Noninvasive nuclear factor-kappaB bioluminescence imaging for the assessment of host-biomaterial interaction in transgenic mice

Abstract

The inflammatory response is a key component in the biocompatibility of biomaterials. Among the factors that control the development of inflammation is a critical molecule nuclear factor-kappaB (NF-kappaB). Therefore, the aim of this study was to assess the feasibility of noninvasive whole-body real-time imaging for the evaluation of host-biomaterial interaction in the NF-kappaB transgenic mice. Transgenic mice, carrying the luciferase gene under the control of NF-kappaB, were constructed. In vivo bioluminescence imaging showed that the constitutive and induced NF-kappaB activities of transgenic mice were detected in most of the lymphoid tissues, demonstrating that NF-kappaB-driven luminescence reflected the inflammatory response in vivo. By the implantation of genipin-cross-linked gelatin conduit (GGC) and bacterial endotoxin-immersed GGC in the dorsal region, we detected a strong and specific luminescent signal from the tissue around the bacterial endotoxin-immersed GGC implant. Histological and immunohistochemical analysis also demonstrated that inflammation, characterized by the infiltration of immune cells, the accumulation of fluid, and the activation of NF-kappaB, was evoked around the same region. The correlation between the bioluminescence imaging and histological changes indicated that noninvasive imaging technique could be used to monitor the real-time inflammation in the implanted mice.