Obesity Prolongs the Pro-Inflammatory Response and Attenuates Bone Healing on Titanium Implants

Abstract

Obesity is a metabolic disease resulting from excess body fat accumulation associated with chronic systemic inflammation. Obesity has been shown to impact the function and activity of neutrophils, macrophages, and T cells, contributing to higher circulating levels of pro-inflammatory cytokines. Biomaterial surface properties such as roughness and hydrophilicity can influence the behavior of immune cells in the peri-implant microenvironment. This study aimed to determine how obesity induced by a high-fat diet (HFD) affects the inflammatory response to modified titanium (Ti) implants and subsequent bone formation. Obese mice had significantly more neutrophils, pro-inflammatory macrophages, and T cells and fewer anti-inflammatory macrophages and mesenchymal stem cells (MSCs) in the peri-implant tissue than lean mice. Obesity also increased circulating adipokines and pro-inflammatory cytokines when compared to lean animals. Bone formation around Ti implants was reduced in obese mice compared to controls. Adoptive transfer of bone marrow cells isolated from obese mice into wild-type mice demonstrated the localized impact of obesity on immune cell function and phenotype, promoting a pro-inflammatory peri-implant microenvironment and attenuating bone formation post-implantation. These results show that obesity significantly affects the inflammatory response to modified Ti implants, prolonging the pro-inflammatory response to the implanted biomaterial and compromising bone formation. Statement of SignificanceObesity has been shown to significantly alter physiological processes, including the behavior of immune cells, inducing a state of systemic chronic inflammation. Our study demonstrates that obesity-induced via a high-fat diet alters immune cell response to implanted biomaterials, with increased pro-inflammatory response and attenuated immunomodulation resulting in decreased biomaterial integration.