There is room for improvement in current rates of successful spinal fusion; one natural area of focus is the interaction between implants and bone. The chemical composition, hydrophilicity, and overall roughness of the surface of an implant play roles in bony fusion [16, 19, 20, 21]. This is because in the first stages of osteointegration, the implant is coated with proteins from the blood and serum—a process that is highly dependent on the chemical and topographical nature of the implant . This protein layer facilitates the migration of mesenchymal progenitor cells into the implant surface via the α2β1 integrin receptor, a major collagen type 1 receptor . These cells must then differentiate into an osteoblastic lineage to form new bone, a process that, again, is driven by the surface properties of the implant, with rough surfaces favoring osteoblastic differentiation . Moreover, the shape of the substructure influences the shape of the cells, promoting differentiation into an osteoblastic form [20, 37].
Roughened titanium has been known to generate an osteoblastic environment, whereas other materials, such as polyetheretherketone (PEEK), have been shown to inhibit such an environment, which can result in the development of an inflammatory fibrous rind [19, 21]. Typical osseous incorporation, such as that used in cementless total hip stems, occurs with a surface roughness in the 100- to 400-μm range . Nanoscale surface technology represents a major innovation in fusion science, whereby host cells are able to interact with an implant on a molecular level via cellular membrane receptors . This interaction can trigger osteoblastic-lineage differentiation and improve fusion results . This process only occurs on a nanoscale (10−9 m) surface because a micron-sized (10−6 m) surface texture is too large to interact with a cell’s membrane .
Surface Engineered Instrumentation
There are two primary types of manufacturing used in the production of spine implants, additive and subtractive . Additive manufacturing, also known as three-dimensional (3D) printing, involves layer-by-layer construction of complex 3D objects using computer-aided design software or the deposition of a material coating on the implant itself . Additive processes can be used to create objects from several types of materials, including ceramics, metals, and polymers . One of the disadvantages of additive manufacturing, however, is that it is currently limited by the raw material (feedstock) size—typically 15 to 45 μm—and cannot produce submicron scale surface technologies without additional processing . Nevertheless, the size of features that can be printed is shrinking as additive technology improves .
The use of PEEK in implants is common, primarily because of its radiolucency and modulus of elasticity that closely resembles that of native bone . However, PEEK is notorious for generating a fibrous encapsulation because of its induction of an inflammatory environment, and this can result in nonunion . The use of a titanium spray on PEEK is a common example of additive “post-processing,” used to improve the surface properties of PEEK, but this method has been associated with increased generation of wear debris . A porous surface may also be applied to PEEK by extruding it through a bed of sodium chloride crystals, which has been shown to improve osteoconductivity but only in the presence of osteogenic mediators .
In subtractive manufacturing, surface features are generated through the removal of material . Acid etching and grit blasting are two forms of subtractive manufacturing . When used in spinal fusion, interbody grafts are produced from treated pieces of titanium, and subtractive technologies are used to produce submicron surface textures. Titanium implants with surfaces that have been roughened through grit blasting or acid etching have been shown to increase osteoblastic differentiation, resulting in increased osteointegration and bone formation . Although subtractive manufacturing is much more commonly used, these techniques currently waste material substrate, and the physical process itself limits the types of designs that can be created.
Nanoroughened titanium surfaces have been shown in vitro to induce greater differentiation of osteoblasts from mesenchymal stem cells, as compared with PEEK-treated surfaces . Olivares-Navarrete et al. grew osteoblast-like cells on three different surfaces: PEEK, smooth titanium alloy, and roughened titanium alloy . They found the highest levels of transforming growth factor beta (TGF-β) and osteoprotegerin—which inhibit osteoclastic activity—and fibroblast growth factor 2, vascular endothelial growth factor A (VEGF-A), and angiopoietin-1—which support angiogenesis—on roughed titanium surfaces, followed by smooth titanium; levels on PEEK surfaces were significantly lower. Moreover, roughened titanium is able to increase osteoblast maturation and produce an osteogenic environment that contains bone morphogenetic proteins (BMPs), as compared with smooth titanium and PEEK. Similar studies have shown that nanoengineered implants increase stimulation of local growth factors, including BMPs, VEGF, and TGF-β [20, 21].
Bioabsorbable interbody fusion is appealing to spine surgeons because the graft is resorbed over time and replaced by host bone. Such structures are advantageous, in theory, because they are more than mere surface treatments; they recreate the extracellular matrix of bone . Polylactic acid (PLA) has been used in the design of bioabsorbable interbody implants, although it has been shown to generate an inflammatory response and to have poor osteoconductivity . To improve the osteoconductivity, nanosized β-tricalcium phosphate (β-TCP) has been incorporated into PLA cages . Cao et al. developed a bioabsorbable cervical fusion cage from PLA and β-TCP that was shown to have greater biomechanical stability in a sheep model, as compared with tricortical iliac crest grafts and PEEK cages, allowing for resorption over time .
Surface Technology for Patients with Osteoporosis
Screw loosening is one of the most common complications of posterior instrumentation in patients with osteoporosis, reported at rates greater than 10% [7, 36]. Hydroxyapatite has been used as a coating to improve pedicle screw osteointegration. There are several methods for creating and applying such coatings: thermal techniques, such as plasma spraying, and sputtering . Plasma spraying produces a thick coating (20 to 100 μm) and is prone to internal defects and fractures but has been shown in animal models to increase pullout strength [14, 28]. Sputtering generates a much thinner coating (1 μm) and has been shown to decrease the amount of cracking . Ohe et al. reported that hydroxyapatite-coated pedicle screws in a porcine osteoporosis model increased the bone–implant interface . The observation that titanium with a roughened texture improves interbody fixation has also led to the hope that pedicle screws could be similarly treated to improve pullout strength . Pedicle screws grit blasted to achieve a nanotextured surface have demonstrated significantly greater pullout strength in vivo, as well as greater bone–screw integration, than smooth titanium screws . Ricker et al. have described the use of nanophase magnesium oxide augmentation of polymethylmethacrylate (PMMA) to increase surface roughness . Patients with osteoporosis may benefit from pedicle screw cementation with PMMA. The augmentation of surface roughness leads to increased osteoblast adhesion on the PMMA cement, and this process has been a target for improved surface technology .
Using Nanotechnology to Fight Infection
Hardware infection can be a life-threatening sequela of spinal fusion surgery . Bacteria adhere to medical implants via the formation of a complex glycocalyx that protects them from antibiotics, making eradication very difficult . The surface features of an implant can decrease bacterial adhesion . Nanoroughened surfaces have been shown to significantly decrease rates of bacterial adhesion, specifically of Staphylococcus aureus, S. epidermidis, and Pseudomonas aeruginosa . Moreover, silver nanoparticles have been shown to have a bactericidal effect while still being biocompatible with bone . They achieve this through the release of silver ions from soluble complexes, which then generate reactive oxygen species that break down bacterial components . Silver nanoparticles can be applied to an implant via silver plasma ion immersion or by vapor deposition . Nanoparticles have also been shown to inhibit bacterial biofilm formation in animal studies. In particular, titanium pedicle screws coated in silver-based nanoparticles have been shown to be bactericidal in rabbits because of their release of silver ions .
The National Nanotechnology Initiative
A driving force behind the research and development of nanotechnology in the USA was the establishment of the National Nanotechnology Initiative (NNI) in 2000. The 2020 federal budget request for the NNI was $1.4 billion, and since 2001, more than $25 billion has been invested in nanotechnology research by federal agencies and independent partners. One of the NNI’s major breakthroughs has been the development of nanocrystalline synthetic bone. This synthetic material is less than 100 nm in size and closely approximates the size of hydroxyapatite crystals found in native tissue. In patients with osteoporosis, poor bone quality and donor-site morbidity have fueled the search for alternatives to iliac crest bone graft. Robbins et al. demonstrated that fusion rates of posterolateral lumbar fusion using bone marrow aspirate, local autograft, and nanocrystalline hydroxyapatite are equivalent to using iliac crest bone graft .
Regulatory and Financial Considerations
Advances in nanotechnology-based implants offer a wide array of possibilities for advancement in spine devices. In 2018, health care spending represented 17.7% of the US gross domestic product . For this reason, the application of potentially expensive new technologies must be focused on pathologies that are currently problematic or serve challenging patient populations [8, 30, 37]. For instance, high rates of pseudarthrosis have been seen in multilevel anterior cervical discectomy and fusion (ACDF)—as high as 37.3% in three-level ACDF . This stands in contrast to one-level ACDF, which in one prospective, randomized study had fusion rates as high as 93.3% . Therefore, a focus on improving surface technology as a means of increasing rates of fusion in multilevel procedures may justify its development costs. Moreover, these devices are regulated to ensure their safety. Currently, devices manufactured using additive processes fall under the regulatory umbrella of the Center for Devices and Radiological Health at the US Food and Drug Administration (FDA). Additive prosthetics generally fall into the same category as other, similar implants, regardless of the manufacturing method .
Overall, nanotechnology surface features offer a rich array of opportunities to advance the field of spine surgery. Nanotextured pedicle screws may allow increased osteointegration with decreased screw pullout. Nanoparticles show promise in decreasing bacterial adhesion and biofilm formation. In 2014, the first nanotechnology-based surface available in a spinal implant was FDA approved . Further research and development will allow a fuller realization of the potential of nanotechnology.
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Conflict of Interest
Yoshihiro Katsuura, MD, Joshua Wright-Chisem, MD, Adam Wright-Chisem, MD, and Sohrab Virk, MD, declare that they have no conflicts of interest. Steven McAnany, MD, reports personal fees from Nuvasive, Titan, Stryker, and K2M.
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Katsuura, Y., Wright-Chisem, J., Wright-Chisem, A. et al. The Importance of Surface Technology in Spinal Fusion. HSS Jrnl (2020). https://doi.org/10.1007/s11420-020-09752-w
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