Hendriks: If we look at the evolution of biomaterials technology then we can see that, initially, the choice of biomedical materials for use in the body was based on achieving a suitable combination of physical properties to match those of the replaced tissue with a ‘biopassive’, minimal toxic response in the host. This “do no harm” paradigm is very well illustrated by the way professor David Williams defined biocompatibility in 1987: “The ability of a material to perform with an appropriate host response in a specific application”.

As our understanding of the pathophysiology of implanted devices at the cellular and molecular levels has increased, so too has our emphasis on better management of the material’s biointerface. Rather than trying to exclusively achieve the bioinert tissue response, the biomaterials field is focusing instead on incorporating bioactive components in the design of biomaterials that could elicit a controlled action and reaction in the physiological environment. Very prominent examples of these second generation “bioactive” biomaterials are heparin coatings for improved blood compatibility, and drug eluting stent coatings for prevention of vascular restenosis.

Now third-generation biomaterials are being designed to stimulate specific cellular responses at the molecular level. These biomaterials take our contemporary understanding of molecular and cell biology steps further by actually incorporating biology into materials design and are helping to achieve the objective regeneration as opposed to repair. For example, molecular modifications of polymer systems can elicit specific interactions with cell surface integrins and thereby stimulate direct cell proliferation, differentiation, and extracellular matrix production and organization. These third-generation "bio-interactive" biomaterials stimulate regeneration of living tissues.

Circling back to the definition of biocompatibility, some 20 years after his original definition, the same professor David Williams revised the original definition of biocompatibility to now read: “The ability of a biomaterial to perform its desired function with respect to a medical therapy, without eliciting any undesirable local or systemic effects in the recipient or beneficiary of that therapy, but generating the most appropriate beneficial cellular or tissue response in that specific situation, and optimising the clinically relevant performance of that therapy”. Clearly this reflects the evolution of biomaterials into second and third generations, where materials have increasingly more activity and interaction with the biological environment. With regard to biocompatibility, the next generations of biomaterials not only focus on “doing no harm”, but actually have the ability obtain a beneficial response.