is related to the behavior of biomaterials
and in that it is a peculiar word because it would seem that are at least two opposing uses of the same term. One is more related with statements on low level of immune response
of a specific material without specifying where the medical device
is used. The other relates more to the clinical success of the whole device of in which a specific biomaterial is part or its whole. So over time there have been some attempts at defining this term. The two more commonly referred to definitions are those of Prof. Williams and that in Dorland's Medical Dictionary
. These definitions also reflect the evolution of insights into how biomaterials interact with the human body
and eventually how those interactions determine the clinical success of a medical device (such as pacemaker
, hip replacement
). Nowadays any medical device would be comprised of more than one material so it might not always be very clear to talk about the biocompatibility of a specific material
Indeed, since the hemostasis of the immune response and repair functions in the body are so complicated it would seem odd to limit biocompatibility oin relation to just any given material. Sometimes one hears of biocompatibility testing that is a large battery of in vitro test that is used in accordance with ISO 10993 (or other similar standards) to determine if a certain material (or rather biomedical product) is biocompatible. These tests do not determine the biocompatibility of a material , but they constitute an important step towards the animal testing and finally clinical trials that will determine the biocompatibility of the material in a given application, and thus medical devices such as implants or drug delivery devices.
The "word" biocompatibility seems have been mentioned for the first time in peer-review journals and meetings in 1970 by RJ Hegyeli (Amer Chem Soc Annual Meeting abstract) and CA Homsy et al (J Macromol Sci Chem A4:3,615, 1970). It took almost two decades before it began to be commonly used in scientific literature (see the graph below).
Recently Williams (again) has been trying to re-evaluate the current knowledge status regarding what factors determine clinical success. Doing so notes that an implant may not always have to be positively bioactive but it must not do any harm (either locally or systematically) (Williams, 2008).
Four definitions of biocompatibility
- "the ability of a material to perform with an appropriate host response in a specific application". – Williams' definition (Williams, 1999).
- "the quality of not having toxic or injurious effects on biological systems". - Dorland's Medical Dictionary.
- "comparison of the tissue response produced through the close association of the implanted candidate material to its implant site within the host animal to that tissue response recognised and established as suitable with control materials" - ASTM
- "refers to 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". (Williams, 2008).
Comments on the above three definitions
- this is also referred to as the Williams' definition. It was defined in the European Society for Biomaterials Consensus Conference I and can more easily be found in "The Williams dictionary of Biomaterials".
- the Dorland Medical definition not recommended according to Williams Dictionary since it only defines biocompatibility as the absence of host response and does not include any desired or positive interactions between the host tissue and the biomaterials.
- the ASTM is not recommended according to Williams Dictionary since it only refers to local tissue responses, in animal models.
- The forth is an expansion or rather more precise version of the first definition noting both that low toxicity and the one should be aware of the different demands between various medical applications of the same material.
All these definitions deal with materials and not with devices. This is a drawback since many medical devices are made of more than one material. Much of the pre-clinical testing of the materials is not conducted on the devices but rather the material itself. But at some stage the testing will have to include the device since the shape, geometry and surface treatment etc of the device will also affect its biocompatibility.
In the literature one quite often stumble upon the adjective form: biocompatible. But according to Williams definition this does make any sense because biocompatibility is contextual, i.e. much more than just the material itself will determine the clinical outcome of the medical device of which the biomaterial is a part. This also points to one of the weaknesses with the current definition because a medical device usually is comprised of more than one material.
The scope of the first definition is so wide that D Williams tried to find suitable subgroups of applications in order to be able to make more narrow definitions. In the MDT article from 2003 the chosen supgroups and their definitions were:
- Biocompatibility of long-term implanted devices
- The biocompatibility of a long-term implantable medical device refers to the ability of the device to perform its intended function, with the desired degree of incorporation in the host, without eliciting any undesirable local or systemic effects in that host
- Biocompatibility of short-term implantable devices
- The biocompatibility of a medical device that is intentionally placed within the cardiovascular system for transient diagnostic or therapeutic purposes refers to the ability of the device to carry out its intended function within flowing blood, with minimal interaction between device and blood that adversely affects device performance, and without inducing uncontrolled activation of cellular or plasma protein cascades.
- Biocompatibility of tissue-engineering products
- The biocompatibility of a scaffold or matrix for a tissue-engineering products refers to the ability to perform as a substrate that will support the appropriate cellular activity, including the facilitation of molecular and mechanical signalling systems, in order to optimise tissue regeneration, without eliciting any undesirable effects in those cells, or inducing any undesirable local or systemic responses in the eventual host.
In these definitions the notion of biocompatibility is related to devices rather than to materials as compared to top three definitions.
There was a consensus conference on biomaterial definitions in Sorrento September 15-16 2005
- The Williams dictionary of Biomaterials, DF Williams, 1999, ISBN 0-85323-921-5
- “Revisiting the definition of biocompatibility”, D Williams, Medical Device Technology 14(8) October 2003
- Dorland's Medical Dictionary
- David F. Williams "On the mechanisms of biocompatibility" Biomaterials, Volume 29, Issue 20, July 2008, Pages 2941-2953