Evaluation of Biocompatibility Using In Vitro Methods: Interpretation and Limitations - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 118

1 Introduction
The clinical success of a medical device, such as a catheter, stent, artificial knee
implant, or simple forceps, is determined on the one hand by its functional
properties, e.g. the mechanical characteristics of the materials and the design of the
device. On the other hand, it is also defined by the way biological tissues will react
that are in contact the implant. In that context, the term biocompatibility is defined
as ''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 meanwhile generating the most
appropriate beneficial cellular or tissue response in that specific situation, and
optimizing the clinically relevant performance of that therapy'' (Definition [ 5 ]
based on [ 155 ]). Thus, biocompatibility testing is the fundamental requirement
when developing new materials and their surfaces for medical devices and tissue
engineered medical products (TEMPs). The cellular and tissue responses towards a
material may be very diverse and they can be classified in many ways, but they can
roughly be divided into (i) strong effects, i.e. modification of cell viability
(cytotoxicity, genotoxicity), (ii) moderate to nearly negligible effects, i.e. irre-
versible to transient changes in cell functionality (e.g. complement activation,
pharmacological effects), or (iii) the absence of measurable effects. The inclusion
of ''appropriate response with respect to its function'' to in the definition
emphasizes that biocompatibility is not a general characteristic but is defined by
the location of implantation and envisioned function of the device material. This
implies that the end-use application should already be known when evaluating
biocompatibility and that the evaluation has to be adapted accordingly. Each end-
use application and therapy may have different requirements. A biomaterial may
fulfil all criteria for a specific therapy to be biocompatible, but may fail and cause
an unwanted tissue reaction in another application and as a result must be defined
in that case as being not biocompatible. For example, in the case of non-absorbable
hernia nets, soft tissue integration is crucial, while in the case of intraocular lenses,
absence of a tissue reaction and cell on-growth are important criteria for bio-
compatibility. The situation gets further complicated by the fact that the materials
will elicit variable and different degrees of reactions in each host, i.e. each patient.
For instance, the stainless steel alloy, UNS S31675, is known to be biocompatible
and can be used as implant material. However, sometimes the host's immune
system may react towards the material immediately or after a while, requiring the
removal of the device, as the steel alloy contains 9-11% nickel (mass/mass).
Although in the majority of cases the absence of the release of toxic compounds
represent a key issue being evaluated, also in this regard the absence of cytotox-
icity does not represent in general a key issue for being biocompatible that must
always be fulfilled. Therefore, interpreting biocompatibility of investigated bio-
materials with regard to the final use of the material is crucial. In the following, the
different test methods and acceptance criteria for biocompatibility are critically
discussed.