Abstract

The goal of the present work was to investigate the relationship between in vivo healing and inflammatory response and in vitro cytokine expression by macrophages of a synthetic bone filler (25% hydroxylapatite-75% β-tricalcium phosphate) bearing a surface nanolayer of collagen. A clinically accepted, state-of-the-art xenograft material was used as a “negative control,” that is, as a material that provides the correct clinical response for the intended use. In vitro data show that both materials exert a very low stimulation of proinflammatory cytokines by macrophages, and this was confirmed by the very mild inflammatory response detected in in vivo tests of local response in a rabbit model. Also, in vitro findings suggest a different mechanism of healing for the test and the control material, with a higher regenerative activity for the synthetic, resorbable filler, as confirmed by in vivo observation and literature reports. Thus, the simple in vitro model adopted provides a reasonable forecast of in vivo results, suggesting that new product development can be guided by in vitro tuning of cell-materials interactions.

Highlights

  • In many cases dental implant therapy requires bone regeneration procedures through bone graft materials

  • We evaluated the endotoxinlike response on the two granular materials by analyzing the expression of interleukin 1β (IL-1β) and interleukin 6 (IL-6) after 4, 24, and 72 hours of cell culture

  • The inflammatory response was generally similar to that observed at 12 weeks with the exception that occasional focal accumulations of lymphocytes were observed around the implants in the bone marrow with both the products

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Summary

Introduction

In many cases dental implant therapy requires bone regeneration procedures through bone graft materials. (1) A “natural” healing mechanism, in which inflammatory cells behavior can be modulated to result in an advantageous biological local environment. (2) New bone ingrowth into the defect site, which should penetrate and replace the graft enabling the optimal balance between form and function. While most of the published papers on bone regeneration through graft materials involve bone cells behavior and new bone formation, inflammatory response at the implant site and its correlation with bone formation and resorption should be investigated. The expression ratio RANKL/OPG is a fundamental value to shift the balance between osteoblast and osteoclast activity and to drive the overall pathways towards bone formation or its resorption. The interaction of RANKL with its receptor RANK serves as a chemotactic and survival factor for osteoclasts [7, 8] and its expression is upregulated by molecules like

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