Cyclosporine A impairs bone repair in critical defects filled with different osteoconductive bone substitutes

Abstract

The aim of this study was to assess the influence of cyclosporine administration on the repair of critical-sized calvaria defects (CSDs) in rat calvaria filled with diverse biomaterials. Sixty animals were divided into two groups: the control (CTR) group (saline solution) and the cyclosporine (CCP) group (cyclosporine, 10 mg/kg/day). These medications were administered daily by gavage, beginning 15 days before the surgical procedure and lasting until the day the animals were euthanized. A CSD (5 mm Ø) was made in the calvaria of each animal, which was allocated to one of 3 subgroups, according to the biomaterial used to fill the defect: coagulum (COA), deproteinized bovine bone (DBB), or biphasic calcium phosphate ceramics of hydroxyapatite and β-phosphate tricalcium (HA/TCP). Euthanasia of the animals was performed 15 and 60 days after the surgical procedure (n = 5 animals/period/ subgroup). Bone repair (formation) assessment was performed through microtomography and histometry, while the analyses of the expression of the BMP2, Osteocalcin, and TGFβ1 proteins were performed using immunohistochemistry. The CSDs not filled with biomaterials demonstrated lower bone formation in the CCP group. At 15 days, less bone formation was observed in the CSDs filled with DBB, a smaller volume of mineralized tissue was observed in the CSDs filled with HA/TCP, and the expression levels of BMP2 and osteocalcin were lower in the CCP group compared to the CTR group. The use of cyclosporine impaired bone repair in CSD, and this effect can be partially explained by the suppression of BMP2 and osteocalcin expression.

Comparison of the osseointegration of implants placed in areas grafted with HA/TCP and native bone

“…However, the volumetric reduction of HA/TCP can be around 20% (Favato et al, 2015) without necessarily being associated with the formation of bone tissue (Prisinoto et al, 2020), which may have influenced the smaller volume of mineralized tissues around the implant in the grafted areas with HA/TCP compared with the volume around implants placed in NB observed in this study. In addition, it is likely that the soft tissues constitute a large part of the newly formed tissues in the grafted area (de Coster et al, 2011;Gonçalves et al, 2020), and this may also have influenced the lower degree of osseointegration and biomechanical locking in implants installed in grafted areas with HA/TCP compared to implants installed in NB areas. In fact, previous preclinical and clinical studies have shown that the further away the grafts are from the bone walls, the smaller is the bone formation in the grafted area (Araújo & Lindhe, 2009;de Coster et al, 2011;Pignaton et al, 2020;Prisinoto et al, 2020) the experimental model used in this study, the implants were installed in the middle of the bone defect, which would be the most critical area for bone formation.…”