Initial bone tissue reactions of hydroxyapatite/collagen–(3-glycidoxypropyl)trimethoxysilane injectable bone paste

We have previously reported that a novel bioresorbable self-setting injectable bone paste composed of hydroxyapatite/collagen bone-like nanocomposite (HAp/Col) and (3-glycidoxypropyl)trimethoxysilane (GPTMS) was successfully prepared and was replaced with new bone within 3 months of implantation in defects created in porcine tibia. In this study, the HAp/Col-GPTMS paste was implanted into bone defects in rat tibiae to investigate the initial kinetics and bone tissue response. Even though more than 35% of GPTMS molecules should be eluted rapidly from directly injected pastes according to previously reported cell culture tests, in this study, energy-dispersive X-ray spectrometry did not detect Si (GPTMS) deposition in tissues surrounding the paste at 1 day postimplantation. Further, no abnormal inflammatory responses were observed in the surrounding tissues over the test period for both directly injected and prehardened pastes. Companying these observations with the results of the previous animal test (in which the paste was fully resorbed and was substituted with new bone), the eluted GPTMS resolved in no harm in vivo from the initial to final (completely resorbed) stages. Material resorption rates calculated from X-ray microcomputed tomography (μ-CT) images decreased with increasing in GPTMS concentration. Histological observations indicated that tartrate-resistant acid phosphatase (TRAP) active cells, (assumed to be osteoclasts), exist on the periphery of pastes. This result suggested that the paste was resorbed by osteoclasts in the same way as the HAp/Col. Since a good correlation was observed between TRAP active areas in histological sections and material resorption rate calculated from μ-CT, the TRAP activity coverage ratio offers the possibility to estimate the osteoclastic resorption ratio of materials, which are replaced with bone via bone remodeling process.