0278-6648/07/$25.00 © 2007 IEEE BEFORE THE LATE 1950S, BIOMECHANI- cal sciences and engineering were in a slump. Prostheses were rudimentary and unimaginative, and biomaterials sci- ence simply did not exist. Until this point, according to The Cultural Body, wooden peg-legs and gold teeth were the only clinically and socially accepted prosthetic devices; the only accepted transplantation procedure was blood transfusion. Three major events helped propel biomechanics out of the dark ages and create the field of biomaterial science as a requisite for the production of functional medical devices. The first major event was the race to the moon. Starting in the late 1950s, massive government spending provided the motivation and resources needed to answer a rather daunting question: how would the human body react to the stress induced during space travel and extended periods of time spent in microgravity? The second major event was the improved technological capability of the digital computer, which was first developed around 1945, that allowed researchers new computational freedom and computational power in the highly complex and nonlinear world of biomechanics. The final event was the birth of modern biology, which provided a sound scientific basis for biomechanics at the microscopic level. In 1951, Linus Pauling began to uncover the basic structure of protein, and in 1953, Watson and Crick revealed the double helical structure of DNA. These three events provided the motivation and technology that led to a proliferation of advancements in bio- medical instrumentation. Within a decade, an explosion of new clinical applications had been realized. Most notably, the artificial hip joint, the artifi- cial kidney and heart, the lung machine, the cardiac pacemaker, and the prosthetic cardiac valve were all produced during that time period. This article will provide a glimpse into a fun- damental part of the process that was developed over the past six decades to create those devices: the materials out of which they are made. A widely accepted and useful defini- tion of a biomaterial offered by Williams is “a nonviable material used in a med- ical device that is intended to interact with biological systems for the purpose of improving health.” A more recent consensus definition of a biomaterial excludes the word “nonviable” due to the development of tissue-engineered scaffolds and hybrid prosthetics in which living cells are combined with nonorgan- ic material. Today, there are a relatively limited number of different biomaterials being used in the clinical setting. Standard polymers, metals, and ceramics encompass the bulk of functional bioma- terials. One may wonder why so few biomaterials are accepted clinically. The answer to this lies in the fact that the positive effect a material has on the mechanical soundness of a device often is negated by its incompatibility with the tissue with which it will be in contact. This problem, referred to as biocompati- bility, is the first issue, in addition to a basic material utility analysis, that an engineer must consider for a candidate biomaterial when improving an existing device or creating a new one. BIOCOMPATIBILITY Biocompatibility is defined by Williams as the ability of a material to perform with an appropriate host response in a specific application. This means that the material must elicit the correct reaction, or lack of reaction, from any tissue with which it is in direct or indirect contact for a particular treat- ment. Identification of a material with good biocompatibility requires a host of different tests. These tests fall into two general categories: in vitro and in vivo. In vitro testing is used to determine the overall tradeoff between performance and biocompatibility that can be reached with a certain material. In vivo testing tackles questions relating to the performance of a biomaterial in a clinical situation. The distinction between in vitro test- ing versus in vivo testing is that in vitro testing occurs in an artificial environ- ment, whereas in vivo testing takes place within a living system. Generally, in vitro tests identify cytotoxicity, cell activation, cell adhesion, or necrosis due to a particular biomaterial using cell cultures. In vitro testing employs three main types of assays to determine basic information about the material in question: direct contact, agar diffusion, and extract dilution. © MASTERSERIES Fundamental considerations for biomaterial selection JONATHAN P. NEWMAN 12 IEEE POTENTIALS