A novel vertical aligned mesoporous silica coated nanohydroxyapatite particle as efficient dexamethasone carrier for potential application in osteogenesis

Abstract

Bone defect is a common problem and inducing osteoblasts differentiation is the key process for the regenerative repair. Recently, the mesoporous silica (MS) coated nanohydroxyapatite (nHA) particles (nHA-MS) has shown enhanced intrinsic potency for bone regeneration, whereas whether the osteogenesis potency can be further enhanced after drug delivery has not been investigated. In this study, the nHA-MS was fabricated by a novel biphase stratification growth way. The cytotoxicity in MC3T3-E1 was validated by MTT assay, apoptosis analysis and cell cycle examination. The cell uptake was observed by confocal laser scanning microscope and transmission electron microscope respectively. After adsorption with dexamethasone (DEX), the osteogenic differentiation was determined both in vitro and in vivo. The synthesized nHA-MS showed a core–shell structure that the nanorod-like nHA was coated by a porous MS shell (∼5 nm pores diameter, ∼50 nm thickness). A dose-dependent cytotoxicity was observed and below 10 µg ml−1 was a safe concentration. The nHA-MS also showed efficient cell uptake efficiency and more efficient in DEX loading and release. After DEX adsorption, the nanoparticles exhibited enhanced osteogenic induction in MC3T3-E1 and rat calvarial bone defect regeneration. In conclusion, the nHA-MS is a favorable platform for drug delivery to obtain more enhanced osteogenesis capabilities.

Nano-Hydroxyapatite as a Delivery System for Promoting Bone Regeneration In Vivo: A Systematic Review

“…The eligible articles included in this review were primary studies published between 2005 and 2021. Nine studies were performed using rats [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], four studies used rabbits [ 29 , 30 , 31 , 32 ], and one study used dogs [ 33 ] as animal models. The total number of animals used is 15–56 for rats, 16–45 for rabbits, and 8 for dogs.…”

“…The total number of animals used is 15–56 for rats, 16–45 for rabbits, and 8 for dogs. However, one of the studies included in this review did not mention the total number of animals involved [ 22 ].…”

“…Most animals had defects created either on the tibia [ 33 ], femur [ 21 , 25 , 31 ], or cranium [ 20 , 22 , 23 , 26 , 27 , 28 , 30 , 32 ] prior to implantation of treatments into the defect sites. Most of the studies used the critical-sized defects with a diameter ranging between 3 and 8 mm in rats, created by drilling circular transosseous defects [ 20 , 21 , 22 , 23 , 26 , 27 , 28 ]. A large-sized defect in dogs used in a study by Itoh et al (2005) was 20 mm in diameter, whilst Su et al (2013) induced a 26 × 5 × 3 mm 3 defect in rabbits.…”

“…Majority of the studies reviewed here reported that animals treated with nHA-based scaffolds, bone grafts, or hydrogel implants displayed effective bone repair compared to the untreated defects ( Table 3 , Table 4 and Table 5 ). Generally, the group of animals with nHA interventions had greater bone volume (BV), tissue volume (TV), percentage of bone volume over tissue volume (% BV/TV), and callus formation at the defect site compared to the untreated animals (blank control) [ 20 , 21 , 22 , 23 , 26 , 27 , 28 , 30 , 31 , 33 ]. The animals without nHA intervention in these studies either did not show any bone bridging [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 33 ] or did not survive throughout the study period [ 32 ].…”

“…Four studies explored the application of nHA for the delivery of other drugs or bioactive molecules such as dexamethasone [ 22 , 27 ], calcitriol [ 21 ], and cisplatin [ 31 ] ( Table 5 ). The conjugation of nHA-based scaffolds or hydrogel systems with these compounds were able to further improve the bone regeneration process.…”