Mohamed N. Rahaman - Materials for Biomedical Engineering

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.

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.

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 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 .

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 at the same time, materials science and engineering are being used to design improved biomaterials having properties more comparable to those of natural tissues.

In the past, materials science and engineering provided the foundation for designing and selecting biomaterials. Biomaterials were normally selected from durable, chemically inert materials that were available off the shelf, and they were engineered to serve a mainly mechanical (or physical) function. Adequate strength and stiffness, for example, are required for the biomaterial to support physiological stresses without deforming permanently into a nonoptimal shape or without fracturing. Chemical inertness is important to minimize the potential for rejection of the biomaterial.

This approach based on materials science and engineering worked well for some applications and it provided a foundation for more recent developments in the biomaterials field. On the other hand, clinical data show that a high percentage of these biomaterials failed within a certain duration, necessitating a second surgical procedure (sometimes referred to as a revision surgery). Implants used for total hip joint replacement are a good example of this approach ( Section 1.5). While the basic design of the hip implant has changed very little in over 50 years, improvements in materials selection over this time have resulted in the creation of implants having better performance and longer lifetime in vivo . However, ~25% of these implants still fail within 10–20 years, necessitating revision surgery.

The last few decades have seen a radical shift in the approach to designing and selecting biomaterials. Biological sciences are now playing a significant role, often comparable to that of materials science and engineering. Advances in biological sciences are being utilized to design biomaterials that serve not just a mechanical (or physical) function. Instead, biomaterials are now being designed to serve, in addition, biological functions such as eliciting or directing specific cellular responses. At the same time, advances in the physical sciences, materials science and engineering are being used to design and create improved biomaterials with greater complexity in structural and chemical characteristics to better mimic biological tissues.

As an example of the shift in biomaterials design over the last few decades, we can select the intravascular stent ( Figure 1.1g). This device is among the most widely used of all implantable medical devices, with over 1.5 million stents implanted annually in patients worldwide. Stents are used when a blood vessel such as an artery becomes blocked (a process referred to as stenosis) due to the accumulation of plaque, a condition that, in many cases, can lead to a heart attack. Stents are tubular in shape and they are inserted into the artery to compress the plaque and to remain at the site to keep the artery open ( Chapter 24).