Objective: Our previous studies found out that one of the main parameter inducing cell reaction of micro/nano particles is their size. These results showed that abrasion particles from various implants have important role in the inflammation cascade. The aim of the present study was to investigate the proinflammatory responses of micro/nano particles made of various materials. Methods: We studied the cytotoxicity and the size effect of titanium, titanium dioxide and poly(DL-Lactic-co-Glycolide) particles by in vivo animal tests and in vitro cell functional examinations. Results: In vivo experiments showed greater neutrophil influx in the rat hypodermical tissue after implantation for particles smaller than 3 mm compared with larger particles. These pathological reactions were reflected to the proinflammatory cytokines and superoxide anion in vitro examinations. In vitro study showed greater oxidant activity and significant increase of proinframmatory cytokines TNF-a and IL-1b with rat macrophages and significant increases in IL-8 expression with fibroblast-like cells from human periodontal ligament by adding particles smaller than 3mm. Therefore, in vivo results were in good agreement with those of in vitro study. Conclusion: These in vitro results suggest that fine particles with size less than 3 mm induce proinflammatory cascade, even if they are made of low-toxicity material e.g., Ti,TiO2 and PLA.

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