Resources

Silicon Nitride – Antipathogenic Powder- AP2

SINTX has developed a powdered form of our silicon nitride, called AP2 (for Antipathogenic Powder), that is now being evaluated as an additive, coating, or composite, used to impart or enhance antipathogenic properties of a variety of products.

This proprietary powder composition shows antibacterial1 properties, antifungal2 properties, and antiviral3 properties. Our material has a dual effect in that it also enhances bone formation when used as a spinal implant, i.e., it is osteogenic4.

Potential Applications

Today, there is a global need to improve protection against pathogens in everyday life. SINTX believes that by incorporating its unique composition of AP2 silicon nitride into products such as face masks and personal protective equipment, it is possible to manufacture surfaces that inactivate viral particles, thereby limiting the spread of the disease.

Work with us as an OEM partner to develop products utilizing our AP2 powder. Our leading R&D and manufacturing teams can collaborate on specialized and niche application development for your company.

Properties of AP2 Powder

Antiviral

Work on AP2 silicon nitride’s antiviral effects builds upon years of research toward understanding the basic biochemistry of silicon nitride, focused on biomedical implants, particularly for the spine. The material’s antiviral attributes are consistent with the known antibacterial behavior of silicon nitride. The results with inactivation of the novel coronavirus SARS-CoV-2 are likewise consistent with an earlier study that showed similar inactivation of other viruses, including influenza A and enterovirus, both of which cause human disease.

Two recent studies (The Lancet Microbe28, The New England Journal of Medicine39) reveal how long the SARS-CoV-2 virus persists on various common surfaces. Strikingly, the authors wrote, the coronavirus was still present on the outward-facing side of a surgical mask on day seven of the investigation. Like other viruses, the prolonged surface viability of SARS-CoV-2 can contribute to the risk of disease transmission.

SINTX Technologies has shown that its silicon nitride can inactivate the SARS-CoV-2 virus within a minute after exposure. SINTX envisions incorporating its silicon nitride into high-contact surfaces such as masks, medical equipment, screens, countertops, and doorknobs in locations where viral persistence is a concern, such as homes, casinos, and cruise ships.
SINTX has filed international patent applications, titled “Antipathogenic Devices and Methods Thereof,” (US Publication No. 2020/0079651 and “Antipathogenic Compositions and Methods Thereof.” (International Publication No. WO 2020/051004 A1). Part of these applications addressed the potential antiviral effect of silicon nitride.

Antibacterial

One of the reasons that SINTX’s materials resist infection is that they demonstrate significantly lower bacterial biofilm formation. In a recent study, the MC2 material (SINTX’s dense silicon nitride) was tested against PEEK (polyetheretherketone) and titanium. Results show that at 4, 24, 48 and 72 hours, MC2 showed much lower bacterial counts when compared to PEEK and titanium36. In rodent studies, no live bacteria were observed around previously inoculated silicon nitride implants at 3 months, whereas comparable PEEK and titanium implants showed persistent, live bacteria 3 months after surgery37. Silicon nitride demonstrates this behavior even in the absence of antibiotics.2

Osteogenic

The surface chemistry and nanostructure topography of silicon nitride are optimal for the stimulation of osteoprogenitor cells to differentiate into osteoblasts27. Several human studies support this observation. A 24-month clinical trial28 compared PEEK polymer cages with autograft bone to porous Si3N4 without added bone graft in cervical fusion. Results showed that porous Si3N4 spacers achieved spinal fusion exclusive of autograft bone. Two other clinical trials comparing cervical fusion rates for non-porous silicon nitride and PEEK cages or allograft spacers showed earlier and more effective fusion with silicon nitride29, 30. Case studies have shown the effectiveness of silicon nitride in abating in- vivo infections31 and in achieving solid arthrodesis in the lumbar spine32.

The AP2 material has been incorporated into plastics with positive results. Our AP2-PEEK composite combines the unique and beneficial bioactivity of silicon nitride with the familiar fit, feel, and processing properties of conventional PEEK33, 34.
AP2-PEEK is produced by compounding AP2 bioceramic into an implant-grade PEEK matrix. Coating delamination concerns are avoided since the bioceramic is uniformly dispersed throughout the polymer volume instead of adhered to the surface. In addition to exhibiting comparable mechanical properties to monolithic PEEK, SN-PEEK has demonstrated improved imaging properties along with resistance to bacterial biofilm formation, and upregulation of bone cell activity during testing in vitro35. As SINTX has demonstrated with PEEK, the AP2 material can be incorporated into many polymer materials.

AntiFungal

Two species of grape vine leaves (Cabernet Sauvignon and Cannonau) with known fungal infection (Plasmopara viticola, also known as downy mildew) were sprayed with a silicon nitride solution of 1.5 volume percent SINTX’s AP2 suspended in water. The illustration shows before and after treatment for Cabernet Sauvignon leaves; results were similar with Cannonau leaves. After 1 minute of exposure, the infected area on the leaves was reduced by ~95%.

Figure 1. Before and after treatment for Cabernet Sauvignon leaves

It is estimated that 15% of the world’s edible annual crops are destroyed because of their susceptibility to plant-based viruses, bacteria, and fungi; one billion metric tons of edible produce annually is thus affected. The economic impact in the US and Canada alone is estimated to be between $1.5 to $5 billion per year. Furthermore, there is increasing concern that the mycotoxins produced by these fungi have an overall negative impact on human health and longevity. SINTX hopes to address these concerns with its unique material technology.

The Chemistry

The reason that Si3N4 shows osseointegration and antipathogenic properties is related to the elutable surface chemistry of silicon nitride,6,7,8. Once implanted, silicon nitride’s surface reacts with water to form silicic acid (H4SiO4) and ammonia (NH3) in accordance with the following chemical reaction:

Si3N4 + 12h3O → 3 Si(OH)4 + 4NH3

Bioavailable silicon in the form of silicic acid enhances osteogenic activity9,10,11,12,13,14,15,16,17 while various nitrogen-based moieties can either be mild disinfectants or powerful oxidants that disrupt microbial cellular functions34,18,19,20,21,22,23,24,25,26. In addition, silicon nitride’s surface charge, wettability, and phase chemistry hinder bacterial attachment and contribute to enhanced osteoconductivity. Our silicon nitride has this fortuitous combination of properties.

Characteristics of AP2

The AP2 material is a fine, submicron powder. A micrograph of the powder (Figure 2) shows that most of particles show the acicular structure typical of β-Si3N4. The particles are less than a micron in length and width consistent with the particle size distribution data shown below (Figure 3).

Figure 2. Micrograph of AP2 Powder


Figure 3. Particle Size Distribution of AP2 Powder

The phase data by X-Ray diffraction demonstrates the crystalline phase of this powder is 100% β-Si3N4 (Figure 4).

Figure 4. Determination of Crystalline Phases by X-Ray Diffraction

To summarize, AP2 powder is a sub-micron ceramic powder with a crystalline phase that is 100% β-Si3N4 and a minority amorphous phase composed of a silicon-yttrium-aluminum-oxynitride (SiYAlON) glass. The powder’s typical properties are summarized in Table 1.

Table 1. Typical Properties of AP2

Property Value Notes
Density (g/cm3) ~3.25  
Particle Size, D50 (µm) 0.6 Laser Diffraction
Specific Surface Area (m2/g) 6 BET, N2 adsorption
Phase Composition 100% β-Si3N4 XRD, JCPDS 33-1160

References

1. Pezzotti et al., “Incorporating Si3N4 into PEEK to Produce Antibacterial, Osteocondutive, and Radiolucent Spinal Implants”, Macromol Biosci 18 [6] (2018).

2. McEntire, B., Bock, R., & Bal, B.S. U.S Application. No. 20200079651. 2020.

3. Pezzotti G., “Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride,” bioRxiv Prepr. 2020;1–16.

4. Marin et al., “KUSA-A1 mesenchymal stem cells response to PEEK-Si3N4 composites,” 17, 100316 (2020).

5. G. Pezzotti, E. Marin, T. Adachi, A. Rondinella, F. Boschetto, W.-L. Zhu, N. Sugano, R.M. Bock, et al., “Bioactive Silicon Nitride: A New Therapeutic Material for Osteoarthropathy,” Sci. Rep., 7 44848 (2017).

6. R.M. Bock, E.N. Jones, D.A. Ray, B.S. Bal, G. Pezzotti, and B.J. McEntire, “Bacteriostatic Behavior of Surface-Modulated Silicon Nitride in Comparison to Polyetheretherketone and Titanium,” J. Biomed. Mater. Res. Part A, 105 [5] 1521–1534 (2017).

7. G. Pezzotti, R.M. Bock, B.J. McEntire, E. Jones, M. Boffelli, W. Zhu, G. Baggio, F. Boschetto, et al., “Silicon Nitride Bioceramics Induce Chemically Driven Lysis in Porphyromonas Gingivalis,” Langmuir, 32 [12] 3024–3035 (2016).

8. R.M. Bock, E. Marin, A. Rondinella, F. Boschetto, T. Adachi, B.J. McEntire, B.S. Bal, and G. Pezzotti, “Development of a SiYAlON Glaze for Improved Osteoconductivity of Implantable Medical Devices,” J. Biomed. Mater. Res. Part B Appl. Biomater., 1–13 (2017).

9. R. Jugdaohsingh, “Silicon and Bone Health,” J Nutr Heal. Aging, 11 [2] 99–110 (2007).

10. M. Jurkic, I. Cepanec, S.K. Pavelic, and K. Pavelic, “Biological and Therapeutic Effects of Ortho-Silicic Acid and some Ortho-Silicic Acid-Releasing Compounds: New Perspectives for Therapy,” Nutr. Metab. (Lond)., 10 [1] 2 (2013).

11. D.M. Reffitt, N. Ogston, R. Jugdaohsingh, H.F.J. Cheung, B.A.J. Evans, R.P.H. Thompson, J.J. Powell, and G.N. Hampson, “Orthosilicic Acid Stimulates Collagen Type 1 Synthesis and Osteoblastic Differentiation in Human Osteoblast-Like Cells in vitro,” Bone, 32 [2] 127–135 (2003).

12. C.C. Perry, “An Overview of Silica in Biology: Its Chemistry and Recent Technological Advances;” pp. 295–313 in Biosilica Evol. Morphog. Nanobiotechnology. Springer, 2009.

13. W. Waked and J. Grauer, “Silicates and Bone Fusion,” Orthopedics, 31 [6] 591–597 (2008).

14. M.-Y. Shie, S.-J. Ding, and H.-C. Chang, “The Role of Silicon in Osteoblast-Like Cell Proliferation and Apoptosis,” Acta Biomater., 7 [6] 2604–2614 (2011).

15. C.D. Seaborn and F.H. Nielsen, “Silicon Deprivation Decreases Collagen Formation in Wounds and Bone, and Ornithine Transaminase Enzyme Activity in Liver,” Biol. Trace Elem. Res., 89 [3] 251–61 (2002).

16. E.-J. Kim, S.-Y. Bu, M.-K. Sung, and M.-K. Choi, “Effects of Silicon on Osteoblast Activity and Bone Mineralization of MC3T3-E1 Cells,” Biol. Trace Elem. Res., 152 [1] 105–112 (2013).

17. Z. Mladenovic, A. Johansson, B. Willman, K. Shahabi, E. Bjorn, and M. Ransjo, “Soluble Silica Inhibits Osteoclast Formation and Bone Resorption in vitro,” Acta Biomater., 10 [1] 406–418 (2014).

18. P. Gilbert and L.E. Moore, “Cationic Antiseptics: Diversity of Action Under a Common Epithet,” J. Appl. Microbiol., 99 [4] 703–715 (2005).

19. M.A. Firmani and L.W. Riley, “Reactive Nitrogen Intermediates Have a Bacteriostatic Effect on Mycobacterium Tuberculosis In Vitro,” J. Clin. Microbiol., 40 [9] 3162–3166 (2002).

20. N.J. Watmough, G. Butland, M.R. Cheesman, J.W.B. Moir, D.J. Richardson, and S. Spiro, “Nitric Oxide in Bacteria: Synthesis and Consumption,” Biochim. Biophys. Acta – Bioenerg., 1411 [2–3] 456–474 (1999).

21. P. Pacher, J.S. Beckman, and L. Liaudet, “Nitric Oxide and Peroxynitrite in Health and Disease,” Physiol. Rev., 87 [1] 315–424 (2007).

22. M.-C. Boutrin, C. Wang, W. Aruni, X. Li, and H.M. Fletcher, “Nitric Oxide Stress Resistance in Porphyromonas Gingivalis is Mediated by a Putative Hydroxylamine Reductase,” J. Bacteriol., 194 [6] 1582–1592 (2012).

23. B. Alvarez and R. Radi, “Peroxynitrite Reactivity with Amino Acids and Proteins,” Amino Acids, 25 [3–4] 295–311 (2003).

24. R.C. Goy, S.T.B. Morais, and O.B.G. Assis, “Evaluation of the Antimicrobial Activity of Chitosan and its Quaternized Derivative on E. Coli and S. aureus Growth,” Brazilian J. Pharmacogn., 26 [1] 122–127 (2016).

25. D.A. Rodionov, I.L. Dubchak, A.P. Arkin, E.J. Alm, and M.S. Gelfand, “Dissimilatory Metabolism of Nitrogen Oxides in Bacteria: Comparative Reconstruction of Transcriptional Networks,” PLoS Comput. Biol., 1 [5] e55–e55 (2005).

26. W. Zhang, H.Y. Wang, A. Oyane, H. Tsurushirra, and P.K. Chu, “Osteoblast Differentiation and Disinfection Induced by Nitrogen Plasma-Treated surfaces,” Biomed. Mater. Eng., 21 [2] 75–82 (2011).

27. Pezzotti, G. et.al. In Situ Spectroscopic Screening of Osteosarcoma Living Cells on Stoichiometry-Modulated Silicon Nitride Bioceramic Surfaces. ACS Biomater. Sci. Eng., 2 [7] 1121–1134 (2016)

28. M.P. Arts, J.F.C. Wolfs, and T.P. Corbin, “Porous Silicon Nitride Spacers versus PEEK Cages for Anterior Cervical Discectomy and Fusion: Clinical and Radiological Results of a Single-Blinded Randomized Controlled Trial,” Eur. Spine J., 1–8 (2017).

29. H.T. Ball, B.J. McEntire, and B.S. Bal, “Accelerated Cervical Fusion of Silicon Nitride versus PEEK Spacers: A Comparative Clinical Study,” J. Spine, 6 [6] 1000396 (2017).

30. M.W. Smith, D.R. Romano, B.J. McEntire, and B.S. Bal, “A Single Center Retrospective Clinical Evaluation of Anterior Cervical Discectomy and Fusion Comparing Allograft Spacers to Silicon Nitride Cages,” J. Spine Surg., 4 [2] 349–360 (2018).

31. W.M. Rambo, “Treatment of Lumbar Discitis using Silicon Nitride Spinal Spacers: A Case Series and Literature Review,” Int. J. Surg. Case Rep., 43 61–68 (2018).

32. W.M. Rambo, “Treatment of Lumbar Discitis using Silicon Nitride Spinal Spacers: A Case Series and Literature Review,” Int. J. Surg. Case Rep., 43 61–68 (2018).

33. Pezzotti, G. et al., “Human Osteoblasts Grow Transitional Si/N Apatite in Quickly Osteointegrated Si3N4 Cervical Insert,” Acta Biomater., 64, 411-420, (2017).

34. Pezzotti, G. et al., “Bioactive Silicon Nitride: A New Therapeutic Material. for Osteoarthropathy,” Sci. Rep., 7 44848 (2017).

35. Pezzotti et al., Macromol. Biosci. 2018, 1800033.

36. D. J. Gorth, et al., “Decreased Bacteria Activity on Si3N4 Surfaces Compared with PEEK or Titanium. Int. J. Nanomedicine, 7, 4829–4840, (2012)

37. T.J. Webster, A.A. Patel, M.N. Rahaman, and B.S. Bal, “Anti-Infective and Osteointegration Properties of Silicon Nitride, Poly (Ether Ether Ketone), and Titanium Implants,” Acta Biomater., 8 [12] 4447–4454 (2012).

38. https://www.medrxiv.org/content/medrxiv/early/2020/03/27/2020.03.15.20036673.full.pdf

39. https://www.nejm.org/doi/full/10.1056/nejmc2004973

Back To Top