Surface topography of silicon nitride affects antimicrobial and osseointegrative properties of tibial implants in a murine model

Abstract

While silicon nitride (Si3N4) is an antimicrobial and osseosintegrative orthopaedic biomaterial, the contribution of surface topography to these properties is unknown. Using a methicillin-resistant strain of Staphylococcus aureus (MSRA), this study evaluated Si3N4 implants in vitro via scanning electron microscopy (SEM) and colony forming unit (CFU) assays, and later in an established in vivo murine tibia model of implant-associated osteomyelitis. In vitro, the “as-fired” Si3N4 implants displayed significant reductions in adherent bacteria versus machined Si3N4 (2.6×104 vs. 8.7×104 CFU, respectively; p< 0.0002). Moreover, SEM demonstrated that MRSA cannot directly adhere to native “as fired” Si3N4. Subsequently, a cross-sectional study was completed in which sterile or MRSA contaminated “as-fired” and machined Si3N4 implants were inserted into the tibiae of 8-week old female Balb/c mice, and harvested on day 1, 3, 5, 7, 10, or 14 post-op for SEM. The findings demonstrated that the antimicrobial activity of the “as-fired” implants resulted from macrophage clearance of the bacteria during biofilm formation on day 1, followed by osseointegration via the apparent recruitment of mesenchymal stem cells (MSC) on days 3–5, which differentiated into osteoblasts on days 7–14. In contrast, the antimicrobial behavior of the machined Si3N4 was due to repulsion of the bacteria, a phenomenon that also limited osteogenesis, as host cells were also unable to adhere to the machined surface. Taken together, these results suggest that the in vivo biological behavior of Si3N4 orthopaedic implants is driven by critical features of their surface nanotopography.

Dense, Strong, and Precise Silicon Nitride-Based Ceramic Parts by Lithography-Based Ceramic Manufacturing

“…They observed bacteria in 88% of the PEEK implants and 12% of the titanium implants whereas no bacteria were present adjacent to the silicon nitride implants. Similar results have also been observed by Ishikawa et al in tibial implants [8]. These properties, together with its excellent biocompatibility and mechanical strength, make silicon nitride to a very attractive material for biomedical engineering [9].…”

Silicon nitride enhances osteoprogenitor cell growth and differentiation via increased surface energy and formation of amide and nanocrystalline HA for craniofacial reconstruction

“…The HA significantly enhanced the hydrophilic character of the surface which ultimately promoted cell proliferation and differentiation. The slightly increased cell growth on the polished Si 3 N 4 compared to the rougher as‐fired Si 3 N 4 surface can be attributed to the nanostructured features on the rough surface that initially inhibit the cell attachment, but the highly reactive as‐fired Si 3 N 4 with its inherent surface properties lead to progressive transformation of cells towards enhanced osseointegration over time as reported by Ishikawa et al (). For both PEEK and Ti6Al4V samples, their contact angles decreased significantly after the first day, but slightly increased again after 4 days.…”

Silicon nitride bioceramics in healthcare

“…In another study, the antimicrobial activity and osseointegration of Si 3 N 4 were investigated in vitro and in vivo to further understand its antimicrobial activity and osseointegration . Using a methicillin‐resistant strain of S .…”

“…In the same study, sterile or MRSA‐contaminated implants of as‐fabricated and machined Si 3 N 4 were inserted for up to 14 days into the tibae of 8‐week‐old mice in vivo. SEM images (Figure ) of the harvested implants showed that the antimicrobial activity of the as‐fabricated implants resulted from macrophage clearance of the bacteria during biofilm formation on day 1, followed by osseointegration through the apparent recruitment of mesenchymal stem cells on days 3‐5, which differentiated into osteoblasts (bone‐forming cells) on days 7‐14.…”

“…As‐fabricated Si 3 N 4 implants with a microrough surface topography have shown enhanced antimicrobial activity and osseointegration when compared to standard implant materials such as stainless steel, titanium (Ti), and polyether ether ketone (PEEK) . Si 3 N 4 bearings have shown lower wear rates than cobalt‐chromium (CoCr) bearings and wear rates comparable to Al 2 O 3 ceramic bearings when articulating against polyethylene (ultrahigh molecular weight polyethylene, UHMWPE, or a cross‐linked UHMWPE, abbreviated XLPE), a commonly used material in orthopedic bearing couples .…”