Cell and tissue reactions to metals and metal bound thiols. Effects of initial cell-surface reactions on the subsequent healing response

Abstract

Foreign materials are intentionally placed into humans in an ever-increasing rate in order to replace or augment a natural function. While certain materials function well in the biological environment, the reasons for their biocompatibility are largely unknown. The trauma caused by the insertion of an implant initiates a healing reaction. This begins with the adsorption of small ions and proteins to the surface, followed by adhesion of cells. It would therefore be logical and desirable to find a marker, molecular or cellular, that could give an indication as to the long-term performance of a material in the biological milieu. A series of in vitro and in vivo tests were performed ranging from 15 seconds to 6 weeks on two materials, gold and titanium. A holistic approach was employed in the designing of the experiments in an effort to preserve the mechanisms of the complex biological systems. Protein adsorption, cell adhesion and activation tests were done in vitro with human plasma, serum or whole blood. In vivo tests were done intraperitoneally in mouse or rat, or in the femur or tibia of rabbit. The cleaning regimen of the titanium implants in rabbit bone, employed oxidation and a final rinsing and storage in water. The results showed distinct differences between the surfaces for protein adsorption and adhesion/activation of platelets. Initially, differences were even observed for the leukocyte adhesion patterns to the surfaces. However, these differences could not be seen with an increase in time. The respiratory burst activity of leukocytes on the different surfaces showed different degrees of activation and suggested different activation pathways. We propose that the respiratory burst response of leukocytes adherent to materials can be used as a cytotoxicity test for materials. The 6 weeks titanium-bone implants did not induce the formation of multinucleated giant cells, were surrounded by richly vascularised loose connective tissue, without signs of fibrous capsule formation, and with continued bone growth toward the surface.