An in vivo toxicity assessment of piezoelectric sodium potassium niobate [NaxK1-xNbO3 (x = 0.2-0.8)] nanoparticulates towards bone tissue engineering approach

Abstract

One of the recent challenges in the design/development of prosthetic orthopedic implants is to address the concern of local/systemic toxicity of debris particles, released due to wear or degradation. Such debris particles often lead to inflammation at the implanted site or aseptic loosening of the prosthesis which results in failure of the implant during long run. Several in vitro studies demonstrated the potentiality of piezoelectric sodium potassium niobate [Na_xK_1-xNbO₃ (x = 0.2, 0.5, 0.8), NKN] as an emerging next-generation polarizable orthopedic implant. In this perspective, we performed an in vivo study to examine the local and systemic toxicity of NKN nanoparticulates, as a first report. In the present study, male Wistar rats were intra-articularly injected to the knee joint with 100 μl of NKN nanoparticulates (25 mg/ml in normal saline). After 7 days of exposure, the histopathological analyses demonstrate the absence of any inflammation or dissemination of nanoparticulates in vital organs such as heart, liver, kidney and spleen. The anti-inflammatory cytokines (IL-4 and IL-10) profile analyses suggest the increased anti-inflammatory response in the treated rats as compared to non-injected (control) rats, preferably for the sodium and potassium rich NKN i.e., Na_0.8K_0.2NbO₃ and Na_0.2K_0.8NbO₃. The biochemical analyses revealed no pathological changes in the liver and kidney of particulate treated rats. The present study is the first proof to confirm the non-toxic nature of NKN nanoparticulates which provides a step forward towards the development of prosthetic orthopedic implants using biocompatible piezoelectric NKN ceramics.

Keywords: Debris; Histopathological analyses; Inflammation; Na(x)K(1-x)NbO(3); Orthopedic implant; Toxicity.