Diabetes induces implant failure by M1-polarized macrophages that persist at bone-implant interface. Yet, the protein layer formed under diabetic condition has been overlooked in studies of macrophage-induced implant failure, even though adsorbed protein can significantly alter cellular interactions with titanium surface. Here, we demonstrate that the protein layer formed under diabetic condition promotes macrophage polarization towards the M1 phenotype, a result of reduced adsorption of albumin on titanium surfaces. Reduced albumin adsorption was attributed to glycation-mediated structural deformation. Furthermore, we show that pre-coating titanium with non-glycated albumin effectively shift macrophage polarization towards M2 phenotype in diabetic conditions. This study highlights the regulatory role of the adsorbed protein in interfacial macrophage polarization, offering a novel perspective for designing titanium implants to restore homeostasis of the immune-microenvironment and enhance implant success in diabetics.
Jiang et al. (2026) studied this question.