Macrophage-associated biocompatibility of titanium revealed by analyzing foreign body reaction at bone-implant interface.

Abstract

Purpose: Titanium implants are widely used to replace pathological joints, bones, and teeth, with successful engraftment requiring osteoblast attachment to the metal surface for bone regeneration. However, the immune response at the bone-implant interface remains unclear, and few studies have examined why titanium elicits a reduced foreign-body reaction (FBR) compared to other metals. This study aimed to elucidate the mechanism underlying titanium biocompatibility by characterizing the immune response at the bone-implant interface in a rat model.

Materials and methods: Copper, machined titanium, and sandblasted/acid-etched titanium rods were fabricated for implantation into rat tibiae. Topographical and chemical features of each rod surface were evaluated. Rods were inserted into rat tibiae, and immune cell subtypes were analyzed by flow cytometry, histomorphometry, and immunohistochemistry. Statistical analyses were performed at a significance level of 0.05.

Results: Flow cytometry of bone marrow cells collected on Days 1, 7, and 35 post-implantation revealed recruitment of macrophages and neutrophils at all implant sites. Histological analysis confirmed immune cell infiltration at the metal-bone interface, with a pronounced FBR surrounding copper rods. Immunohistochemistry demonstrated an abundance of osteoclast-like M1 macrophages at the copper-implant interface. In contrast, M1 macrophages were absent near titanium implants, where reparative M2 macrophages were present.

Conclusion: The recruitment of M1 macrophages at the copper implantation site, but not at the titanium implant, indicates the FBR to copper and underlies the biocompatibility of titanium. Titanium may affect the differentiation of intrabony macrophages to increase its biocompatibility.