THEORETICAL AND PRACTICAL ASPECTS OF TESTING POTENTIAL BIOMATERIALS INVITRO

In vitro methods provide a necessary and useful adjunct to in vivo studies in testing potential biomaterials. One of the most important functions is the screening for toxic effects of the biomaterials. The spectrum of changes elicited ranges from cell death to alterations of cell adhesion, proliferation and biosynthetic activity. Such test systems may involve the direct contact of cells with the biomaterials or the use of soluble extracts of the latter. The rapid, cost-effective and highly sensitive in vitro methods have to be weighed against the problem of validity of extrapolation to the in vivo situation. The first step in testing potential biomaterials may be termed "general" biocompatibility testing and usually involves the use of various cell lines (i.e. transformed cells) which can be easily cultivated and passaged in the laboratory for long periods. Although the latter is convenient and highly sensitive for recognizing and excluding toxic materials at an early stage in the process of toxicity testing, this method cannot be regarded as exhaustive. It is proposed that such screening methods be followed by a second in vitro phase, in which primary and early passage cells of a type relevant to the proposed application of the medical device are used. This "specific" biocompatibility testing is an attempt to simulate the in vivo situation as closely as possible. A further component of such a testing scheme involves the use of relevant biological parameters, such as cell adhesion or the production of specific biosynthetic products by the relevant cell type. It is thus possible to construct a spectrum of in vitro changes, ranging from marked inhibition of growth with frank cell death ("not biocompatible") to marked stimulation of relevant growth and other cell biological parameters ("biocompatible and bioactive"). An expansion of in vitro testing methods can offer a method to "tailor" biomaterials for specific in vivo applications. In conclusion, it must be stressed that all in vitro experimentation, whether "general" of "specific", cannot replace the subsequent in vivo testing. Both components are necessary in an adequate scheme for testing potential biomaterials.