Biological evaluation of zinc‐containing calcium alginate‐hydroxyapatite composite microspheres for bone regeneration

Zinc is an important element for bone structure and metabolism. Its interaction with hydroxyapatite has been investigated for the improvement of bone repair. The objective of this study was to evaluate the in vitro and in vivo biological response to nanostructured calcium alginate‐hydroxyapatite (HA) and zinc‐containing HA (ZnHA). Cytocompatibility was evaluated by applying PrestoBlue reagent after exposing murine pre‐osteoblast cells to extracts of each biomaterial microspheres. After physical and chemical characterization, the biomaterial microspheres were implanted in a critical size calvaria defect (8 mm) in Wistar rats (n = 30) that were randomly divided into the HA and ZnHA groups. Tissue samples were evaluated through histological and histomorphometric analyses after 1, 3, and 6 months (n = 5). The results showed cellular viability for both groups compared to the negative control, and no differences in metabolic activity were observed. The HA group presented a significant reduction of biomaterial compared with the ZnHA group in all experimental periods; however, a considerable amount of new bone formation was observed surrounding the ZnHA spheres at the 6‐month time point compared with the HA group (p