in a science laboratory. Commonly, biomaterials are evaluated in vitro prior to implantation or use in vivo.
1.3 Biomaterials Design and Selection
Biomaterials are normally designed to have some desirable combination of properties that depend on the intended application. For example, a biomaterial designed for use in healing a defect in a hard tissue such as bone would most likely have properties that are different from one designed for use in healing a defect in a soft tissue such as cartilage. A biomaterial designed to deliver drugs or molecules to a specific site in the body should be capable of being formed into a particulate form, normally of spherical shape and size less than several tens of microns, which is vastly different from a three‐dimensional (3D) form for healing a bone defect. The biomaterial may also have to degrade at a desirable rate to release drugs or biomolecules in a controllable manner.
The approach to designing biomaterials has seen a radical shift in the last few decades. Biological sciences are now playing a significantly increasing role, while