Biomedical devices fulfill many important roles in regenerative medicine: stabilizing injured tissue, supporting repair after trauma and restoring biological function. The materials chosen for implanted devices must be biocompatible and have the mechanical strength and stability to perform their intended task immediately post-implantation. An important aspect of device design is not only function at early time points, but compensating for the evolution of device properties over time. This is particularly relevant for devices that degrade in the body, producing degradation products that may also have physiological activity [1].

Even for well-characterized biocompatible materials, the degradation rate post-implantation can be variable due to the physiological environment [2,3]. Once implanted, device interactions are mediated by immune cells such as neutrophils and macrophages [4]. After the initial acute inflammatory reaction, macrophages are responsible for the majority of the foreign body response, and can promote revascularization and support fibrous encapsulation [5]. In addition, macrophages have been proposed to accelerate degradation of polymeric devices, as chronic inflammation has been linked to acidosis, for example within tumor microenvironments [6]. Extrapolating in vivo biomaterial degradation from in vitro degradation studies is problematic. To date, the majority of biomaterial degradation studies are conducted in buffers simulating a neutral physiological environment (saline, pH 7.4, 37°C), and in vivo degradation rates are significantly faster [7].

With in vivo material degradation remaining a black box, we have utilized non-invasive longitudinal imaging to measure the kinetics of material mass loss. Specifically, we have introduced radiopacity to several FDA-approved polymers by incorporating biocompatible tantalum oxide (TaOx) nanoparticle contrast agents into the polymer matrix [8], [9], [10]. This technique has been used to serially image porous tissue engineered devices via computed tomography (CT), a clinical imaging technique that can quickly and clearly distinguish implanted radiopaque material from surrounding tissues [11].

To further validate that TaOx nanoparticle incorporation does not significantly perturb biomaterials interactions post-implantation, we first investigated the in vitro response of macrophages to 0-20wt% TaOx nanoparticle addition to synthetic polymers in use for medical devices: polycaprolactone (PCL) [12] and poly(lactide-co-glycolide) (PLGA) [13]. With nanoparticles stimulating only a low inflammatory response, radiopaque devices were implanted subcutaneously in mice, with and without chronic inflammation induced at the site, to determine if an in vivo effect of inflammation on device degradation could be quantified. While serial monitoring is possible, contrast agent addition and the radiation exposure from CT can also influence the physiological environment around model implanted biomedical devices, skewing reported degradation kinetics. For this reason, we have demonstrated that serial radiation exposure did not influence the time course of degradation. Together this supports the use of TaOx NPs incorporated into polymers as a way to introduce imaging functionality into implanted medical devices, and potentially avoiding catastrophic device failure in the clinic through serial monitoring.