School of Engineering and Materials Science
Research Student Awards
PhD Thesis: Integrin expression at the bone/biomaterial interface
Author: CLARKE, Susan
Supervisor(s): Peter Ravell
The objectives of this study were to visualise integrin expression by cells at the bone/biomaterial interface and to examine this expression in relation to the distribution of integrin ligands within interface tissue. Furthermore, the effect of the presence of metal wear debris on integrin expression by peripheral blood monocytes was investigated in vitro, using generated CoCrMb particles, generated TiAlV particles and TiAlV particles retrieved from periprosthetic tissue.
Samples of interface tissue were obtained from 30 patients undergoing revision of failed, aseptically loose, total joint replacements. Using standard immunohistochemical techniques, 5m frozen serial sections were stained with mAbs to six integrin heterodimers and five integrin ligands (fibronectin, laminin, vitronectin, ICAM-1 and VCAM-1).
Most cells in interface tissue expressed 21 including endothelial cells, giant cells and phagocytic cells. The majority of macrophages, giant cells and cells containing wear debris in the tissue expressed CD11b. Giant cells and cells containing wear debris also expressed V3 in the majority of cases but, overall, the expression of this integrin was less than that of 21 and CD11b. There was little consistency to CD11c expression, with cell types and locations being as often negative as they were positive. CD11a expression was consistently low and was often limited to perivascular T-lymphocytes. Many cases did not show any expression of 41 and when present, it was often limited to a small number of cells deep within the tissue.
This lack of 41 and the combination of CD11a, CD11b and ICAM-1 in interface tissue would suggest that leukocytes are using 2 integrins to marginate and transmigrate rather than the alternative pathway involving 41. This is further supported by a discrepancy found in the staining patterns for 41 and its ligand VCAM-1.
The expression of some integrins and their ligands has been identified in interface tissue and the effect of metal wear debris has been examined in vitro. As binding of integrins to their ligands is essential to cellular function, blocking of these receptors will inhibit many cellular processes and may prolong the life of the implant.