Co-delivery of hydroxyapatite nanoparticles and methylprednisolone using sodium alginate/silk fibroin hydrogel for simultaneous bone mineralization and anti-inflammation actions

Abstract

Bone disorders such as osteoarthritis, rheumatoid arthritis, and bone fractures require simultaneous bone mineralization and anti-inflammatory treatments. Individual therapies might need high doses, increasing the risks of adverse effects. Hence, this research developed a dual-functional sodium alginate/silk fibroin hydrogel (SA/SF) co-encapsulating hydroxyapatite nanoparticles (CaP) for bone mineralization and methylprednisolone (MP) for anti-inflammatory activity. The SA/SF hydrogel was formulated by the ionic crosslinking process with Ca²⁺, where CaP particles and MP were loaded by mechanical mixing. The product structures were confirmed by X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR); the CaP size was determined by dynamic light scattering method; the MP release and bone mineralization was conducted in simulated bodily fluid, utilizing the UV–Vis spectroscopy and scanning electron microscopy, respectively. For the results, the dual-functional hydrogel was successfully prepared, with a MP drug loading efficiency of 97.1 %, a nano-sized CaP of 582 ± 33 nm, and appropriate chemical interactions. In the in vitro bone mineralization test, the SA/SF/CaP-MP hydrogel demonstrated the formation of hydroxyapatite crystals, which gradually increased (proven by crystallinity index, calculated from FT-IR data) as the mineralization time was extended from 0 to 7 days. Moreover, the release of MP from the hydrogel could be significantly controlled and prolonged for 7 days, reaching a maximum release efficiency of 76.12 %. Additionally, the SA/SF/CaP-MP hydrogel did not cause cell membrane irritation, proven by the HET-CAM results. These results collectively demonstrate that the SA/SF/CaP-MP hydrogel provides a promising dual-functional platform for bone regeneration and localized anti-inflammatory treatment.