Extensive proliferation of connective tissue around
Vitallium implants can be observed in young patients who had
limb salvage for primary malignant bone
tumors. The underlying mechanism of excess proliferation and
collagen accumulation is not known. We were therefore interested to show whether the
alloy of the implant induced proliferation of fibroblasts in vitro, acted by a cytotoxic mechanism or generated
free radical cross linking of
collagen with subsequent accumulation. In vitro tests for proliferation and cytotoxicity using the implant material which consists of a series of transition metals, ruled out a proliferation-inducing or cytotoxic effect of the implant. Determination of
ortho-tyrosine (OT), a marker for
hydroxyl radical attack on
phenylalanine, in the proliferating tissues surrounding the implants revealed significantly higher aromatic hydroxylation in the
vitallium surrounding tissue correlating with tissue
collagen content (r = 0.86, p < 0.01). Based upon the findings of increased OT and the presence of higher molecular weight bands on SDS-PAGE, representing more cross linked
collagen, we suggest that
hydroxyl radical attack lead to
free radical mediated cross linking of
collagen with subsequent
collagen accumulation, as
collagen cross-linked to a higher degree is less susceptible to proteolytic degradation.The
hydroxyl radical attack seems to having been generated by the many transitional metals of the
vitallium-
alloy.