Silicon Nitride - Craniomaxillofacial Implant

Today, Craniomaxillofacial (CMF) surgeons are concerned about the performance and high failure rate of existing FDA-cleared CMF implants1. Development of Si3N4 implants for CMF applications has the potential to accelerate bone healing, reduce the incidence of infection, eliminate metal toxicity, enhance radiographic imaging, lessen patient pain and disability, and decrease the overall health-care burden associated with failed or failing implants, as compared to current materials2.

Each year, more than 235,000 Americans undergo reconstructive surgery to repair CMF damage due to injury or disease3,4. Pre-shaped metal, polymer, or bioactive ceramic implants are used in cases that require bone repair or replacement, with an average failure rate of 5.5% (12% to 37% in the orbital region)5. Failures due to poor osseointegration; prosthetic infections; and material corrosion, degradation, and fracture6 often lead to revision surgery, hardware removal, debridement, long-term antibiotic use, and implant replacement. A better material is needed to overcome these problems.

Silicon nitride has the essential physical, mechanical, and biological characteristics to fill this gap. Specifically, it:

  1. Has high strength, toughness, mechanical reliability, wear and corrosion resistance7
  2. Improves osseous integration,8,9,10,11,12
  3. Is antibacterial and inhibits biofilm formation13,14,15,16
  4. Provides high contrast radiographic imaging without artifacts17,18.

Aside from the properties that make silicon nitride attractive in industry, (i.e., superior strength, wear resistance, corrosion resistance, and fracture toughness) there is a related set of attributes that make silicon nitride attractive as a biomaterial:

Surface Topography

Silicon nitride’s topography is apparent at the micron and sub-micron scales. The surface of “as-fired” silicon nitride consists of anisotropic grains that are typically ≤ 1 µm up to 10 µm with individual features (i.e., asperities, sharp corners, points, pits, pockets, and grain intersections) that can range in size from <100nm to 1µm. While this structure is morphologically different from surface-functionalized titanium, it has some common features (e.g., sharp corners, points, and pockets). Ishikawa et al. recently demonstrated that this type of surface microstructure is important in resisting bacterial attachment while concurrently promoting mammalian cell adhesion and proliferation14.

Bone Healing

Silicon nitride turns on osteoblasts (bone-forming cells) and suppresses osteoclasts (bone resorbing cells)19. A manufacturing change called “nitrogen-annealing” results in a near-200% increase in bone formation by cells exposed to silicon nitride20. This finding has excellent implications for speeding up bone healing, bone fusion, and implant integration into the skeleton. Living cells adhere preferentially to silicon nitride over polymer or metal21. Cell adhesion promotes tissue development and enhances the bioactivity of materials. Cell adhesion to silicon nitride is a function of pH, chemical, and ionic changes at the material’s surface.

Bacterial Resistance

Bacterial infection of any biomaterial implant is a serious clinical problem. Silicon nitride offers a potential easy solution; it is inherently resistant to bacteria and biofilm formation22. In addition, a recent study has shown a direct bactericidal effect against an oral pathogen23. The antibacterial behavior of silicon nitride is probably multifactorial, and relates to surface chemistry, surface pH, texture, and electrical charge24. Optimizing these surface properties for specific implants is a clear advantage of the material.

Superior Imaging

Silicon nitride implants are radiolucent with clearly visible boundaries and produce no artifacts or scattering under CT and no distortion under MRI. This enables an exact view of the implant for precise intraoperative placement and postoperative fusion assessment15.

Our Technology is Backed by Strong Data

SINTX has published many studies supporting the benefits of silicon nitride material. Although well-proven in industry25, silicon nitride was first used in a spinal implant trial that began in 198626 with follow-ups at 1, 5, 10, and 30 years. Outcomes showed substantial pain reduction, as well as solid inter-body spine fusion, demonstrating the favorable properties of silicon nitride15.

The biological response of living tissue to silicon nitride was described in detail in a 1989 study27. By 12 weeks, up to 90% of the surface of porous silicon nitride contained woven trabecular bone and 75% of all pores were occupied by mature lamella bone. These results showed the favorable osteoconductive properties of silicon nitride.

Later studies with silicon nitride demonstrated an osteoinductive effect on the proliferation and differentiation of human bone marrow cells and the formation of a mineralized matrix28,29. The Si3N4 materials were hydrophilic, with a negatively charged surface at homeostatic pH; these properties contributed to rapid protein adsorption and bone formation.

Further work on implanted silicon nitride in rabbits showed that osteoblasts and osteocytes directly contacted the Si3N4 implants along with a matrix of collagen I and III. Bone remodeling around the Si3N4 implants was enhanced compared to titanium controls30,31,32.

In another study, researchers compared silicon nitride, titanium (Ti), and polyether ether ketone (PEEK)33. Three months after aseptic implantation into rats, Si3N4 showed better appositional healing (Si3N4, Ti, and PEEK showed appositional healing of 65%, 19%, and 8%, respectively). While the addition of Staphylococcus epidermidis bacteria reduced bone formation; the Si3N4 implants still proved better, (i.e., 25% appositional Osseous integration of metallic and polymeric implants is poor compared to bioactive calcium phosphate ceramics, but the latter materials are weak and prone to in-vivo fracture34. Implant-related infections often lead to chronic osteomyelitis, bone resorption, and implant loosening35. Ions released from metallic implants produce localized adverse tissue reactions and systemic toxicity36. These conditions place the surrounding bone at risk, often requiring revision surgery, hardware removal, debridement, local and systemic antibiotics, extended convalescence, and implant replacement37.

The reason that Si3N4 shows superior osseointegration and osteoconductivity is related to the elutable surface chemistry of silicon nitride38,39,40,41. 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 + 12H2O → 3 Si(OH)4 + 4NH3

Bioavailable silicon in the form of silicic acid enhances osteogenic activity42,43,44,45,46,47,48,49,50 while various nitrogen-based moieties can either be mild disinfectants or powerful oxidants that disrupt microbial cellular functions34,51,52,53,54,55,56,57,58,59. In addition, silicon nitride’s surface charge, wettability, and phase chemistry also contribute to enhanced osteoconductivity.

Several human studies support the above data concerning silicon nitride. A 24-month clinical trial60 compared PEEK 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 nitride61,62. Case studies have shown the effectiveness of silicon nitride in abating in- vivo infections63 and in achieving solid arthrodesis in the lumbar spine64.

Patient specific implants

Rapid prototyping for medical implants is gaining significance in different areas of preoperative planning such as maxillofacial surgery, orthopedics, neurosurgery, and orthognathic surgery65. Using additive manufacturing and 3-dimensional (3D) models patient specific implants can be designed and produced according to patient derived CT data, facilitating superior reconstructive surgery. Three-dimensional printing is attractive for the direct fabrication of bioceramic implants and scaffolds from a computer aided design file. There is much new research and development of novel material developments for the three-dimensional (3D) printing process for ceramics66. Customized ceramic implants can be fabricated with features such as porous and dense regions that match bone structure. The excellent biological in vitro and in vivo behavior of 3D-printed silicon nitride offers many advantages over current materials. SINTX is now developing additive manufacturing for the unique silicon nitride, MC2, which has been utilized in FDA cleared devices.

Conclusion

With an expanding, ageing and more active population, biomaterial innovations will lead to improved biomedical implant safety, high-performance, and lifetime durability. Already well-proven in diverse industrial applications and currently utilized as intervertebral spinal fusion cages, silicon nitride has the foundational evidence to be applied likewise across a range of biomedical applications.

We invite you to contact SINTX Technologies to see how silicon nitride might be beneficial to your patients and practice.

References

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