AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.2124
RESEARCH ARTICLE

Exploring the mechanical strength, antimicrobial performance, and bioactivity of 3D-printed silicon nitride-PEEK composites in cervical spinal cages

Cemile Basgul1* Paul DeSantis1 Tabitha Derr1 Noreen J. Hickok2 Ryan M. Bock3 Steven M. Kurtz1
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1 Implant Research Core, School of Biomedical Science, Engineering, and Health Systems, Drexel University, Philadelphia, United States of America
2 Department of Orthopedics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, United States of America
3 SINTX Technologies, Inc., Salt Lake City, Utah, United States of America
IJB 2024, 10(2), 2124 https://doi.org/10.36922/ijb.2124
Submitted: 27 October 2023 | Accepted: 26 December 2023 | Published: 26 February 2024
© 2024 by the Author(s).. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

 In this study, our goal was to assess the suitability of a polyether-ether-ketone (PEEK) and silicon nitride (Si3N4) polymer composite for antimicrobial three-dimensional (3D)-printed cervical cages. Generic cage designs (PEEK and 15 vol.% Si3N4-PEEK) were 3D-printed, including solid and porous cage designs. Cages were tested in static compression, compression shear, and torsion per ASTM F2077. For antibacterial testing, virgin and composite filament samples were inoculated with Staphylococcus epidermidis and Escherichia coli. In vitro cell testing was conducted using MC3T3-E1 mouse preosteoblasts, where cell proliferation, cumulative mineralization, and osteogenic activity were measured. The 3D-printed PEEK and Si3N4-PEEK cages exhibited adequate mechanical strength for all designs, exceeding 14.7 kN in compression and 6.9 kN in compression shear. Si3N4-PEEK exhibited significantly lower bacterial adhesion levels, with a 93.9% reduction (1.21 log), and enhanced cell proliferation when compared to PEEK. Si3N4-PEEK would allow for custom fabrication of 3D-printed spinal implants that reduce the risk of infection compared to unfilled PEEK or metallic alloys.

 

Keywords
Cervical fusion cage
Anti-infection
Polyether-ether-ketone
Silicon nitride
3D printing
ASTM F2077
Funding
This research was supported, in part, by the National Institute of General Medical Sciences of the National Institutes of Health under award number R41GM146268.
References
  1. Seaman S, Kerezoudis P, Bydon M, Torner JC, Hitchon PW. Titanium vs. polyetheretherketone (PEEK) interbody fusion: meta-analysis and review of the literature. J Clin Neurosci. 2017;44:23-29. doi: 10.1016/j.jocn.2017.06.062
  2. Bydon M, De la Garza-Ramos R, Abt NB, et al. Impact of smoking on complication and pseudarthrosis rates after single- and 2-level posterolateral fusion of the lumbar spine. Spine. 2014;39(21):1765-1770. doi: 10.1097/BRS.0000000000000527
  3. Shriver MF, Lewis DJ, Kshettry VR, Rosenbaum BP, Benzel EC, Mroz TE. Pseudoarthrosis rates in anterior cervical discectomy and fusion: a meta-analysis. Spine J. 2015;15(9):2016-2027. doi: 10.1016/j.spinee.2015.05.010
  4. Dede O, Thuillier D, Pekmezci M, et al. Revision surgery for lumbar pseudarthrosis. Spine J. 2015;15(5):977-982. doi: 10.1016/j.spinee.2013.05.039
  5. Jain S, Eltorai AE, Ruttiman R, Daniels AH. Advances in spinal interbody cages. Orthop Surg. 2016;8(3): 278-284. doi: 10.1111/os.12264
  6. Tan ET, Ling JM, Dinesh SK. The feasibility of producing patient-specific acrylic cranioplasty implants with a low-cost 3D printer. J Neurosurg. 2016;124(5):1531-1537. doi: 10.3171/2015.5.JNS15119
  7. Wilcox B, Mobbs RJ, Wu AM, Phan K. Systematic review of 3D printing in spinal surgery: the current state of play. J Spine Surg. 2017;3(3):433-443. doi: 10.21037/jss.2017.09.01
  8. Bose S, Tarafder S. Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: a review. Acta Biomater. 2012;8(4):1401-1421. doi: 10.1016/j.actbio.2011.11.017
  9. Oosterbos CJ, Vogely H, Nijhof MW, et al. Osseointegration of hydroxyapatite-coated and noncoated Ti6Al4V implants in the presence of local infection: a comparative histomorphometrical study in rabbits. J Biomed Mater Res. 2002;60(3):339-347. doi: 10.1002/jbm.1288
  10. Kurtz SM. Development and clinical performance of PEEK intervertebral cages. In: Kurtz S, ed. PEEK Biomaterials Handbook. 2nd ed. Norwich, NY; 2019: William Andrew Publishing: 263-280. doi: 10.1016/B978-0-12-812524-3.00015-6
  11. Mendenhall S. 2017 Profile of hospital spine programs. Orthop Network News. 2017;28(4):7-10.
  12. Basgul C, Spece H, Sharma N, Thieringer FM, Kurtz SM. Structure, properties, and bioactivity of 3D printed PAEKs for implant applications: a systematic review. J Biomed Mater Res B Appl Biomater. 2021;109(11):1924-1941. doi: 10.1002/jbm.b.34845
  13. Rendas P, Figueiredo L, Machado C, Mourão A, Vidal C, Soares B. Mechanical performance and bioactivation of 3D-printed PEEK for high-performance implant manufacture: a review. Prog Biomater. 2023;12(2):89-111. doi: 10.1007/s40204-022-00214-6
  14. Zheng Z, Liu P, Zhang X, et al. Strategies to improve bioactive and antibacterial properties of polyetheretherketone (PEEK) for use as orthopedic implants. Mater Today Bio. 2022;16:100402. doi: 10.1016/j.mtbio.2022.100402
  15. Roskies M, Jordan JO, Fang D, et al. Improving PEEK bioactivity for craniofacial reconstruction using a 3D printed scaffold embedded with mesenchymal stem cells. J Biomater Appl. 2016;31(1):132-139. doi: 10.1177/0885328216638636 
  16. Hickok N, Rochfort ETJ, Jaekel DJ, Richards RG, Moriarty TF, Poulsson AHC. Bacterial interactions with PEEK. In: Kurtz SM, ed. PEEK Biomaterials Handbook. 2nd ed. Norwich, NY: William Andrew Publishing; 2019: 121-146. doi: 10.1016/B978-0-12-812524-3.00009-0
  17. Basgul C, Yu T, MacDonald DW, Siskey R, Marcolongo M, Kurtz SM. Structure-property relationships for 3D printed PEEK intervertebral lumbar cages produced using fused filament fabrication. J Mater Res. 2018;33(14):2040-2051. doi: 10.1557/jmr.2018.178
  18. Spece H, Yu T, Law A, Marcolongo M, Kurtz SM. 3D printed porous PEEK created via fused filament fabrication for osteoconductive orthopaedic surfaces. J Mech Behav Biomed Mater. 2020:103850. doi: 10.1016/j.jmbbm.2020.103850
  19. Webster TJ, Patel AA, Rahaman MN, Bal BS. Anti-infective and osteointegration properties of silicon nitride, poly(ether ether ketone), and titanium implants. Acta Biomater. 2012;8(12):4447-4454. doi: 10.1016/j.actbio.2012.07.038
  20. Gorth DJ, Puckett S, Ercan B, Webster TJ, Rahaman M, Bal BS. Decreased bacteria activity on Si3N4 surfaces compared with PEEK or titanium. Int J Nanomed. 2012:4829-4840. doi: 10.2147/IJN.S35190
  21. Du X, Lee SS, Blugan G, Ferguson SJ. Silicon nitride as a biomedical material: an overview. Int J Mol Sci. 2022;23(12). doi: 10.3390/ijms23126551
  22. ASTM International. Standard Test Methods for Intervertebral Body Fusion Devices. PA, USA: ASTM; 2022. doi: 10.1520/F2077-22
  23. Knott S, Curry D, Zhao N, et al. Staphylococcus aureus floating biofilm formation and phenotype in synovial fluid depends on albumin, fibrinogen, and hyaluronic acid. Front Microbiol. 2021;12:655873. doi: 10.3389/fmicb.2021.655873
  24. Wu S-H, Li Y, Zhang Y-Q, et al. Porous titanium-6 aluminum-4 vanadium cage has better osseointegration and less micromotion than a poly-ether-ether-ketone cage in sheep vertebral fusion. Artif Organs. 2013;37(12):E191-E201. doi: 10.1111/aor.12153
  25. Quarles LD, Yohay DA, Lever LW, Caton R, Wenstrup RJ. Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development. J Bone Miner Res. 1992;7(6):683-692. doi: 10.1002/jbmr.5650070613
  26. Chen YH, Connelly JP, Florian C, Cui X, Pruett-Miller SM. Short tandem repeat profiling via next-generation sequencing for cell line authentication. Dis Model Mech. 2023;16(10). doi: 10.1242/dmm.050150
  27. Wilkesmann S, Westhauser F, Fellenberg J. Combined fluorescence-based in vitro assay for the simultaneous detection of cell viability and alkaline phosphatase activity during osteogenic differentiation of osteoblast precursor cells. Methods Protoc. 2020;3(2). doi: 10.3390/mps3020030
  28. Peck JH, Sing DC, Nagaraja S, Peck DG, Lotz JC, Dmitriev AE. Mechanical performance of cervical intervertebral body fusion devices: a systematic analysis of data submitted to the Food and Drug Administration. J Biomech. 2017;54:26-32. doi: 10.1016/j.jbiomech.2017.01.032
  29. Monich PR, Henriques B, Novaes de Oliveira AP, Souza JCM, Fredel MC. Mechanical and biological behavior of biomedical PEEK matrix composites: A focused review. Mater Lett. 2016;185:593-597. doi: 10.1016/j.matlet.2016.09.005
  30. Luo C, Liu Y, Peng B, et al. PEEK for oral applications: recent advances in mechanical and adhesive properties. Polymers. 2023;15(2):386. doi: 10.3390/polym15020386 
    1. Manzoor F, Golbang A, Jindal S, et al. 3D printed PEEK/HA composites for bone tissue engineering applications: effect of material formulation on mechanical performance and bioactive potential. J Mech Behav Biomed Mater. 2021;121:104601. doi: 10.1016/j.jmbbm.2021.104601
    2. Javaid S, Dey M, Matzke C, Gupta S. Synthesis and characterization of engineered PEEK‐based composites for enhanced tribological and mechanical performance. J Appl Polym Sci. 2022;139(39):e52886. doi: 10.1002/app.52886
    3. Ill Yong K, Sugino A, Kikuta K, Ohtsuki C, Cho SB. Bioactive composites consisting of PEEK and calcium silicate powders. J Biomater Appl. 2008;24(2):105-118. doi: 10.1177/0885328208094557
    4. Petrovic L, Pohle D, Münstedt H, Rechtenwald T, Schlegel KA, Rupprecht S. Effect of βTCP filled polyetheretherketone on osteoblast cell proliferationin vitro. J Biomed Sci. 2006;13(1):41-46. doi: 10.1007/s11373-005-9032-z
    5. Fogel G, Martin N, Williams GM, et al. Choice of spinal interbody fusion cage material and design influences subsidence and osseointegration performance. World Neurosurg. 2022;162:e626-e634. doi: 10.1016/j.wneu.2022.03.087
    6. Bock RM, Jones EN, Ray DA, Bal BS, Pezzotti G, McEntire BJ. Bacteriostatic behavior of surface modulated silicon nitride in comparison to polyetheretherketone and titanium. J Biomed Mater Res A. 2017;105(5):1521-1534. doi: 10.1002/jbm.a.35987
    7. Pezzotti G, Marin E, Adachi T, et al. Incorporating Si3N4 into PEEK to produce antibacterial, osteocondutive, and radiolucent spinal implants. Macromolecular Bioscience. 2018;18(6):1800033. doi: 10.1002/mabi.201800033
    8. Marin E, Boschetto F, Zanocco M, et al. KUSA-A1 mesenchymal stem cells response to PEEK-Si3N4 composites. Mater Today Chem. 2020;17:100316. doi: 10.1016/j.mtchem.2020.100316
    9. Hu G, Zhu Y, Xu F, et al. Comparison of surface properties, cell behaviors, bone regeneration and osseointegration between nano tantalum/PEEK composite and nano silicon nitride/PEEK composite. J Biomater Sci Polym Ed. 2022;33(1):35-56. doi: 10.1080/09205063.2021.1974812
    10. Breijyeh Z, Jubeh B, Karaman R. Resistance of gram-negative bacteria to current antibacterial agents and approaches to resolve it. Molecules. 2020;25(6). doi: 10.3390/molecules25061340
    11. Dai Y, Guo H, Chu L, et al. Promoting osteoblasts responses in vitro and improving osteointegration in vivo through bioactive coating of nanosilicon nitride on polyetheretherketone. J Orthop Translat. 2020;24: 198-208. doi: 10.1016/j.jot.2019.10.011
    12. Xu Z, Wu H, Wang F, et al. A hierarchical nanostructural coating of amorphous silicon nitride on polyetheretherketone with antibacterial activity and promoting responses of rBMSCs for orthopedic applications. J Mater Chem B. 2019;7(39):6035-6047. doi: 10.1039/C9TB01565E

     

     


     

Conflict of interest
Dr. Ryan M. Bock is currently employed by SINTX, a company specializing in the production of silicon nitride powder. As our research pertains to silicon nitride-based materials, there is a potential conflict of interest that arises due to Dr. Bock’s affiliation with SINTX. Dr. Noreen Hickok and Dr. Steven Kurtz are paid consultants for SINTX and also have a conflict of interest. However, we want to emphasize that the research presented in this paper has been conducted independently and without any undue influence from the company. Dr. Kurtz also reports that he is a member of Gyroid LLC, a scientific and technical consulting firm. Unrelated to the present work, Dr. Kurtz reports institutional funding from 3Spine; Celanese; Ceramtec; DJO Global; Invibio; Lima Corporate; Mitsubishi Chemical Advanced Materials; Orthoplastics; SINTX Technologies; Stryker; Wright Medical Technology; and Zimmer Biomet. Dr. Kurtz is a board member of Formae, Inc., and receives book royalties from Elsevier, Inc. We have taken necessary measures to ensure the integrity and objectivity of the present study, adhering to the highest standards of scientific rigor and ethics. We are committed to transparency and have disclosed Dr. Bock’s, Dr. Hickok’s, and Dr. Kurtz’s conflicts of interest to ensure that the journal’s readers can evaluate our work within this context.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing