Biocompatibility of pure and mixed hydroxyapatite and α-tricalcium phosphate implanted in rabbit bone

Calcium phosphates and hydroxyapatite, in particular, are used as substitute materials in experimental implantology. These materials are primarily used in hard tissue replacement because their chemical and crystallographic characteristics are considered to be similar to the mineral content, osteoconductivity and bioactivity of normal bone. Cytokines, such as interleukin (IL)-1, IL-6, IL-8, IL-10 and antimicrobial protein β-defensin-2 (βDef-2), are used as biomarkers of non-specific reactogenicity. Other biomarkers, including bone morphogenetic protein-2/4 (BMP-2/4), bone regeneration protein osteoprotegerin (OPG), bone matrix protein osteopontin (OP) and osteocalcin (OC), are regarded as specific factors of reactogenicity in bone substitution. The aim of our study was to assess the changes in the distribution and expression of the aforementioned proteins in the lower jaws of rabbits following implantation with pure hydroxyapatite (HAP), α-tricalcium phosphate (α-TCP) or a mix of the two (HAP/α-TCP) manufactured under different temperatures. Our results reveal osteoblast proliferation and regions of granulation tissue formation between biomaterial granules close to the original implantation site, but in the control tissue these changes were less noticeable. Our study showed low variability in the distribution of βDef-2, OPG and all of the tested interleukins and these proteins were less expressed than BMP2/4, OP and OC. But across all experiments, no statistically significant difference in mean βDef-2, IL-1, IL-6, IL-8, IL-10, OP, OC, BMP-2/4 and OPG expression in osteocytes was detected between experimental and control groups. We concluded that pure and mixed HAP and α-TCP sintered at different temperatures do not affect the production of cytokines and bone-specific proteins; regions with osteoblast proliferation and low levels of anti-inflammatory cytokines IL-6 and IL-10 indicates better biocompatibility for HAP/α-TCP and α-TCP-2 biomaterials and the moderate number of BMP-2/4- and a prevalence of OC- and OP-positive osteocytes in experimental tissues implanted with HAP at 3 months after implantation indicates potential bone regeneration stimulated by pure HAP.