Amorphous Silica: A New Antioxidant Role for Rapid Critical‐Sized Bone Defect Healing

Abstract

Traumatic fractures cause structurally unstable sites due to severe bone loss. Such fractures generate a high yield of reactive oxygen species (ROS) that can lead to oxidative stress. Excessive and prolonged ROS activity impedes osteoblast differentiation and instigates long healing times. Stimulation of antioxidants such as superoxide dismutase (SOD1), are crucial to reduce ROS, stimulate osteogenesis, and strengthen collagen and mineral formation. Yet, no current fixative devices have shown an ability to enhance collagen matrix formation through antioxidant expression. This study reports plasma-enhanced chemical vapor deposition based amorphous silicon oxynitride (Si(ON)x) as a potential new fracture healing biomaterial that adheres well to the implant surface, releases Si(+4) to enhance osteogenesis, and forms a surface hydroxyapatite for collagen mineral attachment. These materials provide a sustained release of Si(+4) in physiological environment for extended times. The dissolution rate partially depends on the film chemistry and can be controlled by varying O/N ratio. The presence of Si(+4) enhances SOD1, which stimulates other osteogenic markers downstream and leads to rapid mineral formation. In vivo testing using a rat critical-sized calvarial defect model shows a more rapid bone-regeneration for these biomaterials as compared to control groups, that implies the clinical significance of the presented biomaterial.

Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes

“…After this time, the surface was analysed for the formation of possible hydroxyapatite crystallites (Figure d). We confirmed the presence of these crystals, which resembled nano‐hydroxyapatite (nano‐HA) crystals, as was observed in our previous work (Ilyas et al, ).…”

“…These findings suggest that the silicon ion can limit cell death during the first 24 hr, on cells exposed to unfavourable oxidative stress present in injuries and bone loss. Recently, a few studies have been focused on effects of biomaterials/implants used on oxidative stress induced by bone defects (Ilyas et al, ; Sansone, Pagani, & Melato, ). These studies have focused on the long‐term outcome of oxidative stress and its association with implant loosening and failure (Kinov et al, ; Pietropaoli et al, ; Sansone et al, ).…”

“…All coatings were processed at a substrate temperature of 400°C, a chamber pressure of 900 mTorr, an inductively coupled plasma (ICP) power of 30 W, and an applied excitation frequency of 13.56 MHz. The source and flow rate of gas were as follows: 24 for SiH 4 /AR (15/85%), 155 for N 2 O, 225 for N 2 , and 50 for NH 4 (Ilyas et al, , ).…”

“…Flower Mound, TX, USA) and placed in 4 ml of cell culture medium (α‐MEM) at 37°C and 5% CO 2 , for 6 weeks without cells. The Si 4+ concentration was measured using ICP optical emission spectrometry (ICP‐OES, ICPE‐9000, SHIMAZU Co., Kyoto, Japan) as described in previous publications (Ilyas et al, ). The study was conducted for 6 weeks, with a 1‐week interval, and media change every 48 hr ( n = 3).…”

“…Then, the media was exchanged with growth media with 50 ppm ascorbic acid‐2‐phosphate (AA2P, Sigma‐Aldrich Corp., St. Louis, MO, USA) and glycerol‐2‐phosphate (β‐GP, Sigma‐Aldrich Corp.) for differentiation. At 3 and 4 days after differentiation, the SOD‐1 mRNA levels were measured according to the method described in previous publications (Ilyas et al, ; Odatsu et al, ). We used GAPDH as the housekeeping gene for measuring mRNA levels.…”