Transforaminal lumbar interbody fusion with a silicon nitride cage demonstrates early radiographic fusion.

Background: Degeneration of the lumbar spine is common in aging adults and reflects a significant morbidity burden in this population. In selected patients that prove unresponsive to non-surgical treatment, posterior lumbar fusion (PLF) surgery, with or without adjunctive transforaminal lumbar interbody fusion (TLIF) can relieve pain and improve function. We describe here the radiographic fusion rates for PLF versus TLIF, using an intervertebral spinal cage made of silicon nitride ceramic (chemical formula Si3N4). Methods: This retrospective cohort analysis enrolled 99 patients from August 2013 to January 2017; 17 had undergone PLF at 24 levels, while 82 had undergone TLIF at 104 levels. All operations were performed by a single surgeon at one institution. Radiographic and clinical outcomes were compared between PLF and TLIF at 2 and 6 weeks and then at 3, 6, 12, and 24 months. Results: TLIF patients fused at higher rates compared to PLF at the 3-month (38.5% vs. 8.3%, P=0.006), 6-month (78.7% vs. 35.0%, P<0.001) and 12-month time periods (97.9% vs. 81.3%, P=0.018), with no difference at 24 months (100% vs. 94.4%, P=0.102). Index level segmental motion was significantly less and intervertebral disc height was improved in TLIF over PLF at all follow up intervals. Foraminal height was only greater in early follow up periods (2 weeks, 6 weeks and 3 months). TLIF patients experienced lover rates of PI-LL mismatch which was maintained across long term follow-up. Pelvic tilt was lower following TLIF compared to PLF, with no differences in complication rates between study groups. Conclusions: Our retrospective series demonstrated that TLIF performed with silicon nitride interbody cages led to earlier radiographic fusion, greater restoration of disc and foraminal height, increased segmental rigidity and improved sagittal alignment when compared to PLF alone.

Antifungal activity of polymethyl methacrylate/Si3N4 composites against Candida albicans.

Previous studies using gram-positive and -negative bacteria demonstrated that hydrolysis of silicon nitride (Si3N4) in aqueous suspensions elutes nitrogen and produces gaseous ammonia while buffering pH. According to immunochemistry assays, fluorescence imaging, and in situ Raman spectroscopy, we demonstrate here that the antipathogenic surface chemistry of Si3N4 can be extended to polymethylmethacrylate (PMMA) by compounding it with a minor fraction (~8 vol.%) of Si3N4 particles without any tangible loss in bulk properties. The hydrolytic products, which were eluted from partly exposed Si3N4 particles at the composite surface, exhibited fungicidal action against Candida albicans. Using a specific nitrative stress sensing dye and highly resolved fluorescence micrographs, we observed in situ congestion of peroxynitrite (ONOO-) radicals in the mitochondria of the Candida cells exposed to the PMMA/Si3N4 composite, while these radicals were absent in the mitochondria of identical cells exposed to monolithic PMMA. These in situ observations suggest that the surface chemistry of Si3N4 mimics the antifungal activity of macrophages, which concurrently produce NO radicals and superoxide anions (O2•-) resulting in the formation of candidacidal ONOO-. The fungicidal properties of PMMA/Si3N4 composites could be used in dental appliances to inhibit the uncontrolled growth of Candida albicans and ensuing candidiasis while being synergic with chemoprophylaxis. STATEMENT OF SIGNIFICANCE: In a follow-up of previous studies of gram-positive and gram-negative bacteria, we demonstrate here that the antipathogenic surface chemistry of Si3N4 could be extended to polymethylmethacrylate (PMMA) containing a minor fraction (~8 vol.%) of Si3N4 particles without tangible loss in bulk properties. Hydrolytic products eluted from Si3N4 particles at the composite surface exhibited fungicidal action against Candida albicans. Highly resolved fluorescence microscopy revealed congestion of peroxynitrite (ONOO-) radicals in the mitochondria of the Candida cells exposed to the PMMA/Si3N4 composite, while radicals were absent in the mitochondria of identical cells exposed to monolithic PMMA. The fungicidal properties of PMMA/Si3N4 composites could be used in dental appliances to inhibit uncontrolled growth of Candida albicans and ensuing candidiasis in synergy with chemoprophylaxis.

Silicon nitride: a potent solid-state bioceramic inactivator of ssRNA viruses.

Surface inactivation of human microbial pathogens has a long history. The Smith Papyrus (2600 ~ 2200 B.C.) described the use of copper surfaces to sterilize chest wounds and drinking water. Brass and bronze on doorknobs can discourage microbial spread in hospitals, and metal-base surface coatings are used in hygiene-sensitive environments, both as inactivators and modulators of cellular immunity. A limitation of these approaches is that the reactive oxygen radicals (ROS) generated at metal surfaces also damage human cells by oxidizing their proteins and lipids. Silicon nitride (Si3N4) is a non-oxide ceramic compound with known surface bacterial resistance. We show here that off-stoichiometric reactions at Si3N4 surfaces are also capable of inactivating different types of single-stranded RNA (ssRNA) viruses independent of whether their structure presents an envelop or not. The antiviral property of Si3N4 derives from a hydrolysis reaction at its surface and the subsequent formation of reactive nitrogen species (RNS) in doses that could be metabolized by mammalian cells but are lethal to pathogens. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) tests of viral RNA and in situ Raman spectroscopy suggested that the products of Si3N4 hydrolysis directly react with viral proteins and RNA. Si3N4 may have a role in controlling human epidemics related to ssRNA mutant viruses.

Two-year results of a double-blind multicenter randomized controlled non-inferiority trial of polyetheretherketone (PEEK) versus silicon nitride spinal fusion cages in patients with symptomatic degenerative lumbar disc disorders.

BACKGROUND: During lumbar spinal fusion, spacer cages are implanted to provide vertebral stability, restore sagittal alignment, and maintain disc and foraminal height. Polyetheretherketone (PEEK) is commonly used by most spine surgeons. Silicon nitride (Si3N4) is a less well-known alternative although it was first used as a spacer in lumbar fusion over 30 years ago. The present study was designed to see if Si3N4 cages would perform similarly to PEEK in a randomized controlled trial. METHODS: A non-inferiority multicenter 100-patient study was designed where both the observer and patient were blinded. Single- or double-level transforaminal lumbar interbody fusion with pedicle screw fixation using an oblique PEEK or Si3N4 cage was performed. The primary non-inferiority outcome was the Roland-Morris Disability Questionnaire (RMDQ). Secondary measures included the Oswestry Disability Questionnaire, Visual Analogue Scales (VAS) for back and leg pain, SF-36 Physical and Mental Function indices, patient and surgeon Likert scores on perceived recovery, and X-ray and CT radiological evaluations for subsidence, segmental motion, and fusion. Follow-up evaluations occurred at 3, 6, 12, and 24 months. RESULTS: After exclusions for protocol violations and canceled surgeries, 92 patients were randomized (i.e., 48 for PEEK and 44 for Si3N4). There were no differences in baseline demographics, pre-operative disabilities, or pain scores between the groups. Both treatment arms showed significant improvements in disability, pain, and recovery scores. No significant differences were observed for subsidence, segmental motion, or fusion. For the primary outcome (i.e., RMDQ scores), the non-inferiority of Si3N4 compared to PEEK could not be established using the original protocol criteria. However, the comparison was undermined by larger than anticipated patient fallout coupled with higher than expected RMDQ score standard deviations. A post hoc analysis coupled with a more extensive review of the literature was conducted which resulted in the selection of a revised clinically justified non-inferiority margin; and using this method, the non-inferiority of Si3N4 was affirmed. CONCLUSIONS: This study demonstrated that the use of either PEEK or Si3N4 cages is safe and effective for patients undergoing lumbar spine fusion for chronic degenerative disc disease.

Surface functionalization of PEEK with silicon nitride.

Surface roughness, bioactivity, and antibacterial properties are desirable in skeletal implants. We hot-pressed a mix of particulate sodium chloride (NaCl) salt and silicon nitride (ß-Si3N4) onto the surface of bulk PEEK. NaCl grains were removed by leaching in water, resulting in a porous PEEK surface embedded with sim15 vol% ß-Si3N4particles. This functionalized surface showed the osteogenic and antibacterial properties previously reported in bulk silicon nitride implants. Surface enhancement of PEEK with ß-Si3N4could improve the performance of spinal fusion cages, by facilitating arthrodesis and resisting bacteria.

Clinical outcomes for lumbar fusion using silicon nitride versus other biomaterials.

BACKGROUND: In lumbar fusion surgery, intervertebral spacer cages made of silicon nitride (Si3N4) ceramic are an available option among other biomaterials. While the surface chemistry of Si3N4 is known to favor bone fusion, large-scale clinical studies attesting to its efficacy are lacking. This multicenter retrospective study compared lumbar fusion outcomes for Si3N4 cages to previously reported data for other cage materials. METHODS: Pre-operative patient demographics, comorbidities, changes in visual analog scale (ΔVAS) pain scores, complications, adverse events, and secondary surgical interventions (SSI) were compiled from the records of 450 patients who underwent Si3N4 lumbar spinal fusion at four separate U.S. surgical centers. For comparison, MEDLINE/PubMed and Google Scholar searches identified studies reporting similar outcomes for other biomaterials. A total of 1,025 patients from 26 cohorts reported in 14 publications met inclusion criteria for this control group. RESULTS: Overall, the mean last-follow-up for all patients was 341±293 days (11.4±9.8 months), with the longest follow-up being 6.4 years. Patients with Si3N4 implants were similar in gender and age distribution to the control group but had higher BMI values (30.9±6.1 vs. 25.8±4.1, P<0.01) and lower tobacco use (15.8% vs. 30.0%, P<0.01). Both the Si3N4 and control groups showed significant improvements in VAS pain scores from preoperative to last follow-up. For the Si3N4 group, ΔVAS was 36.8±35.4 points compared to 37.6±22.5 points (P=0.63) for the metadata group. Complications and reoperations for the Si3N4 and the control groups were similar (i.e., 9.8% and 3.1% versus 12.4% and 2.9%, P=0.16 and P=0.84, respectively). CONCLUSIONS: Lumbar fusion with Si3N4 spacers compared favorably with the improvements reported with other commonly used biomaterial cages.

3D-additive deposition of an antibacterial and osteogenic silicon nitride coating on orthopaedic titanium substrate.

A 3D-additive manufacturing approach produced a dense Si3N4 ceramic coating on a biomedical grade commercially pure titanium (cp-Ti) substrate by an automatic laser-sintering procedure. Si3N4 coatings could be prepared with thicknesses from the single to the tens of microns. A coating thickness, t = 15 ± 5 µm, was selected for this study, based on projections of homogeneity and scratching resistance. The Si3N4 coating met the 20 N threshold required for biomaterial applications, according to the standard scratch testing (ASTM C1624-05). The Si3N4 coating imparted both the antibacterial and osteogenic properties of bulk Si3N4 to the cp-Ti substrate. Both properties were comparable to those previously described for bulk Si3N4 biomedical implants. The newly developed Si3N4-coating was applied to commercially available Ti-alloy acetabular shells for total hip arthroplasty. A "glowing" test based on luciferase gene transformation was applied to visualize the colonization of gram-negative Escherichia coli on Si3N4-coated and uncoated Ti-alloy acetabular shells. The results showed that the coating technology conferred resistance to Staphylococcus epidermidis and Escherichia coli adhesion onto the bulk acetabular sockets.

Burst Strength of BIOLOX®delta Femoral Heads and Its Dependence on Low-Temperature Environmental Degradation.

Zirconia-toughened alumina (ZTA) currently represents the bioceramic gold standard for load-bearing components in artificial hip joints. ZTA is long known for its high flexural strength and fracture toughness, both properties arising from a microscopic crack-tip shielding mechanism due to the stress-induced tetragonal-to-monoclinic (t→m) polymorphic transformation of zirconia. However, there have been concerns over the years regarding the long-term structural performance of ZTA since the t→m transformation also spontaneously occurs at the material's surface under low-temperature environmental conditions with a concomitant degradation of mechanical properties. Spontaneous surface degradation has been extensively studied in vitro, but predictive algorithms have underestimated the extent of in vivo degradation observed in retrievals. The present research focused on burst-strength assessments of Ø28 mm ZTA femoral before and after long-term in vitro hydrothermal ageing according to ISO 7206-10. An average burst strength of 52 kN was measured for pristine femoral heads. This value was ~36% lower than results obtained under the same standard conditions by other authors. A further loss of burst strength (~13% in ultimate load) was observed after hydrothermal ageing, with increased surface monoclinic content ranging from ~6% to >50%. Nevertheless, the repetitively stressed and hydrothermally treated ZTA heads exceeded the minimum burst strength stipulated by the US Food and Drug Administration (FDA) despite severe test conditions. Lastly, Raman spectroscopic assessments of phase transformation and residual stresses on the fracture surface of the femoral heads were used to clarify burst-strength fluctuations and the effect of hydrothermal ageing on the material's overall strength degradation.

Enhanced bioactivity of Si3N4 through trench-patterning and back-filling with Bioglass®.

Using a simple and innovative sandblasting process, disks of monolithic biomedical silicon nitride (ß-Si3N4) were texturized with a matrix of regular, discrete square trenches with a total depth in the range of hundreds of microns. The process consisted of sandblasting Si3N4 substrates through a stainless-steel wire-mesh (150 or 200 µm) using abrasive silicon carbide powders (α-SiC, ∼40 µm) under 1,034 kPa (150 psi) of gas pressure. The depth of the porosities could be controlled varying both the treatment time and the distance from the surface. Part of the samples were then filled with 45S5 Bioglass® powders to improve the osteointegration and stimulate the production of bone tissue. Due to the increased macroscopic and microscopic roughness, biological testing using human osteosarcoma cells (SaOS-2) showed improved cell proliferation and greater production of both mineral (hydroxyapatite) and organic (collagen) phases on the patterned surfaces compared to untreated ß-Si3N4 or to the biomedical titanium control samples. Both of these effects were further enhanced when the porosities were filled with Bioglass®.

The role of nitrogen off-stoichiometry in the osteogenic behavior of silicon nitride bioceramics.

The surface chemistry of silicon nitride plays an important role in stimulating osteoblasts to proliferate and produce bone tissue with improved efficiency. This property, which is advantageous in spinal fusion surgery has a chemical origin and is a direct consequence of the cleavage of covalent SN bonds in an aqueous environment. Building upon a wealth of published research on the stimulation of osteoblastic activity by silicon, the aim of this paper is to explore the role of nitrogen and, more specifically, the N/Si atomic ratio on the osteogenic response of Si3N4. The surface stoichiometry of Si3N4 was gradually altered toward a silicon-rich composition by systematically treating the Si3N4 surface with a high-power pulsed laser in an Ar gas atmosphere (i.e., operated at different pulse times, spot sizes, and voltages). Different analytical probes were used to characterize the surface including X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and energy dispersive X-ray spectroscopy (EDS). Osteoconductivity was tested in vitro using SaOS-2 osteosarcoma cells, and samples with different surface stoichiometry were compared for their osteogenic response. These experiments clearly indicated a fundamental role for nitrogen off-stoichiometry in osteogenesis, and showed that both cell proliferation and growth of bone tissue diminished with decreasing nitrogen content.