Role of a nitrogenous bisphosphonate (local delivery) incorporated vitreous coating (with/without polymer) on surgical grade SS316L implant material to improve fixation at the damaged tissue site

Abstract

Nitrogenous bisphosphonate, alendronate sodium (AS) was incorporated in the bilayered (layer 1, impervious and layer 2, porous) vitreous coating of phosphate free bioactive glass (PFBG) coated on surgical grade SS316L blocks, for a possible treatment of peri implant bone loss as a consequence of implantation at the fracture site, by local delivery. The presence of the drug in the pores (dia: 0.5–8 μm) of layer 2 was confirmed by SEM-EDX analysis. To control the drug release and thereby improve the efficacy of the system, the drug loaded vitreous layer was further coated with a thin layer (thickness: 1–2 μm) of poly(D,L-lactic-co-glycolic acid, PLGA). Irrespective of the polymer coating, the drug release kinetics were diffusion controlled from a porous matrix and the drug was fluorescently tagged and internalized by mouse macrophage cells (RAW 264.7) which was analysed by flow cytometry (FACS), followed by assessing the time dependent inhibitory action of the above drug on the osteoclastogenic cytokine, TNFα of the RAW 264.7 cell line, demonstrated by ELISA (enzyme-linked immunosorbent assay), and the same was confirmed and correlated by the time dependent growth inhibition of the transfected (from RAW 264.7 cell line) osteoclast cells by quantitative TRAP staining. The in vivo animal trial exhibited angiogenesis and initiation of bone remodelling in a New Zealand white rabbit model during the study period of 90 days, with or without a polymer coating and this mutual comparison has been highlighted in all the in vitro characterisation results too. In summary, an attempt has been made herewith to establish the versatility of alendronate sodium to promote improved fixation of the PFBG coated SS316L load bearing implants at the damaged tissue site, exhibiting an overall better response in the case of its polymer coated counterpart via an extended release profile, leading to a higher possibility of bone regeneration.