The main goal of this study is to evaluate potential applications of two zirconia—hydroxyapatite composites, Z4H6 and Z6H4, as bone substitutes. Composite plugs were implanted into the distal femoral metaphysis and also onto the longissimus dorsi of 18 adult mixed-breed dogs in order to assess in vivo biocompatibility by immediate clinical and radiographic evaluation 30, 90, and 120 days after implantation. Radiographic examination revealed radiolucency on the defect site. However, a progressive increase in bone density was observed over time, reaching a radiopacity similar to that of bone 120 days after implantation. Histological study revealed that a thin layer of fibroblasts was observed at the implant—bone interface in addition to osteoblastic activity 30 days after implantation, whereas bone neoformation around the implants was detected for the subsequent implantation times (90 and 120 days). Otherwise, the histological evaluation of the implant—muscle interface showed the presence of an initially thick fibrous tissue layer 30 days after implantation, which decreased with longer investigation times (90 and 120 days). The numbers of plasmocytes, lymphocytes, and macrophages gradually reduced as a function implantation time, being completely absent 120 days after implantation with a resulting complete osteointegration process. The zirconia phase content did not affect the bioactive behavior of the implants investigated and did not induce bone formation when implanted into muscle either.
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