Effect of nano-structural properties of biomimetic hydroxyapatite on osteoimmunomodulation

Abstract

Immune cells are sensitive to the microstructural and textural properties of materials. Tuning the structural features of synthetic bone grafts could be a valuable strategy to regulate the specific response of the immune system, which in turn modulates the activity of bone cells. The aim of this study was to analyse the effect of the structural characteristics of biomimetic calcium deficient hydroxyapatite (CDHA) on the innate immune response of macrophages and the subsequent impact on osteogenesis and osteoclastogenesis. Murine RAW 264.7 cells were cultured, under standard and inflammatory conditions, on chemically identical CDHA substrates that varied in microstructure and porosity. The impact on osteogenesis was evaluated by incubating osteoblastic cells (SaOS-2) with RAW-CDHA conditioned extracts. The results showed that macrophages were sensitive to different textural and structural properties of CDHA. Under standard conditions, the impact of inflammatory cytokine production by RAW cells cultured on CDHA played a significant role in the degradation of substrates, suggesting the impact of resorptive behaviour of RAW cells on biomimetic surfaces. Osteoblast differentiation was stimulated by the conditioned media collected from RAW cells cultured on needle-like nanostructured CDHA. The results demonstrated that needle-like nanostructured CDHA was able to generate a favourable osteoimmune environment to regulate osteoblast differentiation and osteogenesis. Under inflammatory conditions, the incubation of RAW cells with less porous CDHA resulted in a decreased gene expression and release of pro-inflammatory cytokines.

Impact of Biomimicry in the Design of Osteoinductive Bone Substitutes: Nanoscale Matters

“…We recently showed through an in vitro study that tuning the nanostructural features of CDHA is an effective method to control the response of immune cells. 15 This is in line with other in vitro studies that have demonstrated that the size and shape of nanocrystals in nanostructured biomaterials exert a direct effect on cells involved in osteoinduction. [16][17][18][19] However, these results cannot be extrapolated to the very different in vivo scenario.…”

“…We observed that macrophages were sensitive to the nanostructural features and, when cultured on needle-like Fine-CDHA substrates, the cytokines generated by macrophages were able to trigger osteoblastic differentiation and osteogenesis. 15 Regarding the degradation behavior, large differences were observed between the different foams, despite the identical or similar chemical composition between groups. Coarse-CDHA foams, with the lowest SSA, were the least resorbable scaffolds, being the only group where scaffold resorption did not progress overtime ( Figure 6A).…”

Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration

“…4). 100 In addition, Jin et al also have demonstrated that the immune response of macrophages could be stimulated through some physicochemical properties of nanostructured biomaterial scaffolds. 65 They have showed the biomimetic hierarchical nanointerface can facilitate M2 macrophage polarization and interleukin-4 secretion to promote stem cell osteogenesis and endogenous bone regeneration.…”

The Influence of Physicochemical Properties of Biomimetic Hydroxyapatite on the In Vitro Behavior of Endothelial Progenitor Cells and Their Interaction with Mesenchymal Stem Cells

“…F-CDHA and C-CDHA, might produce different ionic fluctuations and thereby affect the cellular behaviour to different extents. Another interesting issue is that expected ionic fluctuations might vary depending of medium composition [34,36] as well as presence or not of cells [39] . In the latter case, the layer of cells might reduce the exposure of the substrate to different extents depending on the degree of surface coverage, which in turn would decrease the ionic exchange.…”