The pathogenesis of aseptic loosening of total joint prostheses is not clea
rly understood, Two features are associated with loosened prostheses, namel
y, particulate debris and movement of the implant. While numerous studies h
ave evaluated the cellular response to particulate biomaterials, few have i
nvestigated the influence of movement of the implant on the biological resp
onse to particles. Our aim was therefore to test the hypothesis that excess
ive mechanical stimulation of the periprosthetic tissues induces an inflamm
atory response and that the addition of particulate biomaterials intensifie
s this.
We allocated 66 adult Beagle dogs to four groups as follows: stable implant
s with (I) and without (II) particulate polymethylmethacrylate (PMMA) and m
oving implants with (III) and without (IV) particulate PMMA, They were then
evaluated at 2, 4, 6, 12 and 24 weeks.
The stable implants were well tolerated and a thin, fibrous membrane of con
nective tissue was observed. There was evidence of positive staining in som
e cells for interleukin-6 (IL-6), Addition of particulate PMMA around the s
table implants resulted in an increase in the fibroblastic response and pos
itive staining for IL-6 and tumour necrosis factor-alpha (TNF-alpha). By co
ntrast, movement of the implant resulted in an immediate inflammatory respo
nse characterised by large numbers of histiocytes and cytokine staining for
IL-1 beta, TNF-alpha and IL-6, Introduction of particulate PMMA aggravated
this response. Animals with particulate PMMA and movement of the implant h
ave an intense inflammatory response associated with accelerated bone loss.
Our results indicate that the initiation of the inflammatory response to bi
omaterial particles was much slower than that to gross mechanical instabili
ty. Furthermore, when there was both particulate debris and movement, there
was an amplification of the adverse tissue response as evidenced by the pr
esence of osteolysis and increases in the presence of inflammatory cells an
d their associated cytokines.