In vitro models of biocompatibility: a review

The objectives of this paper were to define in vitro biocompatibility of materials, to discuss some of the issues concerning why conclusions from tissue culture are sometimes different from in vivo biocompatibility, to give highlights of the sequence of the development of these in vitro assays from the early 1950s to their present state of development, and to discuss possible future trends for in vitro testing. In vitro biocompatibility tests were developed to simulate and predict biological reactions to materials when placed into or on tissues in the body. Traditional assays have measured cytotoxicity by means of either an end-stage event, (i.e., permeability of cytoplasmic membranes of dead and dying cells, or some metabolic parameter such as cell division or an enzymatic reaction). In vitro assays for initiation of inflammatory and immune reactions to materials have also begun to appear in the literature. More recently, the concept of dentin barrier tests has been introduced for dental restorative materials. Four models which measure both permeability and biological effects of materials are compared and discussed. Future efforts may be directed toward development of materials which will allow or promote function and differentiation of tissues associated with materials. New analytical procedures and understanding of optimal characteristics of materials should improve our ability to develop more biocompatible materials. Both molecular biology techniques, and altered design of material surfaces may make the materials either more or less reactive to the biological milieu. These trends suggest a greater future role of the biological sciences in the development of biomaterials.