Macrophage response to hydrophilic biomaterials regulates MSC recruitment and T-helper cell populations

Abstract

Successful biomaterial implantation can be achieved by controlling the activation of the immune system. The innate immune system is typically the focus on synthetic material compatibility, but this study shows an effect of surface properties in the innate as well as the adaptive systems. These studies look at how macrophages respond to the implanted materials by releasing factors to regulate the microenvironment and recruit additional cells. Our research demonstrates how macrophage response to material surface properties can create changes in the adaptive immune response by altering T-helper cell populations and stem cell recruitment. Titanium (Ti) implants of varying wettability (rough, and rough-hydrophilic) were placed in the femur of 10-week-old male C57Bl/6, or macrophage ablated clodronate liposome injected and transgenic MaFIA (C57BL/6-Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck/J) mice. The microenvironment surrounding Ti implants was assessed using custom PCR arrays at 3 and 7 days following implantation. Changes in specific T-helper, macrophage and stem cell populations were evaluated locally at the implant surface and systemically in the contralateral leg bone marrow and spleen by flow cytometry at 1, 3 and 7 days. Macrophage importance in T-helper and stem cell population changes with metallic surfaces was examined in both in vitro and in vivo with macrophage ablation models. We demonstrate that surface modifications applied to titanium implants to increase surface roughness and wettability can polarize the adaptive immune response towards a Th2, pro-wound healing phenotype, leading to faster resolution of inflammation and increased stem cell recruitment around rough hydrophilic implants with macrophages present.