Innovative Biomaterial Potentially Reduces Infection Rates in Spinal Fusion Surgery

Spinal Fusion Surgery: Why Material Matters

Today, back pain impacts a vast percentage of the adult population and while the causes vary, the underlying issues are typically a spinal disorder such as spondylolisthesis, scoliosis, severe disc degeneration or spinal fractures, which can be treated with spinal fusion surgery. Fusion surgery essentially "welds" vertebrae together so that they heal into a single solid bone. Systems utilizing specially designed spinal implants and instrumentation are used in these surgical procedures. The implants and instrumentation facilitate fusion, correction of deformities, and they stabilize and strengthen the spine.

Historically, spine surgeons have relied on autograft or allograft bone as an implant material to aid in spinal fusion, however, these materials also present challenges. Use of autograft bone, which is harvested from the iliac crest, induces added patient comorbidity, pain and healing, whereas allograft bone carries a finite risk of disease transmission. Consequently, implants made from bioinert materials such as metals and plastics have grown in favor. Two materials that are in common use today are poly-ether-ether-ketone [PEEK] and titanium [Ti]. Yet, these two materials also have limitations. Ti implants are opaque to x-rays and have less than optimal imaging characteristics in CT and MRI, which does not allow for effective assessment of fusion by clinicians*. Ti implants are also prone to subsidence**. Because of this, titanium devices have essentially been replaced by PEEK. Unfortunately, while PEEK solves some imaging and subsidence issues, PEEK devices are known to migrate and develop pseudarthrosis*** [i.e., loosening of the implant] which is generally associated with the formation of a fibrous tissue layer at the implant’s surface. This fibrous layer dramatically reduces bone attachment resulting in less than optimal clinical outcomes****. In addition, these two bioinert materials can also be resistant to host immune mechanisms and systemic antibiotics, creating an environment for bacterial growth. Bacterial biofilms can form on the surfaces of these devices which may induce chronic infections and reduce fusion rates. Treating implant-related infections is costly and generally requires revision surgery, resulting in extended suffering and disability for patients.

Improving Patient Care

With mounting pressure on physicians and hospitals to provide the highest possible quality of care, the need exists for a biomaterial solution for spinal and reconstructive devices that overcome the shortcomings of the commonly used materials. Silicon nitride [Si3N4] is such a material. Although it is new to medicine, it has a long history of use in many demanding industrial applications. It was first synthesized in 1857 but remained little more than a chemical curiosity for nearly a century. Beginning in the late 1940s, the compound was used as a refractory for industrial furnaces. In the 1970s through 1990s, it was introduced across multiple industries, ultimately providing key components in electronics, turbo machinery, cutting tools, and high speed bearings. Si3N4 is a ceramic which has exceptional properties including very high strength and high fracture toughness [i.e., resistance to breakage]. In fact, it is the most fracture resistant ceramic material commercially available. It also has unique features that make it attractive as a biomaterial. It delivers implants with excellent mechanical properties, superior biocompatibility, anti-infective and osteointegrative characteristics, all of which potentially result in greater clinical efficacy. It is also compatible with all imaging modalities; and promises implants with higher wear resistance and long-term durability.
Amedica is the only company with the scientific know-how to produce medical grade Si3N4, for medical use including a patented platform technology for spinal and reconstructive arthroplasty applications. Si3N4 offers doctors and patients an alternative to PEEK and titanium that is osteopromotive, anti-infective and may result in faster fusion. Amedica is the only company in the world that has FDA clearance to manufacture and distribute Si3N4 implants. In February 2006, Amedica received FDA 510(k) clearance for the first load-bearing ceramic spinal device, and in 2007, for their Valeo Interbody Fusion Devices. In September 2012, Amedica received FDA 510(k) clearance to market second-generation Si3N4-based devices for cervical and lumbar interbody fusion. The clearance addressed design enhancements [threaded insertion feature, additional footprints] and elements to support minimally invasive and lumbar lateral interbody fusion approaches. At the same time, the company announced the expansion of biomaterial claims for these devices based on data published in two peer-reviewed studies conducted at Brown University which demonstrated the superior osteointegration and bacterial-resistant properties of the company’s proprietary Si3N4biomaterial when compared to PEEK or Ti. Si3N4 offers the following key benefits when compared to other traditional devices such as PEEK or Ti.

Advantages of Utilizing Silicon Nitride

Data from the journal article titled “Decreased Bacteria Activity on Si3N4 Surfaces Compared with PEEK or Titanium,” which appeared in the International Journal of Nanomedicine 2012:7 1-12, reported that Si3N4 is far less vulnerable to bacterial colonization [S. epidermidis, S. aureus, P. aeruginosa, E. coli and Enterococcus] than PEEK and Ti.  This in vitro study tested these three biomaterials to understand their respective susceptibility to bacterial infection. Specifically, the surface chemistry, wettability, and nano-structured topography of respective biomaterials, and the effects on bacterial biofilm formation, colonization and growth were investigated. Ti and PEEK were received with as-machined surfaces, and both materials were found to be hydrophobic, with net negative surface charges. Two surface finishes of Si3N4 were examined – as-fired and polished. In contrast to Ti and PEEK, the surface of Si3N4 is hydrophilic, with net positive charge. The researchers found decreased biofilm formation, and fewer live bacteria on both the as-fired and polished Si3N4. These differences may reflect differential surface chemistry and surface nano-structure properties between the biomaterials tested. Additionally, this research also discovered that there was rapid adherence of fibronectin, vitronectin and laminin proteins onto Si3N4 as compared with PEEK and Ti. The absorption of these proteins can decrease susceptibility to bacteria and increase osteointegration.

Si3N4 has also demonstrated superior new bone formation and resistance to bacterial infection when compared to PEEK and Ti in vivo. A study published in the July, 2012 issue of Acta Biomaterialia [2012] compared the osteointegration characteristics of implants made from Si3N4, PEEK and Ti using a common laboratory animal [Wistar rat]. Small samples of the three biomaterials were implanted into the rat’s calvariae [i.e., skull]; at three days, seven days, 14 days, and three months post-operatively, the animals were euthanatized, and calvariae were examined to quantify new bone formation. Three months after surgery absent bacterial injection, new bone formation around Si3N4 was ~69 percent compared with 24 percent and 36 percent for PEEK and Ti, respectively. Specifically, the amount of regenerated bone associated with Si3N4 implants was essentially two- to three- times that of the other two implant materials. Furthermore, in as little as 14 days, Si3N4 demonstrated significantly greater new bone formation at both the surgical site and the implant interface. Quantitative evaluation of osteointegration to adjacent bone was also done by measuring the resistance to implant push-out. Push-out strength testing demonstrated statistically superior bone growth onto Si3N4 when compared to Ti or PEEK.

Finally, Si3N4 implants are radiolucent with clearly visible boundaries. They produce no distortion under MRI and no scattering under CT which enables an exact view of the implant for precise intraoperative placement and postoperative fusion assessment.

Future Applications

Si3N4 is a strong, fracture resistant ceramic that can be manufactured into many different forms providing specific benefits for different types of surgical implants. The technology is currently driving towards a new standard of care for patients suffering from back pain requiring spinal fusion.

In addition to spinal implants, Amedica is currently evaluating the application of Silicon Nitride in many other types of medical devices including hip and knee replacements, dental implants and suture anchors. Si3N4 is a new disruptive biomaterial technology that is poised to penetrate the spine, and other orthopedic or medical markets, with great potential for improving clinical outcomes, patient longevity, and quality of life.

For more information on Silicon Nitride, visit Amedica's website.

*J. Bernero, et al., “Medical Imaging Characteristics of Silicon Nitride,” SAS Conference, Miami, [2008).
**Kirsten Schmieder, Markus Wolzik-Grossmann, Ioannis Pechlivanis, Martin Engelhardt, Martin Scholz, and Albrecht Harders, “Subsidence of the Wing titanium cage after anterior cervical interbody fusion: 2-year follow-up study,” Journal of Neurosurgery: Spine, 4, [6], 447-453, [2006).
***Liu, H., Ploumis, A., Li, C., Yi, X., & Li, H., “ Polyetheretherketone cages alone with allograft for three-level anterior cervical fusion. ISRN Neurology, 2012, 452703. doi:10.5402/2012/452703.
****Olivares-Navarrete, R., Gittens, R., Schneider, J., Hyzy, S., Haithcock, D., Ullrich, P., Schwartz, Z., et al., “Osteoblasts exhibit a more differentiated phenotype and increased bone morphogenetic protein production on titanium alloy substrates than on poly-ether-ether-ketone,” The Spine Journal, 12[3), 265–72. doi:10.1016/j.spinee.2012.02.002.