Differential lymphocyte reactivity to serum-derived metal-protein complexes produced from cobalt-based and titanium-based implant alloy degradation

Nadim James Hallab, Katalin Mikecz, Csaba Vermes, Anastasia Skipor, Joshua J. Jacobs

Research output: Contribution to journalArticle

87 Citations (Scopus)


The lymphocyte response to serum protein complexed with metal from implant alloy degradation was investigated in this in vitro study using primary human lymphocytes from healthy volunteers (n = 10). Cobalt chromium molybdenum alloy (Co-Cr-Mo, ASTM F-75) and titanium alloy (Ti-6A1-4V, ASTM F-136) beads (70 μm) were incubated in agitated human serum at 37°C to simulate naturally occurring metal implant alloy degradation processes. Particulate free serum samples that had been incubated with metal were then separated into molecular weight based fractions. The amounts of soluble Cr and Ti within each serum fraction were measured and correlated with lymphocyte proliferation response to the individual serum fractions. Lymphocytes from each subject were cultured with 11 autologous molecular weight based serum fractions either with or without added metal. Two molecular weight ranges of human serum proteins were associated with the binding of Cr and Ti from Co-Cr-Mo and Ti implant alloy degradation (at <30 and 180-250 kDa). High molecular weight serum proteins ( ∼180 kDa) demonstrated greater lymphocyte reactivity when complexed with Cr alloy and Ti alloy than low (5-30 kDa) and midrange (30-77 kDa) serum proteins. When the amount of lymphocyte stimulation was normalized to both the moles of metal and the moles of protein within each fraction (metal-protein complex reactivity index), Cr from Co-Cr-Mo alloy degradation demonstrated approximately 10-fold greater reactivity than Ti in the higher molecular weight serum proteins ( ∼180 kDa). This in vitro study demonstrated a lymphocyte proliferative response to both Co-Cr-Mo and Ti alloy metalloprotein degradation products. This response was greatest when the metals were complexed with high molecular weight proteins, and with metal-protein complexes formed from Co-Cr-Mo alloy degradation.

Original languageEnglish
Pages (from-to)427-436
Number of pages10
JournalJournal of Biomedical Materials Research
Issue number3
Publication statusPublished - Sep 5 2001


  • Biocompatibility
  • Bioreactivity
  • Immune response
  • Lymphocyte
  • Metal protein complex

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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