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The addition of silicon nitride to PMMA bone cements reduces bacterial attachment while supporting pre-osteoblast viability
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering.ORCID iD: 0000-0003-2018-3409
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.ORCID iD: 0000-0001-9529-650X
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering.ORCID iD: 0000-0001-6663-6536
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Injectable poly (methyl methacrylate) (PMMA) bone cements are widely used in orthopaedics to stabilize fractures and for implant fixation. However, bacterial attachment to bone cements leads to significant complications that can create a need for implant revision. Common attempts at reducing bacterial attachment are through the addition of antibiotics or antibacterial nanometals to the bone cements. However, clinical data is inconclusive on the effectiveness of antibiotic-loaded bone cements and a negative osteoblastic response has been reported for certain additive concentrations. There is therefore a need for an additive that can positively affect osteoblastic behaviour while inhibiting bacterial attachment. Silicon nitride (Si3N4) could be such an additive, with initial studies showing promise in achieving antipathogenic properties. The aim of this study was hence to investigate the possibility of creating a bone cement that can support osteoblast growth while reducing bacterial attachment by introducing silicon nitride powders into an injectable PMMA cement. To this end, commercially available bone cements were doped with 5, 10 and 20% weight/weight (w/w) of Si3N4. Their mechanical properties were examined through compression testing and their radiopacity was evaluated through fluoroscopy imaging. The samples that fulfilled compressive strength requirements had their biological properties tested using Staphylococcus epidermidis bacteria for antibacterial properties and MC3T3-E1 pre-osteoblasts for the examination of cytotoxicity. Bone cements that were doped with up to 20% w/w Si3N4 were radiopaque (only 13% reduction in optical density compared to radiopaque controls) and retained their compressive strength (85.35±2.1 MPa compared to 83.4±1.9MPa for the commercial cements), while significantly reducing bacterial attachment by more than 90% compared to commercial cements and being equally cytocompatible. This study supports further evaluation of Si3N4 as an additive to injectable bone cements as a way to create mechanically stable, radiopaque, bacteriostatic bone cements that could improve osteointegration.

National Category
Materials Engineering
Identifiers
URN: urn:nbn:se:uu:diva-506362OAI: oai:DiVA.org:uu-506362DiVA, id: diva2:1775393
Note

De två sista författarna delar sistaförfattarskapet

Available from: 2023-06-27 Created: 2023-06-27 Last updated: 2023-06-27Bibliographically approved
In thesis
1. Silicon nitride-based materials for spinal and antipathogenic applications
Open this publication in new window or tab >>Silicon nitride-based materials for spinal and antipathogenic applications
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Silicon nitride (Si3N4) is a ceramic material that is well-established in industrial applications due to its stability in demanding environments. The mechanical properties and biocompatibility of the material have led to its approval for clinical use in spinal implants. The unique surface chemistry of Si3N4 has been shown to create a chemical environment that is supportive to bone regeneration while simultaneously reducing bacterial viability, both in vitro and in animal models in vivo. Thus, Si3N4 can be used in the spine to reduce patient recovery times while protecting the implant site from damaging and costly infections. However, results from clinical studies have not shown significant differences between silicon nitride and other spinal implant materials in terms of patient outcomes.   

Thus, the first aim of this thesis was to find ways to optimise the biological properties of the material and in turn create spinal implants that would exhibit significantly higher osteointegration while reducing the incidence of infections. To this end, a thermochemical surface modification was developed that changed the surface chemistry and roughness of the material resulting in increased in vitro bioactivity without affecting its antibacterial behaviour. Furthermore, the possibility of creating an osteoconductive, antibacterial bone cement to be used in vertebroplasties in the spine was explored. By adding up to 20%wt of a Si3N4 powder to poly methyl methacrylate (PMMA) cements, a significant (>90%) reduction of bacterial biofilm formation was achieved without affecting the compressive strength or biocompatibility of the modified bone cements in a negative way.

A secondary objective of the study was to explore the antipathogenic properties of the material, fulfilling the growing need for a world where the spread of dangerous pathogens will be limited. The efficiency of the material against one of the most resilient DNA-viruses, the human adenovirus, was tested. It was found that contact with Si3N4 in both powder and bulk form rapidly reduced infectivity (>98% and >73%, respectively). Based on these results, a thermal modification of silicon nitride powders was developed, that would enhance their antiviral efficiency against SARS-CoV-2 and thus the applicability of the material. It was found that 10%wt modified-Si3N4 slurries rendered the coronavirus non-infectious after less than a minute of contact. The results of these studies proved that silicon nitride can also be used as an antipathogenic agent in environmental applications.

Overall, in this thesis, steps were taken towards the development of Si3N4-based materials that can lead to faster healing, lower infection rates and that can be used to limit the spread of disease.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2023. p. 44
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 2284
National Category
Materials Engineering
Identifiers
urn:nbn:se:uu:diva-506364 (URN)978-91-513-1846-2 (ISBN)
Public defence
2023-09-15, Siegbahnshalen, Ångströmslaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2023-08-25 Created: 2023-06-27 Last updated: 2023-08-25

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Katsaros, IoannisEcheverri, EstefaniaEngqvist, HåkanPersson, CeciliaXia, Wei

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