Novel Bioactive Composite Material for Dental and Bone Restorations
Objectives: Our goal is to develop bioactive composite (inorganic-organic) materials that exhibit anti-inflammatory, anti-microbial and osteogenic properties needed for the next generation of dental and bone restorative needs.
Methods: A facile hydrothermal synthesis procedure was developed to produce a composite material composed of hydroxyapatite (inorganic component, HA) functionalized with 4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (organic component, DHA). Composition and morphology of HA-DHA composite material was validated using powder X-ray diffraction, Fourier Transform Infrared Spectroscopy, Thermal Gravimetric Analysis and Scanning Electron Microscopy. Anti-inflammatory activity of HA-DHA alone and with Aspirin co-treatment was assessed on murine RAW264.7 and human macrophages differentiated from primary CD14+ monocyte cell lines inflamed with Escherichia Coli derived Lipopolysaccharide (LPS-EC) by using the enzyme-linked immunosorbent assay (ELISA). Antimicrobial activity of HA-DHA was evaluated against planktonic and biofilm cultures of Streptococcus mutans (UA159). Osteogenic effect of HA-DHA on human fetal osteoblasts (hFOB1.19) was quantified by Alizarin Red S and Alkaline Phosphatase (ALP) staining.
Results: HA-DHA was validated as pure crystalline HA with DHA content of 13-20 mass %. In RAW264.7 and human microphage cells, co-treatment with HA-DHA and Aspirin downregulated the inflammatory response as evidenced by reduction in inflammatory cytokine TNF-a expression of 17% and 34%, respectively (p<0.05). HA-DHA inhibited planktonic and biofilm S. mutans growth by 40-fold and 6.9-fold, respectively (p<0.05 relative to controls). ALP activity was detected in differentiated osteoblasts treated with HA-DHA. Osteoblasts treated with HA-DHA also manifested mineral formation and deposition directly on the cells adjacent to the bioactive particles and indirectly on nearby osteoblasts, not in contact with any particles.
Conclusions: Novel HA-DHA material displays a spectrum of antimicrobial, anti-inflammatory and osteogenic activities and shows potential to meet several current clinical challenges.