Cytocompatibility and biocompatibility of nanostructured carbonated hydroxyapatite spheres for bone repair

Abstract

Objective The aim of this study was to investigate the in vitro and in vivo biological responses to nanostructured carbonated hydroxyapatite/calcium alginate (CHA) microspheres used for alveolar bone repair, compared to sintered hydroxyapatite (HA).Material and Methods The maxillary central incisors of 45 Wistar rats were extracted, and the dental sockets were filled with HA, CHA, and blood clot (control group) (n=5/period/group). After 7, 21 and 42 days, the samples of bone with the biomaterials were obtained for histological and histomorphometric analysis, and the plasma levels of RANKL and OPG were determined via immunoassay. Statistical analysis was performed by Two-Way ANOVA with post-hoc Tukey test at 95% level of significance.Results The CHA and HA microspheres were cytocompatible with both human and murine cells on an in vitro assay. Histological analysis showed the time-dependent increase of newly formed bone in control group characterized by an intense osteoblast activity. In HA and CHA groups, the presence of a slight granulation reaction around the spheres was observed after seven days, which was reduced by the 42nd day. A considerable amount of newly formed bone was observed surrounding the CHA spheres and the biomaterials particles at 42-day time point compared with HA. Histomorphometric analysis showed a significant increase of newly formed bone in CHA group compared with HA after 21 and 42 days from surgery, moreover, CHA showed almost 2-fold greater biosorption than HA at 42 days (two-way ANOVA, p<0.05) indicating greater biosorption. An increase in the RANKL/OPG ratio was observed in the CHA group on the 7th day.Conclusion CHA spheres were osteoconductive and presented earlier biosorption, inducing early increases in the levels of proteins involved in resorption.

Impact of crystallinity and crystal size of nanostructured carbonated hydroxyapatite on pre‐osteoblast in vitro biocompatibility

“…In accordance with this statement, the present results contribute with in vitro evidence that, even at high doses and after marked internalization, nCHA colloidal suspensions cause no adverse effects to bone cells, most probably due to their state of aggregation. Therefore, our results may provide insights into the results of in vivo studies indicating lack of local toxicity after complete fragmentation of grafted nanostructured CHA biomaterials (Barros et al, 2011;Calasans-Maia et al, 2015;Valiense et al, 2015;Valiense & Fernandes, 2012). Nevertheless, further studies assessing other biological parameters such as oxidative stress and cell differentiation may help clarify the effects of direct and indirect exposure to nCHA materials with different crystallinities on the clinical outcome of bone therapy.…”

“…The synthesis conditions affect the carbonate incorporation, crystallinity, particle size, solubility, and biocompatibility of nanostructured carbonated HA (nCHA) (LeGeros, 2008). Previous studies reported the in vivo degradation of nCHA spheres and granules soon after grafting, which caused an observable release of nanoparticles and agglomerates into the surrounding tissues, even though without apparent impact on the inflammatory response or any adverse effects (Barros et al, 2011;Calasans-Maia et al, 2015;Valiense et al, 2015;Valiense & Fernandes, 2012). Such release of NPs or aggregates as products from the degradation/fragmentation of nanostructured biomaterials is of particular concern for biocompatibility.…”

Evaluation of highly carbonated hydroxyapatite bioceramic implant coatings with hierarchical micro-/nanorod topography optimized for osseointegration

“…15 CHA-related investigations have largely reached a consensus on its excellent biocompatibility and bio-resorption properties, yet conflicting results regarding the biological effects on osteoblasts, including adhesion, proliferation and osteogenic differentiation, are still being reported. [11][12][13]15,16 The genuine biological functions of CHA biomaterials compared with those of HA products still remain ambiguous and relatively undesirable, mostly because the content of carbonate incorporated into HA was either undetermined or limited to a low concentration range according to the available literature. As a matter of fact, HA with a higher carbonate content mimicking early biomineralization could contribute to better cell behaviors, as implied by a study involving a wide spectrum of carbonate concentrations from 0 to 16.1 wt%.…”

Biofilm formation of periodontal pathogens on hydroxyapatite surfaces: Implications for periodontium damage

“…Hydroxyapatite (HA) biomaterials have composition that is highly similar to bone minerals and bone apatite. Hence, HA has been established as a biocompatible material that chemically binds to bone and induces no local or systemic toxicity or inflammation . Dental applications of HA include oral surgeries for implantology and periodontal regeneration, such as pulp capping, apical barrier formation, and repair of periapical defects …”

“…Hence, HA has been established as a biocompatible material that chemically binds to bone and induces no local or systemic toxicity or inflammation. 4,5 Dental applications of HA include oral surgeries for implantology and periodontal regeneration, 4 such as pulp capping, apical barrier formation, and repair of periapical defects. 6,7 In this study, bacterial activities against the dense and porous type HAs were investigated as models for enamel and dentin, respectively.…”